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Sample records for stretch airway smooth

  1. Human airway smooth muscle

    OpenAIRE

    Jongste, Johan

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less likely, squeezing mucus out of mucous glands and pulling open the alveoli next to the airways1 . Any role of airway smooth muscle is necessarily limited, because an important degree of contraction will l...

  2. Human airway smooth muscle

    NARCIS (Netherlands)

    J.C. de Jongste (Johan)

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less

  3. Airway smooth muscle cells : regulators of airway inflammation

    NARCIS (Netherlands)

    Zuyderduyn, Suzanne

    2007-01-01

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

  4. Mediators on human airway smooth muscle.

    Science.gov (United States)

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

    1997-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sonia R Rosner

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

  6. Acetylcholine : a novel regulator of airway smooth muscle remodelling?

    NARCIS (Netherlands)

    Gosens, R; Zaagsma, J; Bromhaar, MG; Nelemans, A; Meurs, H

    2004-01-01

    Increased airway smooth muscle mass is a pathological feature that asthma and chronic obstructive pulmonary disease (COPD) have in common. This increase has gained renewed interest in view of recent developments showing that airway smooth muscle, instead of solely being a contractile partner, is

  7. Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

    NARCIS (Netherlands)

    Yick, C. Y.; Ferreira, D. S.; Annoni, R.; von der Thüsen, J. H.; Kunst, P. W.; Bel, E. H.; Lutter, R.; Mauad, T.; Sterk, P. J.

    2012-01-01

    Background: Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in

  8. Insulin induces airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D.; Gosens, R.; Ris, J. M.; Zaagsma, J.; Meurs, H.; Nelemans, S. A.

    Background and purpose: Recently, the use of inhaled insulin formulations for the treatment of type I and type II diabetes has been approved in Europe and in the United States. For regular use, it is critical that airway function remains unimpaired in response to insulin exposure. Experimental

  9. Plasticity of airway smooth muscle phenotype in airway remodeling

    NARCIS (Netherlands)

    Gosens, Reinoud

    2004-01-01

    Isolated smooth muscle cells in culture do not immediately start dividing, even in a medium containing all nutrients required. Before entering the cell cycle, the cells first accomodate their phenotype to their new environment. They lose their contractile properties and modulate to a proliferative

  10. 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.

    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

  11. Angiogenesis is induced by airway smooth muscle strain.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.

  12. HSP20 phosphorylation and airway smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mariam Ba

    2009-06-01

    Full Text Available Mariam Ba1, Cherie A Singer1, Manoj Tyagi2, Colleen Brophy3, Josh E Baker4, Christine Cremo4, Andrew Halayko5, William T Gerthoffer21Department of Pharmacology, University of Nevada School of Medicine, Reno, NV, USA; 2Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA; 3Harrington Department of Biochemistry, Arizona State University, Tempe, AZ, USA; 4Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA; 5Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, MB, CanadaAbstract: HSP20 (HSPB6 is a small heat shock protein expressed in smooth muscles that is hypothesized to inhibit contraction when phosphorylated by cAMP-dependent protein kinase. To investigate this hypothesis in airway smooth muscle (ASM we showed that HSP20 was constitutively expressed as well as being inducible in cultured hASM cells by treatment with 1 µM isoproterenol or 10 µM salmeterol. In contrast, a mixture of proinflammatory mediators (interleukin-1β, tumor necrosis factor α, and interferon γ inhibited expression of HSP20 by about 50% in 48 hours. To determine whether phosphorylation of HSP20 is sufficient to induce relaxation, canine tracheal smooth muscle was treated with a cell permeant phosphopeptide that mimics the phosphorylation of HSP20. The HSP20 phosphopeptide antagonized carbacholinduced contraction by 60% with no change in myosin light chain phosphorylation. Recombinant full length HSP20 inhibited skeletal actin binding to smooth muscle myosin subfragment 1 (S1, and recombinant cell permeant TAT-HSP20 S16D mutant reduced F-actin filaments in cultured hASM cells. Carbachol stimulation of canine tracheal smooth muscle tissue caused redistribution of HSP20 from large macromolecular complexes (200–500 kDa to smaller complexes (<60 kDa. The results are consistent with HSP20 expression and macromolecular structure being dynamically regulated in airway

  13. Smooth muscle actin and myosin expression in cultured airway smooth muscle cells.

    Science.gov (United States)

    Wong, J Z; Woodcock-Mitchell, J; Mitchell, J; Rippetoe, P; White, S; Absher, M; Baldor, L; Evans, J; McHugh, K M; Low, R B

    1998-05-01

    In this study, the expression of smooth muscle actin and myosin was examined in cultures of rat tracheal smooth muscle cells. Protein and mRNA analyses demonstrated that these cells express alpha- and gamma-smooth muscle actin and smooth muscle myosin and nonmuscle myosin-B heavy chains. The expression of the smooth muscle specific actin and myosin isoforms was regulated in the same direction when growth conditions were changed. Thus, at confluency in 1 or 10% serum-containing medium as well as for low-density cells (50-60% confluent) deprived of serum, the expression of the smooth muscle forms of actin and myosin was relatively high. Conversely, in rapidly proliferating cultures at low density in 10% serum, smooth muscle contractile protein expression was low. The expression of nonmuscle myosin-B mRNA and protein was more stable and was upregulated only to a small degree in growing cells. Our results provide new insight into the molecular basis of differentiation and contractile function in airway smooth muscle cells.

  14. 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.

  15. Human eosinophil–airway smooth muscle cell interactions

    Directory of Open Access Journals (Sweden)

    J. Margaret Hughes

    2000-01-01

    Full Text Available Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

  16. Airway smooth muscle cell culture: application to studies of airway wall remodelling and phenotype plasticity in asthma.

    Science.gov (United States)

    Hirst, S J

    1996-04-01

    Chronic persistent asthma is characterized by poorly reversible airway obstruction. Histopathological studies of airways removed postmortem from patients with severe asthma reveal marked inflammatory and architectural changes associated with airway wall thickening. Increased airway smooth muscle content, occurring as a result of hyperplastic and/or hypertrophic growth, is believed to be one of the principal contributors to airway wall thickening. Intense interest is building to discover the mechanisms responsible for these long-term structural changes. In vitro cell culture offers a powerful and exacting approach to cellular and molecular studies of the long-term regulation of airway smooth muscle function. This review discusses the methodologies for establishing and maintaining cell cultures of airway smooth muscle. It also describes the characteristics of these cells in culture and addresses the potential importance of phenotype plasticity and its possible relationship to altered smooth muscle function in vivo. Drawing on parallels from vascular studies, this review focuses, in particular, on the synthetic nature of the airway smooth muscle cell, emphasizing its potential to alter the composition of the extracellular matrix environment and orchestrate key events in the process of chronic airway remodelling.

  17. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  18. Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity.

    Science.gov (United States)

    Naveed, Shams-Un-Nisa; Clements, Debbie; Jackson, David J; Philp, Christopher; Billington, Charlotte K; Soomro, Irshad; Reynolds, Catherine; Harrison, Timothy W; Johnston, Sebastian L; Shaw, Dominick E; Johnson, Simon R

    2017-04-15

    Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma. To investigate whether MMP-1 could be activated by mast cells and increase asthma severity. Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed. Airway smooth muscle cells generated pro-MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P asthma, airway pro-MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV 1 and worsening asthma symptoms. MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness.

  19. Caveolae facilitate muscarinic receptor-mediated intracellular Ca2+ mobilization and contraction in airway smooth muscle

    NARCIS (Netherlands)

    Gosens, Reinoud; Stelmack, Gerald L.; Dueck, Gordon; Mutawe, Mark M.; Hinton, Martha; McNeill, Karol D.; Paulson, Angela; Dakshinamurti, Shyamala; Gerthoffer, William T.; Thliveris, James A.; Unruh, Helmut; Zaagsma, Johan; Halayko, Andrew J.

    2007-01-01

    Contractile responses of airway smooth muscle ( ASM) determine airway resistance in health and disease. Caveolae microdomains in the plasma membrane are marked by caveolin proteins and are abundant in contractile smooth muscle in association with nanospaces involved in Ca2+ homeostasis. Caveolin-1

  20. Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

    Science.gov (United States)

    Luo, De-Yi; Wazir, Romel; Du, Caigan; Tian, Ye; Yue, Xuan; Wei, Tang-Qiang; Wang, Kun-Jie

    2015-11-01

    The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

  1. The Integrin-blocking Peptide RGDS Inhibits Airway Smooth Muscle Remodeling in a Guinea Pig Model of Allergic Asthma

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Bos, I. Sophie T.; Gosens, Reinoud; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    2010-01-01

    Rationale: Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyper-responsiveness in asthma. The mechanisms driving these changes are, however, incompletely understood. Recently, an important role for extracellular matrix proteins in

  2. Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro : Implications in understanding asthma

    NARCIS (Netherlands)

    Wright, David; Sharma, Pawan; Ryu, Min-Hyung; Risse, Paul-Andre; Ngo, Melanie; Maarsingh, Harm; Koziol-White, Cynthia; Jha, Aruni; Halayko, Andrew J.; West, Adrian R.

    Asthma is a chronic obstructive airway disease characterised by airway hyperresponsiveness (AHR) and airway wall remodelling. The effector of airway narrowing is the contraction of airway smooth muscle (ASM), yet the question of whether an inherent or acquired dysfunction in ASM contractile function

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

    NARCIS (Netherlands)

    Maarsingh, H; Leusink, J; Bos, IST; Zaagsma, J; Meurs, H

    2006-01-01

    Background: Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production - due to competition with neuronal

  4. S100A12 and the Airway Smooth Muscle: Beyond Inflammation and Constriction

    OpenAIRE

    Camoretti-Mercado, Blanca; Karrar, Eltayeb; Nu?ez, Luis; Bowman, Marion A Hofmann

    2012-01-01

    Airway inflammation, lung remodeling, and Airway Hyperresponsiveness (AHR) are major features of asthma and Chronic Obstructive Pulmonary Disease (COPD). The inflammatory response to allergens, air pollutants, and other insults is likely to play a key role in promoting structural changes in the lung including the overabundance of Airway Smooth Muscle (ASM) seen in asthmatics. These alterations or remodeling could, in turn, impact the immunmodulatory actions of the ASM, the ASM's contractile p...

  5. WNT-5A and WNT-5B modulate calcium homeostasis in airway smooth muscle

    NARCIS (Netherlands)

    Koopmans, Tim; Kumawat, Kudleer; Van Den Berge, Maarten; Hoffmann, Roland; Halayko, Andrew J.; Gosens, Reinoud

    2014-01-01

    Rationale Airway hyperresponsiveness is a common feature of asthma explained in part by an excessive contractile response of the airway smooth muscle (ASM). The underlying mechanisms are complex and in need of study. WNT-5A and WNT-5B, two members of the WNT signaling pathway, may be of

  6. Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

    NARCIS (Netherlands)

    Januskevicius, Andrius; Gosens, Reinoud; Sakalauskas, Raimundas; Vaitkiene, Simona; Janulaityte, Ieva; Halayko, Andrew J; Hoppenot, Deimante; Malakauskas, Kestutis

    2017-01-01

    Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact

  7. The purinergic component of human bladder smooth muscle cells’ proliferation and contraction under physiological stretch

    Energy Technology Data Exchange (ETDEWEB)

    Wazir, Romel; Luo, De-Yi; Tian, Ye; Yue, Xuan; Li, Hong; Wang, Kun-Jie, E-mail: kunjiewangatscu@163.com

    2013-07-26

    Highlights: •Stretch induces proliferation and contraction. •Optimum applied stretch in vitro is 5% and 10% equibiaxial stretching respectively. •Expression of P2X1 and P2X2 is upregulated after application of stretch. •P2X2 is possibly more susceptible to stretch related changes. •Purinoceptors functioning may explain conditions with atropine resistance. -- Abstract: Objective: To investigate whether cyclic stretch induces proliferation and contraction of human smooth muscle cells (HBSMCs), mediated by P2X purinoceptor 1 and 2 and the signal transduction mechanisms of this process. Methods: HBSMCs were seeded on silicone membrane and stretched under varying parameters; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (Frequency: 0.05 Hz, 0.1 Hz, 0.2 Hz, 0.5 Hz, 1 Hz). 5-Bromo-2-deoxyuridine assay was employed for proliferative studies. Contractility of the cells was determined using collagen gel contraction assay. After optimal physiological stretch was established; P2X1 and P2X2 were analyzed by real time polymerase chain reaction and Western Blot. Specificity of purinoceptors was maintained by employing specific inhibitors; (NF023 for P2X1, and A317491for P2X2), in some experiments. Results: Optimum proliferation and contractility were observed at 5% and 10% equibiaxial stretching respectively, applied at a frequency of 0.1 Hz; At 5% stretch, proliferation increased from 0.837 ± 0.026 (control) to 1.462 ± 0.023%, p < 0.05. Mean contraction at 10% stretching increased from 31.7 ± 2.3%, (control) to 78.28 ±1.45%, p < 0.05. Expression of P2X1 and P2X2 was upregulated after application of stretch. Inhibition had effects on proliferation (1.232 ± 0.051, p < 0.05 NF023) and (1.302 ± 0.021, p < 0.05 A314791) while contractility was markedly reduced (68.24 ± 2.31, p < 0.05 NF023) and (73.2 ± 2.87, p < 0.05 A314791). These findings shows that mechanical stretch can promote magnitude-dependent proliferative and contractile modulation of HBSMCs in

  8. Mast cell numbers in airway smooth muscle and PC(20)AMP in asthma and COPD

    NARCIS (Netherlands)

    Liesker, J. J. W.; ten Hacken, N. H. T.; Rutgers, S. R.; Zeinstra-Smith, M.; Postma, D. S.; Timens, W.

    Introduction: Most patients with asthma and many patients with COPD show bronchial hyperresponsiveness to adenosine (BHRAMP). BHRAMP may be caused by release of mast cell histamine, which induces smooth muscle contraction. Aim of the study: To evaluate whether mast cell numbers in airway smooth

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

    Science.gov (United States)

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

    2011-12-15

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

  10. Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma

    DEFF Research Database (Denmark)

    Pilecki, Bartosz; Schlosser, Anders; Wulf-Johansson, Helle

    2015-01-01

    . In the current study we investigated the role of MFAP4 in experimental allergic asthma. METHODS: MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used...... to evaluate MFAP4-dependent airway smooth muscle responses. RESULTS: MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development...... and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation...

  11. Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch.

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    Full Text Available Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1 cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2 cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK and p38 activation with peaks at 10 min; (3 azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4 SP600125 (a JNK inhibitor and SB203580 (a p38 inhibitor protected against stretch-induced RASMC death; (5 Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.

  12. Cyclic stretch induces human bladder smooth muscle cell proliferation in vitro through muscarinic receptors.

    Science.gov (United States)

    Dai, Yi; Tian, Ye; Luo, De-Yi; Wazir, Romel; Yue, Xuan; Li, Hong; Wang, Kun-Jie

    2015-03-01

    The present study aimed to investigate whether the cyclic stretch‑induced proliferation of human bladder smooth muscle cells (HBSMCs) is mediated by muscarinic (M) receptors, together with the signal transduction mechanisms involved in this process. HBSMCs seeded onto silicone membranes were subjected to different cyclic stretches (5, 10, 15 and 20%) for 6 and 12 h. As the effect of cyclic stretch on M2 and M3 mRNA expression levels was maximal at 6 h 10% stretch, all subsequent experiments were performed at this stretch. Western blot analysis was used to quantify M2, M3, protein kinase C (PKC) and phosphorylated (p)‑PKC protein expression levels, flow cytometry was employed to examine cell cycle distribution and a 5-bromo‑2-deoxyuridine (BrdU) incorporation assay was used to assess cell proliferation at this stretch. Subsequently, HBSMCs were exposed to different acetylcholine concentrations and/or cyclic stretch, M receptor antagonists [AF-DX16, an M2 receptor antagonist; 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), an M3 receptor antagonist and atropine, a non‑selective antagonist] and GF 109203X, a PKC antagonist, to assess the possible underlying signaling mechanisms. Cyclic stretch was found to increase the proliferation of HBSMCs and the expression levels of M2, M3, PKC and p‑PKC proteins. M receptor and PKC antagonists exerted no apparent effect on nonstretched cells, but reduced the incorporation of BrdU into stretched cells; the most pronounced effects were observed when non‑selective M receptor and PKC antagonists were applied. Notably, 4‑DAMP did not inhibit stretch‑induced PKC activation. These results indicate that the activation of the M3 receptor signaling pathway in stretch‑induced HBSMC proliferation occurs via PKC-independent mechanisms.

  13. The relationship between bronchial hyperresponsiveness to methacholine and airway smooth muscle structure and reactivity.

    Science.gov (United States)

    Armour, C L; Black, J L; Berend, N; Woolcock, A J

    1984-11-01

    The airway responsiveness of a group of 25 patients scheduled for lung resection was studied. 10 of 25 patients had a greater than or equal to 20% fall in FEV1 in response to inhaled methacholine (responders), with PD20 FEV1 values ranging from 0.6 to 7.3 mumol. Methacholine did not induce a 20% fall in FEV1 in 15 patients (non-responders). The sensitivity to carbachol and histamine of the bronchial smooth muscle resected from these patients was similar in tissue from responders and non-responders. There was no correlation between in vivo responsiveness to methacholine and in vitro sensitivity to carbachol or histamine. The volume of smooth muscle in some of these airway preparations was quantitated. There was a significant correlation between the maximum tension change in response to histamine and the volume of smooth muscle in each airway. There was no similar correlation for carbachol. The in vivo responsiveness to methacholine and in vitro sensitivity to histamine or carbachol was not related to the degree of inflammation in the airways studied. It is concluded that in vivo responsiveness cannot be explained in terms of smooth muscle sensitivity and that there may be differences between histamine and carbachol in the mechanism of contraction of airway smooth muscle.

  14. Effects of Bronchial Thermoplasty on Airway Smooth Muscle and Collagen Deposition in Asthma.

    Science.gov (United States)

    Chakir, Jamila; Haj-Salem, Ikhlass; Gras, Delphine; Joubert, Philippe; Beaudoin, Ève-Léa; Biardel, Sabrina; Lampron, Noel; Martel, Simon; Chanez, Pascal; Boulet, Louis-Philippe; Laviolette, Michel

    2015-11-01

    The aim of bronchial thermoplasty is to improve asthma symptoms by reducing central airway smooth muscle mass. Up to now, the reduction of smooth muscle mass has been documented for only 1 group of 10 patients who had 15% or more of their pretreatment total bronchial biopsy area occupied by smooth muscle. To evaluate the effects of bronchial thermoplasty on airway smooth muscle mass and airway collagen deposition in adult patients with asthma, regardless of pretreatment smooth muscle area. Seventeen patients with asthma underwent bronchial thermoplasty over the course of three visits. At Visit 1, bronchial biopsies were taken from the lower lobe that was not treated during this session. At Visit 2 (3-14 wk after the first visit), all 17 patients underwent biopsy of the lower lobe treated during the first procedure. At Visit 3 (7-22 wk after the first visit), nine patients agreed to undergo biopsy of the same lower lobe. Histological and immunohistochemical analyses were performed on the biopsy specimens. Bronchial thermoplasty decreased airway smooth muscle from 12.9 ± 1.2% of the total biopsy surface at Visit 1 to 4.6 ± 0.8% at Visit 2 (P Bronchial thermoplasty also decreased Type I collagen deposition underneath the basement membrane from 6.8 ± 0.3 μm at Visit 1 to 4.3 ± 0.2 μm at Visit 2 (P bronchial thermoplasty reduced the smooth muscle mass of treated airway segments, regardless of the baseline level of muscle mass. Treatment also altered the deposition of collagen. At follow-up, bronchial thermoplasty improved asthma control; however, the limited number of subjects did not allow us to evaluate possible correlations between these improvements and the studied histological parameters. Further studies are needed to confirm these results and evaluate their persistence.

  15. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  16. Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

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    Jian tao Song

    Full Text Available OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21 is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs. METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb. FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4 participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

  17. Overexpression of functional TrkA receptors after internalisation in human airway smooth muscle cells.

    Science.gov (United States)

    Freund-Michel, Véronique; Frossard, Nelly

    2008-10-01

    Trafficking of the TrkA receptor after stimulation by NGF is of emerging importance in structural cells in the context of airway inflammatory diseases. We have recently reported the expression of functional TrkA receptors in human airway smooth muscle cells (HASMC). We have here studied the TrkA trafficking mechanisms in these cells. TrkA disappearance from the cell membrane was induced within 5 min of NGF (3pM) stimulation. Co-immunoprecipitation of clathrin-TrkA was revealed, and TrkA internalisation inhibited either by clathrin inhibitors or by siRNA inducing downregulation of endogenous clathrin. TrkA internalised receptors were totally degraded in lysosomes, with no recycling phenomenon. Newly synthesized TrkA receptors were thereafter re-expressed at the cell membrane within 10 h. TrkA re-synthesis was inhibited by blockade of clathrin-dependent internalisation, but not of TrkA receptors lysosomal degradation. Finally, we observed that NGF multiple stimulations progressively increased TrkA expression in HASMC, which was associated with an increase in NGF/TrkA-dependent proliferation. In conclusion, we show here the occurrence of clathrin-dependent TrkA internalisation and lysosomal degradation in the airway smooth muscle, followed by upregulated re-synthesis of functional TrkA receptors and increased proliferative effect in the human airway smooth muscle. This may have pathophysiological consequences in airway inflammatory diseases.

  18. Phenotype and functional plasticity of airway smooth muscle : role of caveolae and caveolins

    NARCIS (Netherlands)

    Halayko, Andrew J; Tran, Thai; Gosens, Reinoud

    2008-01-01

    Airway smooth muscle (ASM) cells exhibit phenotype plasticity that is under control of external stimuli such as growth factors and the extracellular matrix, and is regulated by a network of intracellular signaling cascades that control transcription and protein translation of phenotype-specific

  19. Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D.; Gosens, Reinout; Bos, I.S.T.; Meurs, Herman; Zaagsma, Hans; Nelemans, Herman

    2004-01-01

    1 Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM

  20. Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs.

    Science.gov (United States)

    Pisarri, T E; Giesbrecht, G G

    1997-05-01

    Cooling intrathoracic airways by filling the pulmonary circulation with cold blood alters pulmonary mechanoreceptor discharge. To determine whether this initiates reflex changes that could contribute to airway obstruction, we measured changes in tracheal smooth muscle tension and bronchial arterial flow evoked by cooling. In nine chloralose-anesthetized open-chest dogs, the right pulmonary artery was cannulated and perfused; the left lung, ventilated separately, provided gas exchange. With the right lung phasically ventilated, filling the right pulmonary circulation with 5 degrees C blood increased smooth muscle tension in an innervated upper tracheal segment by 23 +/- 6 (SE) g from a baseline of 75 g. Contraction began within 10 s of injection and was maximal at approximately 30s. The response was abolished by cervical vagotomy. Bronchial arterial flow increased from 8 +/- 1 to 13 +/- 2 ml/min, with little effect on arterial blood pressure. The time course was similar to that of the tracheal response. This response was greatly attenuated after cervical vagotomy. Blood at 20 degrees C also increased tracheal smooth muscle tension and bronchial flow, whereas 37 degrees C blood had little effect. The results suggested that alteration of airway mechanoreceptor discharge by cooling can initiate reflexes that contribute to airway obstruction.

  1. Potentiation of contraction of rabbit airway smooth muscle by some cyclooxygenase products.

    Science.gov (United States)

    Armour, C L; Johnson, P R; Black, J L

    1988-06-01

    An alteration in smooth muscle sensitivity may be one of the mechanisms of the airway hyperresponsiveness observed in asthma. Indomethacin inhibits experimentally induced airway hyperresponsiveness. We thus examined the effects of the cyclooxygenase products PGD2, PGF2 alpha and a thromboxane A2 analogue U46619 on contractile responses of rabbit airway smooth muscle to histamine, carbachol and electrical field stimulation (EFS). PGD2 did not potentiate any contractile responses. When PGF2 alpha (1 microM) was administered 30 min before cumulative concentration-response curves to histamine and carbachol, no potentiation was observed. However, PGF2 alpha (1 microM) added immediately before EFS and bolus doses of histamine potentiated the contractile responses. U46619 increased the cumulative concentration-responses to both histamine and carbachol. The fact that we could alter smooth muscle sensitivity in vitro with PGF2 alpha and a thromboxane analogue suggests that these mediators may be involved in the airway hyperresponsiveness observed in asthma.

  2. Airway Smooth Muscle as a Target in Asthma and the Beneficial Effects of Bronchial Thermoplasty

    Directory of Open Access Journals (Sweden)

    Luke J. Janssen

    2012-01-01

    Full Text Available Airflow within the airways is determined directly by the lumenal area of that airway. In this paper, we consider several factors which can reduce airway lumenal area, including thickening and/or active constriction of the airway smooth muscle (ASM. The latter cell type can also contribute in part to inflammation, another feature of asthma, through its ability to take on a synthetic/secretory phenotype. The ASM therefore becomes a strategically important target in the treatment of asthma, given these key contributions to the pathophysiology of that disease. Pharmacological approaches have been developed to elicit relaxation of the ASM, but these are not always effective in all patients, nor do they address the long-term structural changes which impinge on the airway lumen. The recent discovery that thermal energy can be used to ablate smooth muscle has led to the development of a novel physical intervention—bronchial thermoplasty—in the treatment of asthma. Here, we review the evolution of this novel approach, consider some of the possible mechanisms that account for its salutary effects, and pose new questions which may lead to even better therapies for asthma.

  3. Airway Smooth Muscle as a Target in Asthma and the Beneficial Effects of Bronchial Thermoplasty

    Science.gov (United States)

    Janssen, Luke J.

    2012-01-01

    Airflow within the airways is determined directly by the lumenal area of that airway. In this paper, we consider several factors which can reduce airway lumenal area, including thickening and/or active constriction of the airway smooth muscle (ASM). The latter cell type can also contribute in part to inflammation, another feature of asthma, through its ability to take on a synthetic/secretory phenotype. The ASM therefore becomes a strategically important target in the treatment of asthma, given these key contributions to the pathophysiology of that disease. Pharmacological approaches have been developed to elicit relaxation of the ASM, but these are not always effective in all patients, nor do they address the long-term structural changes which impinge on the airway lumen. The recent discovery that thermal energy can be used to ablate smooth muscle has led to the development of a novel physical intervention—bronchial thermoplasty—in the treatment of asthma. Here, we review the evolution of this novel approach, consider some of the possible mechanisms that account for its salutary effects, and pose new questions which may lead to even better therapies for asthma. PMID:23024662

  4. 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 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.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.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.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.

  5. PTEN gene silencing contributes to airway remodeling and induces airway smooth muscle cell proliferation in mice with allergic asthma.

    Science.gov (United States)

    Wen, Xin; Yan, Jing; Han, Xin-Rui; Zheng, Gui-Hong; Tang, Ran; Liu, Li-Fang; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

    2018-01-01

    Allergic asthma is a complex genetic disorder that involves interactions between genetic and environmental factors. Usage of PTEN may be a good therapeutic strategy for the management of allergic inflammation. Thus, the present study aims to explore the effects of phosphatase and tensin homolog ( PTEN ) gene silencing on airway remodeling and proliferation of airway smooth muscle cells (ASMCs) in a mouse model of allergic asthma. A total of 56 healthy female BABL/c mice (weighing between 16 to 22 grams) were selected and were assigned on random into ovalbumin (OVA; mice were stimulated with OVA to induce allergic asthma), OVA + si-PTEN, normal saline (NS; mice were treated with normal saline) and NS + si-PTEN groups. Masson staining was employed in order to observe lung tissue sections. Immunohistochemical staining was used to detect the expression of α-SMA + . Gene silencing was conducted in the NS + si-PTEN and OVA + si-PTEN groups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to detect the mRNA and protein expressions of PTEN in ASMCs of each group. CCK-8 assay and flow cytometry were performed to determine the cell proliferation rate and cell cycle. Airway remodeling and changes of smooth muscle layer were found in allergic asthmatic mice with thick airway walls. The expression of alpha smooth muscle actin (α-SMA + ) was significantly higher in ASMCs of the OVA, OVA + si-PTEN and NS + si-PTEN groups compared with ASMCs of the NS group. The mRNA and protein expressions of PTEN reduced in the OVA, OVA + si-PTEN and NS + si-PTEN groups. The rate of ASMCs proliferation in OVA, OVA + si-PTEN and NS + si-PTEN groups were significantly higher than the NS group. The proportion of ASMCs in S and G2 stages increased, while the number of cells in the G1 stage decreased after PTEN gene silencing. These results demonstrated that PTEN gene silencing might promote proliferation of ASMCs and airway remodeling in a

  6. PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    2012-01-01

    Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

  7. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

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    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping, E-mail: wpxie@njmu.edu.cn; Wang, Hong, E-mail: hongwang@njmu.edu.cn

    2015-08-15

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation and migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt

  8. Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype

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    Zaagsma Johan

    2010-04-01

    Full Text Available Abstract Background A major feature of chronic obstructive pulmonary disease (COPD is airway remodelling, which includes an increased airway smooth muscle (ASM mass. The mechanisms underlying ASM remodelling in COPD are currently unknown. We hypothesized that cigarette smoke (CS and/or lipopolysaccharide (LPS, a major constituent of CS, organic dust and gram-negative bacteria, that may be involved in recurrent airway infections and exacerbations in COPD patients, would induce phenotype changes of ASM. Methods To this aim, using cultured bovine tracheal smooth muscle (BTSM cells and tissue, we investigated the direct effects of CS extract (CSE and LPS on ASM proliferation and contractility. Results Both CSE and LPS induced a profound and concentration-dependent increase in DNA synthesis in BTSM cells. CSE and LPS also induced a significant increase in BTSM cell number, which was associated with increased cyclin D1 expression and dependent on activation of ERK 1/2 and p38 MAP kinase. Consistent with a shift to a more proliferative phenotype, prolonged treatment of BTSM strips with CSE or LPS significantly decreased maximal methacholine- and KCl-induced contraction. Conclusions Direct exposure of ASM to CSE or LPS causes the induction of a proliferative, hypocontractile ASM phenotype, which may be involved in airway remodelling in COPD.

  9. β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D

    NARCIS (Netherlands)

    Trian, Thomas; Burgess, Janette K; Niimi, Kyoko; Moir, Lyn M; Ge, Qi; Berger, Patrick; Liggett, Stephen B; Black, Judith L; Oliver, Brian G

    2011-01-01

    BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE:

  10. Effects of cyclic stretch on proliferation of mesenchymal stem cells and their differentiation to smooth muscle cells

    International Nuclear Information System (INIS)

    Ghazanfari, Samane; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali

    2009-01-01

    Bone marrow mesenchymal stem cells (MSCs) are capable of differentiating into a variety of cell types such as vascular smooth muscle cells (SMCs). In this study, we investigated influence of cyclic stretch on proliferation of hMSCs for different loading conditions, alignment of actin filaments, and consequent differentiation to SMCs. Isolated cells from bone marrow were exposed to cyclic stretch utilizing a customized device. Cell proliferation was examined by MTT assay, alignment of actin fibers by a designed image processing code, and cell differentiation by fluorescence staining. Results indicated promoted proliferation of hMSCs by cyclic strain, enhanced by elevated strain amplitude and number of cycles. Such loading regulated smooth muscle α-actin, and reoriented actin fibers. Cyclic stretch led to differentiation of hMSCs to SMCs without addition of growth factor. It was concluded that applying appropriate loading treatment on hMSCs could enhance proliferation capability, and produce functional SMCs for engineered tissues.

  11. Bronchial thermoplasty and the role of airway smooth muscle: are we on the right direction?

    Directory of Open Access Journals (Sweden)

    Menzella F

    2017-09-01

    Full Text Available Francesco Menzella,1 Mirco Lusuardi,2 Carla Galeone,1 Nicola Facciolongo1 1Department of Medical Specialties, Pneumology Unit, IRCCS – Arcispedale Santa Maria Nuova, Reggio Emilia, 2Unit of Respiratory Rehabilitation, AUSL Reggio Emilia, S Sebastiano Hospital, Correggio, Italy Abstract: Asthma is characterized by inflammation of the airways that includes eosinophils, basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have been studies on the role of hypersensitivity and inflammation in asthma, but the role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an endoscopic procedure that is approved by the US Food and Drug Administration (FDA for the treatment of severe refractory asthma, based on the local delivery of radio frequency at 65°C to the airways, with the aim of controlling bronchospasm through a reduction of airway smooth muscle (ASM. Several recent studies have shown significant improvement in clinical outcomes of bronchial thermoplasty for asthma, including symptom control, reduction in exacerbation and hospitalization rates, improved quality of life, and reduction in number of working days or school days lost due to asthma. Data from these recent studies have shown reduction in ASM following bronchial thermoplasty and changes in inflammation patterns. It has also been argued that bronchial thermoplasty may have modulating effects on neuroendocrine epithelial cells, bronchial nerve endings, TRPV1 nerve receptors, and type-C unmyelinated fibers in the bronchial mucosa. This may involve interrupting the central and local reflexes responsible for the activation of bronchospasm in the presence of bronchial hyperreactivity. Several questions remain regarding the use of bronchial thermoplasty, mechanism of action, selection of appropriate patients, and long-term effects. In this review, the role of ASM in the

  12. Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle.

    Science.gov (United States)

    Zhuge, Ronghua; Bao, Rongfeng; Fogarty, Kevin E; Lifshitz, Lawrence M

    2010-01-15

    Ca2+ sparks are short lived and localized Ca2+ transients resulting from the opening of ryanodine receptors in sarcoplasmic reticulum. These events relax certain types of smooth muscle by activating big conductance Ca2+-activated K+ channels to produce spontaneous transient outward currents (STOCs) and the resultant closure of voltage-dependent Ca2+ channels. But in many smooth muscles from a variety of organs, Ca2+ sparks can additionally activate Ca2+-activated Cl(-) channels to generate spontaneous transient inward current (STICs). To date, the physiological roles of Ca2+ sparks in this latter group of smooth muscle remain elusive. Here, we show that in airway smooth muscle, Ca2+ sparks under physiological conditions, activating STOCs and STICs, induce biphasic membrane potential transients (BiMPTs), leading to membrane potential oscillations. Paradoxically, BiMPTs stabilize the membrane potential by clamping it within a negative range and prevent the generation of action potentials. Moreover, blocking either Ca2+ sparks or hyperpolarization components of BiMPTs activates voltage-dependent Ca2+ channels, resulting in an increase in global [Ca2+](i) and cell contraction. Therefore, Ca2+ sparks in smooth muscle presenting both STICs and STOCs act as a stabilizer of membrane potential, and altering the balance can profoundly alter the status of excitability and contractility. These results reveal a novel mechanism underlying the control of excitability and contractility in smooth muscle.

  13. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    International Nuclear Information System (INIS)

    Liu, Gang; Hitomi, Hirofumi; Hosomi, Naohisa; Lei, Bai; Nakano, Daisuke; Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu; Ma, Hong; Griendling, Kathy K.; Nishiyama, Akira

    2011-01-01

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: → Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. → Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. → Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. → Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  14. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  15. Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.

    Science.gov (United States)

    Shariff, Sami; Shelfoon, Christopher; Holden, Neil S; Traves, Suzanne L; Wiehler, Shahina; Kooi, Cora; Proud, David; Leigh, Richard

    2017-06-01

    Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.

  16. The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

    Science.gov (United States)

    Dudášová, A; Keir, S D; Parsons, M E; Molleman, A; Page, C P

    2013-06-01

    (-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders. Copyright © 2013. Published by Elsevier Ltd.

  17. Bronchial thermoplasty and the role of airway smooth muscle: are we on the right direction?

    Science.gov (United States)

    Menzella, Francesco; Lusuardi, Mirco; Galeone, Carla; Facciolongo, Nicola

    2017-01-01

    Asthma is characterized by inflammation of the airways that includes eosinophils, basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have been studies on the role of hypersensitivity and inflammation in asthma, but the role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an endoscopic procedure that is approved by the US Food and Drug Administration (FDA) for the treatment of severe refractory asthma, based on the local delivery of radio frequency at 65°C to the airways, with the aim of controlling bronchospasm through a reduction of airway smooth muscle (ASM). Several recent studies have shown significant improvement in clinical outcomes of bronchial thermoplasty for asthma, including symptom control, reduction in exacerbation and hospitalization rates, improved quality of life, and reduction in number of working days or school days lost due to asthma. Data from these recent studies have shown reduction in ASM following bronchial thermoplasty and changes in inflammation patterns. It has also been argued that bronchial thermoplasty may have modulating effects on neuroendocrine epithelial cells, bronchial nerve endings, TRPV1 nerve receptors, and type-C unmyelinated fibers in the bronchial mucosa. This may involve interrupting the central and local reflexes responsible for the activation of bronchospasm in the presence of bronchial hyperreactivity. Several questions remain regarding the use of bronchial thermoplasty, mechanism of action, selection of appropriate patients, and long-term effects. In this review, the role of ASM in the pathogenesis of asthma and the key aspects of bronchial thermoplasty are discussed, with a focus on the potential clinical effects of this promising procedure, beyond the reduction in ASM.

  18. A key role for STIM1 in store operated calcium channel activation in airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Peel Samantha E

    2006-09-01

    Full Text Available Abstract Background Control of cytosolic calcium plays a key role in airway myocyte function. Changes in intracellular Ca2+ stores can modulate contractile responses, modulate proliferation and regulate synthetic activity. Influx of Ca2+ in non excitable smooth muscle is believed to be predominantly through store operated channels (SOC or receptor operated channels (ROC. Whereas agonists can activate both SOC and ROC in a range of smooth muscle types, the specific trigger for SOC activation is depletion of the sarcoplasmic reticulum Ca2+ stores. The mechanism underlying SOC activation following depletion of intracellular Ca2+ stores in smooth muscle has not been identified. Methods To investigate the roles of the STIM homologues in SOC activation in airway myocytes, specific siRNA sequences were utilised to target and selectively suppress both STIM1 and STIM2. Quantitative real time PCR was employed to assess the efficiency and the specificity of the siRNA mediated knockdown of mRNA. Activation of SOC was investigated by both whole cell patch clamp electrophysiology and a fluorescence based calcium assay. Results Transfection of 20 nM siRNA specific for STIM1 or 2 resulted in robust decreases (>70% of the relevant mRNA. siRNA targeted at STIM1 resulted in a reduction of SOC associated Ca2+ influx in response to store depletion by cyclopiazonic acid (60% or histamine but not bradykinin. siRNA to STIM2 had no effect on these responses. In addition STIM1 suppression resulted in a more or less complete abrogation of SOC associated inward currents assessed by whole cell patch clamp. Conclusion Here we show that STIM1 acts as a key signal for SOC activation following intracellular Ca2+ store depletion or following agonist stimulation with histamine in human airway myocytes. These are the first data demonstrating a role for STIM1 in a physiologically relevant, non-transformed endogenous expression cell model.

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

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2006-01-01

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

  20. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    International Nuclear Information System (INIS)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie

    2013-01-01

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs

  1. Pharmacological inhibition of β-catenin/CBP interaction with the small molecule ICG-001 inhibits proliferation and extracellular matrix production in airway smooth muscle

    NARCIS (Netherlands)

    Koopmans, T.; Crutzen, S.; Halayko, A.J.; Gosens, R.

    2015-01-01

    Rationale Airway hyperresponsiveness is a principle feature of asthma, explained in part by remodeling of airway smooth muscle (ASM), including muscle thickening and increased extracellular matrix (ECM) protein production by the ASM. Current therapies are largely successful in targeting the

  2. The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Safka Katherine

    2008-12-01

    Full Text Available Abstract Background Many cystic fibrosis (CF patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8 is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals. Methods Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects. Cells from the 2nd to 5th passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+]i, cell contraction, migration and proliferation. Results The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM induced a peak Ca2+ release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p 20 in CF than in control cells. In addition, MLC20 expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells. Conclusion ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20 by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.

  3. Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ming; Lv, Zhiqiang; Huang, Linjie [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China); Zhang, Wei [Department of Geratology, the Second People' s Hospital of Shenzhen, Shenzhen 518000 (China); Lin, Xiaoling; Shi, Jianting; Zhang, Wei; Liang, Ruiyun [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China); Jiang, Shanping, E-mail: shanpingjiang@126.com [Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Institute for Respiratory disease of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong Province 510120 (China)

    2015-02-15

    Background: We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism. Methods: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-β1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis. Results: Triptolide significantly inhibited TGF-β1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-β1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment. Conclusions: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway. - Highlights: • In this study, rat airway smooth muscle cells were cultured and made synchronized. • Triptolide inhibited TGF-β1-induced airway smooth muscle cells proliferation. • Triptolide inhibited ASMCs proliferation via negative regulation of Smad signaling pathway.

  4. Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells.

    Science.gov (United States)

    Pan, Shi; Sharma, Pawan; Shah, Sushrut D; Deshpande, Deepak A

    2017-07-01

    Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases. Copyright © 2017 the American Physiological

  5. The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness.

    Science.gov (United States)

    Le Guen, Morgan; Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Brollo, Marion; Longchampt, Elisabeth; Kleinmann, Philippe; Devillier, Philippe; Faisy, Christophe

    2016-11-14

    In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other than high-force stretching) have not been extensively characterized. Hence, the objective of the present study was to investigate the functional and transcriptional response of human bronchi to repetitive mechanical stress caused by low-frequency, low-force cyclic stretching. After preparation and equilibration in an organ bath, human bronchial rings from 66 thoracic surgery patients were stretched in 1-min cycles of elongation and relaxation over a 60-min period. For each segment, the maximal tension corresponded to 80% of the reference contraction (the response to 3 mM acetylcholine). The impact of cyclic stretching (relative to non-stretched controls) was examined by performing functional assessments (epithelium removal and incubation with sodium channel agonists/antagonists or inhibitors of intracellular pathways), biochemical assays of the organ bath fluid (for detecting the release of pro-inflammatory cytokines), and RT-PCR assays of RNA isolated from tissue samples. The application of low-force cyclic stretching to human bronchial rings for 60 min resulted in an immediate, significant increase in bronchial basal tone, relative to non-cyclic stretching (4.24 ± 0.16 g vs. 3.28 ± 0.12 g, respectively; p human bronchi induced a myogenic response rather than activation of the pro-inflammatory signaling pathways mediated by mechanotransduction.

  6. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie, E-mail: kunjiewangatscu@163.com

    2013-08-30

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P < 0.05) and apoptotic cell death rate decreased from 16.4 ± 0.21% (control) to 4.5 ± 0.13% (P < 0.05) applied at 0.1 Hz. Expression of PKC was upregulated with slight increase in JNK and no change in p38MAPK after application of stretch. Inhibition had effects on proliferation (1.075 ± 0.024, P < 0.05 GF109203X); (1.418 ± 0.021, P > 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs.

  7. Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

    Directory of Open Access Journals (Sweden)

    Peixi Liu

    2018-02-01

    Full Text Available Background/Aims: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. Methods: Saccular cerebral aneurysms (n=10 were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. Results: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05. KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. Conclusion: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic

  8. Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

    2018-02-21

    Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

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

    Science.gov (United States)

    Sharma, Pawan; Basu, Sujata; Mitchell, Richard W; Stelmack, Gerald L; Anderson, Judy E; Halayko, Andrew J

    2014-01-01

    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.

  10. Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells.

    Science.gov (United States)

    Berntsen, P; Park, C Y; Rothen-Rutishauser, B; Tsuda, A; Sager, T M; Molina, R M; Donaghey, T C; Alencar, A M; Kasahara, D I; Ericsson, T; Millet, E J; Swenson, J; Tschumperlin, D J; Butler, J P; Brain, J D; Fredberg, J J; Gehr, P; Zhou, E H

    2010-06-06

    The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 microm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 microm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 microM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.

  11. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

    NARCIS (Netherlands)

    Burgess, J. K.; Ketheson, A.; Faiz, A.; Rempel, K. A. Limbert; Oliver, B. G.; Ward, J. P. T.; Halayko, A. J.

    2018-01-01

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness

  12. Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

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    Svensson Holm, Ann-Charlotte B., E-mail: ann-charlotte.svensson@liu.se [Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping University, SE-581 85 Linkoeping (Sweden); Experimental Pathology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Bengtsson, Torbjoern [Department of Biomedicine, School of Health and Medical Sciences, Oerebro University, SE-70182 Oerebro (Sweden); Grenegard, Magnus; Lindstroem, Eva G. [Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping University, SE-581 85 Linkoeping (Sweden)

    2012-03-10

    Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling.

  13. Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

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    Zuyderduyn Suzanne

    2010-09-01

    Full Text Available Abstract Background Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M2 and M3 receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE, TNF-α, PDGF-AB or IL-1β. Results Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-α or PDGF-AB, but not with IL-1β. Pretreatment with GF109203X, a protein kinase C (PKC inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of IκB-kinase-2 (SC514 and MEK1/2 (U0126, both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of IκBα and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1β in hASMc. Conclusions We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of IκBα and ERK1/2. This mechanism could be of importance for COPD patients using anticholinergics.

  14. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells

    NARCIS (Netherlands)

    Baarsma, Hoeke A.; Menzen, Mark H.; Halayko, Andrew J.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud

    2011-01-01

    Baarsma HA, Menzen MH, Halayko AJ, Meurs H, Kerstjens HA, Gosens R. beta-Catenin signaling is required for TGF-beta(1)-induced extracellular matrix production by airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 301: L956-L965, 2011. First published September 9, 2011; doi:

  15. SCA 40: studies of the relaxant effects on cryopreserved human airway and vascular smooth muscle.

    Science.gov (United States)

    Müller-Schweinitzer, E; Fozard, J R

    1997-04-01

    1. 6-Bromo-8-methylaminoimidazol[1,2-a]pyrazine-2carbonitrile (SCA 40) has been claimed to induce relaxation in guinea-pig trachea by opening high conductance, calcium-activated potassium (BKCa) channels. The mechanism of action of SCA 40 has now been further investigated in ring preparations from cryopreserved human airway and vascular smooth muscle preparations in vitro. 2. Human bronchi with spontaneous tone relaxed in response to SCA 40 in a biphasic way. A high affinity component (pD2 8.61 +/- 0.21; mean +/- s.e.mean) accounted for 30% of the response and a low affinity component (pD2 6.53 +/- 0.14) for the remaining 70%. In contrast, in bronchi contracted with carbachol, 1 microM, the concentration-response curve to SCA 40 was monophasic and yielded a pD2 of 6.31 +/- 0.29. 3. SCA 40 relaxed pulmonary and mesenteric arteries and peripheral veins which had been precontracted by 10 nM U46619 nearly completely and in a monophasic way; the pD2 values were 6.37 +/- 0.08, 6.17 +/- 0.15 and 5.45 +/- 0.25, respectively. 4. Lemakalim, an opener of ATP-dependent potassium (KATP) channels, also relaxed human bronchi under spontaneous tone and the vascular tissues. NS 1619, a recognised opener of BKca channels, was inactive up to 10 microM on bronchial and vascular tissues. 5. The SCA 40-induced relaxation of human bronchi was reduced concentration-dependently in the presence of high potassium chloride (20 and 80 mM). However, in the presence of 80 mM KCl and nifedipine, 30 nM, SCA 40 fully relaxed the remaining contractile response with pD2 values of 8.08 +/- 0.13 and 5.27 +/- 0.13 for the high and low affinity component, respectively. 6. Relaxation responses to SCA 40 in human bronchi were resistant to blockade by glibenclamide at concentrations up to 10 microM (which blocked the relaxant response to lemakalim), quinine (30 microM), apamin (100 nM), tetraethylammonium (0.1-1 mM) and charybdotoxin (10-100 nM), thus excluding the involvement of a variety of K+ channels

  16. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

    Science.gov (United States)

    Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

  17. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

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    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  18. Nitric oxide mediates stretch-induced Ca2+ release via activation of phosphatidylinositol 3-kinase-Akt pathway in smooth muscle.

    Science.gov (United States)

    Wei, Bin; Chen, Zheng; Zhang, Xu; Feldman, Morris; Dong, Xian-zhi; Doran, Robert; Zhao, Bao-Lu; Yin, Wen-xuan; Kotlikoff, Michael I; Ji, Guangju

    2008-06-25

    Hollow smooth muscle organs such as the bladder undergo significant changes in wall tension associated with filling and distension, with attendant changes in muscle tone. Our previous study indicated that stretch induces Ca(2+) release occurs in the form of Ca(2+) sparks and Ca(2+) waves in urinary bladder myocytes. While, the mechanism underlying stretch-induced Ca2+ release in smooth muscle is unknown. We examined the transduction mechanism linking cell stretch to Ca(2+) release. The probability and frequency of Ca(2+) sparks induced by stretch were closely related to the extent of cell extension and the time that the stretch was maintained. Experiments in tissues and single myocytes indicated that mechanical stretch significantly increases the production of nitric oxide (NO) and the amplitude and duration of muscle contraction. Stretch-induced Ca(2+) sparks and contractility increases were abrogated by the NO inhibitor L-NAME and were also absent in eNOS knockout mice. Furthermore, exposure of eNOS null mice to exogenously generated NO induced Ca(2+) sparks. The soluble guanylyl cyclase inhibitor ODQ did not inhibit SICR, but this process was effectively blocked by the PI3 kinase inhibitors LY494002 and wortmannin; the phosphorylation of Akt and eNOS were up-regulated by 204+/-28.6% and 258+/-36.8% by stretch, respectively. Moreover, stretch significantly increased the eNOS protein expression level. Taking together, these results suggest that stretch-induced Ca2+ release is NO dependent, resulting from the activation of PI3K/Akt pathway in smooth muscle.

  19. Nitric oxide mediates stretch-induced Ca2+ release via activation of phosphatidylinositol 3-kinase-Akt pathway in smooth muscle.

    Directory of Open Access Journals (Sweden)

    Bin Wei

    2008-06-01

    Full Text Available Hollow smooth muscle organs such as the bladder undergo significant changes in wall tension associated with filling and distension, with attendant changes in muscle tone. Our previous study indicated that stretch induces Ca(2+ release occurs in the form of Ca(2+ sparks and Ca(2+ waves in urinary bladder myocytes. While, the mechanism underlying stretch-induced Ca2+ release in smooth muscle is unknown.We examined the transduction mechanism linking cell stretch to Ca(2+ release. The probability and frequency of Ca(2+ sparks induced by stretch were closely related to the extent of cell extension and the time that the stretch was maintained. Experiments in tissues and single myocytes indicated that mechanical stretch significantly increases the production of nitric oxide (NO and the amplitude and duration of muscle contraction. Stretch-induced Ca(2+ sparks and contractility increases were abrogated by the NO inhibitor L-NAME and were also absent in eNOS knockout mice. Furthermore, exposure of eNOS null mice to exogenously generated NO induced Ca(2+ sparks. The soluble guanylyl cyclase inhibitor ODQ did not inhibit SICR, but this process was effectively blocked by the PI3 kinase inhibitors LY494002 and wortmannin; the phosphorylation of Akt and eNOS were up-regulated by 204+/-28.6% and 258+/-36.8% by stretch, respectively. Moreover, stretch significantly increased the eNOS protein expression level.Taking together, these results suggest that stretch-induced Ca2+ release is NO dependent, resulting from the activation of PI3K/Akt pathway in smooth muscle.

  20. TRIM37 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells.

    Science.gov (United States)

    Dai, Ying; Li, Ying; Cheng, Ruiduo; Gao, Jie; Li, Yanyang; Lou, Chunyan

    2018-02-21

    Tripartite motif 37 (TRIM37) belongs to the TRIM family of proteins and has been reported to be involved in the progression of asthma. However, the effects of TRIM37 on airway smooth muscle cells (ASMCs) proliferation and migration are still unknown. This study aimed to investigate the effects of TRIM37 on cell proliferation and migration in platelet-derived growth factor BB (PDGF-BB)-stimulated ASMCs, and the potential molecular mechanisms was also explored. Our data demonstrated that the expression of TRIM37 was significantly decreased in ASMCs stimulated with PDGF-BB. In addition, overexpression of TRIM37 efficiently suppressed PDGF-BB-induced ASMCs proliferation and migration. Furthermore, overexpression of TRIM37 obviously inhibited the protein expression levels of β-catenin, c-Myc and cyclinD1 in PDGF-BB-stimulated ASMCs. The Wnt/β-catenin pathway activator LiCl significantly reversed the inhibitory effects of TRIM37 on cell proliferation and migration in PDGF-BB-stimulated ASMCs. Taken together, these results demonstrate that TRIM37 inhibits the proliferation and invasion of ASMCs cultured with PDGF-BB through suppressing the Wnt/β-catenin signaling pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle

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    John Matthias

    2005-07-01

    Full Text Available Abstract Background Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8. Human airway smooth muscle cells (HASMC are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC. Methods HASMC in primary culture were exposed to cigarette smoke extract (CSE with or without TNFα. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA and gene expression by real time polymerase chain reaction (PCR. Data were analysed using one-way analysis of variance (ANOVA followed by Bonferroni's t test Results CSE (5, 10 and 15% induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFα enhanced CSE-induced IL-8 release and expression. However, CSE (5–30% inhibited TNFα-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH and associated with the induction of the oxidant sensing protein, heme oxygenase-1. Conclusion Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-α which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD.

  2. Chloroform Extract of Artemisia annua L. Relaxes Mouse Airway Smooth Muscle

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    Jun Huang

    2017-01-01

    Full Text Available Artemisia annua L. belongs to the Asteraceae family, which is indigenous to China. It has valuable pharmacological properties, such as antimalarial, anti-inflammatory, and anticancer properties. However, whether it possesses antiasthma properties is unknown. In the current study, chloroform extract of Artemisia annua L. (CEAA was prepared, and we found that CEAA completely eliminated acetylcholine (ACh or high K+-elicited (80 mM contractions of mouse tracheal rings (TRs. Patch-clamp technique and ion channel blockers were employed to explore the underlying mechanisms of the relaxant effect of CEAA. In whole-cell current recording, CEAA almost fully abolished voltage-dependent Ca2+ channel (VDCC currents and markedly enhanced large conductance Ca2+-activated K+ (BK channel currents on airway smooth muscle cells (ASMCs. In single channel current recording, CEAA increased the opening probability but had no effect on the single channel conductance of BK channels. However, under paxilline-preincubated (a selective BK channel blocker conditions, CEAA only slightly increased BK channel currents. These results indicate that CEAA may contain active components with potent antiasthma activity. The abolished VDCCs by CEAA may mainly contribute to the underlying mechanism through which it acts as an effective antiasthmatic compound, but the enhanced BK currents might play a less important role in the antiasthmatic effects.

  3. Orosomucoid-like 3 (ORMDL3) upregulates airway smooth muscle proliferation, contraction, and Ca2+oscillations in asthma.

    Science.gov (United States)

    Chen, Jun; Miller, Marina; Unno, Hirotoshi; Rosenthal, Peter; Sanderson, Michael J; Broide, David H

    2017-09-07

    Airway hyperresponsiveness is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3 Zp3-Cre mice (which express increased levels of human ORMDL3 [hORMDL3]). Levels of ASM proliferation and contraction were assessed in ASM cells transfected with ORMDL3 in vitro. In addition, airway contractility and calcium oscillations were quantitated in ASM cells in PCLSs derived from naive wild-type and naive hORMDL3 Zp3-Cre mice, which do not have a blood supply. Increased ASM expression of ORMDL3 in vitro resulted in increased ASM proliferation and contractility. PCLSs derived from naive hORMDL3 Zp3-Cre mice, which do not have airway inflammation, exhibit increased airway contractility with increased calcium oscillations in ASM cells. Increased ASM ORMDL3 expression increases levels of ASM sarcoplasmic reticulum Ca 2+ ATPase 2b (SERCA2b), which increases ASM proliferation and contractility. Overall, these studies provide evidence that an intrinsic increase in ORMDL3 expression in ASM can induce increased ASM proliferation and contractility, which might contribute to increased airway hyperresponsiveness in the absence of airway inflammation in asthmatic patients. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways

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    Maryam Keshavarz

    2017-05-01

    Full Text Available An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM involve caveolae. We hypothesized that caveolin-1 (cav-1, a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra- and intrapulmonary bronchi in cav-1 deficient (cav-1−/− and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD treated and non-treated precision-cut lung slices (PCLS. The presence of caveolae was investigated by electron microscopy. Receptor subtypes driving 5-HT-responses were studied by RT-PCR and videomorphometry after pharmacological inhibition with ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a dose dependent contraction in all airway segments. A significantly higher Emax was observed in the caudal trachea. Although, caveolae abundancy was largely reduced in cav-1−/− mice, muscarine-induced airway contraction was maintained, albeit at diminished potency in the middle trachea, in the caudal trachea and in the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from cav-1−/− mice reduced cholinergic constriction by about 50%, indicating that cholesterol-rich plasma domains account for a substantial portion of the muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most prevalent subtypes in the airways. The

  5. Endogenous laminin is required for human airway smooth muscle cell maturation

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    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  6. Fibrocyte localization to the airway smooth muscle is a feature of asthma.

    Science.gov (United States)

    Saunders, Ruth; Siddiqui, Salman; Kaur, Davinder; Doe, Camille; Sutcliffe, Amanda; Hollins, Fay; Bradding, Peter; Wardlaw, Andrew; Brightling, Christopher E

    2009-02-01

    Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction. We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma. We assessed the number of fibrocytes in bronchial biopsy specimens and peripheral blood from subjects with mild-to-severe refractory asthma versus healthy control subjects. In vitro we investigated potential mechanisms controlling fibrocyte migration toward the ASM bundle. Fifty-one subjects with asthma and 33 control subjects were studied. In bronchial biopsy specimens, the number of fibrocytes was increased in the lamina propria of subjects with severe refractory asthma (median [interquartile range] number, 1.9/mm(2) [1.7/mm(2)]) versus healthy control subjects (median [interquartile range] number, 0/mm(2) [0.3/mm(2)], P interquartile range] number, 3.8/mm(2) [9.4/mm(2)]; subjects with mild-to-moderate asthma, median [interquartile range] number, 1.1/mm(2) [2.4/mm(2)]); healthy control subjects, (median [interquartile range] number, 0/mm(2) [0/mm(2)]); P = .0004). In the peripheral blood the fibrocyte number was also increased in subjects with severe refractory asthma (median [interquartile range] number, 1.4 x 10(4)/mL [2.6 x 10(4)/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 x 10(4)/mL [1.0 x 10(4)/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 microm [2.9 microm] vs 17 microm [2.4 microm], P = .0001), which was in part mediated by platelet-derived growth factor (mean inhibition by neutralizing antibody, 16% [95% CI, 2% to 32%], P = .03) but not by activation of chemokine receptors. This study provides the first evidence that fibrocytes are present in the ASM compartment in asthma and that ASM can augment fibrocyte migration. The importance of

  7. The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.

    Science.gov (United States)

    Liu, Xianyan; Hao, Binwei; Ma, Ailing; He, Jinxi; Liu, Xiaoming; Chen, Juan

    Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF- β ) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF- β , along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α -SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF- β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF- β signaling in the pathogenesis of COPD, which warrants further investigation.

  8. Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

    Science.gov (United States)

    Rothdiener, Miriam; Hegemann, Miriam; Uynuk-Ool, Tatiana; Walters, Brandan; Papugy, Piruntha; Nguyen, Phong; Claus, Valentin; Seeger, Tanja; Stoeckle, Ulrich; Boehme, Karen A.; Aicher, Wilhelm K.; Stegemann, Jan P.; Hart, Melanie L.; Kurz, Bodo; Klein, Gerd; Rolauffs, Bernd

    2016-10-01

    Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype.

  9. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

    Science.gov (United States)

    Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

    2012-01-01

    CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

  10. Anti-inflammatory Effects of Thiazolidinediones in Human Airway Smooth Muscle Cells

    Science.gov (United States)

    Zhu, Ming; Flynt, Lesley; Ghosh, Sanjukta; Mellema, Matt; Banerjee, Audreesh; Williams, Erin; Panettieri, Reynold A.; Shore, Stephanie A.

    2011-01-01

    Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) exert anti-inflammatory effects, we examined the effects of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dose-dependently reduced the IL-1β–induced release of IL-6 and vascular endothelial growth factor, the TNF-α–induced release of eotaxin and regulated on activation, normal T expressed and secreted (RANTES), and the IL-4–induced release of eotaxin. Rosiglitazone also inhibited the TNF-α–stimulated release of RANTES. Although TZDs are known to activate peroxisome proliferator–activated receptor-γ (PPARγ), these anti-inflammatory effects were not affected by a specific PPARγ inhibitor (GW 9662) or by the knockdown of PPARγ using short hairpin RNA. Troglitazone and rosiglitazone each caused the activation of adenosine monophosphate-activated protein kinase (AMPK), as detected by Western blotting using a phospho-AMPK antibody. The anti-inflammatory effects of TZDs were largely mimicked by the AMPK activators, 5-amino-4-imidazolecarboxamide ribose (AICAR) and metformin. However, the AMPK inhibitors, Ara A and Compound C, were not effective in preventing the anti-inflammatory effects of troglitazone or rosiglitzone, suggesting that the effects of these TZDs are likely not mediated through the activation of AMPK. These data indicate that TZDs inhibit the release of a variety of inflammatory mediators from human ASM cells, suggesting that they may be useful in the treatment of asthma, and the data also indicate that the effects of TZDs are not mediated by PPARγ or AMPK. PMID:20870897

  11. Impaired Relaxation of Airway Smooth Muscle in Mice Lacking the Actin-Binding Protein Gelsolin.

    Science.gov (United States)

    Mikami, Maya; Zhang, Yi; Danielsson, Jennifer; Joell, Tiarra; Yong, Hwan Mee; Townsend, Elizabeth; Khurana, Seema; An, Steven S; Emala, Charles W

    2017-05-01

    Diverse classes of ligands have recently been discovered that relax airway smooth muscle (ASM) despite a transient increase in intracellular calcium concentrations ([Ca 2+ ] i ). However, the cellular mechanisms are not well understood. Gelsolin is a calcium-activated actin-severing and -capping protein found in many cell types, including ASM cells. Gelsolin also binds to phosphatidylinositol 4,5-bisphosphate, making this substrate less available for phospholipase Cβ-mediated hydrolysis to inositol triphosphate and diacylglycerol. We hypothesized that gelsolin plays a critical role in ASM relaxation and mechanistically accounts for relaxation by ligands that transiently increase [Ca 2+ ] i . Isolated tracheal rings from gelsolin knockout (KO) mice showed impaired relaxation to both a β-agonist and chloroquine, a bitter taste receptor agonist, which relaxes ASM, despite inducing transiently increased [Ca 2+ ] i . A single inhalation of methacholine increased lung resistance to a similar extent in wild-type and gelsolin KO mice, but the subsequent spontaneous relaxation was less in gelsolin KO mice. In ASM cells derived from gelsolin KO mice, serotonin-induced Gq-coupled activation increased both [Ca 2+ ] i and inositol triphosphate synthesis to a greater extent compared to cells from wild-type mice, possibly due to the absence of gelsolin binding to phosphatidylinositol 4,5-bisphosphate. Single-cell analysis showed higher filamentous:globular actin ratio at baseline and slower cytoskeletal remodeling dynamics in gelsolin KO cells. Gelsolin KO ASM cells also showed an attenuated decrease in cell stiffness to chloroquine and flufenamic acid. These findings suggest that gelsolin plays a critical role in ASM relaxation and that activation of gelsolin may contribute to relaxation induced by ligands that relax ASM despite a transient increase in [Ca 2+ ] i .

  12. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    International Nuclear Information System (INIS)

    Pei, Qing-Mei; Jiang, Ping; Yang, Min; Qian, Xue-Jiao; Liu, Jiang-Bo; Kim, Sung-Ho

    2016-01-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  13. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qing-Mei, E-mail: 34713316@qq.com [Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China); Jiang, Ping, E-mail: jiangping@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Yang, Min, E-mail: YangMin@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Qian, Xue-Jiao, E-mail: qianxuejiao@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Liu, Jiang-Bo, E-mail: LJB1984@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China)

    2016-10-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  14. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

    Science.gov (United States)

    Roth, Michael; Zhao, Feng; Zhong, Jun; Lardinois, Didier; Tamm, Michael

    2015-01-01

    Background Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix. Objective We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies. Methods Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days. Results Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects. Conclusion and Clinical Relevance Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC. PMID:26332463

  15. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab.

    Directory of Open Access Journals (Sweden)

    Michael Roth

    Full Text Available Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC activity deposing extracellular matrix.We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.Isolated human ASMC were exposed to serum obtained from: (i healthy controls, or patients with (ii allergic asthma, (iii non-allergic asthma, and (iv atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.Serum from patients with allergies significantly stimulated: (i ASMC proliferation, (ii deposition of collagen type-I (48 hours and (iii of fibronectin (24 hours. One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.

  16. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

    2005-09-01

    Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

  17. The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Chao-Huei Yang

    2016-01-01

    Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

  18. Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Shaikh N

    2017-06-01

    Full Text Available Nooreen Shaikh,1,2 Malcolm Johnson,3 David A Hall,4 Kian Fan Chung,1,2 John H Riley,3 Sally Worsley,5 Pankaj K Bhavsar1,2 1Experimental Studies, National Heart and Lung Institute, Imperial College London, 2Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, 3Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, 4Fibrosis and Lung Injury Development Planning Unit, GlaxoSmithKline, Stevenage, 5Respiratory Research & Development, GlaxoSmithKline, Uxbridge, UK Background: Intracellular mechanisms of action of umeclidinium (UMEC, a long-acting muscarinic receptor antagonist, and vilanterol (VI, a long-acting β2-adrenoceptor (β2R agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs. Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]. Cyclic adenosine monophosphate (cAMP was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2 messenger RNA using real-time quantitative polymerase chain reaction. Results: VI and salmeterol (10–12–10–6 M induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes attenuated VI-induced cAMP production (P<0.05, whereas pretreatment with UMEC (10–8 M, 1 hour restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus

  19. PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells.

    Science.gov (United States)

    Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

    2017-06-01

    Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca 2+ ([Ca 2+ ] cyt ). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca 2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca 2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction. Copyright © 2017 the American Physiological Society.

  20. Extraction of airways with probabilistic state-space models and Bayesian smoothing

    DEFF Research Database (Denmark)

    Raghavendra, Selvan; Petersen, Jens; Pedersen, Jesper Johannes Holst

    2017-01-01

    Segmenting tree structures is common in several image processing applications. In medical image analysis, reliable segmentations of airways, vessels, neurons and other tree structures can enable important clinical. applications. We present a framework for tracking tree structures comprising of el...

  1. Arginase attenuates inhibitory nonadrenergic noncholinergic nerve-induced nitric oxide generation and airway smooth muscle relaxation

    NARCIS (Netherlands)

    Maarsingh, H; Tio, MA; Zaagsma, J; Meurs, H

    2005-01-01

    Background: Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, L-arginine. Using

  2. Relaxation of soman-induced contracture of airway smooth muscle in vitro. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Filbert, M.G.; Moore, D.H.; Adler, M.

    1992-12-31

    A possible role for beta-adrenergic agonists in the management of bronchoconstriction resulting from exposure to anticholinesterase compounds was investigated in vitro in canine tracheal smooth muscle. Norepinephrine, salbutamol and isoproterenol produced partial relaxation of soman-induced contractures. However, the relaxation induced was not sustained; muscle tensions returned to pretreatment levels within minutes despite the continued presence of beta-agonists. Increasing cAMP levels with the non beta-agonist bronchodilators such as thoophylline, a phosphodiesterase inhibitor, or forskolin, a specific stimulator of adenylate cyclase, resulted in more complete and longer lasting relaxation, suggesting that beta-adrenoceptor desensitization may contribute to the failure by beta-agonists to produce sustained relaxation. Nerve agents, Soman, Toxicity, Airway smooth muscle, In vitro, Physiology, Effects.

  3. An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.

    Directory of Open Access Journals (Sweden)

    Gautam Damera

    Full Text Available In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4 in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

  4. The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

    Directory of Open Access Journals (Sweden)

    A.C. Perez

    1998-06-01

    Full Text Available We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05. In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM. Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

  5. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    International Nuclear Information System (INIS)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan; Cui, Yong-Yao

    2012-01-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  6. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com; Cui, Yong-Yao, E-mail: yongyaocui@yahoo.com.cn

    2012-07-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  7. The effects of different size gold nanoparticles on mechanical properties of vascular smooth muscle cells under mechanical stretching

    Science.gov (United States)

    Kieu, Tri Minh

    Nanotechnology is an emerging and promising frontier for medicine and biomedical research due to its potential for applications such as drug delivery, imaging enhancement, and cancer treatment. While these materials may possess significant possibilities, the effects of these particles in the body and how the particles affect the cells is not fully understood. In this study, vascular smooth muscle cells (VSMCs) will be exposed to 5 and 20 nm diameter citrate AuNPs under mechanical conditions. The cytotoxicity properties of these particles will be investigated using LDH and MTT assays. Atomic force microscopy will be used to study how the size of the nanoparticles affect the mechanical properties of the VSMCs. Immunofluorescence staining for alpha actin will also be performed to enhance understanding of the phenotypic shift. The LDH and MTT cytotoxicity assay results demonstrated that neither 5 nor 20 nm diameter nanoparticles are cytotoxic to the cells. However, the mechanical properties and cell morphology of the VSMCs was altered. Under static conditions, both AuNP treatments decreased the mechanical properties of the cells. The size of the nanoparticles had a softening effect on elastic modulus of the cell and sign of a synthetic phenotype was observed. The VSMCs subjected to mechanical stretching exhibited higher elastic modulus compared to the static experimental groups. Again, both AuNPs treatments decreased the mechanical properties of the cells and signs of more synthetic phenotype was seen. However, the size of the nanoparticles did not have any influence on cell's elastic modulus unlike the static treated cells. The mechanical testing condition provided a better look at how these particles would affect the cells in vivo. While the nanoparticles are not cytotoxic to the VSMCs, they are altering the mechanical properties and phenotype of the cell.

  8. Toward a Concept of Stretch Coupling in Smooth Muscle: A Thesis by Lars Thuneberg on Contractile Activity in Neonatal Interstitial Cells of Cajal

    DEFF Research Database (Denmark)

    Huizinga, Jan D; Lammers, Wim J E P; Mikkelsen, Hanne B

    2010-01-01

    The hypothesis was put forward by Thuneberg that rhythmically contracting interstitial cells of Cajal (ICC) were sensing stretch of the musculature and that this information was transmitted to smooth muscle cells via peg and socket contacts. The present study provides the evidence for the contrac...... amongst the physiological properties of the ICC networks of the gut musculature. Anat Rec, 2010. (c) 2010 Wiley-Liss, Inc....

  9. Extraction of Airways with Probabilistic State-Space Models and Bayesian Smoothing

    DEFF Research Database (Denmark)

    Raghavendra, Selvan; Petersen, Jens; Pedersen, Jesper Johannes Holst

    of elongated branches using probabilistic state-space models and Bayesian smoothing. Unlike most existing methods that proceed with sequential tracking of branches, we present an exploratory method, that is less sensitive to local anomalies in the data due to acquisition noise and/or interfering structures....... The evolution of individual branches is modelled using a process model and the observed data is incorporated into the update step of the Bayesian smoother using a measurement model that is based on a multi-scale blob detector. Bayesian smoothing is performed using the RTS (Rauch-Tung-Striebel) smoother, which...

  10. Antagonists of the TMEM16A calcium-activated chloride channel modulate airway smooth muscle tone and intracellular calcium.

    Science.gov (United States)

    Danielsson, Jennifer; Perez-Zoghbi, Jose; Bernstein, Kyra; Barajas, Matthew B; Zhang, Yi; Kumar, Satish; Sharma, Pawan K; Gallos, George; Emala, Charles W

    2015-09-01

    Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of benzbromarone. In human ASM, benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12). TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.

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

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    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

  12. IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells.

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    Nakajima, Masayuki; Kawaguchi, Mio; Ota, Kyoko; Fujita, Junichi; Matsukura, Satoshi; Huang, Shau-Ku; Morishima, Yuko; Ishii, Yukio; Satoh, Hiroaki; Sakamoto, Tohru; Hizawa, Nobuyuki

    2017-06-01

    Interleukin (IL)-17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL-17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL-6 by IL-17F and the involvement of transforming growth factor β-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs. ASMCs were cultured in the presence or absence of IL-17F. The expression of IL-6 gene and protein was analyzed using real-time PCR and ELISA, and the activation of TAK1 and NF-κB was detected by Western blotting. The effect of TAK1 inhibitor 5Z-7-oxozeaenol and NF-κB inhibitor BAY 11-7082 on the expression of IL-6 was investigated. Finally, the short interfering RNAs (siRNAs) targeting TAK1 and a subunit of NF-κB, p65 were transfected into ASMCs. The expression of IL-6 gene and protein was significantly induced by IL-17F. IL-17F activated TAK1 and NF-κB in ASMCs. Transfection of siRNAs targeting TAK1 abolished IL-17F-induced phosphorylation of p65. Both 5Z-7-oxozeaenol and BAY 11-7082 significantly inhibited IL-17F-induced IL-6 production in a dose-dependent manner. Similarly, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-6. Collectively, these results provided evidence supporting the potential importance of the Th17-ASMCs crosstalk via the IL-17F-IL-6 axis in airway inflammation and as a candidate pharmacological target for airway inflammatory diseases such as asthma. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  13. IL‐17F induces IL‐6 via TAK1‐NFκB pathway in airway smooth muscle cells

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    Nakajima, Masayuki; Ota, Kyoko; Fujita, Junichi; Matsukura, Satoshi; Huang, Shau‐Ku; Morishima, Yuko; Ishii, Yukio; Satoh, Hiroaki; Sakamoto, Tohru; Hizawa, Nobuyuki

    2017-01-01

    Abstract Introduction Interleukin (IL)‐17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL‐17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL‐6 by IL‐17F and the involvement of transforming growth factor β‐activated kinase 1 (TAK1) and nuclear factor (NF)‐κB by in ASMCs. Methods ASMCs were cultured in the presence or absence of IL‐17F. The expression of IL‐6 gene and protein was analyzed using real‐time PCR and ELISA, and the activation of TAK1 and NF‐κB was detected by Western blotting. The effect of TAK1 inhibitor 5Z‐7‐oxozeaenol and NF‐κB inhibitor BAY 11‐7082 on the expression of IL‐6 was investigated. Finally, the short interfering RNAs (siRNAs) targeting TAK1 and a subunit of NF‐κB, p65 were transfected into ASMCs. Results The expression of IL‐6 gene and protein was significantly induced by IL‐17F. IL‐17F activated TAK1 and NF‐κB in ASMCs. Transfection of siRNAs targeting TAK1 abolished IL‐17F‐induced phosphorylation of p65. Both 5Z‐7‐oxozeaenol and BAY 11‐7082 significantly inhibited IL‐17F‐induced IL‐6 production in a dose‐dependent manner. Similarly, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL‐6. Conclusions Collectively, these results provided evidence supporting the potential importance of the Th17‐ASMCs crosstalk via the IL‐17F‐IL‐6 axis in airway inflammation and as a candidate pharmacological target for airway inflammatory diseases such as asthma. PMID:28474507

  14. Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling.

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    Yocum, Gene T; Chen, Jun; Choi, Christine H; Townsend, Elizabeth A; Zhang, Yi; Xu, Dingbang; Fu, Xiao W; Sanderson, Michael J; Emala, Charles W

    2017-06-01

    Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed on airway nerve fibers that modulates afferent signals, resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca 2+ -ATPase-2. In guinea pig tracheal ring organ bath experiments, the TRPV1 agonist capsaicin led to ASM contraction, but this contraction was significantly attenuated by the sodium channel inhibitor bupivacaine ( n = 4, P antagonist GR-159897 ( n = 4, P antagonist capsazepine inhibited the maintenance phase of an acetylcholine-induced contraction ( n = 4, P calcium entry in mouse ASM cells in PCLS ( n = 4-7, P = nonsignificant), it did inhibit calcium oscillations ( n = 3, P calcium oscillations. Copyright © 2017 the American Physiological Society.

  15. The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells

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    Amegadzie Bernard

    2005-01-01

    Full Text Available Abstract Background Growing evidence shows that interleukin 13 (IL-13 may play an essential role in the development of airway inflammation and bronchial hyper-responsiveness (BHR, two defining features of asthma. Although the underlying mechanisms remain unknown, a number of reports have shown that IL-13 may exert its deleterious effects in asthma by directly acting on airway resident cells, including epithelial cells and airway smooth muscle cells. In this report, we hypothesize that IL-13 may participate in the pathogenesis of asthma by activating a set of "pro-asthmatic" genes in airway smooth muscle (ASM cells. Methods Microarray technology was used to study the modulation of gene expression of airway smooth muscle by IL-13 and IL-13R130Q. TaqMan™ Real Time PCR and flow cytometry was used to validate the gene array data. Results IL-13 and the IL-13 polymorphism IL-13R130Q (Arg130Gln, recently associated with allergic asthma, seem to modulate the same set of genes, which encode many potentially interesting proteins including vascular cellular adhesion molecule (VCAM-1, IL-13Rα2, Tenascin C and Histamine Receptor H1, that may be relevant for the pathogenesis of asthma. Conclusions The data supports the hypothesis that gene modulation by IL-13 in ASM may be essential for the events leading to the development of allergic asthma.

  16. Differential expression of peroxisome proliferator activated receptor gamma and cyclin D1 does not affect proliferation of asthma- and non-asthma-derived airway smooth muscle cells

    NARCIS (Netherlands)

    Lau, Justine Y; Oliver, Brian G; Moir, Lyn M; Black, Judith L; Burgess, Janette K

    UNLABELLED: PPARgamma levels in asthma- and non-asthma-derived airway smooth muscle cells and PPARgamma activation-induced cell proliferation were investigated. In the presence of FBS, PPARgamma levels were higher in subconfluent asthma-derived cells but lower in confluent cells compared with

  17. Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats

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    Chiba, Yoshihiko; Takada, Yuka; Miyamoto, Shigeki; Mitsui-Saito, Minori; Karaki, Hideaki; Misawa, Miwa

    1999-01-01

    Treatment with acetylcholine (ACh) of a β-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca2+ concentration was clamped at 1 μM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway smooth muscle contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments. PMID:10401547

  18. Role of Meconium in the Reaction of Airways Smooth Musculature in the Newborn with Meconium Aspiration Syndrome (Mas.

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    Hilmi Islami

    2009-11-01

    Full Text Available The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight. We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT: 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%. Tracheal smooth musculature tonus (TSM was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of me-conium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1 in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage. The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.

  19. Role of meconium in the reaction of airways smooth musculature in the newborn with meconium aspiration syndrome (MAS).

    Science.gov (United States)

    Islami, Hilmi; Bexheti, Sadi; Shabani, Ragip; Nuraj, Bajram; Zeqiri, Fehmi; Sukalo, Aziz; Kurtishi, Ilir; Kutllovci, Skender; Qorraj, Hasime; Disha, Mentor

    2009-11-01

    The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight). We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT): 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%). Tracheal smooth musculature tonus (TSM) was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of meconium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1) in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage). The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins) from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.

  20. Arginase attenuates inhibitory nonadrenergic noncholinergic nerve-induced nitric oxide generation and airway smooth muscle relaxation

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    Meurs Herman

    2005-03-01

    Full Text Available Abstract Background Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO production, presumably by competition with epithelial constitutive NO synthase for the common substrate, L-arginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS-mediated relaxation induced by inhibitory nonadrenergic noncholinergic (iNANC nerve stimulation. Methods Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM, while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 μM. Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine. Results EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P Conclusion The results indicate that endogenous arginase activity attenuates iNANC nerve-mediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.

  1. Lead Acetate Induces Epithelium-Dependent Contraction of Airway Smooth Muscle

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    , Ramadan B. Sopi; , Kemajl Bislimi; , Fetah Halili; , Mentor Sopjani; , Burim Neziri; , Muharrem Jakupi

    2016-01-01

    The effect of lead acetate on tracheal smooth muscle (TSM) of dog pups was investigated in this study. In addition we studied the role of epithelium and involvement of nitric oxide (NO) in counteracting the effects of lead acetate on TSM as well as the modifying effects of lead acetate on contractile responses of TSM to acetylcholine (ACh) . Tracheal rings were excised and placed in in vitro organ baths. In vitro administration of lead acetate in increasing concentrations(10-7–10-3 M) induced...

  2. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

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    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  3. The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model.

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    Igor L Chernyavsky

    Full Text Available Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynamics of ASM cells over short and long terms in the normal and inflammatory environments typically observed in asthma. The degree of ASM accumulation can be explained by an increase in the rate at which ASM cells switch between non-proliferative and proliferative states, driven by episodic inflammatory events. Our model explores the idea that remodelling due to ASM hyperplasia increases with the frequency and magnitude of these inflammatory events, relative to certain sensitivity thresholds. It highlights the importance of inflammation resolution speed by showing that when resolution is slow, even a series of small exacerbation events can result in significant remodelling, which persists after the inflammatory episodes. In addition, we demonstrate how the uncertainty in long-term outcome may be quantified and used to design an optimal low-risk individual anti-proliferative treatment strategy. The model shows that the rate of clearance of ASM proliferation and recruitment factors after an acute inflammatory event is a potentially important, and hitherto unrecognised, target for anti-remodelling therapy in asthma. It also suggests new ways of quantifying inflammation severity that could improve prediction of the extent of ASM accumulation. This ASM growth model should prove useful for designing new experiments or as a building block of more detailed multi-cellular tissue-level models.

  4. Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma.

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    Manveen K Gupta

    Full Text Available β2-adrenergic receptor (β2AR agonists (β2-agonist are the most commonly used therapy for acute relief in asthma, but chronic use of these bronchodilators paradoxically exacerbates airway hyper-responsiveness. Activation of βARs by β-agonist leads to desensitization (inactivation by phosphorylation through G-protein coupled receptor kinases (GRKs which mediate β-arrestin binding and βAR internalization. Resensitization occurs by dephosphorylation of the endosomal βARs which recycle back to the plasma membrane as agonist-ready receptors. To determine whether the loss in β-agonist response in asthma is due to altered βAR desensitization and/or resensitization, we used primary human airway smooth muscle cells (HASMCs isolated from the lungs of non-asthmatic and fatal-asthmatic subjects. Asthmatic HASMCs have diminished adenylyl cyclase activity and cAMP response to β-agonist as compared to non-asthmatic HASMCs. Confocal microscopy showed significant accumulation of phosphorylated β2ARs in asthmatic HASMCs. Systematic analysis of desensitization components including GRKs and β-arrestin showed no appreciable differences between asthmatic and non-asthmatic HASMCs. However, asthmatic HASMC showed significant increase in PI3Kγ activity and was associated with reduction in PP2A activity. Since reduction in PP2A activity could alter receptor resensitization, endosomal fractions were isolated to assess the agonist ready β2ARs as a measure of resensitization. Despite significant accumulation of β2ARs in the endosomes of asthmatic HASMCs, endosomal β2ARs cannot robustly activate adenylyl cyclase. Furthermore, endosomes from asthmatic HASMCs are associated with significant increase in PI3Kγ and reduced PP2A activity that inhibits β2AR resensitization. Our study shows that resensitization, a process considered to be a homeostasis maintaining passive process is inhibited in asthmatic HASMCs contributing to β2AR dysfunction which may underlie

  5. CADM1 is a key receptor mediating human mast cell adhesion to human lung fibroblasts and airway smooth muscle cells.

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    Elena P Moiseeva

    Full Text Available Mast cells (MCs play a central role in the development of many diseases including asthma and pulmonary fibrosis. Interactions of human lung mast cells (HLMCs with human airway smooth muscle cells (HASMCs are partially dependent on adhesion mediated by cell adhesion molecule-1 (CADM1, but the adhesion mechanism through which HLMCs interact with human lung fibroblasts (HLFs is not known. CADM1 is expressed as several isoforms (SP4, SP1, SP6 in HLMCs, with SP4 dominant. These isoforms differentially regulate HLMC homotypic adhesion and survival.In this study we have investigated the role of CADM1 isoforms in the adhesion of HLMCs and HMC-1 cells to primary HASMCs and HLFs.CADM1 overexpression or downregulation was achieved using adenoviral delivery of CADM1 short hairpin RNAs or isoform-specific cDNAs respectively.Downregulation of CADM1 attenuated both HLMC and HMC-1 adhesion to both primary HASMCs and HLFs. Overexpression of either SP1 or SP4 isoforms did not alter MC adhesion to HASMCs, whereas overexpression of SP4, but not SP1, significantly increased both HMC-1 cell and HLMC adhesion to HLFs. The expression level of CADM1 SP4 strongly predicted the extent of MC adhesion; linear regression indicated that CADM1 accounts for up to 67% and 32% of adhesion to HLFs for HMC-1 cells and HLMCs, respectively. HLFs supported HLMC proliferation and survival through a CADM1-dependent mechanism. With respect to CADM1 counter-receptor expression, HLFs expressed both CADM1 and nectin-3, whereas HASMCs expressed only nectin-3.Collectively these data indicate that the CADM1 SP4 isoform is a key receptor mediating human MC adhesion to HASMCs and HLFs. The differential expression of CADM1 counter-receptors on HLFs compared to HASMCs may allow the specific targeting of either HLMC-HLF or HLMC-HASMC interactions in the lung parenchyma and airways.

  6. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

    Science.gov (United States)

    Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

    2012-10-04

    Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  7. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

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    Seidel Petra

    2012-10-01

    Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  8. L-thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1.

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    Dekkers, Bart G J; Naeimi, Saeideh; Bos, I Sophie T; Menzen, Mark H; Halayko, Andrew J; Hashjin, Goudarz Sadeghi; Meurs, Herman

    2015-02-01

    Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved. To address this hypothesis, we investigated the effects of triiodothyronine (T3) and l-thyroxine (T4) in the absence and presence of the profibrotic transforming growth factor (TGF)-β1 on human ASM cell phenotype switching. T3 (1-100 nM) and T4 (1-100 nM) did not affect basal ASM proliferation. However, when combined with TGF-β1 (2 ng/ml), T4 synergistically increased the proliferative response, whereas only a minor effect was observed for T3. In line with a switch from a contractile to a proliferative ASM phenotype, T4 reduced the TGF-β1-induced contractile protein expression by ∼50%. Cotreatment with T3 reduced TGF-β1-induced contractile protein expression by ∼25%. The synergistic increase in proliferation was almost fully inhibited by the integrin αvβ3 antagonist tetrac (100 nM), whereas no significant effects of the thyroid receptor antagonist 1-850 (3 μM) were observed. Inhibition of MEK1/2, downstream of the integrin αvβ3, also inhibited the T4- and TGF-β1-induced proliferative responses. Collectively, the results indicate that T4, and to a lesser extent T3, promotes a proliferative ASM phenotype in the presence of TGF-β1, which is predominantly mediated by the membrane-bound T4 receptor αvβ3. These results indicate that thyroid hormones may enhance ASM remodeling in asthma, which could be of relevance for hyperthyroid patients with this disease. Copyright © 2015 the American Physiological Society.

  9. Cigarette smoke extracts promote vascular smooth muscle cell proliferation and enhances contractile responses in the vasculature and airway.

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    Xu, Cang-Bao; Lei, Ying; Chen, Qingwen; Pehrson, Christina; Larsson, Lennart; Edvinsson, Lars

    2010-12-01

    Cigarette smoke exposure is a strong risk factor for cardiovascular and respiratory diseases. However, the knowledge about how cigarette smoke induces damage to vasculature and airway is limited. The present study was designed to examine the effects of cigarette smoke particles extracted by heptane (heptane-soluble smoke particles, HSP), by water (water-soluble smoke particles, WSP) and by DMSO (DMSO-soluble smoke particles, DSP), which represent lipophilic, hydrophilic and ambiphoteric constituents from the cigarette smoke, respectively. Human aortic smooth muscle cell (HASMC) proliferation was assessed in cell culture. Rat resistance artery and airway contractile responses to serotonin, U46619, phenylephrine, noradrenaline, acetylcholine, des-Arg⁹-bradykinin, bradykinin, sarafotoxin 6c and endothelin-1 were monitored by a sensitive myograph system. Immunocytochemistry and cell-based phosphoELISA assay were used to demonstrate activation of extracellular signal-regulated kinases 1/2 (ERK1/2). For the first time, our results demonstrate that although all the three extracts promote HASMC proliferation, the HSP and DSP effects occur earlier. HSP and DSP, but not WSP, increase the contractile responses to sarafotoxin 6c, U46619 or bradykinin in rat mesenteric artery and/or in bronchi. ERK1/2 is activated by HSP and DSP in HASMCs and inhibition of ERK1/2 abrogated the smoke extracts-induced HASMC proliferation, while blockage of nicotinic receptors had no effects, suggesting that the toxic effects of the smoke extracts occur via activation of intracellular ERK1/2 signalling, but not nicotinic receptors. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  10. Effects of age on muscarinic agonist-induced contraction an IP accumulation in airway smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wills-Karp, M. (Johns Hopkins Univ., Baltimore, MD (United States))

    1991-01-01

    The effects of age on carbachol-stimulated force development and ({sup 3}H)inositol phosphate production was studied in tracheal rings from guinea pigs aged 1 month and 25 months of age. The pD{sub 2} for the contractile response to carbachol was significantly reduced in tracheal tissues from old animals as compared to that of the young tissues, respectively. In contrast, inositol phosphate formation was not altered with increasing age when stimulated by carbachol or NaF, a direct activator of G proteins. Carbachol-induced inositol phosphate accumulation was inhibited by treatment with 1{mu}g/ml pertussis toxin, suggesting that IP1 accumulation is coupled to a pertussis-toxin-sensitive protein. The pD{sub 2} values for contraction were significantly different from the pD{sub 2} values for IP1 accumulation, in both young and old tissues, respectively. These data suggest that IP1 accumulation is not responsible for the decreased contractile ability in tracheal smooth muscle during aging.

  11. Ex vivo analysis of the contribution of FGF10+cells to airway smooth muscle cell formation during early lung development.

    Science.gov (United States)

    El Agha, Elie; Kheirollahi, Vahid; Moiseenko, Alena; Seeger, Werner; Bellusci, Saverio

    2017-07-01

    Airway smooth muscle cells (ASMCs) have been widely studied during embryonic lung development. These cells have been shown to control epithelial bifurcation during branching morphogenesis. Fibroblast growth factor 10-positive (FGF10 + ) cells, originally residing in the submesothelial mesenchyme, contribute to ASMC formation in the distal lung. The reported work aims at monitoring the response of FGF10 + progenitors and differentiated ASMCs to growth factor treatment in real time using lineage tracing in the background of an air-liquid interface (ALI) culture system. FGF ligands impose divergent effects on iterative lung branching in vitro. Moreover, time-lapse imaging and endpoint analysis show that FGF9 treatment leads to amplification of the FGF10 + lineage and represses its differentiation to ASMCs. Sonic hedgehog (SHH) treatment reduces the amplification of this lineage and leads to decreased lung branching. Finally, differentiated ASMCs in proximal regions fail to expand upon FGF9 treatment. Our data demonstrate, in real time, that FGF9 is an important regulator of amplification, migration, and subsequent differentiation of ASMC progenitors during early lung development. The attained results agree with previous findings regarding ASMC formation and highlight the complexity of growth factor signaling networks in controlling mesenchymal cell-fate decisions in the developing mouse lung. Developmental Dynamics 246:531-538, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. L-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

    NARCIS (Netherlands)

    Dekkers, Bart G J; Naeimi, Saeideh; Bos, I. Sophie T.; Menzen, Mark H; Halayko, Andrew John; Sadeghi Hashjin, Goudarz; Meurs, Herman

    2015-01-01

    Hypothyroidism may reduce, whereas hyperthyroidism may aggravate asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway

  13. Brief Communication: Contrast-stretching- and histogram-smoothness-based synthetic aperture radar image enhancement for flood map generation

    Science.gov (United States)

    Nazir, F.; Riaz, M. M.; Ghafoor, A.; Arif, F.

    2015-02-01

    Synthetic-aperture-radar-image-based flood map generation is usually a challenging task (due to degraded contrast). A three-step approach (based on adaptive histogram clipping, histogram remapping and smoothing) is proposed for generation of a more visualized flood map image. The pre- and post-flood images are adaptively histogram equalized. The hidden details in difference image are enhanced using contrast-based enhancement and histogram smoothing. A fast-ready flood map is then generated using equalized pre-, post- and difference images. Results (evaluated using different data sets) show significance of the proposed technique.

  14. Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2/3 and increasing MYL-9 expression

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    Cai Zailong

    2011-01-01

    Full Text Available Abstract Background Abnormal proliferation, apoptosis, migration and contraction of airway smooth muscle (ASM cells in airway remodeling in asthma are basically excessive repair responses to a network of inflammatory mediators such as PDGF, but the mechanisms of such responses remain unclear. Nogo-B, a member of the reticulum family 4(RTN4, is known to play a key role in arteriogenesis and tissue repair. Further studies are needed to elucidate the role of Nogo-B in airway smooth muscle abnormalities. Methods A mouse model of chronic asthma was established by repeated OVA inhalation and subjected to Nogo-B expression analysis using immunohistochemistry and Western Blotting. Then, primary human bronchial smooth muscle cells (HBSMCs were cultured in vitro and a siRNA interference was performed to knockdown the expression of Nogo-B in the cells. The effects of Nogo-B inhibition on PDGF-induced HBSMCs proliferation, migration and contraction were evaluated. Finally, a proteomic analysis was conducted to unveil the underlying mechanisms responsible for the function of Nogo-B. Results Total Nogo-B expression was approximately 3.08-fold lower in chronic asthmatic mice compared to naïve mice, which was obvious in the smooth muscle layer of the airways. Interference of Nogo-B expression by siRNA resulted nearly 96% reduction in mRNA in cultured HBSMCs. In addition, knockdown of Nogo-B using specific siRNA significantly decreased PDGF-induced migration of HBSMCs by 2.3-fold, and increased the cellular contraction by 16% compared to negative controls, but had limited effects on PDGF-induced proliferation. Furthermore, using proteomic analysis, we demonstrate that the expression of actin related protein 2/3 complex subunit 5 (ARPC 2/3 decreased and, myosin regulatory light chain 9 isoform a (MYL-9 increased after Nogo-B knockdown. Conclusions These data define a novel role for Nogo-B in airway remodeling in chronic asthma. Endogenous Nogo-B, which may exert

  15. Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Yiyuan; Long, Jiaoyue; Chen, Jun; Jiang, Xuemei; Zhu, Jian; Jin, Yang; Lin, Feng; Zhong, Jun; Xu, Rong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, and Bioengineering College, Chongqing University, Shapingba, Chongqing 400030 (China); Mao, Lizheng [Jiangsu Asialand Biomed-Technology Co. Ltd., Changzhou, Jiangsu 213164 (China); Deng, Linhong, E-mail: dlh@cczu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, and Bioengineering College, Chongqing University, Shapingba, Chongqing 400030 (China); Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164 (China)

    2016-11-15

    A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression promotes

  16. Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

    International Nuclear Information System (INIS)

    Duan, Yiyuan; Long, Jiaoyue; Chen, Jun; Jiang, Xuemei; Zhu, Jian; Jin, Yang; Lin, Feng; Zhong, Jun; Xu, Rong; Mao, Lizheng; Deng, Linhong

    2016-01-01

    A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression promotes

  17. CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro.

    Science.gov (United States)

    Alkhouri, H; Moir, L M; Armour, C L; Hughes, J M

    2014-03-01

    Activated mast cells (MC) numbers on airway smooth muscle (ASM) are increased in eosinophilic asthma. In vitro, asthmatic cytokine-stimulated ASM cell-conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified. To identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis. Confluent, serum-starved ASM cells from donors with and without asthma were stimulated with IL-1β and T-helper (Th)1 (TNFα and IFNγ) or Th2 (IL-4, IL-13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT-PCR and inhibitory role investigated in MC chemotaxis and Ca(2+) mobilization assays. Only CXCL1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine stimulation. CXCL1 mRNA expression was also increased. Exogenous rh-CXCL1 significantly inhibited MC intracellular Ca(2+) mobilization and chemotaxis to either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis. CXCL1 was a major factor regulating MC chemotaxis in vitro. Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma. CXCL1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology. © 2013 John Wiley & Sons Ltd.

  18. Characterising the mechanism of airway smooth muscle β2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    David Van Ly

    Full Text Available Rhinovirus (RV infections account for approximately two thirds of all virus-induced asthma exacerbations and often result in an impaired response to β2 agonist therapy. Using an in vitro model of RV infection, we investigated the mechanisms underlying RV-induced β2 adrenoceptor desensitization in primary human airway smooth muscle cells (ASMC. RV infection of primary human bronchial epithelial cells (HBEC for 24 hours produced conditioned medium that caused β2 adrenoceptor desensitization on ASMCs without an effect on ASMCs viability. Less than 3 kDa size fractionation together with trypsin digestion of RV-induced conditioned medium did not prevent β2 adrenoceptor desensitization, suggesting it could potentially be mediated by a small peptide or lipid. RV infection of BECs, ASMCs and fibroblasts produced prostaglandins, of which PGE2, PGF2α and PGI2 had the ability to cause β2 adrenoceptor desensitization on ASMCs. RV-induced conditioned medium from HBECs depleted of PGE2 did not prevent ASMC β2 adrenoceptor desensitization; however this medium induced PGE2 from ASMCs, suggesting that autocrine prostaglandin production may be responsible. Using inhibitors of cyclooxygenase and prostaglandin receptor antagonists, we found that β2 adrenoceptor desensitization was mediated through ASMC derived COX-2 induced prostaglandins. Since ASMC prostaglandin production is unlikely to be caused by RV-induced epithelial derived proteins or lipids we next investigated activation of toll-like receptors (TLR by viral RNA. The combination of TLR agonists poly I:C and imiquimod induced PGE2 and β2 adrenoceptor desensitization on ASMC as did the RNA extracted from RV-induced conditioned medium. Viral RNA but not epithelial RNA caused β2 adrenoceptor desensitization confirming that viral RNA and not endogenous human RNA was responsible. It was deduced that the mechanism by which β2 adrenoceptor desensitization occurs was by pattern recognition receptor

  19. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  20. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors.

    Science.gov (United States)

    Burgess, J K; Ketheson, A; Faiz, A; Limbert Rempel, K A; Oliver, B G; Ward, J P T; Halayko, A J

    2018-01-16

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

  1. Nicotine Elevated Intracellular Ca2+ in Rat Airway Smooth Muscle Cells via Activating and Up-Regulating α7-Nicotinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Yongliang Jiang

    2014-02-01

    Full Text Available Background: Chronic obstructive pulmonary disease (COPD is characterized by airway remodeling with airway smooth muscle (ASM hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca2+ concentration ([Ca2+]i plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR activation plays a role in the elevation of [Ca2+]i in airway smooth muscle cells (ASMCs. Methods: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. Results: RT-PCR analysis showed that α2-7, β2, and β3-nAChR subunits are expressed in rat ASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca2+]i in cultured rat ASMCs. Acute application of nicotine evoked a rapid increase in [Ca2+]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 µM nicotine for 48 hours. Nicotine-induced Ca2+ response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca2+ responses induced by nicotine. Conclusion: These observations suggest that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.

  2. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

    Science.gov (United States)

    Tan, Xiahui; Khalil, Najwa; Tesarik, Candice; Vanapalli, Karunasri; Yaputra, Viki; Alkhouri, Hatem; Oliver, Brian G G; Armour, Carol L; Hughes, J Margaret

    2012-04-01

    In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

  3. Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation

    Directory of Open Access Journals (Sweden)

    Fox Jane

    2010-12-01

    Full Text Available Abstract Background Agonist stimulation of airway smooth muscle (ASM results in IP3 mediated Ca2+ release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na+ influx. This localised increase in Na+ levels can potentially switch the Na+/Ca2+ exchanger into reverse mode and so result in a further influx of Ca2+. The aim of this study was to characterise the expression and physiological function of the Na+/Ca2+ exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca2+ influx into these cells. Methods The expression profile of NCX (which encodes the Na+/Ca2+ exchanger homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca2+ measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX and target specific siRNA were utilised as tools to inhibit NCX function. Results NCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na+ loading and addition of extracellular Ca2+ induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1 and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca2+ and induced relaxation of porcine

  4. Long-acting β2-agonists increase fluticasone propionate-induced mitogen-activated protein kinase phosphatase 1 (MKP-1 in airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Melanie Manetsch

    Full Text Available Mitogen-activated protein kinase phosphatase 1 (MKP-1 represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol, alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone in primary human airway smooth muscle (ASM cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6 and interleukin 8 (IL-8 secretion. As IL-6 expression (like MKP-1 is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα. Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type.

  5. Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM).

    Science.gov (United States)

    Delmotte, Philippe; Sieck, Gary C

    2015-02-01

    Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca(2+) ([Ca(2+)]cyt) responses to agonist stimulation and Ca(2+) sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca(2+)]cyt induced by agonists leads to a transient increase in mitochondrial Ca(2+) ([Ca(2+)]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca(2+)]mito is blunted despite enhanced [Ca(2+)]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion-ER/SR coupling, decreased mitochondrial Ca(2+) buffering, mitochondrial fragmentation, and increased cell proliferation.

  6. Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma

    NARCIS (Netherlands)

    Januskevicius, Andrius; Vaitkiene, Simona; Gosens, Reinoud; Janulaityte, Ieva; Hoppenot, Deimante; Sakalauskas, Raimundas; Malakauskas, Kestutis

    2016-01-01

    BACKGROUND: Recent studies have suggested that eosinophils may have a direct effect on airway smooth muscle cells (ASMC), causing their proliferation in patients with asthma, but the precise mechanism of the interaction between these cells remains unknown. We propose that changes in Wnt signaling

  7. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    Directory of Open Access Journals (Sweden)

    von Rechenberg Moritz

    2011-01-01

    Full Text Available Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20 and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM. Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Results Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. Conclusions This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  8. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening.

    Science.gov (United States)

    An, Steven S; Askovich, Peter S; Zarembinski, Thomas I; Ahn, Kwangmi; Peltier, John M; von Rechenberg, Moritz; Sahasrabudhe, Sudhir; Fredberg, Jeffrey J

    2011-01-13

    A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  9. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  10. Detection of epithelial to mesenchymal transition in airways of a bleomycin induced pulmonary fibrosis model derived from an α-smooth muscle actin-Cre transgenic mouse

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    2007-01-01

    Full Text Available Abstract Background Epithelial to mesenchymal transition (EMT in alveolar epithelial cells (AECs has been widely observed in patients suffering interstitial pulmonary fibrosis. In vitro studies have also demonstrated that AECs could convert into myofibroblasts following exposure to TGF-β1. In this study, we examined whether EMT occurs in bleomycin (BLM induced pulmonary fibrosis, and the involvement of bronchial epithelial cells (BECs in the EMT. Using an α-smooth muscle actin-Cre transgenic mouse (α-SMA-Cre/R26R strain, we labelled myofibroblasts in vivo. We also performed a phenotypic analysis of human BEC lines during TGF-β1 stimulation in vitro. Methods We generated the α-SMA-Cre mouse strain by pronuclear microinjection with a Cre recombinase cDNA driven by the mouse α-smooth muscle actin (α-SMA promoter. α-SMA-Cre mice were crossed with the Cre-dependent LacZ expressing strain R26R to produce the double transgenic strain α-SMA-Cre/R26R. β-galactosidase (βgal staining, α-SMA and smooth muscle myosin heavy chains immunostaining were carried out simultaneously to confirm the specificity of expression of the transgenic reporter within smooth muscle cells (SMCs under physiological conditions. BLM-induced peribronchial fibrosis in α-SMA-Cre/R26R mice was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. To confirm in vivo observations of BECs undergoing EMT, we stimulated human BEC line 16HBE with TGF-β1 and examined the localization of the myofibroblast markers α-SMA and F-actin, and the epithelial marker E-cadherin by immunofluorescence. Results βgal staining in organs of healthy α-SMA-Cre/R26R mice corresponded with the distribution of SMCs, as confirmed by α-SMA and SM-MHC immunostaining. BLM-treated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some AECs in certain peribronchial areas or even a small

  11. Basic Fibroblast Growth Factor 2 Is a Determinant of CD4 T Cell-Airway Smooth Muscle Cell Communication through Membrane Conduits.

    Science.gov (United States)

    Farahnak, Soroor; McGovern, Toby K; Kim, Rachael; O'Sullivan, Michael; Chen, Brian; Lee, Minhyoung; Yoshie, Haruka; Wang, Anna; Jang, Joyce; Al Heialy, Saba; Lauzon, Anne-Marie; Martin, James G

    2017-11-01

    Activated CD4 T cells connect to airway smooth muscle cells (ASMCs) in vitro via lymphocyte-derived membrane conduits (LMCs) structurally similar to membrane nanotubes with unknown intercellular signals triggering their formation. We examined the structure and function of CD4 T cell-derived LMCs, and we established a role for ASMC-derived basic fibroblast growth factor 2 (FGF2b) and FGF receptor (FGFR)1 in LMC formation. Blocking FGF2b's synthesis and FGFR1 function reduced LMC formation. Mitochondrial flux from ASMCs to T cells was partially FGF2b and FGFR1 dependent. LMC formation by CD4 T cells and mitochondrial transfer from ASMCs was increased in the presence of asthmatic ASMCs that expressed more mRNA for FGF2b compared with normal ASMCs. These observations identify ASMC-derived FGF2b as a factor needed for LMC formation by CD4 T cells, affecting intercellular communication. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  13. Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of beta2-adrenoceptors, the polyamine system and external calcium.

    Science.gov (United States)

    Bordallo, Javier; de Boto, María José García; Meana, Clara; Velasco, Lucía; Bordallo, Carmen; Suárez, Lorena; Cantabrana, Begoña; Sánchez, Manuel

    2008-12-28

    Androgens relax several smooth muscles, including the airways. They also contract ileum and myocardium via nongenomic mechanisms. To find out whether androgens modulate airway smooth muscles in different species and further assess their mechanism of action, regarding the role of beta-adrenoceptors, polyamines and extracellular Ca(2+), and the modulation of contraction, 5 alpha-dihydrotestosterone, testosterone and 5 beta-dihydrotestosterone were used. A preliminary study was performed to evaluate the effect of 5 alpha-dihydrotestosterone, a non-aromatisable derivate of testosterone, in isolated guinea-pig trachea and a more exhaustive characterisation was followed in bovine trachea, to also characterise the effect of testosterone and 5 beta-dihydrotestosterone. The androgens elicited a nongenomic epithelium-independent relaxation of the trachea which had been precontracted. In the bovine trachea, the order of potency was: testosterone>5 alpha-dihydrotestosterone=5 beta-dihydrotestosterone. This effect was inversely proportional to the magnitude of carbachol-raised tone and was independent of beta(2)-adrenoceptors, since the beta-blockers, propranolol and ICI-118,551, and beta(2)-adrenoceptor desensitisation did not modify 5 alpha-dihydrotestosterone-elicited relaxation. 5 alpha-Dihydrotestosterone was unable to displace the radiolabel, [(3)H]dihydroalprenolol, from these receptors in the binding assay. Polyamine synthesis was not involved in this androgen effect, since an ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, was ineffective. The androgens were more effective relaxing bovine trachea precontracted by KCl (80 mM), suggesting a calcium entry blockade, as reported for several smooth muscles. This mechanism might be involved in the observed 5 alpha-dihydrotestosterone facilitation of salbutamol-relaxation. Androgens facilitated carbachol-elicited contraction independently of polyamine synthesis, contrary to what has been reported in the ileum

  14. Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma.

    Science.gov (United States)

    Noble, Peter B; Jones, Robyn L; Cairncross, Alvenia; Elliot, John G; Mitchell, Howard W; James, Alan L; McFawn, Peter K

    2013-05-15

    The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma (n = 5) or had no history of asthma (n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM (P = 0.014), greater maximal airway narrowing under static conditions (P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer (r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group (P = 0.0001) and the group with a history of asthma (P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing (P = 0.02; r = -0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.

  15. Suppression of the increasing level of acetylcholine-stimulated intracellular Ca2+ in guinea pig airway smooth muscle cells by mabuterol.

    Science.gov (United States)

    Song, Xirui; Zhao, Chao; Dai, Cailing; Ren, Yanxin; An, Nan; Wen, Huimin; Pan, L I; Cheng, Maosheng; Zhang, Yuyang

    2015-11-01

    The present study aimed to establish an effective method for the in vitro culture of guinea pig airway smooth muscle (ASM) cells, and also investigate the suppressive effect of mabuterol hydrochloride (Mab) on the increased level of intracellular Ca 2+ in ASM cells induced with acetylcholine (Ach). Two different methods, i.e. with or without collagenase to pretreat tracheal tissues, were applied to the manufacture of ASM cells. Cell viability was determined with the 3-(4,5-dimethylthinazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunocytochemistry and immunofluorescence were used for the identification of ASM cells. Different concentration levels (10 -3 , 10 -4 , 10 -5 , 10 -6 and 10 -7 mmol/l) of Mab were administered 5 min before Ach (10 -4 M) treatment, respectively. The Ca 2+ fluorescent probe, Fura-2/AM or Fluo-3/AM were applied to the inspection of Ca 2+ fluorescent intensity with Varioskan Flash, immunocytometry systems and an inverted system microscope, respectively. The results showed that the fresh method, in which isolated tracheal tissues were previously treated with collagenase for 20 min, was more advantageous for the preparation of guinea pig ASM cells compared to when the enzyme was not used. The time for the ASM cells to initially migrate out of the 'tissue blocks' and the culture having to be generated due to the thick cell density was significantly less. On identification with immunocytochemistry or immunofluorescent staining, >95% of the cells were ASM cells. Mab (10 -3 -10 -7 mmol/l) significantly suppressed the elevation of intracellular Ca 2+ induced by Ach in a concentration-dependent manner. The inhibitory rates of intracellular Ca 2+ by different concentrations of Mab, from low to high, were 14.93, 24.73, 40.06, 48.54 and 57.13%, respectively, when Varioskan Flash was used for determination. In conclusion, this novel method has a shorter harvesting period for ASM cells. Mab can suppress the increasing level of intracellular Ca 2

  16. Airway contractility and remodeling : Links to asthma symptoms

    NARCIS (Netherlands)

    West, Adrian R.; Syyong, Harley T.; Siddiqui, Sana; Pascoe, Chris D.; Murphy, Thomas M.; Maarsingh, Harm; Deng, Linhong; Maksym, Geoffrey N.; Bosse, Ynuk

    Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental triggers, such as viruses or allergens, are

  17. 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

  18. Atomic Stretch: Optimally bounded real-time stretching and beyond

    DEFF Research Database (Denmark)

    Jensen, Rasmus Ramsbøl; Nielsen, Jannik Boll

    2016-01-01

    Atomic Stretch is a plugin for your preferred Adobe video editing tool, allowing real-time smooth and optimally bounded retarget-ting from and to any aspect ratio. The plugin allows preserving of high interest pixels through a protected region, attention redirection through color-modification, co......Atomic Stretch is a plugin for your preferred Adobe video editing tool, allowing real-time smooth and optimally bounded retarget-ting from and to any aspect ratio. The plugin allows preserving of high interest pixels through a protected region, attention redirection through color...

  19. Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

    Science.gov (United States)

    Ji, Yamei; Yang, Xin; Su, Huixia

    2018-02-01

    The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels.

    Science.gov (United States)

    Gao, Wei; Cai, Liting; Xu, Xudong; Fan, Juxiang; Xue, Xiulei; Yan, Xuejiao; Qu, Qinrong; Wang, Xihua; Zhang, Chen; Wu, Guoqiu

    2014-01-01

    Connective tissue growth factor (CTGF) contributes to airway smooth muscle (ASM) cell hyperplasia in asthma. Humanized single-chain variable fragment antibody (scFv) was well characterized as a CTGF antagonist in the differentiation of fibroblast into myofibroblast and pulmonary fibrosis in our previous studies. To further improve the bioactivity of scFv, we constructed a plasmid to express scFv-linker-matrilin-6×His fusion proteins that could self-assemble into the scFv dimers by disulfide bonds in matrilin under non-reducing conditions. An immunoreactivity assay demonstrated that the scFv dimer could highly bind to CTGF in a concentration-dependent manner. The MTT and EdU assay results revealed that CTGF (≥10 ng/mL) promoted the proliferation of ASM cells, and this effect was inhibited when the cells were treated with anti-CTGF scFv dimer. The western blot analysis results showed that increased phosphorylation of Akt and mTOR induced by CTGF could be suppressed by this scFv dimer. Based on these findings, anti-CTGF scFv dimer may be a potential agent for the prevention of airway remodeling in asthma.

  1. Research Upregulation of CD23 (FcεRII Expression in Human Airway Smooth Muscle Cells (huASMC in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    Directory of Open Access Journals (Sweden)

    Lew D Betty

    2005-05-01

    Full Text Available Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4, 15.6 ± 2.7% (GM-CSF and 32.9 ± 13.9% (IL-4/GMCSF combination(n = 3. The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue

  2. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    OpenAIRE

    von Rechenberg Moritz; Peltier John M; Ahn Kwangmi; Zarembinski Thomas I; Askovich Peter S; An Steven S; Sahasrabudhe Sudhir; Fredberg Jeffrey J

    2011-01-01

    Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two qua...

  3. TGF-β-activated kinase 1 (TAK1 signaling regulates TGF-β-induced WNT-5A expression in airway smooth muscle cells via Sp1 and β-catenin.

    Directory of Open Access Journals (Sweden)

    Kuldeep Kumawat

    Full Text Available WNT-5A, a key player in embryonic development and post-natal homeostasis, has been associated with a myriad of pathological conditions including malignant, fibroproliferative and inflammatory disorders. Previously, we have identified WNT-5A as a transcriptional target of TGF-β in airway smooth muscle cells and demonstrated its function as a mediator of airway remodeling. Here, we investigated the molecular mechanisms underlying TGF-β-induced WNT-5A expression. We show that TGF-β-activated kinase 1 (TAK1 is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced TGF-β induction of WNT-5A. Furthermore, we show that TAK1 engages p38 and c-Jun N-terminal kinase (JNK signaling which redundantly participates in WNT-5A induction as only simultaneous, but not individual, inhibition of p38 and JNK suppressed TGF-β-induced WNT-5A expression. Remarkably, we demonstrate a central role of β-catenin in TGF-β-induced WNT-5A expression. Regulated by TAK1, β-catenin is required for WNT-5A induction as its silencing repressed WNT-5A expression whereas a constitutively active mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the transcription factor for WNT-5A and demonstrate its interaction with β-catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-β-induced and TAK1-regulated manner. Collectively, our findings describe a TAK1-dependent, β-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-β which regulates WNT-5A induction.

  4. Intraluminal pressure oscillation enhances subsequent airway contraction in isolated bronchial segments.

    Science.gov (United States)

    Noble, P B; McFawn, P K; Mitchell, H W

    2004-03-01

    A period of deep inspiration in humans has been shown to attenuate subsequent bronchoconstriction, a phenomenon termed bronchoprotection. The bronchoprotective effect of deep inspiration may be caused though a depression in the force production of airway smooth muscle (ASM). We determined the response of whole airway segments and isolated ASM to a period of cyclic stretches. Isovolumetric contraction to electrical field stimulation (EFS) was assessed in porcine bronchial segments before and after intraluminal pressure oscillation from 5 to 25 cmH(2)O for 10 min at 0.5 Hz. Morphometry showed that this pressure oscillation stretched ASM length by 21%. After pressure oscillation, the response to EFS was not reduced but instead was modestly enhanced (P depression in isometric force induced by EFS (P < 0.01). These results suggest that the response of ASM to length oscillation is modified by the airway wall. They also suggest that the phenomenon of bronchoprotection reported in some in vivo studies may not be an intrinsic property of the airway.

  5. Dense-body aggregates as plastic structures supporting tension in smooth muscle cells.

    Science.gov (United States)

    Zhang, Jie; Herrera, Ana M; Paré, Peter D; Seow, Chun Y

    2010-11-01

    The wall of hollow organs of vertebrates is a unique structure able to generate active tension and maintain a nearly constant passive stiffness over a large volume range. These properties are predominantly attributable to the smooth muscle cells that line the organ wall. Although smooth muscle is known to possess plasticity (i.e., the ability to adapt to large changes in cell length through structural remodeling of contractile apparatus and cytoskeleton), the detailed structural basis for the plasticity is largely unknown. Dense bodies, one of the most prominent structures in smooth muscle cells, have been regarded as the anchoring sites for actin filaments, similar to the Z-disks in striated muscle. Here, we show that the dense bodies and intermediate filaments formed cable-like structures inside airway smooth muscle cells and were able to adjust the cable length according to cell length and tension. Stretching the muscle cell bundle in the relaxed state caused the cables to straighten, indicating that these intracellular structures were connected to the extracellular matrix and could support passive tension. These plastic structures may be responsible for the ability of smooth muscle to maintain a nearly constant tensile stiffness over a large length range. The finding suggests that the structural plasticity of hollow organs may originate from the dense-body cables within the smooth muscle cells.

  6. MiR-143-3p controls TGF-β1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1.

    Science.gov (United States)

    Cheng, Wei; Yan, Kun; Xie, Li-Yi; Chen, Feng; Yu, Hong-Chuan; Huang, Yan-Xia; Dang, Cheng-Xue

    2016-10-01

    MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes. However, little is known about the precise role of microRNAs in the functioning of airway smooth muscle cells (ASMCs). Here, we investigated the potential role and mechanisms of the miR-143 -3p on proliferation and the extracellular matrix (ECM) protein production of ASMCs. We demonstrated that miR-143-3p was aberrantly lower in ASMCs isolated from individuals with asthma than in individuals without asthma. Meanwhile, TGF-β1 caused a marked decrease in a time-dependent manner in miR-143-3p expression in ASMCs from asthmatics. Additionally, the overexpression of miR- 143-3p robustly reduced TGF-β1-induced ASMCs proliferation and downregulated CDK and cyclin expression, whereas the inhibition of miR-143-3p significantly enhanced ASMCs proliferation and upregulated the level of CDKs and cyclins. Re-expression of miR-143-3p attenuated ECM protein deposition reflected as a marked decrease in the expression of type I collagen and fibronectin, whereas miR-143-3p downregulation caused an opposite effect on the expression of type I collagen and fibronectin. Moreover, qRT-PCR and western blot analysis indicated that miR-143-3p negatively regulated the expression of nuclear factor of activated T cells 1 (NFATc1). Subsequent analyses demonstrated that NFATc1 was a direct and functional target of miR-143-3p, which was validated by the dual luciferase reporter assay. Most importantly, the overexpression of NFATc1 effectively reversed the inhibition of miR-143-3p on TGF-β1-induced proliferation, and strikingly abrogated the effect of miR-143-3p on the expression of CDK4 and Cyclin D1. Together, miR-143-3p may function as an inhibitor of asthma airway remodeling by suppressing proliferation and ECM protein deposition in TGF-β1-mediated ASMCs via the negative regulation of NFATc1 signaling, suggesting miR-143-3p as a potential therapeutic target for asthma. Copyright © 2016 Elsevier Ltd

  7. Developing a Stretching Program.

    Science.gov (United States)

    Beaulieu, J E

    1981-11-01

    In brief: Although stretching exercises can prevent muscle injuries and enhance athletic performance, they can also cause injury. The author explains the four most common types of stretching exercises and explains why he considers static stretching the safest. He also sets up a stretching routine for runners. In setting up a safe stretching program, one should (1) precede stretching exercises with a mild warm-up; (2) use static stretching; (3) stretch before and after a workout; (4) begin with mild and proceed to moderate exercises; (5) alternate exercises for muscle groups; (6) stretch gently and slowly until tightness, not pain, is felt; and (7) hold the position for 30 to 60 seconds.

  8. Stretch Sensor Device

    DEFF Research Database (Denmark)

    2013-01-01

    The invention relates to a method for determining stretch values and movement of body parts, e.g. a foot, by analysing stretch data from a stretch sensor. By analysing data from the stretch sensor it is possible to determine stretch samples which are associated with particular motion phases...

  9. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis.

    Science.gov (United States)

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong

    2017-02-01

    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (Pazithromycin-treated rats (Pazithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (PAzithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl− Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth Muscle

    Science.gov (United States)

    Bao, Rongfeng; Lifshitz, Lawrence M.; Tuft, Richard A.; Bellvé, Karl; Fogarty, Kevin E.; ZhuGe, Ronghua

    2008-01-01

    Ca2+ sparks are highly localized, transient releases of Ca2+ from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca2+ sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca2+-activated K+ channels, and also gate Ca2+-activated Cl− (Cl(Ca)) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca2+ sparks is well understood, little information is available on how Ca2+ sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl(Ca) channels in spark sites in airway myocytes from mouse. Ca2+ sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca2+ current underlying a Ca2+ spark (ICa(spark)), with an appropriate correction for endogenous fixed Ca2+ buffer, which was characterized by flash photolysis of NPEGTA. We found that ICa(spark) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca2+ sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the ICa(spark) by less than 3 ms, and its rising phase matches the duration of the ICa(spark). We further determined that Cl(Ca) channels on average are exposed to a [Ca2+] of 2.4 μM or greater during Ca2+ sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca2+] produced by a reaction-diffusion simulation with measured ICa(spark). Finally we estimated that the number of Cl(Ca) channels localized in Ca2+ spark sites could account for all the Cl(Ca) channels in the entire cell. Taken together these results lead us to propose a model in which RyRs and Cl(Ca) channels in Ca2+ spark sites localize

  11. A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle.

    Science.gov (United States)

    Bao, Rongfeng; Lifshitz, Lawrence M; Tuft, Richard A; Bellvé, Karl; Fogarty, Kevin E; ZhuGe, Ronghua

    2008-07-01

    Ca(2+) sparks are highly localized, transient releases of Ca(2+) from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca(2+) sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca(2+)-activated K(+) channels, and also gate Ca(2+)-activated Cl(-) (Cl((Ca))) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca(2+) sparks is well understood, little information is available on how Ca(2+) sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl((Ca)) channels in spark sites in airway myocytes from mouse. Ca(2+) sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca(2+) current underlying a Ca(2+) spark (I(Ca(spark))), with an appropriate correction for endogenous fixed Ca(2+) buffer, which was characterized by flash photolysis of NPEGTA. We found that I(Ca(spark)) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca(2+) sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the I(Ca(spark)) by less than 3 ms, and its rising phase matches the duration of the I(Ca(spark)). We further determined that Cl((Ca)) channels on average are exposed to a [Ca(2+)] of 2.4 microM or greater during Ca(2+) sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca(2+)] produced by a reaction-diffusion simulation with measured I(Ca(spark)). Finally we estimated that the number of Cl((Ca)) channels localized in Ca(2+) spark sites could account for all the Cl((Ca)) channels in the entire cell. Taken together these results lead us to propose a model in which

  12. 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

    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

  13. Airway Remodelling in Asthma: From Benchside to Clinical Practice

    Directory of Open Access Journals (Sweden)

    Céline Bergeron

    2010-01-01

    Full Text Available Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.

  14. 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.

  15. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

  16. A functional role for WNT-5A in driving airway myocyte proliferation

    NARCIS (Netherlands)

    Koopmans, Tim; Kumawat, Kuldeep; Van Den Berge, Maarten; Meurs, Herman; Gosens, Reinoud

    2013-01-01

    Increased airway smooth muscle (ASM) mass is a common pathological feature associated with chronic airway diseases, notably asthma. The mechanisms, however, remain poorly understood. The WNT (Wingless/integrase-1) signaling pathway has been implicated in various proliferative diseases, including

  17. Stretching Safely and Effectively

    Science.gov (United States)

    ... of stretching before or after hitting the trail, ballet floor or soccer field. Before you plunge into ... ballistic stretching on strength and muscular fatigue of ballet dancers and resistance-trained women. Journal of Strength ...

  18. Glutamate receptors and the airways hyperreactivity.

    Science.gov (United States)

    Strapkova, Anna; Antosova, Martina

    2012-03-01

    It is proposed the link between the hyperactivity of NMDA receptors and airway hyperresponsiveness. We investigated the effect of agents modulating the activity of NMDA receptors in the ovalbumin-induced airway hyperreactivity in guinea pigs. The airways hyperreactivity was influenced by the agonist (NMDA) and selective antagonist - competitive (AP-5) and non-competitive (MK-801) of NMDA receptors. Airway responsiveness to histamine or acetylcholine was evaluated in in vitro conditions. NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. MK 801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle, while the former, non-competitive antagonist was more effective. We recorded more pronounced response in tracheal than in lung tissue smooth muscle with more considerable response to acetylcholine than to histamine. The results of experiments show the modification of airway smooth muscles responses by agents modulating the activity of NMDA receptors. They confirm the possibility of NMDA receptors participation in experimental airway hyperreactivity. The results enlarge information regarding the link of the inflammatory diseases and glutamatergic system.

  19. Smooth approximations

    Czech Academy of Sciences Publication Activity Database

    Hájek, Petr Pavel; Johanis, M.

    2010-01-01

    Roč. 259, č. 3 (2010), s. 561-582 ISSN 0022-1236 R&D Projects: GA AV ČR IAA100190801 Institutional research plan: CEZ:AV0Z10190503 Keywords : C-P-smooth * Banach spaces * Lipschitz Subject RIV: BA - General Mathematics Impact factor: 1.196, year: 2010 http://www.sciencedirect.com/science/article/pii/S0022123610001795

  20. Stretched Wire Mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Bowden, Gordon; /SLAC

    2005-09-06

    Stretched wires are beginning to play an important role in the alignment of accelerators and synchrotron light sources. Stretched wires are proposed for the alignment of the 130 meter long LCLS undulator. Wire position technology has reached sub-micron resolution yet analyses of perturbations to wire straightness are hard to find. This paper considers possible deviations of stretched wire from the simple 2-dimensional catenary form.

  1. 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

  2. Stretching: Does It Help?

    Science.gov (United States)

    Vardiman, Phillip; Carrand, David; Gallagher, Philip M.

    2010-01-01

    Stretching prior to activity is universally accepted as an important way to improve performance and help prevent injury. Likewise, limited flexibility has been shown to decrease functional ability and predispose a person to injuries. Although this is commonly accepted, appropriate stretching for children and adolescents involved with sports and…

  3. Dynamic stretching is effective as static stretching at increasing flexibility

    OpenAIRE

    Coons, John M.; Gould, Colleen E.; Kim, Jwa K.; Farley, Richard S.; Caputo, Jennifer L.

    2017-01-01

    This study examined the effect of dynamic and static (standard) stretching on hamstring flexibility. Twenty-five female volleyball players were randomly assigned to dynamic (n = 12) and standard (n = 13) stretching groups. The experimental group trained with repetitive dynamic stretching exercises, while the standard modality group trained with static stretching exercises. The stretching interventions were equivalent in the time at stretch and were performed three days a week for four weeks. ...

  4. Purinergic signaling in the airways.

    Science.gov (United States)

    Burnstock, Geoffrey; Brouns, Inge; Adriaensen, Dirk; Timmermans, Jean-Pierre

    2012-10-01

    Evidence for a significant role and impact of purinergic signaling in normal and diseased airways is now beyond dispute. The present review intends to provide the current state of knowledge of the involvement of purinergic pathways in the upper and lower airways and lungs, thereby differentiating the involvement of different tissues, such as the epithelial lining, immune cells, airway smooth muscle, vasculature, peripheral and central innervation, and neuroendocrine system. In addition to the vast number of well illustrated functions for purinergic signaling in the healthy respiratory tract, increasing data pointing to enhanced levels of ATP and/or adenosine in airway secretions of patients with airway damage and respiratory diseases corroborates the emerging view that purines act as clinically important mediators resulting in either proinflammatory or protective responses. Purinergic signaling has been implicated in lung injury and in the pathogenesis of a wide range of respiratory disorders and diseases, including asthma, chronic obstructive pulmonary disease, inflammation, cystic fibrosis, lung cancer, and pulmonary hypertension. These ostensibly enigmatic actions are based on widely different mechanisms, which are influenced by the cellular microenvironment, but especially the subtypes of purine receptors involved and the activity of distinct members of the ectonucleotidase family, the latter being potential protein targets for therapeutic implementation.

  5. L-arginine supplementation and experimental airway hyperreactivity.

    Science.gov (United States)

    Antosova, M; Strapkova, A

    2013-01-01

    The interest in L-arginine metabolism was triggered primarily by the discovery of nitric oxide (NO) synthesis in mammals and its remarkable biological roles. The real role of L-arginine in the airway hyperreactivity (AHR) has not been established yet. Therefore, we studied whether supplementation of L-arginine can influence the experimental AHR evoked by two different triggers - allergen and exogenous irritant (toluene vapours). Male TRIK strain guinea pigs were used in the study. We used two patterns of pretreatment with L-arginine in vivo, short- and long-term, in a dose of 300 mg/kg administered i.p., after which we studied reactivity of airway smooth muscles in vitro. Pretreatment with L-arginine for 3 days decreased the airway smooth muscle reactivity induced by toluene vapour, whereas pretreatment for 17 days was without any additional effect on smooth muscle reactivity. The short-term pretreatment in ovalbumin-induced hyperreactivity caused an increase in airway smooth muscle reactivity to lower concentrations of both bronchoconstrictors. On the other side, this pretreatment significantly decreased smooth muscle reactivity to high concentrations of both bronchoconstrictors. Supplementation of L-arginine resulted in a modification of the airway smooth muscle response. The effect of supplementation was different depending on the AHR trigger, airway region and pretreatment duration. The results also underscore the importance of an optimal L-arginine level for the control of bronchial tone.

  6. Biocatalysis: Unmasked by stretching

    Science.gov (United States)

    Kharlampieva, Eugenia; Tsukruk, Vladimir V.

    2009-09-01

    The biocatalytic activity of enzyme-loaded responsive layer-by-layer films can be switched on and off by simple mechanical stretching. Soft materials could thus be used to trigger biochemical reactions under mechanical action, with potential therapeutic applications.

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

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2016-12-01

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

  8. Strategy as stretch and leverage.

    Science.gov (United States)

    Hamel, G; Prahalad, C K

    1993-01-01

    Global competition is not just product versus product or company versus company. It is mind-set versus mind-set. Driven to understand the dynamics of competition, we have learned a lot about what makes one company more successful than another. But to find the root of competitiveness--to understand why some companies create new forms of competitive advantage while others watch and follow--we must look at strategic mind-sets. For many managers, "being strategic" means pursuing opportunities that fit the company's resources. This approach is not wrong, Gary Hamel and C.K. Prahalad contend, but it obscures an approach in which "stretch" supplements fit and being strategic means creating a chasm between ambition and resources. Toyota, CNN, British Airways, Sony, and others all displaced competitors with stronger reputations and deeper pockets. Their secret? In each case, the winner had greater ambition than its well-endowed rivals. Winners also find less resource-intensive ways of achieving their ambitious goals. This is where leverage complements the strategic allocation of resources. Managers at competitive companies can get a bigger bang for their buck in five basic ways: by concentrating resources around strategic goals; by accumulating resources more efficiently; by complementing one kind of resource with another; by conserving resources whenever they can; and by recovering resources from the market-place as quickly as possible. As recent competitive battles have demonstrated, abundant resources can't guarantee continued industry leadership.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

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

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  12. 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.

  13. 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.

  14. Improving multigrid for 3-D electro-magnetic diffusion on stretched grids

    NARCIS (Netherlands)

    Jönsthövel, T.B.; Oosterlee, C.W.; Mulder, W.A.

    2006-01-01

    We evaluated multigrid techniques for 3D diffusive electromagnetism. The Maxwell equations and Ohm's law were discretised on stretched grids, with stretching in all coordinate directions. We compared standard multigrid to alternative multigrid approaches with linewise smoothing and semi-coarsening,

  15. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema on t...... in causing airway narrowing, the latter most likely due to loss of elastic recoil of surrounding tissue....

  16. 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

  17. Stretching & Flexibility: An Interactive Encyclopedia of Stretching. [CD-ROM].

    Science.gov (United States)

    2002

    This CD-ROM offers 140 different stretches in full-motion video sequences. It focuses on the proper techniques for overall physical fitness, injury prevention and rehabilitation, and 23 different sports (e.g., golf, running, soccer, skiing, climbing, football, and baseball). Topics include stretching for sports; stretching awareness and education…

  18. Airway remodeling and its reversibility in equine asthma

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  19. Transient Mechanical Response of Lung Airway Tissue during Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Israr Bin Muhammad Ibrahim

    2016-01-01

    Full Text Available Patients with acute lung injury, airway and other pulmonary diseases often require Mechanical Ventilation (MV. Knowledge of the stress/strain environment in lung airway tissues is very important in order to avoid lung injuries for patients undergoing MV. Airway tissue strains responsible for stressing the lung’s fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. Multi-level modeling is adopted to investigate the transient mechanical response of the tissue under MV. First, airflow through a lung airway bifurcation (Generation 4–6 is modeled using Computational Fluid Dynamics (CFD to obtain air pressure during 2 seconds of MV breathing. Next, the transient air pressure was used in structural analysis to obtain mechanical strain experienced by the airway tissue wall. Structural analysis showed that airway tissue from Generation 5 in one bifurcation can stretch eight times that of airway tissue of the same generation number but with different bifurcation. The results suggest sensitivity of load to geometrical features. Furthermore, the results of strain levels obtained from the tissue analysis are very important because these strains at the cellular-level can create inflammatory responses, thus damaging the airway tissues.

  20. Stretching the Border

    DEFF Research Database (Denmark)

    Horstmann, Alexander

    2014-01-01

    In this paper, I hope to add a complementary perspective to James Scott’s recent work on avoidance strategies of subaltern mountain people by focusing on what I call the refugee public. The educated Karen elite uses the space of exile in the Thai borderland to reconstitute resources and to re-ent......-based organizations succeed to stretch the border by establishing a firm presence that is supported by the international humanitarian economy in the refugee camps in Northwestern Thailand....

  1. Dynamics and structure of stretched flames

    Energy Technology Data Exchange (ETDEWEB)

    Law, C.K. [Princeton Univ., NJ (United States)

    1993-12-01

    This program aims to gain fundamental understanding on the structure, geometry, and dynamics of laminar premixed flames, and relate these understanding to the practical issues of flame extinction and stabilization. The underlying fundamental interest here is the recent recognition that the response of premixed flames can be profoundly affected by flame stretch, as manifested by flow nonuniformity, flame curvature, and flame/flow unsteadiness. As such, many of the existing understanding on the behavior of premixed flames need to be qualitatively revised. The research program consists of three major thrusts: (1) detailed experimental and computational mapping of the structure of aerodynamically-strained planar flames, with emphasis on the effects of heat loss, nonequidiffusion, and finite residence time on the flame thickness, extent of incomplete reaction, and the state of extinction. (2) Analytical study of the geometry and dynamics of stretch-affected wrinkled flame sheets in simple configurations, as exemplified by the Bunsen flame and the spatially-periodic flame, with emphasis on the effects of nonlinear stretch, the phenomena of flame cusping, smoothing, and tip opening, and their implications on the structure and burning rate of turbulent flames. (3) Stabilization and blowoff of two-dimensional inverted premixed and stabilization and determining the criteria governing flame blowoff. The research is synergistically conducted through the use of laser-based diagnostics, computational simulation of the flame structure with detailed chemistry and transport, and mathematical analysis of the flame dynamics.

  2. CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Deepak A. Deshpande

    2018-01-01

    Full Text Available Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+ signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3 and CD38-cyclic ADP-ribose (CD38/cADPR are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

  3. Cyclic Stretch Alters Vascular Reactivity of Mouse Aortic Segments

    Directory of Open Access Journals (Sweden)

    Arthur Leloup

    2017-10-01

    Full Text Available Large, elastic arteries buffer the pressure wave originating in the left ventricle and are constantly exposed to higher amplitudes of cyclic stretch (10% than muscular arteries (2%. As a crucial factor for endothelial and smooth muscle cell function, cyclic stretch has, however, never been studied in ex vivo aortic segments of mice. To investigate the effects of cyclic stretch on vaso-reactivity of mouse aortic segments, we used the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC. The aortic segments were clamped at frequencies of 6–600 bpm between two variable preloads, thereby mimicking dilation as upon left ventricular systole and recoiling as during diastole. The preloads corresponding to different transmural pressures were chosen to correspond to a low, normal or high amplitude of cyclic stretch. At different time intervals, cyclic stretch was interrupted, the segments were afterloaded and isometric contractions by α1-adrenergic stimulation with 2 μM phenylephrine in the absence and presence of 300 μM L-NAME (eNOS inhibitor and/or 35 μM diltiazem (blocker of voltage-gated Ca2+ channels were measured. As compared with static or cyclic stretch at low amplitude (<10 mN or low frequency (0.1 Hz, cyclic stretch at physiological amplitude (>10 mN and frequency (1–10 Hz caused better ex vivo conservation of basal NO release with time after mounting. The relaxation of PE-precontracted segments by addition of ACh to stimulate NO release was unaffected by cyclic stretch. In the absence of basal NO release (hence, presence of L-NAME, physiological in comparison with aberrant cyclic stretch decreased the baseline tension, attenuated the phasic contraction by phenylephrine in the absence of extracellular Ca2+ and shifted the smaller tonic contraction more from a voltage-gated Ca2+ channel-mediated to a non-selective cation channel-mediated. Data highlight the need of sufficient mechanical activation of endothelial and

  4. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of ... Pulmonary Exacerbations Clinical Care Guidelines SCREENING & TREATING DEPRESSION & ANXIETY GUIDELINES Clinician Resources As a clinician, you’re ...

  5. Kontrola kvalitete stretch folije

    OpenAIRE

    Gržanić, Nino

    2016-01-01

    U završnom radu opisan je postupak ekstrudiranja i kontrole kvalitete stretch folije koji se koristi u firmi Bomark-Pak radi osiguravanja najbolje kvalitete. Kontrola kreče kod uvoza repromaterijala, nastavlja se kod izrade folije na stroju, te se glavni dio odvija nakon izrade gotovg proizvoda. U radu ćemo detaljno objasniti svaki pojedini korak, zašto se on vrši, te uz pomoć kojih mjernih instrumenata se izvršava.

  6. L-ornithine derived polyamines in cystic fibrosis airways.

    Directory of Open Access Journals (Sweden)

    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  7. Time course of airway remodelling after an acute chlorine gas exposure in mice

    Science.gov (United States)

    Tuck, Stephanie A; Ramos-Barbón, David; Campbell, Holly; McGovern, Toby; Karmouty-Quintana, Harry; Martin, James G

    2008-01-01

    Accidental chlorine (Cl2) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl2 exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl2 gas. Mice were exposed to 800 ppm Cl2 gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl2 exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl2 exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl2 exposure. At 10 days after Cl2 exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl2 gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling. PMID:18702818

  8. Time course of airway remodelling after an acute chlorine gas exposure in mice

    Directory of Open Access Journals (Sweden)

    McGovern Toby

    2008-08-01

    Full Text Available Abstract Accidental chlorine (Cl2 gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl2 exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl2 gas. Mice were exposed to 800 ppm Cl2 gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl2 exposure (≤ 24 hrs post-exposure was characterized by airway epithelial cell apoptosis (increased TUNEL staining and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl2 exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA, with maximal proliferation occurring 5 days after Cl2 exposure. At 10 days after Cl2 exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl2 gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.

  9. Regulation of GPCR-mediated smooth muscle contraction : implications for asthma and pulmonary hypertension

    NARCIS (Netherlands)

    Wright, D B; Tripathi, S; Sikarwar, A; Santosh, K T; Perez-Zoghbi, J; Ojo, O O; Irechukwu, N; Ward, J P T; Schaafsma, D

    Contractile G-protein-coupled receptors (GPCRs) have emerged as key regulators of smooth muscle contraction, both under healthy and diseased conditions. This brief review will discuss some key topics and novel insights regarding GPCR-mediated airway and vascular smooth muscle contraction as

  10. Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

    NARCIS (Netherlands)

    Gosens, Reinout; Schaafsma, D.; Grootte Bromhaar, M.M; Vrugt, B.; Zaagsma, Hans; Meurs, Herman; Nelemans, Herman

    2004-01-01

    Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor

  11. DEVELOPMENT OF DEFORMATION STRIPS WHILE STRETCHING OF CYLINDRICAL SAMPLES

    Directory of Open Access Journals (Sweden)

    Y. V. Vasilevich

    2011-01-01

    Full Text Available Deformation strips have been experimentally revealed and described while stretching of cylindrical samples by means of computer thermography. It has been established that temperature of shift strip surface grows smoothly up to the stage of crack origin in material defect. Sharp growth of surface temperature occurs when tensile stresses reach tensile strength. Change in surface temperature occurs wavy after destruction (while cooling the sample. Processes of material destruction origin and development  characterize temperature changes in deformation strips.

  12. Responsiveness of the human airway in vitro during deep inspiration and tidal oscillation.

    Science.gov (United States)

    Noble, Peter B; Jones, Robyn L; Needi, Elangovan Thaya; Cairncross, Alvenia; Mitchell, Howard W; James, Alan L; McFawn, Peter K

    2011-06-01

    In healthy individuals, deep inspiration produces bronchodilation and reduced airway responsiveness, which may be a response of the airway wall to mechanical stretch. The aim of this study was to examine the in vitro response of isolated human airways to the dynamic mechanical stretch associated with normal breathing. Human bronchial segments (n = 6) were acquired from patients without airflow obstruction undergoing lung resection for pulmonary neoplasms. The side branches were ligated and the airways were mounted in an organ bath chamber. Airway narrowing to cumulative concentrations of acetylcholine (3 × 10(-6) M to 3 × 10(-3) M) was measured under static conditions and in the presence of "tidal" oscillations with intermittent "deep inspiration." Respiratory maneuvers were simulated by varying transmural pressure using a motor-controlled syringe pump (tidal 5 to 10 cmH(2)O at 0.25 Hz, deep inspiration 5 to 30 cmH(2)O). Airway narrowing was determined from decreases in lumen volume. Tidal oscillation had no effect on airway responses to acetylcholine which was similar to those under static conditions. Deep inspiration in tidally oscillating, acetylcholine-contracted airways produced potent, transient (inspiration produces bronchodilation and a transient reduction in airway responsiveness, which can explain the beneficial effects of deep inspiration in bronchial provocation testing in vivo.

  13. Smoothed square well potential

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, P. [Institute for Nuclear Research Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary); Vertse, T. [Institute for Nuclear Research Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary); University of Debrecen, Faculty of Informatics, Debrecen (Hungary)

    2017-07-15

    The classical square well potential is smoothed with a finite range smoothing function in order to get a new simple strictly finite range form for the phenomenological nuclear potential. The smoothed square well form becomes exactly zero smoothly at a finite distance, in contrast to the Woods-Saxon form. If the smoothing range is four times the diffuseness of the Woods-Saxon shape both the central and the spin-orbit terms of the Woods-Saxon shape are reproduced reasonably well. The bound single-particle energies in a Woods-Saxon potential can be well reproduced with those in the smoothed square well potential. The same is true for the complex energies of the narrow resonances. (orig.)

  14. Desmin modulates lung elastic recoil and airway responsiveness.

    Science.gov (United States)

    Shardonofsky, Felix R; Capetanaki, Yassemi; Boriek, Aladin M

    2006-05-01

    Desmin is a structural protein that is expressed in smooth muscle cells of both airways and alveolar ducts. Therefore, desmin could be well situated to participate in passive and contractile force transmission in the lung. We hypothesized that desmin modulates lung compliance, lung recoil pressure, and airway contractile response. To test this hypothesis, respiratory system complex impedance (Zin,rs) at different positive end-expiratory pressure (PEEP) levels and quasi-static pressure-volume data were obtained in desmin-null and wild-type mice at baseline and during methacholine administration. Airways and lung tissue properties were partitioned by fitting Zin,rs to a constant-phase model. Relative to controls, desmin-null mice showed 1) lower values for lung stiffness and recoil pressure at baseline and induced airway constriction, 2) greater negative PEEP dependence of H and airway resistance under baseline conditions and cholinergic stimulation, and 3) airway hyporesponsiveness. These results demonstrate that desmin is a load-bearing protein that stiffens the airways and consequently the lung and modulates airway contractile response.

  15. Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice

    Science.gov (United States)

    Reznikov, Leah R.; Meyerholz, David K.; Adam, Ryan J.; Abou Alaiwa, Mahmoud; Jaffer, Omar; Michalski, Andrew S.; Powers, Linda S.; Price, Margaret P.; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma. PMID:27820848

  16. 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.

  17. Rhinovirus and airway allergy

    Directory of Open Access Journals (Sweden)

    Mutsuo Yamaya

    2004-01-01

    Full Text Available Rhinoviruses cause the majority of common colds, which often provoke wheezing in patients with asthma. The precise mechanisms responsible for the rhinovirus infection-induced exacerbations of bronchial asthma remain uncertain. However, several reports have demonstrated airway hyperresponsiveness, increases in chemical mediators in airway secretions, such as kinin and histamine, and airway inflammation in patients with bronchial asthma after rhinovirus infection. Rhinovirus infection induces the accumulation of inflammatory cells in airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Rhinovirus affects the barrier function of airway epithelial cells and activates airway epithelial cells and other cells in the lung to produce proinflammatory cytokines, including various types of interleukins, granulocyte-macrophage colony stimulating factor and RANTES, and histamine. Rhinovirus also stimulates the expression of intercellular adhesion molecule-1 (ICAM-1 and low-density lipoprotein receptors in the airway epithelium, receptors for major and minor rhinoviruses. Rhinovirus infection is inhibited by treatment with soluble ICAM-1 and by the reduction of ICAM-1 expression in airway epithelial cells after treatment with either glucocorticoid or erythromycin. Both soluble ICAM-1 and erythromycin have been reported to reduce the symptoms of common colds. Herein, we review the pathogenesis and management of rhinovirus infection-induced exacerbation of bronchial asthma and the relationship between rhinovirus infection and airway allergy.

  18. [Regeneration of airway epithelium].

    Science.gov (United States)

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Stretch-minimising stream surfaces

    KAUST Repository

    Barton, Michael

    2015-05-01

    We study the problem of finding stretch-minimising stream surfaces in a divergence-free vector field. These surfaces are generated by motions of seed curves that propagate through the field in a stretch minimising manner, i.e., they move without stretching or shrinking, preserving the length of their arbitrary arc. In general fields, such curves may not exist. How-ever, the divergence-free constraint gives rise to these \\'stretch-free\\' curves that are locally arc-length preserving when infinitesimally propagated. Several families of stretch-free curves are identified and used as initial guesses for stream surface generation. These surfaces are subsequently globally optimised to obtain the best stretch-minimising stream surfaces in a given divergence-free vector field. Our algorithm was tested on benchmark datasets, proving its applicability to incompressible fluid flow simulations, where our stretch-minimising stream surfaces realistically reflect the flow of a flexible univariate object. © 2015 Elsevier Inc. All rights reserved.

  20. Acute Muscle Stretching and Shoulder Position Sense

    OpenAIRE

    Björklund, Martin; Djupsjöbacka, Mats; Crenshaw, Albert G

    2006-01-01

    Context: Stretching is common among athletes as a potential method for injury prevention. Stretching-induced changes in the muscle spindle properties are a suggested mechanism, which may imply reduced proprioception after stretching; however, little is known of this association.

  1. Smoothness of limit functors

    Indian Academy of Sciences (India)

    We show that X is representable by a smooth closed subscheme of X . This result generalizes a theorem of Conrad et al. (Pseudo-reductive groups (2010) Cambridge Univ. Press) where the case when X is an affine smooth group and G G m , S acts as a group automorphisms of X is considered. It also occurs as a special ...

  2. Smoothness of limit functors

    Indian Academy of Sciences (India)

    We show that Xλ is representable by a smooth closed subscheme of X. This result generalizes a theorem of Conrad et al. (Pseudo-reductive groups. (2010) Cambridge Univ. Press) where the case when X is an affine smooth group and. Gm,S acts as a group automorphisms of X is considered. It also occurs as a special case.

  3. Quantum State Smoothing.

    Science.gov (United States)

    Guevara, Ivonne; Wiseman, Howard

    2015-10-30

    Smoothing is an estimation method whereby a classical state (probability distribution for classical variables) at a given time is conditioned on all-time (both earlier and later) observations. Here we define a smoothed quantum state for a partially monitored open quantum system, conditioned on an all-time monitoring-derived record. We calculate the smoothed distribution for a hypothetical unobserved record which, when added to the real record, would complete the monitoring, yielding a pure-state "quantum trajectory." Averaging the pure state over this smoothed distribution yields the (mixed) smoothed quantum state. We study how the choice of actual unraveling affects the purity increase over that of the conventional (filtered) state conditioned only on the past record.

  4. Smooth polyhedral surfaces

    KAUST Repository

    Günther, Felix

    2017-03-15

    Polyhedral surfaces are fundamental objects in architectural geometry and industrial design. Whereas closeness of a given mesh to a smooth reference surface and its suitability for numerical simulations were already studied extensively, the aim of our work is to find and to discuss suitable assessments of smoothness of polyhedral surfaces that only take the geometry of the polyhedral surface itself into account. Motivated by analogies to classical differential geometry, we propose a theory of smoothness of polyhedral surfaces including suitable notions of normal vectors, tangent planes, asymptotic directions, and parabolic curves that are invariant under projective transformations. It is remarkable that seemingly mild conditions significantly limit the shapes of faces of a smooth polyhedral surface. Besides being of theoretical interest, we believe that smoothness of polyhedral surfaces is of interest in the architectural context, where vertices and edges of polyhedral surfaces are highly visible.

  5. Hydraulic fracture during epithelial stretching.

    Science.gov (United States)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  6. Soleus stretch reflex during cycling

    DEFF Research Database (Denmark)

    Grey, Michael James; Pierce, C. W.; Milner, T. E.

    2001-01-01

    the crank cycle, producing ankle dorsiflexion perturbations of similar trajectory. The stretch reflex was greatest during the power phase of the crank cycle and was decreased to the level of background EMG during recovery. Matched perturbations were induced under static conditions at the same crank angle...... active cycling as has been shown with the H-reflex. This lack of depression may reflect a decreased susceptibility of the stretch reflex to inhibition, possibly originating from presynaptic mechanisms....

  7. 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...... the interior and exterior airway wall surface in three dimensions, and branches were matched in consecutive scans by image registration. Emphysema was defined as attenuation referred to as % low-attenuation area 910 (%LAA910). Emphysema limits were set at

  8. Laplacians on smooth distributions

    Science.gov (United States)

    Kordyukov, Yu. A.

    2017-10-01

    Let M be a compact smooth manifold equipped with a positive smooth density μ and let H be a smooth distribution endowed with a fibrewise inner product g. We define the Laplacian Δ_H associated with (H,μ,g) and prove that it gives rise to an unbounded self-adjoint operator in L^2(M,μ). Then, assuming that H generates a singular foliation \\mathscr F, we prove that, for any function \\varphi in the Schwartz space \\mathscr S( R), the operator \\varphi(Δ_H) is a smoothing operator in the scale of longitudinal Sobolev spaces associated with \\mathscr F. The proofs are based on pseudodifferential calculus on singular foliations, which was developed by Androulidakis and Skandalis, and on subelliptic estimates for Δ_H. Bibliography: 35 titles.

  9. 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

    , neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response...... 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......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...

  10. Can Treadmill Perturbations Evoke Stretch Reflexes in the Calf Muscles?

    Science.gov (United States)

    Sloot, Lizeth H; van den Noort, Josien C; van der Krogt, Marjolein M; Bruijn, Sjoerd M; Harlaar, Jaap

    2015-01-01

    Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8±1.0°, the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms). Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally measure reflexes during

  11. Can Treadmill Perturbations Evoke Stretch Reflexes in the Calf Muscles?

    Directory of Open Access Journals (Sweden)

    Lizeth H Sloot

    Full Text Available Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8±1.0°, the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms. Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally

  12. Relationship Between Stretch Duration And Shoulder Musculature ...

    African Journals Online (AJOL)

    To date, studies focussing on the effect of stretching on flexibility have focused almost solely on the effect of chronic stretching rather than the effects of acute stretching performed immediately prior to physical activity. The effects of different static stretches were assessed on passive shoulder range of motion (ROM).

  13. Upper Airway Control in Airway Defense

    Directory of Open Access Journals (Sweden)

    Poliacek I

    2016-04-01

    Full Text Available Upper airways (UA are an organic component of the respiratory tract, they serve to respiration, respiratory tract protection and defense, phonation, deglutition, etc. The functions of UA are regulated by motor control of the oral, pharyngeal, and laryngeal muscles.

  14. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low...

  15. Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression.

    Science.gov (United States)

    Woodruff, Prescott G; Dolganov, Gregory M; Ferrando, Ronald E; Donnelly, Samantha; Hays, Steven R; Solberg, Owen D; Carter, Roderick; Wong, Hofer H; Cadbury, Peggy S; Fahy, John V

    2004-05-01

    Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50-83% (p 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.

  16. Effects of Flavin7 on allergen induced hyperreactivity of airways

    Directory of Open Access Journals (Sweden)

    Franova S

    2009-12-01

    Full Text Available Abstract Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4, and interleukin 5 (IL-5 in bronchoalveolar lavage fluid (BALF. Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

  17. FUZZY BASED CONTRAST STRETCHING FOR MEDICAL IMAGE ENHANCEMENT

    Directory of Open Access Journals (Sweden)

    T.C. Raja Kumar

    2011-07-01

    Full Text Available Contrast Stretching is an important part in medical image processing applications. Contrast is the difference between two adjacent pixels. Fuzzy statistical values are analyzed and better results are produced in the spatial domain of the input image. The histogram mapping produces the resultant image with less impulsive noise and smooth nature. The probabilities of gray values are generated and the fuzzy set is determined from the position of the input image pixel. The result indicates the good performance of the proposed fuzzy based stretching. The inverse transform of the real values are mapped with the input image to generate the fuzzy statistics. This approach gives a flexible image enhancement for medical images in the presence of noises.

  18. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: January 2018 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  20. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... a Family Parenting as an Adult With CF Treatments & Therapies People with cystic fibrosis are living longer ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... another member of your CF care team can show you how to perform many different ACTs and ... of children with CF and a respiratory therapist talk about the different techniques they use for airway ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... There are different ways to clear your airways. Most are easy to do. Infants and toddlers will ... best ACT is the one that you are most likely to perform as part of your daily ...

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CYSTIC FIBROSIS Learn about cystic fibrosis, a genetic lung disorder that affects the pancreas and other organs, ... Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and Huffing High- ...

  4. Airway protective mechanisms.

    Science.gov (United States)

    Pitts, Teresa

    2014-02-01

    Cough and swallow are highly coordinated reflex behaviors whose common purpose is to protect the airway. The pharynx is the common tube for air and food/liquid movement from the mouth into the thorax, has been largely overlooked, and is potentially seen as just a passive space. The thyropharyngeus muscle responds to cough inducing stimuli to prepare a transient holding area for material that has been removed from the subglottic airway. The cricopharyngeus muscle participates with the larynx to ensure regulation of pressure when a bolus/air is moving from the upper airway through to the thorax (i.e., inspiration or swallow) or the reverse (i.e., expiration reflex or vomiting). These vital mechanisms have not been evaluated in clinical conditions but could be impaired in many neurodegenerative diseases, leading to aspiration pneumonia. These newly described airway protective mechanisms need further study, especially in healthy and pathologic human populations.

  5. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care ... attack bacteria. Choose What's Best for You Your respiratory therapist or another member of your CF care ...

  6. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing ... Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest Wall Oscillation ( ...

  7. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CFTR Modulator Therapies Mucus Thinners Nebulizer Care at Home Vascular Access Devices PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  8. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ultimately help find a ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... the smaller airways to attack bacteria. Choose What's Best for You Your respiratory therapist or another member ... specific ACTs for you to try. However, the best ACT is the one that you are most ...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

  12. Airway Protective Mechanisms

    OpenAIRE

    Pitts, Teresa

    2013-01-01

    Cough and swallow are highly coordinated reflex behaviors whose common purpose is to protect the airway. The pharynx is the common tube for air and food/liquid movement from the mouth into the thorax, has been largely overlooked, and is potentially seen as just a passive space. The thyropharyngeus muscle responds to cough inducing stimuli to prepare a transient holding area for material that has been removed from the subglottic airway. The cricopharyngeus muscle participates with the larynx t...

  13. New airways for resuscitation?

    Science.gov (United States)

    Cook, T M; Hommers, C

    2006-06-01

    Over the last 15 years supraglottic airway devices (SADs), most notably the classic laryngeal mask airway (LMA) have revolutionised airway management in anaesthesia. In contrast for resuscitation, both in and outside hospital, facemask ventilation and tracheal intubation remain the mainstays of airway management. However there is evidence that both these techniques have complications and are often poorly performed by inexperienced personnel. Tracheal intubation also has the potential to cause serious harm or death through unrecognised oesophageal intubation. SADs may have a role in airway management for resuscitation as first responder devices, rescue devices or for use during patient extraction. In particular they may be beneficial as the level of skill required to use the device safely may be less than for the tracheal tube. Concerns have been expressed over the ability to ventilate the lungs successfully and also the risk of aspiration with SADs. The only SADs recommended by ILCOR in its current guidance are the classic LMA and combitube. Several SADs have recently been introduced with claims that ventilation and airway protection is improved. This pragmatic review examines recent developments in SAD technology and the relevance of this to the potential for using SADs during resuscitation. In addition to examining research directly related to resuscitation both on bench models and in patients the review also examines evidence from anaesthetic practice. SADS discussed include the classic, intubating and Proseal LMAs, the combitube, the laryngeal tube, laryngeal tube sonda mark I and II and single use laryngeal masks.

  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. Modeling the dispersion effects of contractile fibers in smooth muscles

    Science.gov (United States)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  16. 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.

  17. Acute effects of unilateral static stretching on handgrip strength of the stretched and non-stretched limb.

    Science.gov (United States)

    Jelmini, Jacob D; Cornwell, Andrew; Khodiguian, Nazareth; Thayer, Jennifer; Araujo, And John

    2018-02-16

    To determine the effects of an acute bout of unilateral static stretching on handgrip strength of both the stretched and non-stretched limb. It was reasoned that if the non-stretched limb experienced a decrease in force output, further evidence for a neural mechanism to explain a post-stretch force reduction would be obtained as no mechanical adaptation would have occurred. Thirty participants performed maximum voluntary unilateral handgrip contractions of both limbs before and after stretching the finger flexors of the strength-dominant side only. Each trial was assessed for peak force, muscle activity (iEMG), and rate of force generation. Following the stretching bout, peak force and iEMG decreased by 4.4% (p = 0.001) and 6.4% (p = 0.000) respectively in the stretched limb only. However, rate of force generation was significantly impaired in both the stretched (- 17.3%; p = 0.000) and non-stretched limbs (- 10.8%; p = 0.003) 1 min post-stretch, and remained similarly depressed for both limbs 15 min later. Acute stretching negatively impacts rate of force generation more than peak force. Moreover, a reduced rate of force generation from the non-stretched limb indicates the presence of a cross-over inhibitory effect through the nervous system, which provides additional evidence for a neural mechanism.

  18. Extubation of the difficult airway.

    Science.gov (United States)

    Faris, Khaldoun; Zayaruzny, Maksim; Spanakis, Spiro

    2011-01-01

    Managing the airway in the intensive care unit (ICU) is complicated by a wide array of physiologic factors. Difficult airway may be a consequence of patient’s anatomy or airway edema developed during the ICU stay and mechanical ventilation. The incidence of failed airways and of cardiac arrest related to airway instrumentation in the ICU is much higher than that of elective intubations performed in the operating room. In this article, we will provide a framework for identifying a difficult airway, criteria for safe extubation, as well as review the devices that are available for airway management in the ICU. Proficiency in identifying a potentially difficult airway and thorough familiarity with strategies and techniques of securing the airway are necessary for safe practice of critical care medicine

  19. Soleus stretch reflex during cycling

    DEFF Research Database (Denmark)

    Grey, Michael James; Pierce, C. W.; Milner, T. E.

    2001-01-01

    The modulation and strength of the human soleus short latency stretch reflex was investigated by mechanically perturbing the ankle during an unconstrained pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A torque pulse was applied to the crank at various positions durin...

  20. On the generalised stretch function

    Czech Academy of Sciences Publication Activity Database

    Kharlamov, Alexander A.; Filip, Petr

    2012-01-01

    Roč. 21, č. 4 (2012), s. 272-278 ISSN 1022-1344 R&D Projects: GA ČR GA103/09/2066 Institutional research plan: CEZ:AV0Z20600510 Keywords : molecular length * recurrence equations * rubber * strain * stretch functions Subject RIV: BK - Fluid Dynamics Impact factor: 1.606, year: 2012

  1. Optical tweezers stretching of chromatin

    NARCIS (Netherlands)

    Pope, L.H.; Bennink, Martin L.; Greve, Jan

    2003-01-01

    Recently significant success has emerged from exciting research involving chromatin stretching using optical tweezers. These experiments, in which a single chromatin fibre is attached by one end to a micron-sized bead held in an optical trap and to a solid surface or second bead via the other end,

  2. Transient filament stretching rheometer II

    DEFF Research Database (Denmark)

    Kolte, Mette Irene; Rasmussen, Henrik K.; Hassager, Ole

    1997-01-01

    The Lagrangian sspecification is used to simulate the transient stretching filament rheometer. Simulations are performed for dilute PIB-solutions modeled as a four mode Oldroyd-B fluid and a semidilute PIB-solution modeled as a non-linear single integral equation. The simulations are compared...

  3. Biaxial stretching of polyethylene, (2)

    International Nuclear Information System (INIS)

    Sakami, Hiroshi; Iida, Shozo

    1976-01-01

    The mechanism of oriented crystallization in mutually perpendicular direction to each other was investigated on the crosslinked linear polyethylene stretched successively and biaxially above melting point of raw material. To investigate the mechanism, the shrinkage stress, the degree of polarization and DSC of the film at the fixed length were measured on the crystallization process. The behavior observed on crystallization could be divided into that in the first period and that in the second period. The first period showed the domain of highly oriented crystallization of the crosslinked molecular chain, and in the second period the fold type crystals grew with highly oriented crystals in the first period as nuclear. Therefore, the formation of bi-component crystal structure is supposed for the crystallization. The biaxially oriented crystallization proceeded as follows: the uniaxial orientation to MD was observed in the first stretching in the initial stage, and then the further processing by the second stretching at a right angle caused the fold type crystallization of molecular chain oriented to TD. The film stretched fully and biaxially could be considered to have the oriented crystalline structure in which highly oriented fibril crystals and fold type crystals distribute at random. (auth.)

  4. Temporal dynamics of recurrent airway symptoms and cellular random walk.

    Science.gov (United States)

    Suki, Béla; Frey, Urs

    2003-11-01

    Asthma is a complex chronic inflammatory disease of the small airways that has dramatically increased in prevalence in industrialized countries during the last decades. Risk factors for adult asthma have been related to the complex array of gene-environment interactions and exposure of the immune system to allergens in early childhood. In genetically predisposed subjects, continuous exposure to environmental agents such as allergens or infections can lead to recurrent airway symptoms characterized by recurrent episodes of airway inflammation and bronchoconstriction with clinical symptoms of cough, dyspnea, or wheezing. In this study, we report that the longterm temporal dynamics of recurrent airway symptoms in a population of unselected infants display a complex intermittent pattern and that the distribution of interepisode intervals follows a power law. We interpret the data by using a model of the dynamics of attack episodes in which an attack is triggered by an avalanche of airway constrictions. We map the dynamics of this model to the known problem of a random walk in the presence of an absorbing boundary in which the walker corresponds to the fluctuations in contractile state of airway smooth muscle cells. These findings may provide new insight into the mechanisms of otherwise unexplained symptom episodes.

  5. Generalizing smooth transition autoregressions

    DEFF Research Database (Denmark)

    Chini, Emilio Zanetti

    We introduce a variant of the smooth transition autoregression - the GSTAR model - capable to parametrize the asymmetry in the tails of the transition equation by using a particular generalization of the logistic function. A General-to-Specific modelling strategy is discussed in detail...

  6. Smoothed Complexity Theory

    NARCIS (Netherlands)

    Bläser, Markus; Manthey, Bodo

    Smoothed analysis is a new way of analyzing algorithms introduced by Spielman and Teng. Classical methods like worst-case or average-case analysis have accompanying complexity classes, such as P and Avg-P, respectively. Whereas worst-case or average-case analysis give us a means to talk about the

  7. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

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

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

  8. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

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

    2014-01-01

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

  9. Airway Inflammation after Bronchial Thermoplasty for Severe Asthma.

    Science.gov (United States)

    Denner, Darcy R; Doeing, Diana C; Hogarth, D Kyle; Dugan, Karen; Naureckas, Edward T; White, Steven R

    2015-09-01

    Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radioablation. Although this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation. We examined the presence of bronchoalveolar lavage cytokines and expression of smooth muscle actin in patients with severe asthma before and in the weeks after bronchial thermoplasty. Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe before and 3 and 6 weeks after initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage and for the presence of α-SMA in endobronchial biopsies. α-SMA expression was decreased in endobronchial biopsies of 7 of 11 subjects by Week 6. In bronchoalveolar lavage fluid, both transforming growth factor-β1 and regulated upon activation, normal T-cell expressed and secreted (RANTES)/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty. Clinical improvement and reduction in α-SMA after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.

  10. Time stretch and its applications

    Science.gov (United States)

    Mahjoubfar, Ata; Churkin, Dmitry V.; Barland, Stéphane; Broderick, Neil; Turitsyn, Sergei K.; Jalali, Bahram

    2017-06-01

    Observing non-repetitive and statistically rare signals that occur on short timescales requires fast real-time measurements that exceed the speed, precision and record length of conventional digitizers. Photonic time stretch is a data acquisition method that overcomes the speed limitations of electronic digitizers and enables continuous ultrafast single-shot spectroscopy, imaging, reflectometry, terahertz and other measurements at refresh rates reaching billions of frames per second with non-stop recording spanning trillions of consecutive frames. The technology has opened a new frontier in measurement science unveiling transient phenomena in nonlinear dynamics such as optical rogue waves and soliton molecules, and in relativistic electron bunching. It has also created a new class of instruments that have been integrated with artificial intelligence for sensing and biomedical diagnostics. We review the fundamental principles and applications of this emerging field for continuous phase and amplitude characterization at extremely high repetition rates via time-stretch spectral interferometry.

  11. Equine recurrent airway obstruction

    Directory of Open Access Journals (Sweden)

    Artur Niedźwiedź

    2014-10-01

    Full Text Available Equine Recurrent Airway Obstruction (RAO, also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their lives, therefore they should be properly managed. In therapy the most importanthing is to eliminate dustexposure, administration of corticosteroids and use bronchodilators to improve pulmonary function.

  12. Advanced Pediatric Airway Simulation.

    Science.gov (United States)

    Myer, Charles M; Jabbour, Noel

    2017-10-01

    Simulation is an emerging and viable means to increase pediatric airway surgical training. A variety of simulators currently exist that may be used or modified for laryngoscopy, bronchoscopy, and endoscopic intervention, although anatomic realism and utility for complex procedures are limited. There is a need for further development of improved endoscopic and anatomic models. Innovative techniques are enabling small-scale manufacturing of generalizable and patient-specific simulators. The high acuity of the pediatric airway patient makes the use of simulation an attractive modality for training, competency maintenance, and patient safety quality-improvement studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. BSDB: the Biomolecule Stretching Database

    Science.gov (United States)

    Cieplak, Marek; Sikora, Mateusz; Sulkowska, Joanna I.; Witkowski, Bartlomiej

    2011-03-01

    Despite more than a decade of experiments on single biomolecule manipulation, mechanical properties of only several scores of proteins have been measured. A characteristic scale of the force of resistance to stretching, Fmax , has been found to range between ~ 10 and 480 pN. The Biomolecule Stretching Data Base (BSDB) described here provides information about expected values of Fmax for, currently, 17 134 proteins. The values and other characteristics of the unfolding proces, including the nature of identified mechanical clamps, are available at www://info.ifpan.edu.pl/BSDB/. They have been obtained through simulations within a structure-based model which correlates satisfactorily with the available experimental data on stretching. BSDB also lists experimental data and results of the existing all-atom simulations. The database offers a Protein-Data-Bank-wide guide to mechano-stability of proteins. Its description is provided by a forthcoming Nucleic Acids Research paper. Supported by EC FUNMOL project FP7-NMP-2007-SMALL-1, and European Regional Development Fund: Innovative Economy (POIG.01.01.02-00-008/08).

  14. Revealed smooth nontransitive preferences

    DEFF Research Database (Denmark)

    Keiding, Hans; Tvede, Mich

    2013-01-01

    In the present paper, we are concerned with the behavioural consequences of consumers having nontransitive preference relations. Data sets consist of finitely many observations of price vectors and consumption bundles. A preference relation rationalizes a data set provided that for every observed...... many observations of price vectors, lists of individual incomes and aggregate demands. We apply our main result to characterize market data sets consistent with equilibrium behaviour of pure-exchange economies with smooth nontransitive consumers....... consumption bundle, all strictly preferred bundles are more expensive than the observed bundle. Our main result is that data sets can be rationalized by a smooth nontransitive preference relation if and only if prices can normalized such that the law of demand is satisfied. Market data sets consist of finitely...

  15. Stretching

    Science.gov (United States)

    ... this topic for: Teens Dehydration Safety Tips: Running Knee Injuries Repetitive Stress Injuries Sports and Exercise Safety Dealing With Sports Injuries Sports Center Strains and Sprains View more Partner Message About Us Contact Us ...

  16. Smooth Phase Interpolated Keying

    Science.gov (United States)

    Borah, Deva K.

    2007-01-01

    Smooth phase interpolated keying (SPIK) is an improved method of computing smooth phase-modulation waveforms for radio communication systems that convey digital information. SPIK is applicable to a variety of phase-shift-keying (PSK) modulation schemes, including quaternary PSK (QPSK), octonary PSK (8PSK), and 16PSK. In comparison with a related prior method, SPIK offers advantages of better performance and less complexity of implementation. In a PSK scheme, the underlying information waveform that one seeks to convey consists of discrete rectangular steps, but the spectral width of such a waveform is excessive for practical radio communication. Therefore, the problem is to smooth the step phase waveform in such a manner as to maintain power and bandwidth efficiency without incurring an unacceptably large error rate and without introducing undesired variations in the amplitude of the affected radio signal. Although the ideal constellation of PSK phasor points does not cause amplitude variations, filtering of the modulation waveform (in which, typically, a rectangular pulse is converted to a square-root raised cosine pulse) causes amplitude fluctuations. If a power-efficient nonlinear amplifier is used in the radio communication system, the fluctuating-amplitude signal can undergo significant spectral regrowth, thus compromising the bandwidth efficiency of the system. In the related prior method, one seeks to solve the problem in a procedure that comprises two major steps: phase-value generation and phase interpolation. SPIK follows the two-step approach of the related prior method, but the details of the steps are different. In the phase-value-generation step, the phase values of symbols in the PSK constellation are determined by a phase function that is said to be maximally smooth and that is chosen to minimize the spectral spread of the modulated signal. In this step, the constellation is divided into two groups by assigning, to information symbols, phase values

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... NACFC Carolyn and C Richard Mattingly Leadership in Mental Health Care Award Mary M. Kontos Award NACFC Reflections ... help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway clearance. ... Instagram Email Find a Clinical Trial Help us blaze ...

  18. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... center. Carrier Testing for Cystic Fibrosis CFTR-Related Metabolic Syndrome (CRMS) How Babies Are Screened in IRT-Only ... Nutrition in Children and Adults Clinical Care Guidelines Nutrition in Pediatrics Clinical ... Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Leaders About Us News Blog Chapters ... different ways to clear your airways. Most are easy to do. Infants and toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they can ...

  20. Upper airway evaluation

    International Nuclear Information System (INIS)

    Hoffman, E.A.; Gefter, W.B.; Schnall, M.; Nordberg, J.; Listerud, J.; Lenkinski, R.E.

    1988-01-01

    The authors are evaluating upper-airway sleep disorders with magnetic resonance (MR) imaging and x-ray cine computed tomography (CT). Fixed structural anatomy is visualized with multisection spin-echo MR imaging, the dynamic component with cine CT. Unique aspects of the study are described in this paper

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... and Their Families When There's More Than One Person With CF in the Same School Daily Life ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... be taken through a nebulizer during ACTs. Inhaled antibiotics should be taken after ACTs are finished and the lungs are as clear of mucus as possible. This will allow the medication to reach deeply into the smaller airways to attack bacteria. Choose What's Best for You Your respiratory therapist ...

  3. Obstetric airway management

    African Journals Online (AJOL)

    face mask. There were 66 cases of aspiration (0.15%) and two mortalities. Both of the mortalities occurred secondary to solid food aspiration. Mendelson correctly identified delayed gastric emptying in the labouring patient, coupled with the loss of airway reflexes during general anaesthesia, as contributory factors to the ...

  4. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

  5. Positive airway pressure treatment

    Science.gov (United States)

    ... and depression and a better mood Normal sleep patterns Lower blood pressure (in people with high blood pressure) Your health care provider will prescribe the type of PAP machine that ... patterns. Bilevel positive airway pressure (BiPAP or BIPAP) has ...

  6. Smooth functors vs. differential forms

    NARCIS (Netherlands)

    Schreiber, U.; Waldorf, K.

    2011-01-01

    We establish a relation between smooth 2-functors defined on the path 2-groupoid of a smooth manifold and differential forms on this manifold. This relation can be understood as a part of a dictionary between fundamental notions from category theory and differential geometry. We show that smooth

  7. Extraglottic airway devices: technology update

    Directory of Open Access Journals (Sweden)

    Sharma B

    2017-08-01

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

  8. Effect of stretching techniques on hamstring flexibility in female ...

    African Journals Online (AJOL)

    Flexibility can be achieved by a variety of stretching techniques and the benefits of stretching are known. However, controversy remains about the best type of stretching for achieving a particular goal or outcome. The four most basic stretches are static stretching, dynamic stretching, PNF hold-relax and PNF contract-relax ...

  9. Smoothly Varying Bright Blazars

    Science.gov (United States)

    Van Alfen, Nicholas; Hindman, Lauren; Moody, Joseph Ward; Biancardi, Rochelle; Whipple, Parkes; Gaunt, Caleb

    2018-01-01

    It is becoming increasingly apparent that blazar light can vary sinusoidally with periods of hundreds of days to tens of years. Such behavior is expected of, among other things, jets coming from binary black holes. To look for general variability in lesser-known blazars and AGN, in 2015-2016 we monitored 182 objects with Johnson V-band magnitudes reported as being < 16. In all, this campaign generated 22,000 frames from 2,000 unique pointings. We find that approximately one dozen of these objects show evidence of smooth variability consistent with sinusoidal periods. We report on the entire survey sample, highlighting those that show sinusoidal variations.

  10. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

    Science.gov (United States)

    Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

    2014-05-01

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Bending and stretching of plates

    CERN Document Server

    Mansfield, E H; Hemp, W S

    1964-01-01

    The Bending and Stretching of Plates deals with elastic plate theory, particularly on small- and large-deflexion theory. Small-deflexion theory concerns derivation of basic equations, rectangular plates, plates of various shapes, plates whose boundaries are amenable to conformal transformation, plates with variable rigidity, and approximate methods. Large-deflexion theory includes general equations and some exact solutions, approximate methods in large-deflexion theory, asymptotic large-deflexion theories for very thin plates. Asymptotic theories covers membrane theory, tension field theory, a

  12. Stretching of macromolecules and proteins

    International Nuclear Information System (INIS)

    Strick, T R; Dessinges, M-N; Charvin, G; Dekker, N H; Allemand, J-F; Bensimon, D; Croquette, V

    2003-01-01

    In this paper we review the biophysics revealed by stretching single biopolymers. During the last decade various techniques have emerged allowing micromanipulation of single molecules and simultaneous measurements of their elasticity. Using such techniques, it has been possible to investigate some of the interactions playing a role in biology. We shall first review the simplest case of a non-interacting polymer and then present the structural transitions in DNA, RNA and proteins that have been studied by single-molecule techniques. We shall explain how these techniques permit a new approach to the protein folding/unfolding transition

  13. 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.

  14. Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities

    Science.gov (United States)

    Adam, Ryan J.; Hisert, Katherine B.; Dodd, Jonathan D.; Grogan, Brenda; Launspach, Janice L.; Barnes, Janel K.; Gallagher, Charles G.; Sieren, Jered P.; Gross, Thomas J.; Fischer, Anthony J.; Cavanaugh, Joseph E.; Hoffman, Eric A.; Singh, Pradeep K.; Welsh, Michael J.; McKone, Edward F.; Stoltz, David A.

    2016-01-01

    BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, CF transmembrane conductance regulator (CFTR) is present in airway smooth muscle (ASM), and ASM from newborn CF pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect in ASM function. We hypothesized that restoring CFTR activity would decrease smooth muscle tone in people with CF. METHODS. To increase or potentiate CFTR function, we administered ivacaftor to 12 adults with CF with the G551D-CFTR mutation; ivacaftor stimulates G551D-CFTR function. We studied people before and immediately after initiation of ivacaftor (48 hours) to minimize secondary consequences of CFTR restoration. We tested smooth muscle function by investigating spirometry, airway distensibility, and vascular tone. RESULTS. Ivacaftor rapidly restored CFTR function, indicated by reduced sweat chloride concentration. Airflow obstruction and air trapping also improved. Airway distensibility increased in airways less than 4.5 mm but not in larger-sized airways. To assess smooth muscle function in a tissue outside the lung, we measured vascular pulse wave velocity (PWV) and augmentation index, which both decreased following CFTR potentiation. Finally, change in distensibility of <4.5-mm airways correlated with changes in PWV. CONCLUSIONS. Acute CFTR potentiation provided a unique opportunity to investigate CFTR-dependent mechanisms of CF pathogenesis. The rapid effects of ivacaftor on airway distensibility and vascular tone suggest that CFTR dysfunction may directly cause increased smooth muscle tone in people with CF and that ivacaftor may relax smooth muscle. FUNDING. This work was funded in part from an unrestricted grant from the Vertex Investigator-Initiated Studies Program. PMID:27158673

  15. PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION STRETCHING VERSUS STATIC STRETCHING ON SPRINTING PERFORMANCE AMONG COLLEGIATE SPRINTERS

    Directory of Open Access Journals (Sweden)

    Jayaram Maharjan

    2015-08-01

    Full Text Available Background: A warm-up is important part of preparation for sprinting. There is popularity of doing stretching as part of warm up before athletic activity. The static stretching and PNF stretching is performed by athletes but their effectiveness on sprinting performance is in state of debate. The objective is to determine the effect of static stretching and PNF stretching on sprinting performance in college sprinters and to compare the effects of PNF stretching over static stretching on sprinting performance in college sprinters. Method: A total of 100 subjects were taken for the study that fulfill the inclusion criteria and all were divided into group- A (static stretching and group- B (PNF stretching by simple random sampling method. Both the groups received 5 minutes of warm-up exercises. Pre-Post design was used, which consisted of running a 40-yard sprint immediately following 2 stretching conditions aimed at the lower limb muscles Results: In static stretching group sprint time changed from 6.55 with standard deviation of 0.93 to 6.12 with standard deviation of 1.02 (P.605. Conclusion: Hence both static stretching and PNF stretching can be performed before sprinting activity to improve the sprinting performance.

  16. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Bhaskar, K.R.; DeFeudis O'Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO 2 , (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14 C acetate and 14 C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  17. Smooth functions statistics

    International Nuclear Information System (INIS)

    Arnold, V.I.

    2006-03-01

    To describe the topological structure of a real smooth function one associates to it the graph, formed by the topological variety, whose points are the connected components of the level hypersurface of the function. For a Morse function, such a graph is a tree. Generically, it has T triple vertices, T + 2 endpoints, 2T + 2 vertices and 2T + 1 arrows. The main goal of the present paper is to study the statistics of the graphs, corresponding to T triple points: what is the growth rate of the number φ(T) of different graphs? Which part of these graphs is representable by the polynomial functions of corresponding degree? A generic polynomial of degree n has at most (n - 1) 2 critical points on R 2 , corresponding to 2T + 2 = (n - 1) 2 + 1, that is to T = 2k(k - 1) saddle-points for degree n = 2k

  18. Causes of the difficult airway.

    Science.gov (United States)

    Orfanos, John G; Quereshy, Faisal A

    2010-03-01

    Recognizing a potentially difficult airway is important in avoiding a life-threatening emergency. There are 2 separate scenarios for considering the difficult airway: difficult mask ventilation (DMV) and difficult tracheal intubation (DTI). DMV can be described as lacking the ability to maintain oxygen saturation or lacking the ability to reverse signs of inadequate ventilation with positive-pressure mask ventilation under general anesthesia. DTI remains constant among anesthesia-related patient injuries, and is the third most common respiratory-related episode leading to death and possible brain damage. It is important to preoperatively assess every patient by completing a full history and physical. A thorough history can provide clues in detecting a possible difficult airway. Airway impairment has been further subdivided into the anatomic regions that affect the airway, namely above the larynx, supraglottic, glottic, subglottic, and tracheobronchial. This article discusses the factors that can result in a difficult airway. Copyright 2010. Published by Elsevier Inc.

  19. 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.

  20. Cooperative regulation of GSK-3 by muscarinic and PDGF receptors is associated with airway myocyte proliferation

    NARCIS (Netherlands)

    Gosens, Reinoud; Dueck, Gordon; Rector, Edward; Nunes, Raquel O.; Gerthoffer, William T.; Unruh, Helmut; Zaagsma, Johan; Meurs, Herman; Halayko, Andrew J.

    2007-01-01

    Muscarinic receptors and platelet-derived growth factor (PDGF) receptors synergistically induce proliferation of airway smooth muscle (ASM), but the pathways that regulate these effects are not yet completely identified. We hypothesized that glycogen synthase kinase-3 (GSK-3), a kinase that

  1. Associations between airway hyperresponsiveness, obesity, and lipoproteins in a longitudinal cohort

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Hancox, Robert; Nair, Parameswaran

    2013-01-01

    Background Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function...

  2. Contact angles on stretched solids

    Science.gov (United States)

    Mensink, Liz; Snoeijer, Jacco

    2017-11-01

    The surface energy of solid interfaces plays a central role in wetting, as they dictate the liquid contact angle. Yet, it has been challenging to measure the solid surface energies independently, without making use of Young's law. Here we present Molecular Dynamics (MD) simulations by which we measure the surface properties for all interfaces, including the solids. We observe change in contact angles upon stretching the solid substrates, showing that the surface energy is actually strain dependent. This is clear evidence of the so-called Shuttleworth effect, making it necessary to distinguish surface energy from surface tension. We discuss how this effect gives rise to a new class of elasto-capillary phenomena. ERC Consolidator Grant No. 616918.

  3. A COMPARISION BETWEEN CROSSBODY STRETCH VERSUS SLEEPER STRETCH IN PERIARTHRITIS OF SHOULDER

    Directory of Open Access Journals (Sweden)

    Shaik Raheem Saheb

    2015-12-01

    Full Text Available Background: Recently Cross body stretch and Sleeper stretch are used to improve internal rotation Range of motion in Shoulder Pathologies. It was proposed to study the effect of cross body stretch and sleeper stretch in subjects with periarthritis of shoulder. Methods: 60 subjects with a mean age of 53 years having clinical diagnosis of Periarthritis of shoulder and full filled the inclusive criteria are taken. After the initial measurements, the subjects are randomly assigned into 2 stretching groups. Group-A performed the Sleeper stretch. Group-B performed a Cross body stretch. Both Groups performed the Stretch in Duration of 6weeks – once daily for 5 repetitions holding each stretch for 30 seconds for 5 days a week. Along with this technique conventional physiotherapy like IFT, overhead pulleys, Pendula exercises, Wall climbing exercises, mariners wheel exercises are performed. After the treatment, subjects were evaluated for their pain profile using visual analogue scale, Goniometer for measuring Range of motion. Results: For within group comparison we used Paired t-test analysis, For Between group comparison we used Independent t-test for statistical analysis. At the end of 6 weeks It was found that subjects treated with cross-body stretch showed significant improvement in terms of VAS scores and Range of motion scores (P=0.000 and patients treated with Sleeper stretch showed significant improvement in terms of VAS scores and Range of motion scores (P=0.000. When compared between Groups the VAS and Range of motion scores showed a significant improvement in Cross body stretch Group than the Sleeper stretch Group (P=0.000. Conclusion: It was concluded that both stretching techniques were found improvement in Range of motion and VAS and Cross-body Stretch showed more Significant improvement than the sleeper Stretch after 6 weeks treatment.

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

    African Journals Online (AJOL)

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

  5. Anharmonic Bend-Stretch Coupling in Water

    NARCIS (Netherlands)

    Lindner, Jörg; Vöhringer, Peter; Pshenichnikov, Maxim S.; Cringus, Dan; Wiersma, Douwe A.; Corkum, Paul; Jonas, David M.; Miller, R.J. Dwayne.; Weiner, Andrew M.

    2006-01-01

    Following excitation of the H-O-H bending mode of water molecules in solution the stretching mode region is monitored over its entire width. The anharmonic coupling between the two modes results in a substantial change of the transient stretch absorption that decays with the bend depopulation time.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. Anisotropic instability of a stretching film

    Science.gov (United States)

    Xu, Bingrui; Li, Minhao; Deng, Daosheng

    2017-11-01

    Instability of a thin liquid film, such as dewetting arising from Van der Waals force, has been well studied, and is typically characterized by formation of many droplets. Interestingly, a thin liquid film subjected to an applied stretching during a process of thermal drawing is evolved into an array of filaments, i.e., continuity is preserved along the direction of stretching while breakup occurs exclusively in the plane of cross section. Here, to understand this anisotropic instability, we build a physical model by considering both Van der Waals force and the effect of stretching. By using the linear instability analysis method and then performing a numerical calculation, we find that the growth rate of perturbations at the cross section is larger than that along the direction of stretching, resulting in the anisotropic instability of the stretching film. These results may provide theoretical guidance to achieve more diverse structures for nanotechnology.

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

    Directory of Open Access Journals (Sweden)

    Jennifer M. Bratt

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Numerical Simulation for Mechanism of Airway Narrowing in Asthma

    Science.gov (United States)

    Bando, Kiyoshi; Yamashita, Daisuke; Ohba, Kenkichi

    A calculation model is proposed to examine the generation mechanism of the numerous lobes on the inner-wall of the airway in asthmatic patients and to clarify luminal occlusion of the airway inducing breathing difficulties. The basement membrane in the airway wall is modeled as a two-dimensional thin-walled shell having inertia force due to the mass, and the smooth muscle contraction effect is replaced by uniform transmural pressure applied to the basement membrane. A dynamic explicit finite element method is used as a numerical simulation method. To examine the validity of the present model, simulation of an asthma attack is performed. The number of lobes generated in the basement membrane increases when transmural pressure is applied in a shorter time period. When the remodeling of the basement membrane occurs characterized by thickening and hardening, it is demonstrated that the number of lobes decreases and the narrowing of the airway lumen becomes severe. Comparison of the results calculated by the present model with those measured for animal experiments of asthma will be possible.

  11. Rhinosinusitis and the lower airways

    NARCIS (Netherlands)

    Hellings, Peter W.; Hens, Greet

    2009-01-01

    The interaction between upper and lower airway disease has been recognized for centuries, with recent studies showing a direct link between upper and airway inflammation in allergic patients. The mechanisms underlying the interaction between nasal and bronchial inflammation have primarily been

  12. Smoothness in Binomial Edge Ideals

    Directory of Open Access Journals (Sweden)

    Hamid Damadi

    2016-06-01

    Full Text Available In this paper we study some geometric properties of the algebraic set associated to the binomial edge ideal of a graph. We study the singularity and smoothness of the algebraic set associated to the binomial edge ideal of a graph. Some of these algebraic sets are irreducible and some of them are reducible. If every irreducible component of the algebraic set is smooth we call the graph an edge smooth graph, otherwise it is called an edge singular graph. We show that complete graphs are edge smooth and introduce two conditions such that the graph G is edge singular if and only if it satisfies these conditions. Then, it is shown that cycles and most of trees are edge singular. In addition, it is proved that complete bipartite graphs are edge smooth.

  13. Role of ROCK2 in CD4+cells in allergic airways responses in mice.

    Science.gov (United States)

    Kasahara, D I; Mathews, J A; Ninin, F M C; Wurmbrand, A P; Liao, J K; Shore, S A

    2017-02-01

    Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. To determine the role of ROCK2 acting within CD4 + cells in allergic airways responses. ROCK2-haploinsufficient (ROCK2 +/- ) and wild-type mice were sensitized with ovalbumin (OVA). ROCK2 +/- mice then received either CD4 + cells from ROCK2-sufficient OVA TCR transgenic (OT-II) mice or saline i.v. 48 h before challenge with aerosolized OVA. Wild-type mice received saline before challenge. Allergic airways responses were measured 48 h after the last challenge. Allergic airways responses were also assessed in mice lacking ROCK2 only in CD4 + cells (ROCK2 CD 4Cre mice) vs. control (CD4-Cre and ROCK2 flox/flox ) mice. OVA-induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL-13, IL-5, and eotaxin were reduced in ROCK2 +/- vs. wild-type mice, as were airway hyperresponsiveness and mucous hypersecretion. In ROCK2 +/- mice, adoptive transfer with CD4 + cells from OT-II mice restored effects of OVA on lymphocytes, eosinophils, IL-13, IL-5, and mucous hypersecretion to wild-type levels, whereas eotaxin and airway hyperresponsiveness were not affected. ROCK2 inhibitors reduced IL-13-induced release of eotaxin from airway smooth muscle (ASM), similar to effects of these inhibitors on ASM contractility. Despite the ability of adoptive transfer to restore allergic airways inflammation in ROCK2-insufficient mice, allergic inflammation was not different in ROCK2 CD 4Cre vs. control mice. ROCK2 contributes to allergic airways responses likely via effects within ASM cells and within non-lymphocyte cells involved in lymphocyte activation and migration into the airways. © 2016 John Wiley & Sons Ltd.

  14. Allergic Fungal Airway Disease.

    Science.gov (United States)

    Rick, E M; Woolnough, K; Pashley, C H; Wardlaw, A J

    Fungi are ubiquitous and form their own kingdom. Up to 80 genera of fungi have been linked to type I allergic disease, and yet, commercial reagents to test for sensitization are available for relatively few species. In terms of asthma, it is important to distinguish between species unable to grow at body temperature and those that can (thermotolerant) and thereby have the potential to colonize the respiratory tract. The former, which include the commonly studied Alternaria and Cladosporium genera, can act as aeroallergens whose clinical effects are predictably related to exposure levels. In contrast, thermotolerant species, which include fungi from the Candida, Aspergillus, and Penicillium genera, can cause a persistent allergenic stimulus independent of their airborne concentrations. Moreover, their ability to germinate in the airways provides a more diverse allergenic stimulus, and may result in noninvasive infection, which enhances inflammation. The close association between IgE sensitization to thermotolerant filamentous fungi and fixed airflow obstruction, bronchiectasis, and lung fibrosis suggests a much more tissue-damaging process than that seen with aeroallergens. This review provides an overview of fungal allergens and the patterns of clinical disease associated with exposure. It clarifies the various terminologies associated with fungal allergy in asthma and makes the case for a new term (allergic fungal airway disease) to include all people with asthma at risk of developing lung damage as a result of their fungal allergy. Lastly, it discusses the management of fungirelated asthma.

  15. Possible role of differential growth in airway wall remodeling in asthma

    KAUST Repository

    Moulton, D. E.

    2011-01-20

    Possible role of differential growth in airway wall remodeling in asthma. J Appl Physiol 110: 1003-1012, 2011. First published January 20, 2011; doi:10.1152/japplphysiol.00991.2010.- Airway remodeling in patients with chronic asthma is characterized by a thickening of the airway walls. It has been demonstrated in previous theoretical models that this change in thickness can have an important mechanical effect on the properties of the wall, in particular on the phenomenon of mucosal folding induced by smooth muscle contraction. In this paper, we present a model for mucosal folding of the airway in the context of growth. The airway is modeled as a bilayered cylindrical tube, with both geometric and material nonlinearities accounted for via the theory of finite elasticity. Growth is incorporated into the model through the theory of morphoelasticity. We explore a range of growth possibilities, allowing for anisotropic growth as well as different growth rates in each layer. Such nonuniform growth, referred to as differential growth, can change the properties of the material beyond geometrical changes through the generation of residual stresses. We demonstrate that differential growth can have a dramatic impact on mucosal folding, in particular on the critical pressure needed to induce folding, the buckling pattern, as well as airway narrowing. We conclude that growth may be an important component in airway remodeling. Copyright © 2011 the American Physiological Society.

  16. An interventional airway delivery service for congenital high airway obstruction.

    Science.gov (United States)

    Yaneza, M M C; Cameron, A; Clement, W A; Fairgrieve, R; Ledingham, M A; Morrissey, M S; Simpson, J; Wynne, D M; Kubba, H

    2015-08-01

    Congenital airway obstruction is rare but potentially fatal. We developed a complex airways interventional delivery team to manage such cases. Antenatal imaging detects airway compromise at an early stage and facilitates the planning of delivery procedures ('ex utero intrapartum treatment' and 'operation on placental support') which maintain feto-placental circulation whilst an airway is secured. A retrospective review was performed of cases in which ENT input was required at birth for airway obstruction. Four neonates were delivered before implementation of the service: two were intubated and another two underwent tracheostomy but died in the peri-natal period. Seven neonates were delivered after implementation of the service: six were intubated and one underwent immediate tracheostomy. Five subsequently underwent tracheostomy (three have since been decannulated). One child with multiple congenital anomalies died due to respiratory failure. Airway obstruction was caused by lymphatic malformation, teratoma, costo-craniomandibular syndrome and choristoma. In the absence of other anomalies, interventional airway delivery led to reduced mortality and improved outcomes.

  17. Stretch due to Penile Prosthesis Reservoir Migration

    Directory of Open Access Journals (Sweden)

    E. Baten

    2016-03-01

    Full Text Available A 43-year old patient presented to the emergency department with stretch, due to impossible deflation of the penile prosthesis, 4 years after successful implant. A CT-scan showed migration of the reservoir to the left rectus abdominis muscle. Refilling of the reservoir was inhibited by muscular compression, causing stretch. Removal and replacement of the reservoir was performed, after which the prosthesis was well-functioning again. Migration of the penile prosthesis reservoir is extremely rare but can cause several complications, such as stretch.

  18. Very smooth points of spaces of operators

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    ball has a very smooth point then the space has the Radon–Nikodým property. We give an example of a smooth Banach space without any very smooth points. Keywords. Very smooth points; spaces of operators; M-ideals. 1. Introduction. A Banach space X is said to be very smooth if every unit vector has a unique norming.

  19. Smooth analysis in Banach spaces

    CERN Document Server

    Hájek, Petr

    2014-01-01

    This bookis aboutthe subject of higher smoothness in separable real Banach spaces.It brings together several angles of view on polynomials, both in finite and infinite setting.Also a rather thorough and systematic view of the more recent results, and the authors work is given. The book revolves around two main broad questions: What is the best smoothness of a given Banach space, and its structural consequences? How large is a supply of smooth functions in the sense of approximating continuous functions in the uniform topology, i.e. how does the Stone-Weierstrass theorem generalize into in

  20. Effect of modified hold-relax stretching and static stretching on hamstring muscle flexibility.

    Science.gov (United States)

    Ahmed, Hashim; Iqbal, Amir; Anwer, Shahnawaz; Alghadir, Ahmad

    2015-02-01

    [Purpose] The aim of present study was to compare the effectiveness of modified hold-relax stretching and static stretching in improving the hamstring muscle flexibility. [Subjects and Methods] Forty-five male subjects with hamstring tightness were included in this study. The subjects were randomly placed into three groups: the modified hold-relax stretching, static stretching and control groups. The modified hold-relax stretching group performed 7 seconds of isometric contraction and then relaxed for 5 seconds, and this was repeated five times daily for five consecutive days. The static stretching group received 10 minutes of static stretching with the help of a pulley and weight system for five consecutive days. The control group received only moist heat for 20 minutes for five consecutive days. A baseline reading of passive knee extension (PKE) was taken prior to the intervention; rest measurements were taken immediate post intervention on day 1, day 3, day 5, and after a 1 week follow-up, i.e., at the 12th day. [Results] On comparing the baseline readings of passive knee extension (PKE), there was no difference noted between the three groups. On comparing the posttest readings on day 5 between the 3 groups, a significant difference was noted. However, post hoc analysis revealed an insignificant difference between the modified hold-relax stretching and static stretching groups. There was a significant difference between the static stretching and control groups and between the modified hold-relax stretching and control groups. [Conclusion] The results of this study indicate that both the modified hold-relax stretching technique and static stretching are equally effective, as there was no significant difference in improving the hamstring muscle flexibility between the two groups.

  1. Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats

    Science.gov (United States)

    Hoang, Laura L.; Nguyen, Yen P.; Aspeé, Rayza; Bolton, Sarah J.; Shen, Yi-hsin; Wang, Lei; Kenyon, Nicholas J.; Smiley-Jewell, Suzette

    2016-01-01

    Airway remodeling is strongly correlated with the progression of chronic obstructive pulmonary disease (COPD). In this study, our goal was to characterize progressive structural changes in site-specific airways, along with the temporal and spatial expression of transforming growth factor (TGF)-β in the lungs of male spontaneously hypertensive rats exposed to tobacco smoke (TS). Our studies demonstrated that TS-induced changes of the airways is dependent on airway generation and exposure duration for proximal, midlevel, and distal airways. Stratified squamous epithelial cell metaplasia was evident in the most proximal airways after 4 and 12 weeks but with minimal levels of TGF-β–positive epithelial cells after only 4 weeks of exposure. In contrast, epithelial cells in midlevel and distal airways were strongly TGF-β positive at both 4 and 12 weeks of TS exposure. Airway smooth muscle volume increased significantly at 4 and 12 weeks in midlevel airways. Immunohistochemistry of TGF-β was also found to be significantly increased at 4 and 12 weeks in lymphoid tissues and alveolar macrophages. ELISA of whole-lung homogenate demonstrated that TGF-β2 was increased after 4 and 12 weeks of TS exposure, whereas TGF-β1 was decreased at 12 weeks of TS exposure. Airway levels of messenger RNA for TGF-β2, as well as platelet-derived growth factor-A, granulocyte-macrophage colony–stimulating factor, and vascular endothelial growth factor-α, growth factors regulated by TGF-β, were significantly decreased in animals after 12 weeks of TS exposure. Our data indicate that TS increases TGF-β in epithelial and inflammatory cells in connection with airway remodeling, although the specific role of each TGF-β isoform remains to be defined in TS-induced airway injury and disease. PMID:26637070

  2. Airway necrosis after salvage esophagectomy

    International Nuclear Information System (INIS)

    Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

    2010-01-01

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

  3. Airway fibroepithelial polyposis

    Directory of Open Access Journals (Sweden)

    Gonzalo Labarca

    2017-01-01

    Full Text Available Fibroepithelial polyps are benign lesions, frequently found in the skin and genitourinary tract. Airway involvement is rare, and few case reports have been published. Our patient was a 79 y.o. male smoker, who was referred to us with a 3-month history of dry cough. At physical examination, the patient looked well, but a chest CT showed a 6-mm polyp lesion in his trachea. A flexible bronchoscopy confirmed this lesion, and forceps biopsies were performed. Argon plasma coagulation was used to completely resect and treat the lesion. Pathological analysis revealed a fibroepithelial polyp (FP. The aim of this manuscript is to report a case of FP with bronchoscopic management and to review the current literature about this condition.

  4. Airway Complications After Lung Transplantation.

    Science.gov (United States)

    Frye, Laura; Machuzak, Michael

    2017-12-01

    Airway complications remain a significant source of morbidity and mortality after lung transplantation. The incidence of complications is wide-ranging depending on the definition of the event, and there is still no universally accepted grading system for airway findings after transplantation. Additionally, although surgical technique and organ preservation have improved, other modifiable risk factors remain unclear. The management is as wide-ranging as the definitions. A multimodality approach is often needed with airway stenting reserved for refractory cases and stent management by a transplant team with expertise in placement and management of long-term complications." Copyright © 2017. Published by Elsevier Inc.

  5. Investing in a Large Stretch Press

    Science.gov (United States)

    Choate, M.; Nealson, W.; Jay, G.; Buss, W.

    1986-01-01

    Press for forming large aluminum parts from plates provides substantial economies. Study assessed advantages and disadvantages of investing in large stretch-forming press, and also developed procurement specification for press.

  6. Excluded Volume Effects in Gene Stretching

    OpenAIRE

    Lam, Pui-Man

    2002-01-01

    We investigate the effects excluded volume on the stretching of a single DNA in solution. We find that for small force F, the extension h is not linear in F but proportion to F^{\\chi}, with \\chi=(1-\

  7. Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

    2018-03-01

    Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

  8. DNA stretching on functionalized gold surfaces.

    OpenAIRE

    Zimmermann, R M; Cox, E C

    1994-01-01

    We describe a method for anchoring bacteriophage lambda DNA by one end to gold by Au-biotin-streptavidin-biotin-DNA bonds. DNA anchored to a microfabricated Au line could be aligned and stretched in flow and electric fields. The anchor was shown to resist a force of at least 11 pN, a linkage strong enough to allow DNA molecules of chromosome size to be stretched and aligned.

  9. Comparison of two stretching methods and optimization of stretching protocol for the piriformis muscle.

    Science.gov (United States)

    Gulledge, Brett M; Marcellin-Little, Denis J; Levine, David; Tillman, Larry; Harrysson, Ola L A; Osborne, Jason A; Baxter, Blaise

    2014-02-01

    Piriformis syndrome is an uncommon diagnosis for a non-discogenic form of sciatica whose treatment has traditionally focused on stretching the piriformis muscle (PiM). Conventional stretches include hip flexion, adduction, and external rotation. Using three-dimensional modeling, we quantified the amount of (PiM) elongation resulting from two conventional stretches and we investigated by use of a computational model alternate stretching protocols that would optimize PiM stretching. Seven subjects underwent three CT scans: one supine, one with hip flexion, adduction, then external rotation (ADD stretch), and one with hip flexion, external rotation, then adduction (ExR stretch). Three-dimensional bone models were constructed from the CT scans. PiM elongation during these stretches, femoral neck inclination, femoral head anteversion, and trochanteric anteversion were measured. A computer program was developed to map PiM length over a range of hip joint positions and was validated against the measured scans. ExR and ADD stretches elongated the PiM similarly by approximately 12%. Femoral head and greater trochanter anteversion influenced PiM elongation. Placing the hip joints in 115° of hip flexion, 40° of external rotation and 25° of adduction or 120° of hip flexion, 50° of external rotation and 30° of adduction increased PiM elongation by 30-40% compared to conventional stretches (15.1 and 15.3% increases in PiM muscle length, respectively). ExR and ADD stretches elongate the PiM similarly and therefore may have similar clinical effectiveness. The optimized stretches led to larger increases in PiM length and may be more easily performed by some patients due to increased hip flexion. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  10. Effects of proprioceptive neuromuscular facilitation stretching and static stretching on maximal voluntary contraction.

    Science.gov (United States)

    Miyahara, Yutetsu; Naito, Hisashi; Ogura, Yuji; Katamoto, Shizuo; Aoki, Junichiro

    2013-01-01

    This study was undertaken to investigate and compare the effects of proprioceptive neuromuscular facilitation (PNF) stretching and static stretching on maximal voluntary contraction (MVC). Thirteen male university students (age, 20 ± 1 years; height, 172.2 ± 4.6 cm; weight, 68.4 ± 6.7 kg; mean ± SD) completed 3 different conditions on 3 nonconsecutive days in randomized order: static stretching (SS), PNF stretching (PNF), and no stretching (control, CON). Each condition consisted of a 5-minute rest accompanied by one of the following activities: (a) control, (b) SS, or (c) PNF stretching. The hip flexion range of motion (ROM) was evaluated immediately before and after the activity. The MVC of knee flexion was then measured. Surface electromyography was recorded from the biceps femoris and vastus lateralis muscles during MVC tests and stretching. Although increases in ROM were significantly greater after PNF than after SS (p < 0.01), the decreases in MVC were similar between the 2 treatments. These results suggest that, although PNF stretching increases ROM more than SS, PNF stretching and SS is detrimental to isometric maximal strength.

  11. Stenting of major airway constriction

    International Nuclear Information System (INIS)

    Wu Xiaomei

    2002-01-01

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

  12. 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...

  13. Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c.

    Science.gov (United States)

    Liu, Gang; Cooley, Marion A; Nair, Prema M; Donovan, Chantal; Hsu, Alan C; Jarnicki, Andrew G; Haw, Tatt Jhong; Hansbro, Nicole G; Ge, Qi; Brown, Alexandra C; Tay, Hock; Foster, Paul S; Wark, Peter A; Horvat, Jay C; Bourke, Jane E; Grainge, Chris L; Argraves, W Scott; Oliver, Brian G; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

    2017-12-01

    Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c -/- ) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c -/- mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show

  14. 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

  15. Antimicrobial peptides in the airway.

    Science.gov (United States)

    Laube, D M; Yim, S; Ryan, L K; Kisich, K O; Diamond, G

    2006-01-01

    The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.

  16. Calcineurin /NFAT activation-dependence of leptin synthesis and vascular growth in response to mechanical stretch

    Directory of Open Access Journals (Sweden)

    Nadia Soudani

    2016-09-01

    Full Text Available Background and Aims- Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca+2/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC hypertrophy and leptin synthesis. Methods and Results- Rat portal vein (RPV organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM, the selective calcineurin inhibitor FK506 (1 nM and the ERK1/2 inhibitor PD98059 (1 μM. The transcription inhibitor actinomycin D (0.1M and the translation inhibitor cycloheximide (1 mM significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM. In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL, the ROCK inhibitor Y-27632 (10 μM, and the actin depolymerization agents Latrunculin B (50 nM and cytochalasin D (1 μM reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3. Conclusions- Mechanical stretch-induced VSMC hypertrophy and leptin

  17. Comparison of active stretching technique and static stretching technique on hamstring flexibility.

    Science.gov (United States)

    Meroni, Roberto; Cerri, Cesare Giuseppe; Lanzarini, Carlo; Barindelli, Guido; Morte, Giancesare Della; Gessaga, Viviana; Cesana, Gian Carlo; De Vito, Giovanni

    2010-01-01

    To compare a passive and an active stretching technique to determine which one would produce and maintain the greatest gain in hamstring flexibility. To determine whether a passive or an active stretching technique results in a greater increase in hamstring flexibility and to compare whether the gains are maintained. Randomized controlled trial. Institutional. Sixty-five volunteer healthy subjects completed the enrollment questionnaire, 33 completed the required 75% of the treatment after 6 weeks, and 22 were assessed 4 weeks after the training interruption. A 6-week stretching program with subjects divided into 2 groups with group 1 performing active stretching exercises and group 2 performing passive stretching exercises. Range of motion (ROM) was measured after 3 and 6 weeks of training and again 4 weeks after the cessation of training and compared with the initial measurement. After 3 weeks of training, the mean gain in group 1 (active stretching) on performing the active knee extension range of motion (AKER) test was 5.7 degrees, whereas the mean gain in group 2 (passive stretching) was 3 degrees (P = .015). After 6 weeks of training, the mean gain in group 1 was 8.7 degrees , whereas the mean gain in group 2 was 5.3 degrees (P = .006). Twenty-two subjects were reassessed 4 weeks after the cessation of the training with the maintained gain of ROM in group 1 being 6.3 degrees , whereas the maintained gain in group 2 was 0.1 degrees (P = .003). Active stretching produced the greater gain in the AKER test, and the gain was almost completely maintained 4 weeks after the end of the training, which was not seen with the passive stretching group. Active stretching was more time efficient compared with the static stretching and needed a lower compliance to produce effects on flexibility.

  18. Bronchodilator responsiveness of peripheral airways in smokers with normal spirometry.

    Science.gov (United States)

    Jetmalani, Kanika; Chapman, David G; Thamrin, Cindy; Farah, Claude S; Berend, Norbert; Salome, Cheryl M; King, Gregory G

    2016-10-01

    Cigarette smoke exposure increases airway smooth muscle (ASM) contractility. Abnormalities in peripheral airway function in smokers with normal spirometry could be due to the effects of ASM tone. We aimed to determine the contribution of ASM tone to peripheral airway function in smokers with normal spirometry from the response to bronchodilator (BD). Ventilation heterogeneity in peripheral conductive (Scond) and acinar (Sacin) airways were measured in 50 asymptomatic smokers and 20 never-smokers using multiple breath nitrogen washout, before and 20 min after inhalation of 200 µg salbutamol and 80 µg ipratropium bromide. Z-scores were calculated to define abnormality in Sacin and Scond. Nineteen smokers had abnormal Sacin, and 12 had abnormal Scond; 7 had abnormalities in both. After BD, Sacin improved in smokers with normal Sacin (6.5 ± 15.9%, P = 0.02), smokers with abnormal Sacin (9.2 ± 16.9%, P = 0.03) and in control subjects (11.7 ± 18.2%, P = 0.01), with no differences in improvements between groups. Sacin remained abnormal in 15/19 smokers and their post-BD values correlated with smoking exposure (r = 0.53, P = 0.02). After BD, Scond improved in smokers with abnormal Scond (28.3 ± 15.9%, P = 0.002) and normalized in 9/12 subjects, but not in those with normal Scond (0.25 ± 32.7%, P = 0.44) or control subjects (-1.7 ± 21.2%, P = 0.64). In smokers with normal spirometry, abnormal conductive airway function could be attributed to increased bronchomotor tone. In contrast, bronchomotor tone in acinar airways is unaffected by smoking and functional abnormality. There may be different causal mechanisms underlying acinar and conductive airway abnormalities in smokers with normal spirometry. © 2016 Asian Pacific Society of Respirology.

  19. Vessel-guided airway tree segmentation

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......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...

  20. 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.

  1. How to determine local stretching and tension in a flow-stretched DNA molecule

    DEFF Research Database (Denmark)

    Pedersen, Jonas Nyvold; Marie, Rodolphe; Kristensen, Anders

    2016-01-01

    We determine the nonuniform stretching of and tension in amega base pairs-long fragment of deoxyribonucleic acid (DNA) that is flow stretched in a nanofluidic chip. We use no markers, do not know the contour length of the DNA, and do not have the full DNA molecule inside our field of view. Instead...

  2. The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease

    DEFF Research Database (Denmark)

    Hua, Xiaoqin; Deuse, Tobias; Chen, Yi-Je

    2013-01-01

    The calcium-activated potassium channel KCa3.1 is critically involved in T-cell activation as well as in the proliferation of smooth muscle cells and fibroblasts. We sought to investigate whether KCa3.1 contributes to the pathogenesis of obliterative airway disease (OAD) and whether knockout or p...

  3. The Effects of Periodic Wall Stretch on Surfactant and Liquid Transport

    Science.gov (United States)

    Bull, Joseph; Halpern, David; Grotberg, James

    1999-11-01

    The cycle-mean transport of soluble surfactant and airway surface liquid is examined using a mathematical model of Marangoni flows which accounts for airway branching and for time-periodic radial and axial airway stretch. The transport of surfactant and liquid is fundamental to surfactant replacement therapy as well as liquid and surfactant clearance from healthy lungs. The majority of surfactant and liquid transport occurs in the cycle-mean spreading which follows the very brief initial transient spreading phase. We consider either delivery of surfactants into the lung, by setting the proximal boundary condition to a higher concentration compared to the distal boundary condition, or removal from the lung by switching these end conditions. Starting with a steady-state, non-cycled, non-uniform, surfactant distribution we find that transport of surfactant into the lung is enhanced for larger strain amplitudes and frequency, though frequency is less important. For surfactant clearance from the lung we find, as in the case of delivery, that larger strain amplitude enhances transport. But, cycling frequency has the opposite effect with larger frequencies leading to reduced transport. Liquid clearance is enhanced by larger strain amplitudes and slower frequencies. This work supported by NIH grant HL-41126 and NSF grant CTS-9412523.

  4. CURRENT CONCEPTS IN MUSCLE STRETCHING FOR EXERCISE AND REHABILITATION

    Science.gov (United States)

    2012-01-01

    Stretching is a common activity used by athletes, older adults, rehabilitation patients, and anyone participating in a fitness program. While the benefits of stretching are known, controversy remains about the best type of stretching for a particular goal or outcome. The purpose of this clinical commentary is to discuss the current concepts of muscle stretching interventions and summarize the evidence related to stretching as used in both exercise and rehabilitation. PMID:22319684

  5. CURRENT CONCEPTS IN MUSCLE STRETCHING FOR EXERCISE AND REHABILITATION

    OpenAIRE

    Page, Phil

    2012-01-01

    Stretching is a common activity used by athletes, older adults, rehabilitation patients, and anyone participating in a fitness program. While the benefits of stretching are known, controversy remains about the best type of stretching for a particular goal or outcome. The purpose of this clinical commentary is to discuss the current concepts of muscle stretching interventions and summarize the evidence related to stretching as used in both exercise and rehabilitation.

  6. Cyclic mechanical stretch reduces myofibroblast differentiation of primary lung fibroblasts.

    Science.gov (United States)

    Blaauboer, Marjolein E; Smit, Theo H; Hanemaaijer, Roeland; Stoop, Reinout; Everts, Vincent

    2011-01-07

    In lung fibrosis tissue architecture and function is severely hampered by myofibroblasts due to excessive deposition of extracellular matrix and tissue contraction. Myofibroblasts differentiate from fibroblasts under the influence of transforming growth factor (TGF) β(1) but this process is also controlled mechanically by cytoskeletal tension. In healthy lungs, the cytoskeleton of fibroblasts is mechanically strained during breathing. In stiffer fibrotic lung tissue, this mechanical stimulus is reduced, which may influence fibroblast-to-myofibroblast differentiation. Therefore, we investigated the effect of cyclic mechanical stretch on fibroblast-to-myofibroblast differentiation. Primary normal human lung fibroblasts were grown on BioFlex culture plates and stimulated to undergo myofibroblast differentiation by 10 ng/ml TGFβ(1). Cells were either or not subjected to cyclic mechanical stretch (sinusoidal pattern, maximum elongation 10%, 0.2 Hz) for a period of 48 h on a Flexercell apparatus. mRNA expression was analyzed by real-time PCR. Cyclic mechanical loading reduced the mRNA expression of the myofibroblast marker α-smooth muscle actin and the extracellular matrix proteins type-I, type-III, and type-V collagen, and tenascin C. These outcomes indicate that fibroblast-to-myofibroblast differentiation is reduced. Cyclic mechanical loading did not change the expression of the fibronectin ED-A splice variant, but did decrease the paracrine expression of TGFβ(1), thereby suggesting a possible regulation mechanism for the observed effects. The data suggest that cyclic loading experienced by healthy lung cells during breathing may prevent fibroblasts from differentiating towards myofibroblasts. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Multiscale Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  8. Chaotic behaviour from smooth and non-smooth optical solitons ...

    Indian Academy of Sciences (India)

    2016-07-14

    Jul 14, 2016 ... obtain the preferable media to reduce the influ- ence of perturbation of solitons in optical fibre propagation. This paper is organized as follows. In §2, we give the smooth and compacton solitons of the perturbation system by phase diagram analysis. In §3, we discuss the chaotic behaviour of the perturbed ...

  9. Smoothing quadratic and cubic splines

    OpenAIRE

    Oukropcová, Kateřina

    2014-01-01

    Title: Smoothing quadratic and cubic splines Author: Kateřina Oukropcová Department: Department of Numerical Mathematics Supervisor: RNDr. Václav Kučera, Ph.D., Department of Numerical Mathematics Abstract: The aim of this bachelor thesis is to study the topic of smoothing quadratic and cubic splines on uniform partitions. First, we define the basic con- cepts in the field of splines, next we introduce interpolating splines with a focus on their minimizing properties for odd degree and quadra...

  10. Summary of the stretching tectonics research

    International Nuclear Information System (INIS)

    Yu Dagan

    1994-01-01

    The rise of stretching tectonics is established on the basis of recent structural geology theory, the establishment of metamorphic nucleus complex structural model on one hand plays an important promoting art to the development of stretching structure, on the other hand, it needs constant supplement and perfection in practice. Metamorphic nucleus complex is the carrier of comparatively deep geological information in vertical section of the crust and has wide distribution in the era of south China. Evidently, it can be taken as the 'key' to understanding the deep and studying the basement, Strengthening the study will play the important promoting role to the deep prospecting. The study of stretching tectonics is not only limited within the range of structure and metamorphism, but combine with the studies of sedimentation, magmatism, metamorphism and mineralization, thus form a new field of tectonic geology of self-developing system

  11. Optofluidic time-stretch microscopy: recent advances

    Science.gov (United States)

    Lei, Cheng; Nitta, Nao; Ozeki, Yasuyuki; Goda, Keisuke

    2018-04-01

    Flow cytometry is an indispensable method for valuable applications in numerous fields such as immunology, pathology, pharmacology, molecular biology, and marine biology. Optofluidic time-stretch microscopy is superior to conventional flow cytometry methods for its capability to acquire high-quality images of single cells at a high-throughput exceeding 10,000 cells per second. This makes it possible to extract copious information from cellular images for accurate cell detection and analysis with the assistance of machine learning. Optofluidic time-stretch microscopy has proven its effectivity in various applications, including microalga-based biofuel production, evaluation of thrombotic disorders, as well as drug screening and discovery. In this review, we discuss the principles and recent advances of optofluidic time-stretch microscopy.

  12. Optofluidic time-stretch quantitative phase microscopy.

    Science.gov (United States)

    Guo, Baoshan; Lei, Cheng; Wu, Yi; Kobayashi, Hirofumi; Ito, Takuro; Yalikun, Yaxiaer; Lee, Sangwook; Isozaki, Akihiro; Li, Ming; Jiang, Yiyue; Yasumoto, Atsushi; Di Carlo, Dino; Tanaka, Yo; Yatomi, Yutaka; Ozeki, Yasuyuki; Goda, Keisuke

    2018-03-01

    Innovations in optical microscopy have opened new windows onto scientific research, industrial quality control, and medical practice over the last few decades. One of such innovations is optofluidic time-stretch quantitative phase microscopy - an emerging method for high-throughput quantitative phase imaging that builds on the interference between temporally stretched signal and reference pulses by using dispersive properties of light in both spatial and temporal domains in an interferometric configuration on a microfluidic platform. It achieves the continuous acquisition of both intensity and phase images with a high throughput of more than 10,000 particles or cells per second by overcoming speed limitations that exist in conventional quantitative phase imaging methods. Applications enabled by such capabilities are versatile and include characterization of cancer cells and microalgal cultures. In this paper, we review the principles and applications of optofluidic time-stretch quantitative phase microscopy and discuss its future perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Bias of purine stretches in sequenced chromosomes

    DEFF Research Database (Denmark)

    Ussery, David; Soumpasis, Dikeos Mario; Brunak, Søren

    2002-01-01

    We examined more than 700 DNA sequences (full length chromosomes and plasmids) for stretches of purines (R) or pyrimidines (Y) and alternating YR stretches; such regions will likely adopt structures which are different from the canonical B-form. Since one turn of the DNA helix is roughly 10 bp, we...... measured the fraction of each genome which contains purine (or pyrimidine) tracts of lengths of 10 by or longer (hereafter referred to as 'purine tracts'), as well as stretches of alternating pyrimidines/purine ('pyr/pur tracts') of the same length. Using this criteria, a random sequence would be expected...... to contain 1.0% of purine tracts and also 1.0% of the alternating pyr/pur tracts. In the vast majority of cases, there are more purine tracts than would be expected from a random sequence, with an average of 3.5%, significantly larger than the expectation value. The fraction of the chromosomes containing pyr...

  14. Bias of purine stretches in sequenced chromosomes

    DEFF Research Database (Denmark)

    Ussery, David; Soumpasis, Dikeos Mario; Brunak, Søren

    2002-01-01

    We examined more than 700 DNA sequences (full length chromosomes and plasmids) for stretches of purines (R) or pyrimidines (Y) and alternating YR stretches; such regions will likely adopt structures which are different from the canonical B-form. Since one turn of the DNA helix is roughly 10 bp, we...... to contain 1.0% of purine tracts and also 1.0% of the alternating pyr/pur tracts. In the vast majority of cases, there are more purine tracts than would be expected from a random sequence, with an average of 3.5%, significantly larger than the expectation value. The fraction of the chromosomes containing pyr......, in eukaryotes there is an abundance of long stretches of purines or alternating purine/pyrimidine tracts, which cannot be explained in this way; these sequences are likely to play an important role in eukaryotic chromosome organisation....

  15. Anisotropic dewetting on stretched elastomeric substrates.

    Science.gov (United States)

    Qiao, L; He, L H

    2008-08-01

    We study the instability of a very thin liquid film resting on a uniformly stretched soft elastomeric substrate driven by van der Waals forces. A linear stability analysis shows that the critical fluctuation wavelength in the tensile direction is larger than those in the other directions. The magnitudes of the critical wavelengths are adjustable in the sense that they depend on the principal stretch of the substrate. For example, when the principal stretch of the substrate varies from 1.0 (unstretched) to 3.0, the range of the critical wavelength in the tensile direction increases by 7.0% while that normal to the tensile direction decreases by 8.7%. Therefore, the phenomenon may find potential applications in creating tunable topographically patterned surfaces with nano- to microscale features.

  16. Flow of nanofluid by nonlinear stretching velocity

    Science.gov (United States)

    Hayat, Tasawar; Rashid, Madiha; Alsaedi, Ahmed; Ahmad, Bashir

    2018-03-01

    Main objective in this article is to model and analyze the nanofluid flow induced by curved surface with nonlinear stretching velocity. Nanofluid comprises water and silver. Governing problem is solved by using homotopy analysis method (HAM). Induced magnetic field for low magnetic Reynolds number is not entertained. Development of convergent series solutions for velocity and skin friction coefficient is successfully made. Pressure in the boundary layer flow by curved stretching surface cannot be ignored. It is found that magnitude of power-law index parameter increases for pressure distibutions. Magnitude of radius of curvature reduces for pressure field while opposite trend can be observed for velocity.

  17. Lattice stretching bistability and dynamic heterogeneity

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Savin, A. V.; Zolotaryuk, A. V.

    2012-01-01

    A simple one-dimensional lattice model is suggested to describe the experimentally observed plateau in force-stretching diagrams for some macromolecules. This chain model involves the nearest-neighbor interaction of a Morse-like potential (required to have a saturation branch) and a harmonic second......-neighbor coupling. Under an external stretching applied to the chain ends, the intersite Morse-like potential results in the appearance of a double-well potential within each chain monomer, whereas the interaction between the second neighbors provides a homogeneous bistable (degenerate) ground state, at least...

  18. Stretching and folding mechanism in foams

    Energy Technology Data Exchange (ETDEWEB)

    Tufaile, Alberto [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)], E-mail: tufaile@usp.br; Pedrosa Biscaia Tufaile, Adriana [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)

    2008-10-13

    We have described the stretching and folding of foams in a vertical Hele-Shaw cell containing air and a surfactant solution, from a sequence of upside-down flips. Besides the fractal dimension of the foam, we have observed the logistic growth for the soap film length. The stretching and folding mechanism is present during the foam formation, and this mechanism is observed even after the foam has reached its respective maximum fractal dimension. Observing the motion of bubbles inside the foam, large bubbles present power spectrum associated with random walk motion in both directions, while the small bubbles are scattered like balls in a Galton board.

  19. Nonlinear smoothing for random fields

    NARCIS (Netherlands)

    Aihara, ShinIchi; Bagchi, Arunabha

    1995-01-01

    Stochastic nonlinear elliptic partial differential equations with white noise disturbances are studied in the countably additive measure set up. Introducing the Onsager-Machlup function to the system model, the smoothing problem for maximizing the modified likelihood functional is solved and the

  20. Immediate effects of quantified hamstring stretching: hold-relax proprioceptive neuromuscular facilitation versus static stretching.

    Science.gov (United States)

    Puentedura, Emilio J; Huijbregts, Peter A; Celeste, Shelley; Edwards, Dale; In, Alastair; Landers, Merrill R; Fernandez-de-Las-Penas, Cesar

    2011-08-01

    To compare the immediate effects of a hold-relax proprioceptive neuromuscular facilitation stretching (HR-PNF) versus static stretch (SS) on hamstring flexibility in healthy, asymptomatic subjects. Thirty subjects (13 female; mean age 25.7 ± 3.0, range 22-37) without excessive hamstring muscle flexibility were randomly assigned to one of two stretch groups: HR-PNF or SS. The left leg was treated as a control and did not receive any intervention. The right leg was measured for ROM pre- and post-stretch interventions, with subjects receiving randomly assigned interventions one week apart. Data were analyzed with a 3 (intervention: HR-PNF, SS, control) × 2 (time: pre and post) factorial ANOVA with repeated measures and appropriate post-hoc analyses. A significant interaction was observed between intervention and time for hamstring extensibility, F(2,58) = 25.229, p < .0005. Main effect of intervention for the tested leg was not significant, p = .782 indicating that there was no difference between the two stretch conditions. However, main effect for time was significant (p < .0005), suggesting that hamstring extensibility (for both stretching conditions) after intervention was greater than before. No significant differences were found when comparing the effectiveness of HR-PNF and SS techniques. Both stretching methods resulted in significant immediate increases in hamstring length. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Postoperative Airway Obstruction by a Bone Fragment

    Directory of Open Access Journals (Sweden)

    Patrick Schober

    2017-01-01

    Full Text Available Postoperative airway obstructions are potentially life-threatening complications. These obstructions may be classified as functional (sagging tongue, laryngospasm, or bronchospasm, pathoanatomical (airway swelling or hematoma within the airways, or foreign body-related. Various cases of airway obstruction by foreign bodies have previously been reported, for example, by broken teeth or damaged airway instruments. Here we present the exceptional case of a postoperative airway obstruction due to a large fragment of the patient’s maxillary bone, left accidentally in situ after transoral surgical tumor resection. Concerning this type of airway obstruction, we discuss possible causes, diagnosis, and treatment options. Although it is an exceptional case after surgery, clinicians should be aware of this potentially life-threatening complication. In summary, this case demonstrates that the differential diagnosis of postoperative airway obstructions should include foreign bodies derived from surgery, including tissue and bone fragments.

  2. Clinical review: Management of difficult airways

    Science.gov (United States)

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

    2006-01-01

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

  3. Clinical review: management of difficult airways.

    Science.gov (United States)

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

    2006-01-01

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

  4. Extraction of Airways from CT (EXACT'09)

    NARCIS (Netherlands)

    Lo, P.; Ginneken, B. van; Reinhardt, J.M.; Tarunashree, Y.; Jong, P.A. de; Irving, B.; Fetita, C.; Ortner, M.; Pinho, R.; Sijbers, J.; Feuerstein, M.; Fabijanska, A.; Bauer, C.; Beichel, R.; Mendoza, C.S.; Wiemker, R.; Lee, J. van der; Reeves, A.P.; Born, S.; Weinheimer, O.; Rikxoort, E.M. van; Tschirren, J.; Mori, K.; Odry, B.; Naidich, D.P.; Hartmann, I.J.; Hoffman, E.A.; Prokop, M.; Pedersen, J.H.; de Bruijne, M.

    2012-01-01

    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate fifteen different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference

  5. 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......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...

  6. Comparing the Laryngeal Mask Airway, Cobra Perilaryngeal Airway and Face Mask in Children Airway Management.

    Science.gov (United States)

    Tekin, Beyza; Hatipoğlu, Zehra; Türktan, Mediha; Özcengiz, Dilek

    2016-04-01

    We compared the effects of the laryngeal mask airway (LMA), face mask and Cobra perilaryngeal airway (PLA) in the airway management of spontaneously breathing paediatric patients undergoing elective inguinal surgery. In this study, 90 cases of 1-14-year-old children undergoing elective inguinal surgery were scheduled. The patients were randomly divided into three groups. Anaesthesia was provided with sevoflurane and 50%-50% nitrous oxide and oxygen. After providing an adequate depth of anaesthesia, supraglottic airway devices were inserted in the group I and II patients. The duration and number of insertion, haemodynamic parameters, plateau and peak inspiratory pressure and positive end-expiratory pressure of the patients were recorded preoperatively, after induction and at 5, 10, 15 and 30 min peroperatively. There were no statistical differences between the groups in terms of haemodynamic parameters (p>0.05). In group II, instrumentation success was higher and instrumentation time was shorter than group II. The positive end-expiratory pressure and plateau and peak inspiratory pressure values were statistically lower in group II (pairway safety and to avoid possible complications, LMA and Cobra PLA could be alternatives to face mask and that the Cobra PLA provided lower airway pressure and had a faster and more easy placement than LMA.

  7. Clinical review: Management of difficult airways

    OpenAIRE

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

    2006-01-01

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

  8. Airway management in Ludwig's angina.

    Science.gov (United States)

    Neff, S P; Merry, A F; Anderson, B

    1999-12-01

    A 37-year-old 91 kg man presented with features of Ludwig's angina. Anaesthesia for incision and drainage of his submandibular abscess was undertaken by two specialist anaesthetists with an otorhinolaryngological surgeon prepared for immediate tracheostomy. After preoxygenation, gas induction with sevoflurane in oxygen was followed by a gush of pus into the oral cavity and laryngospam causing acute upper airway obstruction. This resolved with 25 mg of suxamethonium and an endotracheal tube was passed into the trachea with difficulty. Options for management of the difficult airway in Ludwig's angina are discussed.

  9. Realistic searches on stretched exponential networks

    Indian Academy of Sciences (India)

    Vol. 71, No. 2. — journal of. August 2008 physics pp. 313–317. Realistic searches on stretched exponential networks. PARONGAMA SEN. Department of Physics, University of Calcutta, 92 Acharya Prafulla Chandra Road,. Kolkata 700 009, India .... [4] S Milgram, Psychology Today 1, 60 (1967). J Travers and S Milgram, ...

  10. Filament stretching rheometry of polymer melts

    DEFF Research Database (Denmark)

    Hassager, Ole; Nielsen, Jens Kromann; Rasmussen, Henrik Koblitz

    2005-01-01

    The Filament Stretching Rheometry (FSR) method developed by Sridhar, McKinley and coworkers for polymer solutions has been extended to be used also for polymer melts. The design of a melt-FSR will be described and differences to conventional melt elongational rheometers will be pointed out. Results...

  11. Cloud Network Helps Stretch IT Dollars

    Science.gov (United States)

    Collins, Hilton

    2012-01-01

    No matter how many car washes or bake sales schools host to raise money, adding funds to their coffers is a recurring problem. This perpetual financial difficulty makes expansive technology purchases or changes seem like a pipe dream for school CIOs and has education technologists searching for ways to stretch money. In 2005, state K-12 school…

  12. The stretch zone of automotive steel sheets

    Indian Academy of Sciences (India)

    on steel grade, on the rolling direction as well as on the loading rate. Stretch zones ... This interaction is demonstrated at a fracture surface as a bounded transition between initiatory crack (e.g., fatigue) and either ... The materials examined in this study are three grades of thin automotive steel sheets: XSG,. HR 45 and DP.

  13. Fractional behaviour at cyclic stretch-bending

    NARCIS (Netherlands)

    Emmens, W.C.; van den Boogaard, Antonius H.; Kazantzis, A.V.; de Hosson, J.Th.M.; Kolleck, R

    2010-01-01

    The fractional behaviour at cyclic stretch-bending has been studied by performing tensile tests at long specimens that are cyclically bent at the same time, on mild steel, dual-phase steel, stainless steel, aluminium and brass. Several types of fracture are observed, these are discussed, as are the

  14. Emergency surgical airway management in Denmark

    DEFF Research Database (Denmark)

    Rosenstock, C V; Nørskov, A K; 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...

  15. Airway Complications following ingestion of corrosive | Ezike ...

    African Journals Online (AJOL)

    Conclusions: Corrosive ingestion is a major health problem in our environment. The proximal third of the oesophagus and the upper airway are mostly affected. These frequently result in life threatening airway complications demanding urgent tracheostomy. Key words: Corrosives, Burns, Airway, Respiratory distress.

  16. Is surgical airway necessary for airway management in deep neck infections and Ludwig angina?

    Science.gov (United States)

    Wolfe, Mary M; Davis, James W; Parks, Steven N

    2011-02-01

    Deep neck infections are potentially life-threatening conditions because of airway compromise. Management requires early recognition, antibiotics, surgical drainage, and effective airway control. The Surgical Education and Self-Assessment Program 12 states that awake tracheostomy is the treatment of choice for these patients. With advanced airway control techniques such as retrograde intubation, GlideScope, and fiberoptic intubation, surgical airway is not required. A retrospective analysis of all deep neck abscesses treated from December 1999 to July 2006 was performed. All patients who underwent urgent or emergent surgery for Ludwig angina and submental, submandibular, sublingual, and parapharyngeal abscesses (Current Procedural Terminology codes 41015, 41016, 41017, 42320, and 42725) were included in our review. Charts were studied for age, presence of true Ludwig angina, presence of airway compromise, airway management, morbidity/mortality, and the requirement for surgical airway. Of 29 patients, 6 (20%) had symptoms consistent with true Ludwig angina. Nineteen (65.5%) had evidence of airway compromise. Eight (42%) of these 19 patients required advanced airway control techniques. No patient required a surgical airway, and no mortality resulted from airway compromise. Advance airway control techniques were required more often in patients with airway compromise (P Ludwig angina and deep neck abscesses requires good clinical judgment. Patients with deep neck infections and symptoms of airway compromise may be safely managed with advanced airway control techniques. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Rho-kinase inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contraction.

    Science.gov (United States)

    Hanazaki, Motohiko; Yokoyama, Masataka; Morita, Kiyoshi; Kohjitani, Atsushi; Sakai, Hiroyasu; Chiba, Yoshihiko; Misawa, Miwa

    2008-06-01

    Airway smooth muscle contraction is not caused by the increase in intracellular Ca(2+) ([Ca(2+)](i)) alone because agonist stimulation increases tension at the same [Ca(2+)](i) (increase in Ca(2+) sensitivity). The small G protein Rho A and Rho-kinase (ROCK) play important roles in the regulation of Ca(2+) sensitivity. In this study, we investigated the effects of three ROCK inhibitors (fasudil, Y-27632, and H-1152) on rat airway smooth muscle contraction and the effects of ROCK inhibitors on propofol-induced bronchodilatory effects. Ring strips from intrapulmonary bronchus of male Wistar rats were placed in 400-microL organ baths containing Krebs-Henseleit solution. After obtaining stable contraction with 30 microM acetylcholine, (1) propofol (1 microM-1 mM) was cumulatively applied; (2) cumulative doses of Y-27632 (0.01-300 microM), fasudil (0.01-100 microM), or H-1152 (0.01-100 microM) were applied; (3) propofol (1 microM-1 mM), with Y-27632, fasudil or H-1152 (0.03 microM or 0.1 microM), was cumulatively applied. (1) Propofol produced concentration-dependent relaxation of rat bronchial smooth muscle. (2) All ROCK inhibitors produced concentration-dependent relaxation. (3) 0.03 microM Y-27632 and fasudil had no significant effect on the concentration-response curve for propofol, while 0.1 microM of both agents significantly shifted concentration-response curves to the left and decreased EC(50). H-1152 (both 0.03 microM and 0.1 microM) significantly sifted the concentration-response curve for propofol to the left and decreased EC(50). ROCK inhibitors, especially H-1152, can attenuate the contraction of rat airway smooth muscle. The combined use of ROCK inhibitors and propofol causes greater relaxation.

  18. EFFECTIVENESS OF PNF STRETCHING AND CYCLIC STRETCHING OF CALF TIGHTNESS ON COLLEGE GOING GIRLS

    Directory of Open Access Journals (Sweden)

    Ashlesha Sirari

    2015-06-01

    Full Text Available Background: Flexibility helps with injury prevention, the reduction of soreness following a workout, and a general sense of well-being. There are different stretching techniques and protocols for improvements in calf extensibility and flexibility. The purpose of the study was to investigate the effectiveness of two techniques i.e. CYCLIC and PNF stretching which improves calf flexibility. This study was done to find the effectiveness of calf Cyclic and PNF stretching technique to improve calf flexibility. Methods: 30 subjects with age group 21-22 years were randomly allocated to 2 groups equally. Group 1(n=15 were given CYCLIC and group 2(n=15 were given PNF stretching technique. Plantar flexion was used to measure the calf tightness which was done before and after the treatment. Treatment was given for 7 days and on the 7th day the calf tightness was again measured. Results: The mean difference of the CYCLIC is 4.6 and mean difference of PNF is 4.7 which indicate that CYCLIC and PNF both are effective to improve calf flexibility but PNF is more effective than CYCLIC to improve calf flexibility. Conclusion: The neurophysiological basis of PNF, stating that the excitatory efficient of the neuromuscular spindle or the inhibitory afferent of the Golgi tendon organ (GTO or both are responsible for the effects. During PNF stretch and isometric contraction of stretched agonists for extended period may cause activation of its neuromuscular spindle. The increase in tension created during the isometric contraction of the pre – lengthened agonist contracts concentrically. Both the fascia & the spindle of the agonist adjust to the nearly lengthened position. These impulses travel via causing post synaptic inhibition of the motor neuron to agonist increasing the tension from the GTO. These impulses can override the impulses coming from the neuromuscular spindles arousing the muscle to reflexly resist to the change in length, thus helping in lengthening

  19. Smooth paths of conditional expectations

    OpenAIRE

    Andruchow, Esteban; Larotonda, Gabriel

    2010-01-01

    Let A be a von Neumann algebra with a finite trace $\\tau$, represented in $H=L^2(A,\\tau)$, and let $B_t\\subset A$ be sub-algebras, for $t$ in an interval $I$. Let $E_t:A\\to B_t$ be the unique $\\tau$-preserving conditional expectation. We say that the path $t\\mapsto E_t$ is smooth if for every $a\\in A$ and $v \\in H$, the map $$ I\

  20. Aspects of smooth muscle function in molluscan catch muscle.

    Science.gov (United States)

    Twarog, B M

    1976-10-01

    1) Catch in Mytilus ABRM may be a specialization of a mechanism common to all muscles that gives rise to stretch resistance in the resting state. Catch appears to be due to actin myosin interaction. Since this interaction is regulated by nerves, it provides a convenient model for studying resting stretch resistance. 2) Studies of the structure of Mytilus ABRM revela two types of intercellular connections: a) direct connections between muscle fibers [these nexal (gap) junctions interconnect the muscle cells electrically]; b) muscle fiber-collagen-muscle fiber connections [these provide mechanical connections between muscle cells via collagen fibers]. The structure of Mytilus ABRM supports speculation that smooth muscle filaments are organized into contractile units. 3) A rise in cAMP levels occurs in response to the relaxing transmitter, serotonin. It is not certain whether the cAMP system directly controls the ability of the contractile proteins to interact or whether it regulates intracellular levels of Ca2+. 4) Calcium ions in activation are derived from two sources: an internal source, probably the sarcoplasmic reticulum, and an external source, across the muscle membrane. 5) The nature of catch remains in question, although most evidence favors the linkage hypothesis.

  1. Anaesthesia and subglottic airway obstruction

    African Journals Online (AJOL)

    Keywords: shared airway; jet ventilation; TIVA/TCI; laser excision; monitoring. Abstract. In this article, we describe the anaesthetic ... (Submitted: 2009-07-14, Accepted: 2010-10-04). S Afr J Anaesth Analg 2011;17(2):182-184 ... Jet ventilation and TCI/TIVA (total intravenous anaesthesia) are our techniques of choice for ...

  2. allergy, asthma airway and anaphylaxis

    African Journals Online (AJOL)

    The perioperative preparation of children presenting for surgery aims to identify medical problems that might influence the outcome and to institute management strategies to reduce those risks. Respiratory and airway complications remain the most significant cause of morbidity and mortality in modern paediatric ...

  3. Pharyngeal airway changes following mandibular setback surgery

    Directory of Open Access Journals (Sweden)

    Babu Ramesh

    2005-01-01

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

  4. Passive Stretch Versus Active Stretch on Intervertebral Movement in Non - Specific Neck Pain

    International Nuclear Information System (INIS)

    Abd El - Aziz, A.H.; Amin, D.I.; Moustafa, I.

    2016-01-01

    Neck pain is one of the most common and painful musculoskeletal conditions. Point prevalence ranges from 6% to 22% and up to 38% of the elderly population, while lifetime prevalence ranges from 14,2% to 71%. Up till now no randomized study showed the effect between controversy of active and passive stretch on intervertebral movement. The purpose: the current study was to investigate the effect of the passive and active stretch on intervertebral movement in non - specific neck pain. Material and methods: Forty five subjects from both sexes with age range between 18 and 30 years and assigned in three groups, group I (15) received active stretch, ultrasound and TENS. Group II (15) received passive stretch, ultrasound and TENS. Group III (15) received ultrasound and TENS. The radiological assessment was used to measure rotational and translational movement of intervertebral movement before and after treatment. Results: MANOVA test was used for radiological assessment before and after treatment there was significant increase in intervertebral movement in group I as p value =0.0001. Conclusion: active stretch had a effect in increasing the intervertebral movement compared to the passive stretch

  5. How to Stretch Your Ankle After a Sprain

    Science.gov (United States)

    ... Ankle After A Sprain How to Stretch Your Ankle After A Sprain Page Content You should perform the following stretches ... Consider these home exercises when recuperating from an ankle sprain. Perform them twice per day. While seated, bring ...

  6. Surgical airway in emergency department intubation.

    Science.gov (United States)

    Reid, Lindsay A; Dunn, Mark; Mckeown, Dermot W; Oglesby, Angela J

    2011-06-01

    To determine the frequency of and primary indication for surgical airway during emergency department intubation. Prospectively collected data from all intubations performed in the emergency department from January 1999 to July 2007 were analysed to ascertain the frequency of surgical airway access. Original data were collected on a structured proforma, entered into a regional database and analysed. Patient records were then reviewed to determine the primary indication for a surgical airway. Emergency department intubation was undertaken in 2524 patients. Of these, only five patients (0.2%) required a surgical airway. The most common indication for a surgical airway was trauma in four of the five patients. Two patients had attempted rapid sequence induction before surgical airway. Two patients had gaseous inductions and one patient received no drugs. In all five patients, surgical airway was performed secondary to failed endotracheal intubation attempt(s) and was never the primary technique used. In our emergency department, surgical airway is an uncommon procedure. The rate of 0.2% is significantly lower than rates quoted in other studies. The most common indication for surgical airway was severe facial or neck trauma. Our emergency department has a joint protocol for emergency intubation agreed by the Departments of Emergency Medicine, Anaesthesia and Critical Care at the Edinburgh Royal Infirmary. We believe that the low surgical airway rate is secondary to this collaborative approach. The identified low rate of emergency department surgical airway has implications for training and maintenance of skills for emergency medicine trainees and physicians.

  7. Effect of Bronchial Thermoplasty on Airway Closure

    Directory of Open Access Journals (Sweden)

    Robert Brown

    2007-01-01

    Full Text Available Background Bronchial Thermoplasty, a procedure that applies thermal energy to the airway wall has been shown to impair the ability of airway to contract in response to methacholine chloride (Mch. The technique has been advocated as an alternative treatment for asthma that may permanently limit airway narrowing. In previous experimental studies in dogs and humans, it was shown that those airways treated with bronchial thermoplasty had significant impairment of Mch responsiveness. Methods In the present study, we investigated the ability of canine airways to close completely with very high concentrations of Mch after bronchial thermoplasty. Bronchial thermoplasty was performed on dogs using the Alair System, comprising a low power RF controller and a basket catheter with four electrodes. A local atomization of Mch agonist was delivered directly to the epithelium of the same airway locations with repeated challenges. Airway size was measured with computed tomography, and closure was considered to occur in any airway where the lumen fell below the resolution of the scanner (< 1 mm. Results Our results show that, while treated airways still have the capacity to close at very high doses of Mch, this ability is seriously impaired after treatment, requiring much higher doses. Conclusions Bronchial thermoplasty as currently applied seems to simply shift the entire dose response curve toward increasing airway size. Thus, this procedure simply serves to minimize the ability of airways to narrow under any level of stimulation.

  8. Airway malacia in children with achondroplasia.

    Science.gov (United States)

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

    2014-02-01

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

  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...... the Danish Lung Cancer Screening Trial. This includes methods for extracting airway surfaces from the images and ways of achieving comparable measurements in airway branches through matching and anatomical labelling. The methods were used to study effects of differences in inspiration level at the time...

  10. Airway hyperresponsiveness in FVB/N delta F508 cystic fibrosis transmembrane conductance regulator mice.

    Science.gov (United States)

    Bazett, Mark; Haston, Christina K

    2014-07-01

    Airway hyperresponsiveness is a feature of clinical CF lung disease. In this study, we investigated whether the FVB/N ΔF508 CFTR mouse model has altered airway mechanics. Mechanics were measured in 12-14week old FVB/N Cftr(tm1Eur) (ΔF508) mice and wildtype littermates using the FlexiVent small animal ventilator. Lung disease was assayed by immunohistochemistry, histology and bronchoalveolar lavage analysis. Cftr(tm1Eur) mice presented with increased airway resistance, compared to wildtype littermates, in response to methacholine challenge. No differences in bronchoalveolar cell number or differential, or in tissue lymphocyte, goblet cell or smooth muscle actin levels were evident in mice grouped by Cftr genotype. The bronchoalveolar lavage of Cftr(tm1Eur) mice included significantly increased levels of interleukin 12(p40) and CXCL1 compared to controls. We conclude that the pulmonary phenotype of Cftr(tm1Eur) mice includes airway hyperresponsiveness in the absence of overt lung inflammation or airway remodeling. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. Polygonal approximation and energy of smooth knots

    OpenAIRE

    Rawdon, Eric J.; Simon, Jonathan K.

    2003-01-01

    We establish a fundamental connection between smooth and polygonal knot energies, showing that the Minimum Distance Energy for polygons inscribed in a smooth knot converges to the Moebius Energy of the smooth knot as the polygons converge to the smooth knot. However, the polygons must converge in a ``nice'' way, and the energies must be correctly regularized. We determine an explicit error bound between the energies in terms of the number of the edges of the polygon and the Ropelength of the ...

  12. Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.

    Science.gov (United States)

    Bano, Saidullah; Swati, Omanwar; Kambadur, Muralidhar; Mohammad, Fahim

    2016-01-01

    The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K + ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed. In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.

  13. IL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.

    Directory of Open Access Journals (Sweden)

    Mariona Pinart

    Full Text Available IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R(-/- and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R(-/-, chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R(-/- mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R(-/- mice. p38-mitogen-activated protein kinase (MAPK and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R(-/- ozone-exposed mice. Lung inflammation scores were not altered in IL-17R(-/- mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R(-/- mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

  14. Rigid Bronchoscope Combined with Soft Electronic Bronchoscope for Treatment of Main Airway Neoplasma

    Directory of Open Access Journals (Sweden)

    Hongwu WANG

    2009-02-01

    Full Text Available Background and objective Main airway severe obstruction is a problem facing difficulty flexible bronchoscope because the patient is not able to breath smoothly under prostration, and death from suffocation is a frequent outcome. Managing the airway of patients with critical tracheal stenosis remains a formidable challenge to bronchoscopists. This study is to evaluate the application and efficacy of argon plasma coagulation (APC and cryoextraction for thetreatment of endobronchial neoplasma under rigid bronchoscope combined with flexible bronchoscope. Methods Two groups of airway pathologically proved neoplasma were retrospectively reviewed for the different endobronchial intervation modalities. Group A: Argon plasma coagulation (APC and cryoextraction were used for the treatment of endobronchial neoplasma under rigid bronchoscope combined with electronic bronchoscope in 19 cases with tracheobronchial carcinoma. Rigid bronchoscope was inserted into trachea with general anesthesia. Then the endobronchial tumor was removed by the combination APC and cryoextraction. Group B: APC and grasp or cryoextraction were used for the debulking of endobronchial tumor under flexible bronchoscope in 20 cases with airway tumor. Results Both tracheal and bronchial obstruction were more severe in Group A than those in Group B, but the tumor debulking was higher for the first time in Group A than in Group B. There were no difference on debulking volume between trachea and bronchus in the same group. The procedures were less complex in Group A than in Group B. The clinical improvement was better in Group A than inGroup B. There were no severe complications directly related to the procedures. Conclusion The combination of APC and cryoextraction is a rapid and effective method for the treatment of endoluminal airway tumor under rigid bronchoscope combined with electronic bronchoscope. Cryoextraction could rapidly debulk airway tumor and APC could effectively ablate

  15. Transparent conducting film: Effect of mechanical stretching to ...

    Indian Academy of Sciences (India)

    Administrator

    posite was fixed to a tabletop clamp and unidirectionally stretched after cutting the paper support at two opposite sides. To hold the film under the stretched condition, both edges of stretched CNT-mat/transparent-film composite was then adhered to a PMMA substrate by epoxy glue and both the sheet resistance and the ...

  16. Effects of dynamic stretches on Isokinetic hamstring and Quadriceps ...

    African Journals Online (AJOL)

    In conclusion, dynamic stretches have positive effects on muscle strength, H/Q ratios and ROM. Therefore, dynamic stretches may increase performance and reduce the risk of injury to athletes. Keywords: Quadriceps; Hamstrings; Muscles Isokinetic; Dynamic stretches. South African Journal for Research in Sport, Physical ...

  17. Stretched cell cycle model for proliferating lymphocytes

    Science.gov (United States)

    Dowling, Mark R.; Kan, Andrey; Heinzel, Susanne; Zhou, Jie H. S.; Marchingo, Julia M.; Wellard, Cameron J.; Markham, John F.; Hodgkin, Philip D.

    2014-01-01

    Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G1 phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G2/M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics. PMID:24733943

  18. String Stretching, Frequency Modulation, and Banjo Clang

    OpenAIRE

    Politzer, David

    2014-01-01

    The banjo’s floating bridge, string break angle, and flexible drumhead all contribute to substantial audio range frequency modulation. From the world of electronic music synthesis, it is known that modulating higher frequency sounds with lower acoustic frequencies leads to metallic and bell-like tone. The mechanics of the banjo does just that quite naturally, modulating fundamentals and harmonics with the motion of the bridge. In technical terms, with a floating bridge, string stretching is f...

  19. The stretch zone of automotive steel sheets

    Indian Academy of Sciences (India)

    The stretch zone of automotive steel sheets. L' AMBRIŠKO1,∗ and L PEŠEK2. 1Institute of Structural Engineering, Faculty of Civil Engineering,. Technical University of Košice, Vysokoškolská 4, 042 00 Košice, Slovak Republic. 2Department of Materials Science, Faculty of Metallurgy,. Technical University of Košice, Letná 9, ...

  20. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  1. Spontaneous bending of pre-stretched bilayers.

    Science.gov (United States)

    DeSimone, Antonio

    2018-01-01

    We discuss spontaneously bent configurations of pre-stretched bilayer sheets that can be obtained by tuning the pre-stretches in the two layers. The two-dimensional nonlinear plate model we use for this purpose is an adaptation of the one recently obtained for thin sheets of nematic elastomers, by means of a rigorous dimensional reduction argument based on the theory of Gamma-convergence (Agostiniani and DeSimone in Meccanica. doi:10.1007/s11012-017-0630-4, 2017, Math Mech Solids. doi:10.1177/1081286517699991, arXiv:1509.07003, 2017). We argue that pre-stretched bilayer sheets provide us with an interesting model system to study shape programming and morphing of surfaces in other, more complex systems, where spontaneous deformations are induced by swelling due to the absorption of a liquid, phase transformations, thermal or electro-magnetic stimuli. These include bio-mimetic structures inspired by biological systems from both the plant and the animal kingdoms.

  2. Stretch Moduli of Ribonucleotide Embedded Short DNAs

    Science.gov (United States)

    Chiu, Hsiang-Chih; Koh, Kyung Duk; Riedo, Elisa; Storici, Francesca

    2013-03-01

    Understanding the mechanical properties of DNA is essential to comprehending the dynamics of many cellular functions. DNA deformations are involved in many mechanisms when genetic information needs to be stored and used. In addition, recent studies have found that Ribonucleotides (rNMPs) are among the most common non-standard nucleotides present in DNA. The presences of rNMPs in DNA might cause mutation, fragility or genotoxicity of chromosome but how they influence the structure and mechanical properties of DNA remains unclear. By means of Atomic Force Microscopy (AFM) based single molecule spectroscopy, we measure the stretch moduli of double stranded DNAs (dsDNA) with 30 base pairs and 5 equally embedded rNMPs. The dsDNAs are anchored on gold substrate via thiol chemistry, while the AFM tip is used to pick up and stretch the dsDNA from its free end through biotin-streptavidin bonding. Our preliminary results indicate that the inclusion of rNMPs in dsDNA might significantly change its stretch modulus, which might be important in some biological processes.

  3. Short Durations of Static Stretching when Combined with Dynamic Stretching do not Impair Repeated Sprints and Agility

    Science.gov (United States)

    Wong, Del P.; Chaouachi, Anis; Lau, Patrick W.C.; Behm, David G.

    2011-01-01

    This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performed (90 s total). Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. Key points The duration of combined static and dynamic stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit and reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). No significant differences in RSA and COD between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. The short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. PMID:24149890

  4. A theoretical model of the application of RF energy to the airway wall and its experimental validation

    Science.gov (United States)

    2010-01-01

    Background Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF) energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall. Methods An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model. Results Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations. The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty. Conclusions The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest that comparing model results

  5. A theoretical model of the application of RF energy to the airway wall and its experimental validation

    Directory of Open Access Journals (Sweden)

    Brown Robert H

    2010-11-01

    Full Text Available Abstract Background Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall. Methods An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model. Results Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations. The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty. Conclusions The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest

  6. Effect of Bronchial Thermoplasty on Airway Closure.

    Science.gov (United States)

    Brown, Robert; Wizeman, William; Danek, Christopher; Mitzner, Wayne

    2007-10-12

    BACKGROUND: Bronchial Thermoplasty, a procedure that applies thermal energy to the airway wall has been shown to impair the ability of airway to contract in response to methacholine chloride (Mch). The technique has been advocated as an alternative treatment for asthma that may permanently limit airway narrowing. In previous experimental studies in dogs and humans, it was shown that those airways treated with bronchial thermoplasty had significant impairment of Mch responsiveness. METHODS: In the present study, we investigated the ability of canine airways to close completely with very high concentrations of Mch after bronchial thermoplasty. Bronchial thermoplasty was performed on dogs using the Alair System, comprising a low power RF controller and a basket catheter with four electrodes. A local atomization of Mch agonist was delivered directly to the epithelium of the same airway locations with repeated challenges. Airway size was measured with computed tomography, and closure was considered to occur in any airway where the lumen fell below the resolution of the scanner (Bronchial thermoplasty as currently applied seems to simply shift the entire dose response curve toward increasing airway size. Thus, this procedure simply serves to minimize the ability of airways to narrow under any level of stimulation.

  7. Income and Consumption Smoothing among US States

    DEFF Research Database (Denmark)

    Sørensen, Bent; Yosha, Oved

    We quantify the amount of cross-sectional income and consumption smoothing achieved within subgroups of states, such as regions or clubs, e.g. the club of rich states. We find that there is much income smoothing between as well as within regions. By contrast, consumption smoothing occurs mainly...... states. The fraction of a shock to gross state products smoothed by the federal tax-transfer system is the same for various regions and other clubs of states. We calculate the scope for consumption smoothing within various regions and clubs, finding that most gains from risk sharing can be achieved...... within US regions. Since a considerable fraction of shocks to gross state product are smoothed within regions, we conclude that existing markets achieve a substantial fraction of the potential welfare gains from interstate income and consumption smoothing. Nonetheless, non-negligible welfare gains may...

  8. The Relevance of Stretch Intensity and Position: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Nikos eApostolopoulos

    2015-08-01

    Full Text Available Stretching exercises to increase the range of motion (ROM of joints have been used by sports coaches and medical professionals for improving performance and rehabilitation. The ability of connective and muscular tissues to change their architecture in response to stretching is important for their proper function, repair and performance. Given the dearth of relevant data in the literature, this review examined two key elements of stretching: stretch intensity and stretch position; and their significance to ROM, delayed onset muscle soreness (DOMS, and inflammation in different populations. A search of three databases, Pub-Med, Google Scholar, and Cochrane Reviews, identified 152 articles, which were subsequently categorized into four groups; athletes (n = 24, clinical (n = 29, elderly (n = 12, and general population (n = 87. The use of different populations facilitated a wider examination of the stretching components and their effects. All 152 articles incorporated information regarding duration, frequency and stretch position, whereas only 79 referred to the intensity of stretching and 22 of these 79 studies were deemed high quality. It appears that the intensity of stretching is relatively under-researched, and the importance of body position and its influence on stretch intensity, is largely unknown. In conclusion, this review has highlighted areas for future research, including stretch intensity and position and their effect on musculo-tendinous tissue, in relation to the sensation of pain, delayed onset muscle soreness, inflammation, as well as muscle health and performance

  9. Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Manyu Li

    Full Text Available Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR, and receptor activity-modifying protein 1 (RAMP1. RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR

  10. Hamstring Stiffness Returns More Rapidly After Static Stretching Than Range of Motion, Stretch Tolerance, and Isometric Peak Torque.

    Science.gov (United States)

    Hatano, Genki; Suzuki, Shigeyuki; Matsuo, Shingo; Kataura, Satoshi; Yokoi, Kazuaki; Fukaya, Taizan; Fujiwara, Mitsuhiro; Asai, Yuji; Iwata, Masahiro

    2017-12-18

    Hamstring injuries are common, and lack of hamstring flexibility may predispose to injury. Static stretching increases range of motion (ROM) but also results in reduced muscle strength after stretching. The effects of stretching on the hamstring muscles and the duration of these effects remain unclear. To determine the effects of static stretching on the hamstrings and the duration of these effects. Randomized crossover study. University laboratory. Twenty-four healthy volunteers. We measured the torque-angle relationship (ROM, passive torque (PT) at the onset of pain, and passive stiffness) and isometric muscle force using an isokinetic dynamometer. After a 60-minute rest, the ROM of the dynamometer was set at maximum tolerable intensity; this position was maintained for 300 seconds while static passive torque (SPT) was measured continuously. We remeasured the torque-angle relationship and isometric muscle force after rest periods of 10, 20, and 30 minutes. Change in SPT during stretching; changes in ROM, PT at the onset of pain, passive stiffness, and isometric muscle force before stretching compared with 10, 20, and 30 minutes after stretching. SPT decreased significantly during stretching. Passive stiffness decreased significantly 10 and 20 minutes after stretching, but there was no significant pre- vs. post-stretching difference after 30 minutes. PT at the onset of pain and ROM increased significantly after stretching at all rest intervals, while isometric muscle force decreased significantly after all rest intervals. The effect of static stretching on passive stiffness of the hamstrings was not maintained as long as the changes in ROM, stretch tolerance, and isometric muscle force. Therefore, frequent stretching is necessary to improve the viscoelasticity of the muscle-tendon unit. Muscle force was decreased for 30 minutes after stretching; this should be considered prior to activities requiring maximal muscle strength.

  11. WNT and β-catenin signalling in airway smooth muscle: emerging concepts for asthma

    NARCIS (Netherlands)

    Koopmans, Tim

    2017-01-01

    Astma is een veelvoorkomende chronische ontstekingsziekte van de luchtwegen die wordt gekenmerkt door terugkerende symptomen, belemmering van de luchtstroom en bronchospasme. De luchtweg-gladde spier draagt in belangrijke mate bij aan deze toegenomen vernauwing, middels samentrekking, toename in

  12. SHORT DURATIONS OF STATIC STRETCHING WHEN COMBINED WITH DYNAMIC STRETCHING DO NOT IMPAIR REPEATED SPRINTS AND AGILITY

    OpenAIRE

    Del P. Wong; Anis Chaouachi; Patrick W.C. Lau; David G. Behm

    2011-01-01

    This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performe...

  13. 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.

  14. 75 FR 13079 - Action Affecting Export Privileges; MAHAN AIRWAYS; Mahan Airways, Mahan Tower, No. 21, Azadegan...

    Science.gov (United States)

    2010-03-18

    ... Regulations and TDO, a United Kingdom court found Mahan Airways in contempt of court on February 1, 2010, for... contempt finding against Mahan Airways in the U.K. litigation, which I understand is still ongoing. I note...

  15. 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...... from scratch, we propose to construct the reference using results from all algorithms that are to be evaluated. We start by subdividing each segmented airway tree into its individual branch segments. Each branch segment is then visually scored by trained observers to determine whether...... 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...

  16. Airway injury during high-level exercise.

    Science.gov (United States)

    Kippelen, Pascale; Anderson, Sandra D

    2012-05-01

    Airway epithelial cells act as a physical barrier against environmental toxins and injury, and modulate inflammation and the immune response. As such, maintenance of their integrity is critical. Evidence is accumulating to suggest that exercise can cause injury to the airway epithelium. This seems the case particularly for competitive athletes performing high-level exercise, or when exercise takes place in extreme environmental conditions such as in cold dry air or in polluted air. Dehydration of the small airways and increased forces exerted on to the airway surface during severe hyperpnoea are thought to be key factors in determining the occurrence of injury of the airway epithelium. The injury-repair process of the airway epithelium may contribute to the development of the bronchial hyper-responsiveness that is documented in many elite athletes.

  17. Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma

    Directory of Open Access Journals (Sweden)

    Zhihua Yu

    2017-08-01

    Full Text Available Airway smooth muscle cells (SMC proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca2+ levels play an important role in regulating cell proliferation. We have previously reported KCa3.1 channels regulated human bronchial smooth muscle (HBSM cells proliferation via the Ca2+ influx as a consequence of membrane hyperpolarization. However, the role of potassium channels KCa3.1 in airway remodeling as well as the mechanism for extracellular Ca2+ influx induced by the activation of KCa3.1 remains unknown. Here we demonstrated that KCa3.1 channels deficiency attenuated airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR in a mouse model of chronic asthma. The gene expressions of repressor element 1-silencing transcription factor (REST and c-Jun, two transcriptional regulators of KCa3.1 channels, were correlated negatively or positively with KCa3.1 channels expressions both in vivo and in vitro using real-time PCR and Western blot analyses. RNAi-mediated knockdown or pharmacological blockade of KCa3.1 and TRPV4 significantly attenuated HBSM cells proliferation. Using confocal imaging and custom data analysis software, blockade of TRPV4 decreased the Ca2+ influx induced by 1-EBIO-mediated KCa3.1 activation. Double-labeled staining showed that KCa3.1 and TRPV4 channels colocalized in HBSM cells. These results demonstrate that KCa3.1 channels regulate the proliferation phenotype of HBSM cells via TRPV4 channels in the process of chronic asthma, making it a potential therapeutic target to treat chronic asthma.

  18. Efficacy of static stretching and proprioceptive neuromuscular facilitation stretch on hamstrings length after a single session.

    Science.gov (United States)

    O'Hora, John; Cartwright, Abigail; Wade, Clive D; Hough, Alan D; Shum, Gary L K

    2011-06-01

    A number of studies have investigated the efficacy of several repetitions of proprioceptive neuromuscular facilitation stretching (PNF) and static stretching (SS). However, there is limited research comparing the effects of a single bout of these stretching maneuvers. The aim of this study was to compare the effectiveness of a single bout of a therapist-applied 30-second SS vs. a single bout of therapist-applied 6-second hamstring (agonist) contract PNF. Forty-five healthy subjects between the ages of 21 and 35 were randomly allocated to 1 of the 2 stretching groups or a control group, in which no stretching was received. The flexibility of the hamstring was determined by a range of passive knee extension, measured using a universal goniometer, with the subject in the supine position and the hip at 90° flexion, before and after intervention. A significant increase in knee extension was found for both intervention groups after a single stretch (SS group = 7.53°, p < 0.01 and PNF group = 11.80°, p < 0.01). Both interventions resulted in a significantly greater increase in knee extension when compared to the control group (p < 0.01). The PNF group demonstrated significantly greater gains in knee extension compared to the SS group (mean difference 4.27°, p < 0.01). It can be concluded that a therapist applied SS or PNF results in a significant increase in hamstring flexibility. A hamstring (agonist) contract PNF is more effective than an SS in a single stretching session. These findings are important to physiotherapists or trainers working in clinical and sporting environments. Where in the past therapists may have spent time conducting multiple repetitions of a PNF and an SS, a single bout of either technique may be considered just as effective. A key component of the study methodology was the exclusion of a warm-up period before stretching. Therefore, the findings of efficacy of a single PNF are of particular relevance in sporting environments and busy clinical

  19. SHORT DURATIONS OF STATIC STRETCHING WHEN COMBINED WITH DYNAMIC STRETCHING DO NOT IMPAIR REPEATED SPRINTS AND AGILITY

    Directory of Open Access Journals (Sweden)

    Del P. Wong

    2011-06-01

    Full Text Available This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA and change of direction (COD. Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s. Three dynamic stretching exercises of 30 s duration were then performed (90 s total. Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p < 0.001. However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (< 90 s static stretching may not have provided sufficient stimulus to elicit performance impairments

  20. Cellular ATP release in the lung and airway

    Directory of Open Access Journals (Sweden)

    Satoru Ito

    2016-11-01

    Full Text Available Adenosine triphosphate (ATP is a universal energy source synthesized by mitochondrial oxidative phosphorylation and cytosolic glycolysis and transported by the vesicular nucleotide transporter for storage in secretory vesicles. Extracellular ATP regulates physiological functions and homeostasis of the respiratory system and is associated with pathogenesis of respiratory diseases. Thus, modulation of ATP and purinergic signaling may be a novel therapeutic approach to pulmonary disease. ATP is released from alveolar epithelial cells, airway epithelial cells, airway smooth muscle cells, fibroblasts and endothelial cells in response to various chemical and mechanical stimuli. In addition to conductive pathways such as connexins and pannexins, vesicular exocytosis is involved in the mechanisms of ATP release from the cells. Imaging approaches enable us to visualize ATP release from not only cultured cells but also lung tissue ex vivo. Extracellular vesicles, exosomes and membrane-derived microvesicles, containing cytoplasmic proteins, mRNA and microRNA, represent important mediators of cell-to-cell communication and the intercellular microenvironment. However, it is not known whether extracellular vesicles contain ATP as an intercellular messenger. Future studies are necessary to elucidate the mechanisms of cellular ATP release and purinergic signaling in the respiratory system.

  1. Improvised bubble continuous positive airway pressure (BCPAP ...

    African Journals Online (AJOL)

    Improvised bubble continuous positive airway pressure (BCPAP) device at the National Hospital Abuja gives immediate improvement in respiratory rate and oxygenation in neonates with respiratory distress.

  2. To Stretch and Search for Better Ways

    Science.gov (United States)

    Moore, John W.

    2000-06-01

    There's a lot to do to get each issue of this Journal ready for publication, and there's a lot that can go awry during that process. We the editorial staff do our utmost to make certain that each issue is the best it can possibly be, but, of necessity, a lot of our effort is focused on solving problems, correcting errors, and avoiding pitfalls. It is not surprising that we sometimes lose sight of the bigger picture--all of the things that came out as well as or better than we hoped they would. Therefore it gives us great pleasure when a reader applauds (and thereby rewards) our efforts. One such communication inspired this editorial. I have appreciated the extra effort put forward by the staff to make the Journal really come alive. The high quality of the Journal serves as an incentive to chemical educators to stretch and search for better ways to inspire our students. I fervently hope that we do encourage you "to stretch and search for better ways", not only to inspire students but in everything you do. Stretching and searching for better ways is what life, science, chemistry, and teaching are all about, and it is a wonderfully stimulating and exciting way to approach anything and everything. Sometimes, though, one's ability to stretch is akin to that of a rubber band exposed too long to sunlight. Change becomes a threat or a burden instead of an opportunity. This often happens in one area but not others, as in the case of someone doing original research but whose lecture notes are yellow with age, or someone who experiments with new teaching approaches but neglects the latest chemical discoveries. Whatever its manifestation, failure to stretch and search for better ways is a great loss, both for the individual directly involved and for others. Fortunately there are many who continually stretch and search, often in conjunction with JCE. For example, some time ago the Chair of the Board of Publication, Jerry Bell, challenged Journal readers to become Journal

  3. Optical stretching on chip with acoustophoretic prefocusing

    DEFF Research Database (Denmark)

    Khoury Arvelo, Maria; Laub Busk, L.; Bruus, Henrik

    2012-01-01

    prefocusing. This focusing mechanism aims for target particles to always ow in the correct height relative to the optical stretcher, and is induced by a piezo-electric ultrasound transducer attached underneath the chip and driven at a frequency leading to a vertical standing ultrasound wave...... in the microchannel. Trapping and manipulation is demonstrated for dielectric beads. In addition, we show trapping, manipulation and stretching of red blood cells and vesicles, whereby we extract the elastic properties of these objects. Our design points towards the construction of a low-cost, high-throughput lab-on-a-chip...

  4. Viscous flows stretching and shrinking of surfaces

    CERN Document Server

    Mehmood, Ahmer

    2017-01-01

    This authored monograph provides a detailed discussion of the boundary layer flow due to a moving plate. The topical focus lies on the 2- and 3-dimensional case, considering axially symmetric and unsteady flows. The author derives a criterion for the self-similar and non-similar flow, and the turbulent flow due to a stretching or shrinking sheet is also discussed. The target audience primarily comprises research experts in the field of boundary layer flow, but the book will also be beneficial for graduate students.

  5. Radial smoothing and closed orbit

    International Nuclear Information System (INIS)

    Burnod, L.; Cornacchia, M.; Wilson, E.

    1983-11-01

    A complete simulation leading to a description of one of the error curves must involve four phases: (1) random drawing of the six set-up points within a normal population having a standard deviation of 1.3 mm; (b) random drawing of the six vertices of the curve in the sextant mode within a normal population having a standard deviation of 1.2 mm. These vertices are to be set with respect to the axis of the error lunes, while this axis has as its origins the positions defined by the preceding drawing; (c) mathematical definition of six parabolic curves and their junctions. These latter may be curves with very slight curvatures, or segments of a straight line passing through the set-up point and having lengths no longer than one LSS. Thus one gets a mean curve for the absolute errors; (d) plotting of the actually observed radial positions with respect to the mean curve (results of smoothing)

  6. Evolution on a smooth landscape

    Science.gov (United States)

    Kessler, David A.; Levine, Herbert; Ridgway, Douglas; Tsimring, Lev

    1997-05-01

    We study in detail a recently proposed simple discrete model for evolution on smooth landscapes. An asymptotic solution of this model for long times is constructed. We find that the dynamics of the population is governed by correlation functions that although being formally down by powers of N (the population size), nonetheless control the evolution process after a very short transient. The long-time behavior can be found analytically since only one of these higher order correlators (the two-point function) is relevant. We compare and contrast the exact findings derived herein with a previously proposed phenomenological treatment employing mean-field theory supplemented with a cutoff at small population density. Finally, we relate our results to the recently studied case of mutation on a totally flat landscape.

  7. Mechanics of Vascular Smooth Muscle.

    Science.gov (United States)

    Ratz, Paul H

    2015-12-15

    Vascular smooth muscle (VSM; see Table 1 for a list of abbreviations) is a heterogeneous biomaterial comprised of cells and extracellular matrix. By surrounding tubes of endothelial cells, VSM forms a regulated network, the vasculature, through which oxygenated blood supplies specialized organs, permitting the development of large multicellular organisms. VSM cells, the engine of the vasculature, house a set of regulated nanomotors that permit rapid stress-development, sustained stress-maintenance and vessel constriction. Viscoelastic materials within, surrounding and attached to VSM cells, comprised largely of polymeric proteins with complex mechanical characteristics, assist the engine with countering loads imposed by the heart pump, and with control of relengthening after constriction. The complexity of this smart material can be reduced by classical mechanical studies combined with circuit modeling using spring and dashpot elements. Evaluation of the mechanical characteristics of VSM requires a more complete understanding of the mechanics and regulation of its biochemical parts, and ultimately, an understanding of how these parts work together to form the machinery of the vascular tree. Current molecular studies provide detailed mechanical data about single polymeric molecules, revealing viscoelasticity and plasticity at the protein domain level, the unique biological slip-catch bond, and a regulated two-step actomyosin power stroke. At the tissue level, new insight into acutely dynamic stress-strain behavior reveals smooth muscle to exhibit adaptive plasticity. At its core, physiology aims to describe the complex interactions of molecular systems, clarifying structure-function relationships and regulation of biological machines. The intent of this review is to provide a comprehensive presentation of one biomachine, VSM. Copyright © 2015 John Wiley & Sons, Inc.

  8. Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

    Science.gov (United States)

    Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

    2015-04-01

    Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-15

    some patients with asthma. - Highlights: • Nicotine from smoking impaired epithelial COX-2-mediated airway relaxation. • Nicotine's effects were at least partially mediated by α7-nicotinic receptors. • Kinin-receptor-mediated airway relaxations are mediated by EP2 receptors in mice. • Nicotine reduced mPGES-1 mRNA and protein expressions in airway smooth muscle. • Dexamethasone could not restore nicotine-impaired airway relaxations.

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

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    . - Highlights: • Nicotine from smoking impaired epithelial COX-2-mediated airway relaxation. • Nicotine's effects were at least partially mediated by α7-nicotinic receptors. • Kinin-receptor-mediated airway relaxations are mediated by EP2 receptors in mice. • Nicotine reduced mPGES-1 mRNA and protein expressions in airway smooth muscle. • Dexamethasone could not restore nicotine-impaired airway relaxations

  11. Protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland.

    Directory of Open Access Journals (Sweden)

    Hyun Jae Lee

    Full Text Available Protease-activated receptor 2 (PAR2, a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+-sensitive dye Fura2-AM was used to determine intracellular Ca(2+ concentration ([Ca(2+](i by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP elevated intracellular Ca(2+ and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+ and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+-dependent and cystic fibrosis transmembrane conductance regulator-independent.

  12. Twist-stretch profiles of DNA chains

    Science.gov (United States)

    Zoli, Marco

    2017-06-01

    Helical molecules change their twist number under the effect of a mechanical load. We study the twist-stretch relation for a set of short DNA molecules modeled by a mesoscopic Hamiltonian. Finite temperature path integral techniques are applied to generate a large ensemble of possible configurations for the base pairs of the sequence. The model also accounts for the bending and twisting fluctuations between adjacent base pairs along the molecules stack. Simulating a broad range of twisting conformation, we compute the helix structural parameters by averaging over the ensemble of base pairs configurations. The method selects, for any applied force, the average twist angle which minimizes the molecule’s free energy. It is found that the chains generally over-twist under an applied stretching and the over-twisting is physically associated to the contraction of the average helix diameter, i.e. to the damping of the base pair fluctuations. Instead, assuming that the maximum amplitude of the bending fluctuations may decrease against the external load, the DNA molecule first over-twists for weak applied forces and then untwists above a characteristic force value. Our results are discussed in relation to available experimental information albeit for kilo-base long molecules.

  13. Very smooth points of spaces of operators

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Our notation and terminology is standard and can be found in [HWW]. For a Banach space X by ∂eX1 we denote the set of extreme points. 2. Very smooth points. Let M ⊂ X be a closed subspace. It was observed in [MR] that if x ∈ M is a smooth point of X then it is a smooth point of M. It is easy to see that if every continuous.

  14. Smooth GERBS, orthogonal systems and energy minimization

    Energy Technology Data Exchange (ETDEWEB)

    Dechevsky, Lubomir T., E-mail: ltd@hin.no, E-mail: pza@hin.no; Zanaty, Peter, E-mail: ltd@hin.no, E-mail: pza@hin.no [Faculty of Technology, Narvik University College, 2 Lodve Lange' s St., P.O.Box 385, Narvik N-8505 (Norway)

    2013-12-18

    New results are obtained in three mutually related directions of the rapidly developing theory of generalized expo-rational B-splines (GERBS) [7, 6]: closed-form computability of C{sup ∞}-smooth GERBS in terms of elementary and special functions, Hermite interpolation and least-squares best approximation via smooth GERBS, energy minimizing properties of smooth GERBS similar to those of the classical cubic polynomial B-splines.

  15. Smoothed analysis of complex conic condition numbers

    OpenAIRE

    Buergisser, Peter; Cucker, Felipe; Lotz, Martin

    2006-01-01

    Smoothed analysis of complexity bounds and condition numbers has been done, so far, on a case by case basis. In this paper we consider a reasonably large class of condition numbers for problems over the complex numbers and we obtain smoothed analysis estimates for elements in this class depending only on geometric invariants of the corresponding sets of ill-posed inputs. These estimates are for a version of smoothed analysis proposed in this paper which, to the best of our knowledge, appears ...

  16. Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Kang, Ji Young; Jo, Mi Ran; Kang, Hyeon Hui; Kim, Sung Kyoung; Kim, Myoung Sook; Kim, Yong Hyun; Kim, Seok Chan; Kwon, Soon Seog; Lee, Sook Young; Kim, Jin Woo

    2016-02-01

    We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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

  18. Income and Consumption Smoothing among US States

    DEFF Research Database (Denmark)

    Sørensen, Bent; Yosha, Oved

    within regions but not between regions. This suggests that capital markets transcend regional barriers while credit markets are regional in their nature. Smoothing within the club of rich states is accomplished mainly via capital markets whereas consumption smoothing is dominant within the club of poor...... states. The fraction of a shock to gross state products smoothed by the federal tax-transfer system is the same for various regions and other clubs of states. We calculate the scope for consumption smoothing within various regions and clubs, finding that most gains from risk sharing can be achieved...

  19. IMAGE-BASED IN VIVO QUANTITATIVE ASSESSMENT OF HUMAN AIRWAY OPENING AND CONTRACTILITY BY FIBER OPTICAL NASOPHARYNGOSCOPY IN HEALTHY AND ASTHMATIC SUBJECTS

    Directory of Open Access Journals (Sweden)

    LINHONG DENG

    2013-04-01

    Full Text Available Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD. Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could

  20. Effects of stretching the scalene muscles on slow vital capacity.

    Science.gov (United States)

    Lee, Juncheol; Hwang, Sehee; Han, Seungim; Han, Dongwook

    2016-06-01

    [Purpose] The purpose of this study was to examine whether stretching of the scalene muscles would improve slow vital capacity (SVC). [Subjects and Methods] The subjects of this study were 20 healthy female students to whom the study's methods and purpose were explained and their agreement for participation was obtained. The SVC was measured using spirometry (Pony FX, COSMED Inc., Italy). The intervention used was stretching of the scalene muscles. Stretching was carried out for 15 min, 10 times at per each portion of scalene muscles: the anterior, middle, and posterior parts. [Results] Expiratory vital capacity (EVC) and tidal volume (Vt) noticeably increased after stretching. However, there were no changes in any of the SVC items in the control group. [Conclusion] This study demonstrated that stretching of the scalene muscles can effectively improve SVC. In particular, we confirmed that stretching of the scalene muscles was effective in increasing EVC and Vt, which are items of SVC.

  1. Mechanical stretch influence on lifetime of dielectric elastomer films

    Science.gov (United States)

    Iannarelli, A.; Niasar, M. Ghaffarian

    2017-04-01

    Film pre-stretching is a widely adopted solution to improve dielectric strength of the DEA systems. However, to date, long term reliability of this solution has not been investigated. In this work it is explored how the dielectric elastomer lifetime is affected by film pre-stretching. The dielectric loss of soft polydimethylsiloxane (PDMS) films is studied for different stretch ratios by measuring tanδ. Additionally, time-to-breakdown was measured at DC electric stress for different stretch ratios. For this purpose, accelerated life test (ALT) were performed. The results obtained are compared with non-pre-stretched samples. This study suggests that no additional dielectric losses are caused by film stretching up to 80% of original dimensions.

  2. Teaching consultants airway management skills.

    Science.gov (United States)

    Nargozian, Charles

    2004-01-01

    Airway management skills are integral to the practice of anaesthesiology and also to the practice of emergency medicine and allied health professions such as respiratory care, emergency medical technology, and emergency and critical care nursing. The basic information to be taught is the same but the level of detail will vary depending on the audience. The learning process usually involves progression from didactic lessons to skills training on inanimate models to supervised clinical practice. Modalities that may be used for skills training include cadavers, recently dead patients, videotapes, mannequins, simulators and virtual reality trainers. To maintain knowledge and skills, review and possible retraining should be conducted on an approximately annual basis.

  3. Airway management: induced tension pneumoperitoneum.

    Science.gov (United States)

    Ahmed, Khedher; Amine, El Ghali Mohamed; Abdelbaki, Azouzi; Jihene, Ayachi; Khaoula, Meddeb; Yamina, Hamdaoui; Mohamed, Boussarsar

    2016-01-01

    Pneumoperitoneum is not always associated with hollow viscus perforation. Such condition is called non-surgical or spontaneous pneumoperitoneum. Intrathoracic causes remain the most frequently reported mechanism inducing this potentially life threatening complication. This clinical condition is associated with therapeutic dilemma. We report a case of a massive isolated pneumoperitoneum causing acute abdominal hypertension syndrome, in a 75 year female, which occurred after difficult airway management and mechanical ventilation. Emergent laparotomy yielded to full recovery. The recognition of such cases for whom surgical management can be avoided is primordial to avoid unnecessary laparotomy and its associated morbidity particularly in the critically ill.

  4. Native Small Airways Secrete Bicarbonate

    OpenAIRE

    Shamsuddin, A. K. M.; Quinton, Paul M.

    2014-01-01

    Since the discovery of Cl− impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl− transport. However, loss of bicarbonate (HCO3−) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3− transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3− secretion in small airways, the principle site of morbidi...

  5. Airway management in spontaneously breathing anaesthetized children: comparison of the Laryngeal Mask Airway with the cuffed oropharyngeal airway.

    Science.gov (United States)

    Mamaya, Biruta

    2002-06-01

    The efficacy and safety of the smallest size of the cuffed oropharyngeal airway (COPA) for school age, spontaneously breathing children was investigated and compared with the Laryngeal Mask Airway (LMA). Seventy children of school age (7-16 years) were divided into two groups: the COPA (n=35) and the LMA (n=35). Induction was with propofol i.v. or halothane, nitrous oxide, oxygen and fentanyl. After depression of laryngopharyngeal reflexes, a COPA size 8 cm or an LMA was inserted. Ventilation was manually assisted until spontaneous breathing was established. For maintenance, propofol i.v. and fentanyl or halothane with nitrous oxide were used. Local anaesthesia or peripheral blocks were also used. Both extratracheal airways had a highly successful insertion rate, but more positional manoeuvres to achieve a satisfactory airway were required with the COPA, 28.6% versus LMA 2.9%. The need to change the method of airway management was higher (8.6%) in the COPA group. After induction, the need for assisted ventilation was higher in the LMA group 54.3% versus 20% in the COPA group. Airway reaction to cuff inflation was higher in the LMA group 14.3% versus COPA 5.7%. Problems during surgery were similar, except continuous chin support to establish an effective airway was more frequent (11.4%) in the COPA group. In the postoperative period, blood on the device and incidence of sore throat were detected less in the COPA group. The COPA is a good extratracheal airway that provides new possibilities for airway management in school age children with an adequate and well sealed airway, during spontaneous breathing or during short-term assisted manual ventilation.

  6. Proprioceptive neuromuscular facilitation stretching : mechanisms and clinical implications.

    Science.gov (United States)

    Sharman, Melanie J; Cresswell, Andrew G; Riek, Stephan

    2006-01-01

    Proprioceptive neuromuscular facilitation (PNF) stretching techniques are commonly used in the athletic and clinical environments to enhance both active and passive range of motion (ROM) with a view to optimising motor performance and rehabilitation. PNF stretching is positioned in the literature as the most effective stretching technique when the aim is to increase ROM, particularly in respect to short-term changes in ROM. With due consideration of the heterogeneity across the applied PNF stretching research, a summary of the findings suggests that an 'active' PNF stretching technique achieves the greatest gains in ROM, e.g. utilising a shortening contraction of the opposing muscle to place the target muscle on stretch, followed by a static contraction of the target muscle. The inclusion of a shortening contraction of the opposing muscle appears to have the greatest impact on enhancing ROM. When including a static contraction of the target muscle, this needs to be held for approximately 3 seconds at no more than 20% of a maximum voluntary contraction. The greatest changes in ROM generally occur after the first repetition and in order to achieve more lasting changes in ROM, PNF stretching needs to be performed once or twice per week. The superior changes in ROM that PNF stretching often produces compared with other stretching techniques has traditionally been attributed to autogenic and/or reciprocal inhibition, although the literature does not support this hypothesis. Instead, and in the absence of a biomechanical explanation, the contemporary view proposes that PNF stretching influences the point at which stretch is perceived or tolerated. The mechanism(s) underpinning the change in stretch perception or tolerance are not known, although pain modulation has been suggested.

  7. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB

    Directory of Open Access Journals (Sweden)

    Wang-Jian Zha

    2013-01-01

    Full Text Available Persistent activation of nuclear factor κB (NF-κB has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA- induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL- 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1 levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

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

    Directory of Open Access Journals (Sweden)

    Haahtela Tari

    2006-11-01

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

  9. Bronchology Treatment Of The Malignant Airway Stenosis

    International Nuclear Information System (INIS)

    Slivka, R. et al

    2007-01-01

    Central airway stenosis is benign or malignant etiology. Multidiscplinary approach is useful in treatment central airway stenosis. In inoperable cases, interventional bronchology is good therapeutic alternative. We can use NdYAG laser, argon plasma coagulation, elektrocautery, cryotherapy, photodynamic therapy and stents for obstruction release. In malignant stenosis, we combine often methods of the interventional bronchology with brachytherapy, chemotherapy and external radiotherapy. (author)

  10. Correlation between structure and conductivity in stretched Nafion

    Science.gov (United States)

    Allahyarov, Elshad; Taylor, Philip

    2008-03-01

    We have used coarse-grained simulation methods to investigate the effect of stretching-induced structure orientation on the proton conductivity of Nafion-like polyelectrolyte membranes. Recent experimental data on the morphology of ionomers describe Nafion as an aggregation of polymeric backbone chains forming elongated objects embedded in a continuous ionic medium. Uniaxial stretching of a recast Nafion film causes a preferential orientation of these objects in the direction of stretching. Our simulations of humid Nafion show that this has a strong effect on the proton conductivity, which is enhanced along the stretching direction, while the conductivity perpendicular to the stretched polymer backbone is strongly reduced. Stretching also causes the perfluorinated side chains to orient perpendicular to the stretching axis. The sulphonate multiplets shrink in diameter as the stretching is increased and show a spatially periodic ordering in their distribution. This in turn affects the distribution of contained water at low water contents. The water forms a continuous network with narrow bridges between small water clusters absorbed in head-group multiplets. We find the morphological changes in the stretched Nafion to be retained upon removal of the uniaxial stress.

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

    Science.gov (United States)

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

    2015-07-01

    Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. We developed a quality improvement program-the Difficult Airway Response Team (DART)-to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had 3 core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a Web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index >40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous or current tracheostomy. Twenty

  12. Video laryngoscopes and the obstetric airway.

    Science.gov (United States)

    Scott-Brown, S; Russell, R

    2015-05-01

    The pitfalls surrounding securing the airway in the obstetric patient are well documented. From Tunstall's original failed intubation drill onwards, there has been progress both in recognition of the difficulties of airway management in the pregnant patient and development of algorithms to enhance patient safety. Current trends in obstetric anaesthesia have resulted in a significant decrease in exposure of anaesthetists, especially trainees, to caesarean section under general anaesthesia, compounding the difficulties in safely managing the airway. Video laryngoscopes have recently appeared in airway algorithms. They improve glottic visualisation and are useful in the management of the difficult non-obstetric airway, including those in morbidly obese patients and in the setting of a rapid-sequence induction. There is growing interest in the potential use of video laryngoscopes in the obstetric population and as a teaching tool to maximise training opportunities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Local Transfer Coefficient, Smooth Channel

    Directory of Open Access Journals (Sweden)

    R. T. Kukreja

    1998-01-01

    Full Text Available Naphthalene sublimation technique and the heat/mass transfer analogy are used to determine the detailed local heat/mass transfer distributions on the leading and trailing walls of a twopass square channel with smooth walls that rotates about a perpendicular axis. Since the variation of density is small in the flow through the channel, buoyancy effect is negligible. Results show that, in both the stationary and rotating channel cases, very large spanwise variations of the mass transfer exist in he turn and in the region immediately downstream of the turn in the second straight pass. In the first straight pass, the rotation-induced Coriolis forces reduce the mass transfer on the leading wall and increase the mass transfer on the trailing wall. In the turn, rotation significantly increases the mass transfer on the leading wall, especially in the upstream half of the turn. Rotation also increases the mass transfer on the trailing wall, more in the downstream half of the turn than in the upstream half of the turn. Immediately downstream of the turn, rotation causes the mass transfer to be much higher on the trailing wall near the downstream corner of the tip of the inner wall than on the opposite leading wall. The mass transfer in the second pass is higher on the leading wall than on the trailing wall. A slower flow causes higher mass transfer enhancement in the turn on both the leading and trailing walls.

  14. Excitation of Mytilus smooth muscle.

    Science.gov (United States)

    Twarog, B M

    1967-10-01

    1. Membrane potentials and tension were recorded during nerve stimulation and direct stimulation of smooth muscle cells of the anterior byssus retractor muscle of Mytilus edulis L.2. The resting potential averaged 65 mV (range 55-72 mV).3. Junction potentials reached 25 mV and decayed to one half maximum amplitude in 500 msec. Spatial summation and facilitation of junction potentials were observed.4. Action potentials, 50 msec in duration and up to 50 mV in amplitude were fired at a membrane potential of 35-40 mV. No overshoot was observed.5. Contraction in response to neural stimulation was associated with spike discharge. Measurement of tension and depolarization in muscle bundles at high K(+) indicated that tension is only produced at membrane potentials similar to those achieved by spike discharge.6. Blocking of junction potentials, spike discharge and contraction by methantheline, an acetylcholine antagonist, supports the hypothesis that the muscle is excited by cholinergic nerves. However, evidence of a presynaptic action of methantheline complicates this argument.

  15. Smooth horizons and quantum ripples

    International Nuclear Information System (INIS)

    Golovnev, Alexey

    2015-01-01

    Black holes are unique objects which allow for meaningful theoretical studies of strong gravity and even quantum gravity effects. An infalling and a distant observer would have very different views on the structure of the world. However, a careful analysis has shown that it entails no genuine contradictions for physics, and the paradigm of observer complementarity has been coined. Recently this picture was put into doubt. In particular, it was argued that in old black holes a firewall must form in order to protect the basic principles of quantum mechanics. This AMPS paradox has already been discussed in a vast number of papers with different attitudes and conclusions. Here we want to argue that a possible source of confusion is the neglect of quantum gravity effects. Contrary to widespread perception, it does not necessarily mean that effective field theory is inapplicable in rather smooth neighbourhoods of large black hole horizons. The real offender might be an attempt to consistently use it over the huge distances from the near-horizon zone of old black holes to the early radiation. We give simple estimates to support this viewpoint and show how the Page time and (somewhat more speculative) scrambling time do appear. (orig.)

  16. [Laryngeal tube II : alternative airway for children?].

    Science.gov (United States)

    Schalk, R; Scheller, B; Peter, N; Rosskopf, W; Byhahn, C; Zacharowski, K; Meininger, D

    2011-06-01

    Difficult airway situations both expected and unexpected, present major challenges to every anesthesiologist, especially in pediatric anesthesia. However, the integration of extraglottic airway devices, such as the laryngeal mask, into the algorithm of difficult airways has improved the handling of difficult airway situations. A device for establishing a supraglottic airway, the laryngeal tube (LT), was introduced in 1999. The LT is an extraglottic airway designed to secure a patent airway during either spontaneous breathing or controlled ventilation. The design of the device has been revised several times and a further development is the LTS II/LTS-D, which provides an additional channel for the insertion of a gastric drain tube. This article reports on the successful use of the LTS II in 12 children aged from 2 days to 6 years when endotracheal intubation, alternative mask or laryngeal mask ventilation failed. Use of the LTS II was associated with a high level of success, securing the airway when other techniques had failed. The potential advantage of the LTS II over the standard LT is an additional suction port, which allows gastric tube placement and can be used as an indirect indicator of correct placement. With a modified insertion technique using an Esmarch manoeuvre, placement was simple and fast to perform. In emergency situations when direct laryngoscopy fails or is too time-consuming the LTS II tube is recommended as an alternative device to secure the airway. As with all extraglottic airway devices, familiarity and clinical experience with the respective device and the corresponding insertion technique are essential for safe and successful use, especially in emergency situations.

  17. Effects of contract-relax vs static stretching on stretch-induced strength loss and length-tension relationship

    DEFF Research Database (Denmark)

    Balle, S S; Magnusson, S P; McHugh, M P

    2015-01-01

    The purpose of this study was to determine the acute effects of contract-relax stretching (CRS) vs static stretching (SS) on strength loss and the length-tension relationship. We hypothesized that there would be a greater muscle length-specific effect of CRS vs SS. Isometric hamstring strength...... loss compared with SS. These results support the use of SS for stretching the hamstrings....

  18. EFFECTIVENESS OF PNF STRETCHING VERSUS STATIC STRETCHING ON PAIN AND HAMSTRING FLEXIBILITY FOLLOWING MOIST HEAT IN INDIVIDUALS WITH KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Meena .V

    2016-10-01

    Full Text Available Background: Osteoarthritis (OA is a degenerative joint disease and one of the major public health problem that causesfunctional impairment and reduced quality of life. To compare the effectiveness of PNF Hold relax stretching versus Static stretching on pain and flexibility of hamstring following moist heat in individuals with knee osteoarthritis. Hamstring tightness is the major problem in knee osteoarthritis individuals. Therefore the need of study is comparing the effectiveness of PNF Hold relax stretching versus static stretching on pain and flexibility of hamstrings following moist heat in knee osteoarthritis participants. Determining the effects of PNF Hold relax stretching versus Static stretching along with moist heat on pain and hamstring flexibility by VAS and Active knee extension range of motion in knee osteoarthritis individuals. Methods: 30 subjects with symptoms of knee osteoarthritis were randomly distributed into 2 groups 15 in each group. PNF Hold relax stretching along with moist heat is compared to Static stretching along with moist heat. Pain was measured by Visual Analogue Scale (VAS and hamstring flexibility by Active knee Extension Range of Motion (AKEROM by universal goniometer. Measurements are taken pre and post intervention. Results: The results indicated PNF Hold relax stretching along with moist heat showed a statistically significant improvement in pain (p<0.05 and improvement in hamstring flexibility (p<0.05 when compared to Static stretching along with moist heat. Conclusion: Subjects with PNF Hold relax stretching along with moist heat showed significant improvement in pain reduction and improving hamstring flexibility than Static stretching along with moist heat.

  19. The effect of warm-up, static stretching and dynamic stretching on hamstring flexibility in previously injured subjects

    OpenAIRE

    O'Sullivan, Kieran; Murray, Elaine; Sainsbury, David

    2009-01-01

    Abstract Background Warm-up and stretching are suggested to increase hamstring flexibility and reduce the risk of injury. This study examined the short-term effects of warm-up, static stretching and dynamic stretching on hamstring flexibility in individuals with previous hamstring injury and uninjured controls. Methods A randomised crossover study design, over 2 separate days. Hamstring flexibility was assessed using passive knee extension range of motion (PKE ROM). 18 previously injured indi...

  20. LABOR GYMNASTICS: STRETCHING EXERCISE X FLEXIONAMENT

    Directory of Open Access Journals (Sweden)

    Jacqueline Amorin Anchieta Borges da Silva, Isabel Cristina Taranto e Fernanda Piasecki

    2006-12-01

    Full Text Available Nowadays, there are many opportunities for the society to live a healthful and long life. At the same time, never people was so sedentary and without harmony. Without a healthy body and with “an occupied mind” the human loses exactly what more it needs: the disposal to produce, to coexist and to live a good life. In this context, the present research aimed to revise some terms related to labor gymnastics, which is focused in the prevention of risks related to hours of working and in the reduction of muscular tension levels that may be originated during a day of work. Thus, the present study will make a differentiation between the use of stretching and flexionament during labor gymnastic sessions.

  1. Stretched Lens Array Photovoltaic Concentrator Technology Developed

    Science.gov (United States)

    Piszczor, Michael F., Jr.; O'Neill, Mark J.

    2004-01-01

    Solar arrays have been and continue to be the mainstay in providing power to nearly all commercial and government spacecraft. Light from the Sun is directly converted into electrical energy using solar cells. One way to reduce the cost of future space power systems is by minimizing the size and number of expensive solar cells by focusing the sunlight onto smaller cells using concentrator optics. The stretched lens array (SLA) is a unique concept that uses arched Fresnel lens concentrators to focus sunlight onto a line of high-efficiency solar cells located directly beneath. The SLA concept is based on the Solar Concentrator Array with Refractive Linear Element Technology (SCARLET) design that was used on NASA's New Millennium Deep Space 1 mission. The highly successful asteroid/comet rendezvous mission (1998 to 2001) demonstrated the performance and long-term durability of the SCARLET/SLA solar array design and set the foundation for further improvements to optimize its performance.

  2. Aerothermodynamic properties of stretched flames in enclosures

    Science.gov (United States)

    Rotman, D. A.; Oppenheim, A. K.

    Flames are stretched by being pulled along their frontal surface by the flow field in which they reside. Their trajectories tend to approach particle paths, acquiring eventually the role of contact boundaries, -interfaces between the burnt and unburnt medium that may broaden solely as a consequence of diffusion. Fundamental properties of flow fields governing such flames are determined here on the basis of the zero Mach number model, providng a rational method of approach to the computational analysis of combustion fields in enclosures where, besides the aerodynamic properties flow, the thermodynamic process of compression must be taken into account. To illustrate its application, the method is used to reveal the mechanism of formation of a tulip-shape flame in a rectangular enclosure under nonturbulent flow conditions.

  3. Very smooth points of spaces of operators

    Indian Academy of Sciences (India)

    Home; Journals; Proceedings – Mathematical Sciences; Volume 113; Issue 1 ... We show that when the space of compact operators is an -ideal in the space of bounded operators, a very smooth operator attains its norm at a unique vector (up to a constant multiple) and ( ) is a very smooth point of the range space.

  4. Adams operations in smooth K-theory

    OpenAIRE

    Bunke, Ulrich

    2009-01-01

    We show that the Adams operations in complex K-theory lift to operations in smooth K-theory. The main result is a Riemann-Roch type theorem about the compatibility of the Adams operations and the integration in smooth K-theory.

  5. Smoothed Analysis of Local Search Algorithms

    NARCIS (Netherlands)

    Manthey, Bodo; Dehne, Frank; Sack, Jörg-Rüdiger; Stege, Ulrike

    2015-01-01

    Smoothed analysis is a method for analyzing the performance of algorithms for which classical worst-case analysis fails to explain the performance observed in practice. Smoothed analysis has been applied to explain the performance of a variety of algorithms in the last years. One particular class of

  6. Effect of Perinatal secondhand tobacco smoke exposure on in vivo and intrinsic airway structure/function in non-human primates

    International Nuclear Information System (INIS)

    Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.; Peake, Janice L.; Pinkerton, Kent E.

    2009-01-01

    Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in responsiveness. Pregnant rhesus monkeys were exposed to filtered air (FA) or SHS (1 mg/m 3 total suspended particulates) for 6 h/day, 5 days/week starting at 50 days gestational age. The mother/infant pairs continued the SHS exposures postnatally. At 3 months of age each infant: 1) had in vivo lung function measurements in response to inhaled methacholine, or 2) the right accessory lobe filled with agarose, precision-cut to 600 μm slices, and bathed in increasing concentrations of methacholine. The lumenal area of the central airway was determined using videomicrometry followed by fixation and histology with morphometry. In vivo tests showed that perinatal SHS increases baseline respiratory rate and decreases responsiveness to methacholine. Perinatal SHS did not alter intrinsic airway responsiveness in the bronchi. However in respiratory bronchioles, SHS exposure increased airway responsiveness at lower methacholine concentrations but decreased it at higher concentrations. Perinatal SHS did not change eosinophil profiles, epithelial volume, smooth muscle volume, or mucin volume. However it did increase the number of alveolar attachments in bronchi and respiratory bronchioles. In general, as mucin increased, airway responsiveness decreased. We conclude that perinatal SHS exposure alters in vivo and intrinsic airway responsiveness, and alveolar attachments

  7. Smoothing a Piecewise-Smooth: An Example from Plankton Population Dynamics

    DEFF Research Database (Denmark)

    Piltz, Sofia Helena

    2016-01-01

    In this work we discuss a piecewise-smooth dynamical system inspired by plankton observations and constructed for one predator switching its diet between two different types of prey. We then discuss two smooth formulations of the piecewise-smooth model obtained by using a hyperbolic tangent funct...

  8. Electroforesis of Whey and Stretching Water Protein of Mozzarella Cheese Production from Factorial Experimental of Coagulation and Stretching Temperature

    Directory of Open Access Journals (Sweden)

    Purwadi Purwadi

    2012-02-01

    Full Text Available The use of lime juice as acidifier in the making of Mozzarella cheese was aimed to learn the protein profile of whey and stretching water produced with treatment of coagulation and stretching temperature. The treatment of coagulation temperature was G1 = 30oC, G2 = 35oC, G3 = 40oC, and G4 = 45oC, and the treatment of stretching temperature was M1 = 70oC, M2 = 75oC, M3 = 80oC, and M4 = 85oC. The research result showed that coagulation temperature of 30 and 35 oC gave the same protein profile of whey as well as coagulation temperature of 40 and 45oC, while coagulation temperature of 30 and 35oC with coagulation temperatur of 40 and 45oC gave different protein profile of whey. Different coagulation temperature gave different protein profile of whey and stretching water, while different stretching temperature gave the same protein profile of stretching water. Coagulation temperature of 30 and 35oC gave the same protein profile of stretching water as well as coagulation temperature of 40 and 45oC, while coagulation temperature of 30 and 35oC with temperature of 40 and 45oC gave different protein profile of stretching water. Keywords: protein profile, Mozzarella cheese, coagulation temperature, stretching temperature

  9. EFFICACY OF MODIFIED PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION STRETCHING WITH CRYOTHERAPY OVER MANUAL PASSIVE STRETCHING WITH CRYOTHERAPY ON HAMSTRING FLEXIBILITY

    Directory of Open Access Journals (Sweden)

    Shamik Bhattacharjee

    2016-04-01

    Full Text Available Background: Healthy individuals, to ease and accomplish their activities of daily living they need flexible body without any tightness in the muscles, particularly those used for a definite function. Cooling soft tissues in a lengthened position after stretching has been shown to promote more lasting increases in soft tissue length and minimize post stretch muscle soreness. There are less documented studies which compared modified proprioceptive neuromuscular facilitation (PNF stretch over passive manual stretch with cold application commonly after the interventions. Methods: Thirty high school going healthy students were divided into two groups- Group I received Passive Manual stretching (n=15 and Group II received modified PNF stretching (n=15 and both groups received cold application after the interventions for 10 minutes commonly for 5 days. ROM was taken on day 1, day 5 and day 7. Results: After day 7, Group II with Modified PNF stretching along with cold application showed a significant increase in range of motion tested with active knee extension test (AKET. Conclusion: Modified PNF stretching is considered to be the effective intervention in increasing and maintaining ROM in AKET over passive manual stretching with cold applications commonly after the interventions.

  10. Immediate Effects of Proprioceptive Neuromuscular Facilitation Stretching Programs Compared With Passive Stretching Programs for Hamstring Flexibility: A Critically Appraised Topic.

    Science.gov (United States)

    Hill, Kristian J; Robinson, Kendall P; Cuchna, Jennifer W; Hoch, Matthew C

    2017-11-01

    Clinical Scenario: Increasing hamstring flexibility through clinical stretching interventions may be an effective means to prevent hamstring injuries. However the most effective method to increase hamstring flexibility has yet to be determined. For a healthy individual, are proprioceptive neuromuscular facilitation (PNF) stretching programs more effective in immediately improving hamstring flexibility when compared with static stretching programs? Summary of Key Findings: A thorough literature search returned 195 possible studies; 5 studies met the inclusion criteria and were included. Current evidence supports the use of PNF stretching or static stretching programs for increasing hamstring flexibility. However, neither program demonstrated superior effectiveness when examining immediate increases in hamstring flexibility. Clinical Bottom Line: There were consistent findings from multiple low-quality studies that indicate there is no difference in the immediate improvements in hamstring flexibility when comparing PNF stretching programs to static stretching programs in physically active adults. Strength of Recommendation: Grade B evidence exists that PNF and static stretching programs equally increase hamstring flexibility immediately following the stretching program.

  11. Effects of acute stretching on the maximal expression of strength ...

    African Journals Online (AJOL)

    This study compared the effects of four treatments (n = 12 each) [10 minutes of quiet sitting, without stretching (NS); two minutes warm up on an arm ergometer at 25 watts resistance (WU); 10 second-hold static stretching (each) of the shoulder, chest and arm muscle groups (ST10); and two sets of 20 second-hold static ...

  12. The stretch reflex and the contributions of C David Marsden.

    Science.gov (United States)

    Bhattacharyya, Kalyan B

    2017-01-01

    The stretch reflex or myotatic reflex refers to the contraction of a muscle in response to its passive stretching by increasing its contractility as long as the stretch is within physiological limits. For ages, it was thought that the stretch reflex was of short latency and it was synonymous with the tendon reflex, subserving the same spinal reflex arc. However, disparities in the status of the two reflexes in certain clinical situations led Marsden and his collaborators to carry out a series of experiments that helped to establish that the two reflexes had different pathways. That the two reflexes are dissociated has been proved by the fact that the stretch reflex and the tendon reflex, elicited by stimulation of the same muscle, have different latencies, that of the stretch reflex being considerably longer. They hypothesized that the stretch reflex had a transcortical course before it reached the spinal motor neurons for final firing. Additionally, the phenomenon of stimulus-sensitive cortical myoclonus lent further evidence to the presence of the transcortical loop where the EEG correlate preceded the EMG discharge. This concept has been worked out by later neurologists in great detail, and the general consensus is that indeed, the stretch reflex is endowed with a conspicuous transcortical component.

  13. Chaperones in Polyglutamine Aggregation : Beyond the Q-Stretch

    NARCIS (Netherlands)

    Kuiper, E. F. E.; de Mattos, Eduardo P.; Jardim, Laura B.; Kampinga, Harm H.; Bergink, Steven

    2017-01-01

    Expanded polyglutamine (polyQ) stretches in at least nine unrelated proteins lead to inherited neuronal dysfunction and degeneration. The expansion size in all diseases correlates with age at onset (AO) of disease and with polyQ protein aggregation, indicating that the expanded polyQ stretch is the

  14. Stretched exponential relaxation and ac universality in disordered dielectrics

    DEFF Research Database (Denmark)

    Milovanov, Alexander V.; Rypdal, Kristoffer; Juul Rasmussen, Jens

    2007-01-01

    are stretched exponential character of dielectric relaxation, power-law power spectral density, and anomalous dependence of ac conduction coefficient on frequency. We propose a self-consistent model of dielectric relaxation in which the relaxations are described by a stretched exponential decay function...

  15. Time and direction preparation of the long latency stretch reflex.

    Science.gov (United States)

    Nikaido, Yasutaka; Hatanaka, Ryota; Jono, Yasutomo; Nomura, Yoshifumi; Tani, Keisuke; Chujo, Yuta; Hiraoka, Koichi

    2016-06-01

    This study investigated time and direction preparation of motor response to force load while intending to maintain the finger at the initial neutral position. Force load extending or flexing the index finger was given while healthy humans intended to maintain the index finger at the initial neutral position. Electromyographic activity was recorded from the first dorsal interosseous muscle. A precue with or without advanced information regarding the direction of the forthcoming force load was given 1000ms before force load. Trials without the precue were inserted between the precued trials. A long latency stretch reflex was elicited by force load regardless of its direction, indicating that the long latency stretch reflex is elicited not only by muscle stretch afferents, but also by direction-insensitive sensations. Time preparation of motor response to either direction of force load enhanced the long latency stretch reflex, indicating that time preparation is not mediated by afferent discharge of muscle stretch. Direction preparation enhanced the long latency stretch reflex and increased corticospinal excitability 0-20ms after force load when force load was given in the direction stretching the muscle. These enhancements must be induced by preset of the afferent pathway mediating segmental stretch reflex. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The stretch reflex and the contributions of C David Marsden

    Directory of Open Access Journals (Sweden)

    Kalyan B Bhattacharyya

    2017-01-01

    Full Text Available The stretch reflex or myotatic reflex refers to the contraction of a muscle in response to its passive stretching by increasing its contractility as long as the stretch is within physiological limits. For ages, it was thought that the stretch reflex was of short latency and it was synonymous with the tendon reflex, subserving the same spinal reflex arc. However, disparities in the status of the two reflexes in certain clinical situations led Marsden and his collaborators to carry out a series of experiments that helped to establish that the two reflexes had different pathways. That the two reflexes are dissociated has been proved by the fact that the stretch reflex and the tendon reflex, elicited by stimulation of the same muscle, have different latencies, that of the stretch reflex being considerably longer. They hypothesized that the stretch reflex had a transcortical course before it reached the spinal motor neurons for final firing. Additionally, the phenomenon of stimulus-sensitive cortical myoclonus lent further evidence to the presence of the transcortical loop where the EEG correlate preceded the EMG discharge. This concept has been worked out by later neurologists in great detail , and the general consensus is that indeed, the stretch reflex is endowed with a conspicuous transcortical component.

  17. Transparent conducting film: Effect of mechanical stretching to ...

    Indian Academy of Sciences (India)

    We describe in this paper a transparent conducting film (TCF). It is a fibrous layer of multiwalled carbon nanotubes (MWNTs), labeled a dilute CNT mat, that was prepared and unidirectionally stretched to improve both the optical and electrical properties. After stretching by 80% strain, transmittance at 550 nm wavelength ...

  18. The effects of acute self myofascial release (MFR) and stretching ...

    African Journals Online (AJOL)

    Baseline measurements were taken initially and then participants were randomly divided into four groups (control [n=10, static stretching [n=10], dynamic stretching [n=10] and self MFR [n=10]). Each group performed a 60-minute intervention. During the intervention programme the various groups took part in prescribed ...

  19. Transparent conducting film: Effect of mechanical stretching to ...

    Indian Academy of Sciences (India)

    Administrator

    The number of pixels inside a rectangle counted on the Adobe Photoshop. Figure 6. Sheet resistance and transmittance at 550 nm wave- length of a dilute CNT mat before and after stretch. Five sam- ples were stretched by 40 and 110% strain respectively and average data is shown in each case. A polyurethane elastomer.

  20. Does Postexercise Static Stretching Alleviate Delayed Muscle Soreness?

    Science.gov (United States)

    Buroker, Katherine C.; Schwane, James A.

    1989-01-01

    Because many experts recommend stretching after exercise to relieve muscle soreness, 23 subjects performed a 30-minute step test to induce delayed muscle soreness. There was neither temporary relief of pain immediately after stretching nor a reduction in pain during the 3-day postexercise period. (Author/SM)

  1. Mechanical stretch influence on lifetime of dielectric elastomer films

    NARCIS (Netherlands)

    Iannarelli, A.; Ghaffarian Niasar, M.; Bar-Cohen, Yoseph

    2017-01-01

    Film pre-stretching is a widely adopted solution to improve dielectric strength of the DEA systems. However, to date, long term reliability of this solution has not been investigated. In this work it is explored how the dielectric elastomer lifetime is affected by film pre-stretching. The dielectric

  2. Post-extubation airway obstruction. Literature review

    Directory of Open Access Journals (Sweden)

    Álvaro SÁNCHEZ-TABERNERO

    2017-03-01

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

  3. Color analysis of the human airway wall

    Science.gov (United States)

    Gopalakrishnan, Deepa; McLennan, Geoffrey; Donnelley, Martin; Delsing, Angela; Suter, Melissa; Flaherty, Dawn; Zabner, Joseph; Hoffman, Eric A.; Reinhardt, Joseph M.

    2002-04-01

    A bronchoscope can be used to examine the mucosal surface of the airways for abnormalities associated with a variety of lung diseases. The diagnosis of these abnormalities through the process of bronchoscopy is based, in part, on changes in airway wall color. Therefore it is important to characterize the normal color inside the airways. We propose a standardized method to calibrate the bronchoscopic imaging system and to tabulate the normal colors of the airway. Our imaging system consists of a Pentium PC and video frame grabber, coupled with a true color bronchoscope. The calibration procedure uses 24 standard color patches. Images of these color patches at three different distances (1, 1.5, and 2 cm) were acquired using the bronchoscope in a darkened room, to assess repeatability and sensitivity to illumination. The images from the bronchoscope are in a device-dependent Red-Green-Blue (RGB) color space, which was converted to a tri-stimulus image and then into a device-independent color space sRGB image by a fixed polynomial transformation. Images were acquired from five normal human volunteer subjects, two cystic fibrosis (CF) patients and one normal heavy smoker subject. The hue and saturation values of regions within the normal airway were tabulated and these values were compared with the values obtained from regions within the airways of the CF patients and the normal heavy smoker. Repeated measurements of the same region in the airways showed no measurable change in hue or saturation.

  4. Nurses' Awareness about Principles of Airway Suctioning.

    Science.gov (United States)

    Heidari, Mohammad; Shahbazi, Sara

    2017-08-01

    Airway suctioning is one of the most common interventions for patients with respiratory disorders and having adequate knowledge in implementing this technique is quite crucial for nurses. To assess the nurses' awareness about principles of airway suctioning. This study was a cross-sectional study done on 85 staff nurses' in Vali-Asr hospital. Sampling was based on census data collection. A researcher made questionnaire was used for assessment of nurses' awareness about the principles of airway suctioning. The validity and reliability (Cronbach's alpha=0.78) of the questionnaire have been examined and proved. The level of nurses' awareness about airway suctioning was measured based on the questionnaire that includes demographic and specialty information in the form of eight questions of 3-selection-item. The maximum and minimum score of knowledge ranged between 0-8. The data obtained was statistically analysed using SPSS software Version 16.0 and was analysed using descriptive statistics and Pearson correlation coefficient. The results reveal that the nurses' awareness about principles of airway suctioning was average. There was a significant association between knowledge and gender of nurses (pprinciples of airway suctioning was more than men. The results indicate that nurses' awareness of airway suctioning technique was in an average state. Considering the importance of this technique and the effects this technique has on the patients' haemodynamic status, we recommend in-service courses.

  5. The effect of calf stretching box on stretching calf muscle compliance: a prospective, randomized single-blinded controlled trial.

    Science.gov (United States)

    Chadchavalpanichaya, Navaporn; Srisawasdi, Gulapar; Suwannakin, Atchara

    2010-12-01

    To study the effect of calf stretching box usage in increasing the compliance of performing calf stretching exercise as compared to the conventional exercise method. To study the effect of calf stretching box usage in decreasing the calf muscle tightness and complications as compared to the conventional exercise method. Eighty patients older than 45 years old with calf muscles tightness were enrolled in a prospective, randomized single-blinded controlled trial at the out-patient Rehabilitation medicine clinic, Siriraj Hospital, Bangkok Thailand between April and August 2009. Patients were randomized into two groups, the study group (stretching by using calf stretching box) and the control group (stretching by the conventional exercise method). Patients in both groups were asked to hold the stretch for at least 1 minute and to perform the stretching program at least two times per day, every day for two weeks. Furthermore, they were asked to record the real frequency and duration of their exercise and complications in a logbook every day. Thirty-eight patients in each group completed the study. The baseline characteristics of the patients in both groups were similar. The study group had higher frequency and longer duration of performing calf stretching exercise than the control group. They also reported more decrease of calf muscle tightness with less pain complication (shoulder pain, knee pain, low back pain, and calf muscle pain) than the control group (p calf muscle and degree of ankle range of motion between the two groups. Stretching calf muscle with calf stretching box can increase compliance, decrease calf muscle tightness and decrease complications when compared with the conventional exercise method.

  6. The effect of warm-up, static stretching and dynamic stretching on hamstring flexibility in previously injured subjects.

    Science.gov (United States)

    O'Sullivan, Kieran; Murray, Elaine; Sainsbury, David

    2009-04-16

    Warm-up and stretching are suggested to increase hamstring flexibility and reduce the risk of injury. This study examined the short-term effects of warm-up, static stretching and dynamic stretching on hamstring flexibility in individuals with previous hamstring injury and uninjured controls. A randomised crossover study design, over 2 separate days. Hamstring flexibility was assessed using passive knee extension range of motion (PKE ROM). 18 previously injured individuals and 18 uninjured controls participated. On both days, four measurements of PKE ROM were recorded: (1) at baseline; (2) after warm-up; (3) after stretch (static or dynamic) and (4) after a 15-minute rest. Participants carried out both static and dynamic stretches, but on different days. Data were analysed using Anova. Across both groups, there was a significant main effect for time (p static stretching (p = 0.04) but significantly decreased after dynamic stretching (p = 0.013). The increased flexibility after warm-up and static stretching reduced significantly (p 0.05). Using ANCOVA to adjust for the non-significant (p = 0.141) baseline difference between groups, the previously injured group demonstrated a greater response to warm-up and static stretching, however this was not statistically significant (p = 0.05). Warm-up significantly increased hamstring flexibility. Static stretching also increased hamstring flexibility, whereas dynamic did not, in agreement with previous findings on uninjured controls. The effect of warm-up and static stretching on flexibility was greater in those with reduced flexibility post-injury, but this did not reach statistical significance. Further prospective research is required to validate the hypothesis that increased flexibility improves outcomes. ACTRN12608000638336.

  7. Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

    Science.gov (United States)

    Berry, David C.; Seitz, S. Robert

    2011-01-01

    The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

  8. Stretch reflex regulation in healthy subjects and patients with spasticity

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Petersen, Nicolas; Crone, Clarissa

    2005-01-01

    In recent years, part of the muscle resistance in spastic patients has been explained by changes in the elastic properties of muscles. However, the adaptive spinal mechanisms responsible for the exaggeration of stretch reflex activity also contribute to muscle stiffness. The available data suggest...... of the spastic symptoms. A recent finding also shows no sign of exaggerated stretch reflexes in muscles voluntarily activated by the spastic patient in general. This is easily explained by the control of stretch reflex activity in healthy subjects. In healthy subjects, the stretch reflex activity is increased...... movements, antagonist muscles should remain silent and maximally relaxed. This is ensured by increasing transmission in several spinal inhibitory pathways. In spastic patients, this control is inadequate, and therefore stretch reflexes in antagonist muscles are easily evoked at the beginning of voluntary...

  9. Bruxism: Is There an Indication for Muscle-Stretching Exercises?

    Science.gov (United States)

    Gouw, Simone; de Wijer, Anton; Creugers, Nico Hj; Kalaykova, Stanimira I

    Bruxism is a common phenomenon involving repetitive activation of the masticatory muscles. Muscle-stretching exercises are a recommended part of several international guidelines for musculoskeletal disorders and may be effective in management of the jaw muscle activity that gives rise to bruxism. However, most studies of muscle-stretching exercises have mainly focused on their influence on performance (eg, range of motion, coordination, and muscle strength) of the limb or trunk muscles of healthy individuals or individuals with sports-related injuries. Very few have investigated stretching of the human masticatory muscles and none muscle-stretching exercises in the management of (sleep) bruxism. This article reviews the literature on muscle-stretching exercises and their potential role in the management of sleep bruxism or its consequences in the musculoskeletal system.

  10. Acute effect of different stretching methods on isometric muscle strength

    Directory of Open Access Journals (Sweden)

    Gabriel Vasconcellos de Lima Costa e Silva

    2014-03-01

    This study investigated the acute effect of static stretching methods (SS and proprioceptive neuromuscular facilitation (PNF on the static muscle strength (SMS. Eleven young male subjects with strength training experience, performed 3 tests with a 48h interval between them, randomly selected, where each one subject carried out all procedures: a hand grip without stretching; b hand grip preceded by static stretching of wrist flexors muscles; c hand grip preceded by PNF stretching of wrist flexors muscles. The Shapiro-Wilk test verified the normality of data, and a one-way ANOVA with repeated measures, followed by Tukey’s post hoc test, evaluated the differences between the groups. The significance was set at p 0.05. In conclusion, both stretching methods had caused negative effects on isometric strength, reducing its levels.

  11. Linear and nonlinear buckling analysis of a locally stretched plate

    Energy Technology Data Exchange (ETDEWEB)

    Kilardj, Madina; Ikhenzzen, Ghania [University of Sciences and Technology Houari Boumediene (U.S.T.H.B), Bab Ezzouar, Algiers (Algeria); Merssager, Tanguy; Kanit, Toufik [Laboratoire de Mecanique de Lille Universite Lille 1, Cite ScientifiqueVilleneuve d' Ascq cedex (France)

    2016-08-15

    Uniformly stretched thin plates do not buckle unless they are in special boundary conditions. However, buckling commonly occurs around discontinuities, such as cracks, cuts, narrow slits, holes, and different openings, of such plates. This study aims to show that buckling can also occur in thin plates that contain no defect or singularity when the stretching is local. This specific stability problem is analyzed with the finite element method. A brief literature review on stretched plates is presented. Linear and nonlinear buckling stress analyses are conducted for a partially stretched rectangular plate, and various load cases are considered to investigate the influence of the partial loading expanse on the critical tensile buckling load. Results are summarized in iso-stress areas, tables and graphs. Local stretching on one end of the plate induces buckling in the thin plate even without geometrical imperfection.

  12. Smooth halos in the cosmic web

    International Nuclear Information System (INIS)

    Gaite, José

    2015-01-01

    Dark matter halos can be defined as smooth distributions of dark matter placed in a non-smooth cosmic web structure. This definition of halos demands a precise definition of smoothness and a characterization of the manner in which the transition from smooth halos to the cosmic web takes place. We introduce entropic measures of smoothness, related to measures of inequality previously used in economy and with the advantage of being connected with standard methods of multifractal analysis already used for characterizing the cosmic web structure in cold dark matter N-body simulations. These entropic measures provide us with a quantitative description of the transition from the small scales portrayed as a distribution of halos to the larger scales portrayed as a cosmic web and, therefore, allow us to assign definite sizes to halos. However, these ''smoothness sizes'' have no direct relation to the virial radii. Finally, we discuss the influence of N-body discreteness parameters on smoothness

  13. Neurite development in PC12 cells on flexible micro-textured substrates under cyclic stretch.

    Science.gov (United States)

    Haq, Furqan; Keith, Charles; Zhang, Guigen

    2006-01-01

    We investigated the combined effect of micro-texture and mechanical strain on neuronal cell development such as neurite length and neurite density in a rat pheochromocytoma cell line (PC12 cells). Cells were seeded on flexible silicone substrates with micro-texture or no texture (smooth) and cultured under static and dynamic conditions. In the static condition substrates were not stretched and in the dynamic conditions substrates were subjected to cyclic uniaxial stretching at three different strain levels of 4%, 8%, and 16% with each at three different strain rates at 0.1, 0.5, and 1.0 Hz. Results showed that of all cell cultures there was no significant difference in neurite development between cells on smooth and textured substrates, except in the static and 4% at 0.1 Hz conditions, where micro-texture induced significantly longer neurites. With both types of substrates, a lower mechanical condition (4% at 1.0 Hz or 16% at 0.1 Hz) resulted in more and longer neurites and lower cell density, and a higher mechanical condition (16% at 1.0 Hz) resulted in fewer and shorter neurites and lower cell density as compared to the static condition. These findings suggest that the effect of the micro-texture on neurite development is more prominent in low mechanical conditions than in high mechanical conditions and that the strain level and strain rate have an interrelated effect on neurite development: a higher strain level at a lower strain rate has a similar effect as a lower strain level at a higher strain rate in terms of promoting neurite development.

  14. 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 volume...... pulse wave. We performed digital photoplethysmography during sleep at night in 94 consecutive patients who underwent polysomnography and 29 patients treated with nCPAP. Digital volume pulse waves were obtained independently of an investigator and were quantified using an algorithm for continuous.......01; n = 94) and the arousal index (Spearman correlation, r = 0.21; p CPAP treatment, the AHI was significantly reduced from 27 ± 3 events · h(-1) to 4 ± 2 events · h(-1) (each n = 29; p

  15. Acute effects of different stretching durations on passive torque, mobility, and isometric muscle force.

    Science.gov (United States)

    Matsuo, Shingo; Suzuki, Shigeyuki; Iwata, Masahiro; Banno, Yasuhiro; Asai, Yuji; Tsuchida, Wakako; Inoue, Takayuki

    2013-12-01

    Static stretching is widely applied in various disciplines. However, the acute effects of different durations of stretching are unclear. Therefore, this study was designed to investigate the acute effects of different stretching durations on muscle function and flexibility, and provide an insight into the optimal duration of static stretching. This randomized crossover trial included 24 healthy students (17 men and 7 women) who stretched their right hamstrings for durations of 20, 60, 180, and 300 seconds in a random order. The following outcomes were assessed using an isokinetic dynamometer as markers of lower-limb function and flexibility: static passive torque (SPT), dynamic passive torque (DPT), stiffness, straight leg raise (SLR), and isometric muscle force. Static passive torque was significantly decreased after all stretching durations (p stretching compared with that after 20-second stretching, and stiffness decreased significantly after 180- and 300-second stretching (p stretching (p stretching durations (p stretching than after 20-second stretching and higher after 300-second stretching than after 60-second stretching (p muscle force significantly decreased after all stretching durations (p stretching is associated with a decrease in SPT but an increase in SLR. Over 180 seconds of stretching was required to decrease DPT and stiffness, but isometric muscle force decreased regardless of the stretching duration. In conclusion, these results indicate that longer durations of stretching are needed to provide better flexibility.

  16. Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation

    Directory of Open Access Journals (Sweden)

    Mettey Yvette

    2006-08-01

    Full Text Available Abstract Background The airway functions are profoundly affected in many diseases including asthma, chronic obstructive pulmonary disease (COPD and cystic fibrosis (CF. CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR gene, which normally encodes a multifunctional and integral membrane protein, the CF transmembrane conductance regulator (CFTR expressed in airway epithelial cells. Methods To demonstrate that CFTR is also expressed in tracheal smooth muscle cells (TSMC, we used iodide efflux assay to analyse the chloride transports in organ culture of rat TSMC, immunofluorescence study to localize CFTR proteins and isometric contraction measurement on isolated tracheal rings to observe the implication of CFTR in the bronchodilation. Results We characterized three different pathways stimulated by the cAMP agonist forskolin and the isoflavone agent genistein, by the calcium ionophore A23187 and by hypo-osmotic challenge. The pharmacology of the cAMP-dependent iodide efflux was investigated in detail. We demonstrated in rat TSMC that it is remarkably similar to that of the epithelial CFTR, both for activation (using three benzo [c]quinolizinium derivatives and for inhibition (glibenclamide, DPC and CFTRinh-172. Using rat tracheal rings, we observed that the activation of CFTR by benzoquinolizinium derivatives in TSMC leads to CFTRinh-172-sensitive bronchodilation after constriction with carbachol. An immunolocalisation study confirmed expression of CFTR in tracheal myocytes. Conclusion Altogether, these observations revealed that CFTR in the airways of rat is expressed not only in the epithelial cells but also in tracheal smooth muscle cells leading to the hypothesis that this ionic channel could contribute to bronchodilation.

  17. Magnetic resonance imaging of the pediatric airway

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  18. 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 experience 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: Fifty-seven 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...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma.......BACKGROUND: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti......-inflammatory treatment. OBJECTIVE: We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects. METHODS: Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10...

  20. Pre-exercise stretching does not impact upon running economy.

    Science.gov (United States)

    Hayes, Philip R; Walker, Adrian

    2007-11-01

    Pre-exercise stretching has been widely reported to reduce performance in tasks requiring maximal or near-maximal force or torque. The purpose of this study was to compare the effects of 3 different pre-exercise stretching routines on running economy. Seven competitive male middle and long-distance runners (mean +/- SD) age: 32.5 +/- 7.7 years; height: 175.0 +/- 8.8 cm; mass: 67.8 +/- 8.6 kg; V(.-)O2max: 66.8 +/- 7.0 ml x kg(-1) x min(-1)) volunteered to participate in this study. Each participant completed 4 different pre-exercise conditions: (a) a control condition, (b) static stretching, (c) progressive static stretching, and (d) dynamic stretching. Each stretching routine consisted of 2 x 30-second stretches for each of 5 exercises. Dependent variables measured were sit and reach test before and after each pre-exercise routine, running economy (ml x kg(-1) x km(-1)), and steady-state oxygen uptake (ml x kg(-1) x min(-1)), which were measured during the final 3 minutes of a 10-minute run below lactate threshold. All 3 stretching routines resulted in an increase in the range of movement (p = 0.008). There was no change in either running economy (p = 0.915) or steady-state V(.-)O2 (p = 0.943). The lack of change in running economy was most likely because it was assessed after a period of submaximal running, which may have masked any effects from the stretching protocols. Previously reported reductions in performance have been attributed to reduced motor unit activation, presumably IIX. In this study, these motor units were likely not to have been recruited; this may explain the unimpaired performance. This study suggests that pre-exercise stretching has no impact upon running economy or submaximal exercise oxygen cost.