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Sample records for experimental asthma models

  1. Lifetime-dependent effects of bisphenol A on asthma development in an experimental mouse model.

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    Susanne Petzold

    Full Text Available BACKGROUND: Environmental factors are thought to contribute significantly to the increase of asthma prevalence in the last two decades. Bisphenol A (BPA is a xenoestrogen commonly used in consumer products and the plastic industry. There is evidence and an ongoing discussion that endocrine disruptors like BPA may affect human health and also exert alterations on in the immune system. The aim of this study was to investigate age-dependent effects of BPA on the asthma risk using a murine model to explain the controversial results reported till date. METHODS: BALB/c mice were exposed to BPA via the drinking water for different time periods including pregnancy and breastfeeding. To induce an asthma phenotype, mice were sensitized to ovalbumin (OVA, followed by an intrapulmonary allergen challenge. RESULTS: BPA exposure during pregnancy and breastfeeding had no significant effect on asthma development in the offspring. In contrast, lifelong exposure from birth until the last antigen challenge clearly increased eosinophilic inflammation in the lung, airway hyperreactivity and antigen-specific serum IgE levels in OVA-sensitized adult mice compared to mice without BPA exposure. Surprisingly, BPA intake during the sensitization period significantly reduced the development of allergic asthma. This effect was reversed in the presence of a glucocorticoid receptor antagonist. CONCLUSIONS: Our results demonstrate that the impact of BPA on asthma risk is strongly age-dependent and ranges from asthma-promoting to asthma-reducing effects. This could explain the diversity of results from previous studies regarding the observed health impact of BPA.

  2. Preliminary studies on the effect of rebamipide against the trypsin and egg-albumin induced experimental model of asthma.

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    Gohil, Priyanshee; Thakkar, Himani; Gohil, Unnati; Deshpande, Shrikalp

    2011-12-01

    The present investigation was carried out to study the effect of rebamipide in experimentally induced bronchial asthma in mice. Trypsin and egg-albumin induced chronic model of asthma was used and various parameters were measured on the 35th day. The asthmatic control group showed lower level of haemoglobin saturation with oxygen, tidal volume, airflow rate and higher respiratory rate, serum bicarbonate level, eosinophil count in bronchoalveolar lavage fluid and histamine level compared to the normal control group. Dexamethasone and rebamipide treated groups showed the return of all the above parameters towards normal values. Histopathological examination of lungs showed more prominent alveolar and muscular layer destruction in the asthmatic control group than in dexamethasone and rebamipide treated groups. Rebamipide showed a beneficial effect and might be used for the treatment of bronchial asthma.

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

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

    2015-06-01

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

  4. Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

    National Research Council Canada - National Science Library

    Bergquist, M; Jonasson, S; Hjoberg, J; Hedenstierna, G; Hanrieder, Jörg

    2014-01-01

    ...; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods...

  5. Animal models of asthma: utility and limitations

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    Aun MV

    2017-11-01

    Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

  6. Models of asthma: density-equalizing mapping and output benchmarking

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    Fischer Tanja C

    2008-02-01

    Full Text Available Abstract Despite the large amount of experimental studies already conducted on bronchial asthma, further insights into the molecular basics of the disease are required to establish new therapeutic approaches. As a basis for this research different animal models of asthma have been developed in the past years. However, precise bibliometric data on the use of different models do not exist so far. Therefore the present study was conducted to establish a data base of the existing experimental approaches. Density-equalizing algorithms were used and data was retrieved from a Thomson Institute for Scientific Information database. During the period from 1900 to 2006 a number of 3489 filed items were connected to animal models of asthma, the first being published in the year 1968. The studies were published by 52 countries with the US, Japan and the UK being the most productive suppliers, participating in 55.8% of all published items. Analyzing the average citation per item as an indicator for research quality Switzerland ranked first (30.54/item and New Zealand ranked second for countries with more than 10 published studies. The 10 most productive journals included 4 with a main focus allergy and immunology and 4 with a main focus on the respiratory system. Two journals focussed on pharmacology or pharmacy. In all assigned subject categories examined for a relation to animal models of asthma, immunology ranked first. Assessing numbers of published items in relation to animal species it was found that mice were the preferred species followed by guinea pigs. In summary it can be concluded from density-equalizing calculations that the use of animal models of asthma is restricted to a relatively small number of countries. There are also differences in the use of species. These differences are based on variations in the research focus as assessed by subject category analysis.

  7. Asthma

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    ... babies. Poor asthma control increases the risk of preeclampsia, a condition in which a pregnant woman develops ... other conditions that can interfere with your asthma management. Watch for Signs That Your Asthma Is Getting ...

  8. Asthma

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    ... their experiences with clinical research. More Information Related Health Topics Cough How the Lungs Work Oxygen Therapy Pulmonary Function Tests Other Resources NHLBI Resources "Asthma Action Plan" "Asthma and Physical Activity in the School" "At-A-Glance: Asthma" "How Asthma-Friendly Is ...

  9. Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma.

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    Zhu, Jie; Message, Simon D; Qiu, Yusheng; Mallia, Patrick; Kebadze, Tatiana; Contoli, Marco; Ward, Christine K; Barnathan, Elliot S; Mascelli, Mary Ann; Kon, Onn M; Papi, Alberto; Stanciu, Luminita A; Jeffery, Peter K; Johnston, Sebastian L

    2014-06-01

    The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = -0.89, P = .029), the PC10 correlated inversely with CD4+ (r = -0.67, P = .023) and CD8+ cells (r = -0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = -0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = -0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and

  10. Inhalable dry-emulsion formulation of cyclosporine A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.

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    Onoue, Satomi; Sato, Hideyuki; Ogawa, Kumiko; Kojo, Yoshiki; Aoki, Yosuke; Kawabata, Yohei; Wada, Koichi; Mizumoto, Takahiro; Yamada, Shizuo

    2012-01-01

    The main purpose of the present study was to develop a novel respirable powder (RP) formulation of cyclosporine A (CsA) using a spray-dried O/W-emulsion (DE) system. DE formulation of CsA (DE/CsA) was prepared by spray-drying a mixture of erythritol and liquid O/W emulsion containing CsA, polyvinylpyrrolidone, and glyceryl monooleate as emulsifying agent. The DE/CsA powders were mixed with lactose carriers to obtain an RP formulation of DE/CsA (DE/CsA-RP), and its physicochemical, pharmacological, and pharmacokinetic properties were evaluated. Spray-dried DE/CsA exhibited significant improvement in dissolution behavior with ca. 4500-fold increase of dissolution rate, and then, nanoemulsified particles were reconstituted with a mean diameter of 317 nm. Laser diffraction analysis on the DE/CsA-RP suggested high dispersion of DE/CsA on the surface of the lactose carrier. Anti-inflammatory properties of the inhaled DE/CsA-RP were characterized in antigen-sensitized asthma/COPD-model rats, in which the DE/CsA-RP was more potent than the RP formulation of physical mixture containing CsA and erythritol in inhibiting inflammatory responses, possibly due to the improved dissolution behavior. Pharmacokinetic studies demonstrated that systemic exposure of CsA after intratracheal administration of the DE/CsA-RP at a pharmacologically effective dose (100 μg-CsA/rat) was 50-fold less than that of the oral CsA dosage form at a toxic dose (10 mg/kg). From these findings, use of inhalable DE formulation of CsA might be a promising approach for the treatment of airway inflammatory diseases with improved pharmacodynamics and lower systemic exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Anti-inflammatory and anti-remodelling effects of ISU201, a modified form of the extracellular domain of human BST2, in experimental models of asthma: association with inhibition of histone acetylation.

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    Cristan Herbert

    Full Text Available There are few alternatives to glucocorticosteroids for treatment of asthma. We assessed the activity of a novel protein drug designated ISU201, the extracellular domain of the human cell surface protein BST2, stabilised by fusion with the Fc region of IgG, in mouse models of mild chronic asthma and an acute exacerbation of asthma. The ability of ISU201 to suppress airway inflammation and remodelling was compared with that of dexamethasone. Female BALB/c mice were systemically sensitised with ovalbumin, then received controlled low-level challenge with aerosolised ovalbumin for 6 weeks, which induced lesions of mild chronic asthma, and were treated with drugs during the final 2 weeks. Alternatively, sensitised mice received 4 weeks of chronic low-level challenge and were treated 24 and 2 hours before a final single moderate-level challenge, which triggered acute airway inflammation simulating an asthmatic exacerbation. Inflammation and remodelling were quantified, as was the expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid and tissues. To identify cellular targets of ISU201, we assessed the effects of the drug on activated lymphocytes, macrophages and airway epithelial cells. In the model of mild chronic asthma, ISU201 was as effective as dexamethasone in suppressing airway inflammation and most changes of remodelling. In the model of an allergen-induced acute exacerbation of chronic asthma, ISU201 was also an effective anti-inflammatory agent, although it was less active than dexamethasone. The drug acted on multiple cellular targets, suppressing production of pro-inflammatory cytokines by lymphocytes and macrophages. ISU201 significantly reduced acetylation of histone H4 in airway epithelial cells, suggesting at least one potential mechanism of action. We conclude that in these models of asthma, ISU201 is a broad-spectrum inhibitor of both airway inflammation and remodelling. Thus, unlike drugs which target specific

  12. Asthma

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    Kim Harold

    2011-11-01

    Full Text Available Abstract Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA inhalers are preferred for most adults who fail to achieve control with ICS therapy. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma, but should only be prescribed by physicians with appropriate training in allergy. Regular monitoring of asthma control, adherence to therapy and inhaler technique are also essential components of asthma management. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma.

  13. TLR3 Blockade in Rhinovirus-Induced Experimental Asthma Exacerbations: A Randomized Controlled Study

    NARCIS (Netherlands)

    Silkoff, Philip E.; Flavin, Susan; Gordon, Robert; Loza, Mathew J.; Sterk, Peter J.; Lutter, Rene; Diamant, Zuzana; Turner, Ronald B.; Lipworth, Brian J.; Proud, David; Singh, Dave; Eich, Andreas; Backer, Vibeke; Gern, James E.; Herzmann, Christian; Halperin, Scott A.; Mensinga, Tjeert T.; del Vecchio, Alfred M.; Branigan, Patrick; San Mateo, Lani; Baribaud, Frédéric; Barnathan, Elliot S.; Johnston, Sebastian L.

    2017-01-01

    Human rhinoviruses (HRV) commonly precipitate asthma exacerbations. TLR3, an innate pattern-recognition receptor, is triggered by HRV driving inflammation that may worsen asthma. To evaluate an inhibitory monoclonal antibody to TLR3, CNTO3157, on experimental HRV-16 inoculation in healthy and

  14. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes

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    J-H. Zhang

    2017-11-01

    Full Text Available Vitamin D (25(OHD3 is an essential nutrient that plays a role in the immune system. Serum 25(OHD3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3–4 weeks old into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OHD3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OHD3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

  15. Prevalence of self-reported smoking experimentation in adolescents with asthma or allergic rhinitis.

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    Fernandes, Silvia de Sousa Campos; Andrade, Cláudia Ribeiro de; Caminhas, Alessandra Pinheiro; Camargos, Paulo Augusto Moreira; Ibiapina, Cássio da Cunha

    2016-04-01

    To determine the prevalence of smoking experimentation among adolescents with asthma or allergic rhinitis. This was a cross-sectional study involving adolescent students (13-14 years of age) in the city of Belo Horizonte, Brazil. The participants completed the Centers for Disease Control and Prevention and International Study of Asthma and Allergies in Childhood questionnaires, both of which have been validated for use in Brazil. We calculated the prevalence of smoking experimentation in the sample as a whole, among the students with asthma symptoms, and among the students with allergic rhinitis symptoms, as well as in subgroups according to gender and age at smoking experimentation. The sample comprised 3,325 adolescent students. No statistically significant differences were found regarding gender or age. In the sample as a whole, the prevalence of smoking experimentation was 9.6%. The mean age for smoking experimentation for the first time was 11.1 years of age (range, 5-14 years). Among the adolescents with asthma symptoms and among those with allergic rhinitis symptoms, the prevalence of self-reported smoking experimentation was 13.5% and 10.6%, respectively. The proportion of adolescents with symptoms of asthma or allergic rhinitis who reported smoking experimentation is a cause for concern, because there is strong evidence that active smoking is a risk factor for the occurrence and increased severity of allergic diseases.

  16. Biomarkers of disease and treatment in murine and cynomolgus models of chronic asthma.

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    Louten, Jennifer; Mattson, Jeanine D; Malinao, Maria-Christina; Li, Ying; Emson, Claire; Vega, Felix; Wardle, Robert L; Van Scott, Michael R; Fick, Robert B; McClanahan, Terrill K; de Waal Malefyt, Rene; Beaumont, Maribel

    2012-01-01

    Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. The total protein content from thymic stromal lymphopoietin transgenic (TSLP Tg) mouse BAL fluid was ascertained by shotgun proteomics analysis. A subset of these potential markers was further analyzed in BAL fluid, BAL cell mRNA, and lung tissue mRNA during the stages of asthma and following corticosteroid treatment. Validation was conducted in murine and NHP models of allergic asthma. Over 40 proteins were increased in the BAL fluid of TSLP Tg mice that were also detected by qRT-PCR in lung tissue and BAL cells, as well as in OVA-sensitive mice and house dust mite-sensitive NHP. Previously undescribed as asthma biomarkers, KLK1, Reg3γ, ITLN2, and LTF were modulated in asthmatic mice, and Clca3, Chi3l4 (YM2), and Ear11 were the first lung biomarkers to increase during disease and the last biomarkers to decline in response to therapy. In contrast, GP-39, LCN2, sICAM-1, YM1, Epx, Mmp12, and Klk1 were good indicators of early therapeutic intervention. In NHP, AMCase, sICAM-1, CLCA1, and GP-39 were reduced upon treatment with corticosteroids. These results significantly advance our understanding of the biomarkers present in various tissue compartments in animal models of asthma, including those induced early during asthma and modulated with therapeutic intervention, and show that BAL cells (or their surrogate, induced sputum cells) are a viable choice for biomarker examination.

  17. A NONLINEAR MATHEMATICAL MODEL FOR ASTHMA: EFFECT OF ENVIRONMENTAL POLLUTION

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    NARESHA RAM

    2009-04-01

    Full Text Available In this paper, we explore a nonlinear mathematical model to study the spread of asthma due to inhaled pollutants from industry as well as tobacco smoke from smokers in a variable size population. The model is analyzed using stability theory of differential equations and computer simulation. It is shown that with an increase in the level of air pollutants concentration, the asthmatic (diseased population increases. It is also shown that along with pollutants present in the environment, smoking (active or passive also helps in the spread of asthma. Moreover, with the increase in the rate of interaction between susceptibles and smokers, the persistence of the spread of asthma is higher. A numerical study of the model is also performed to see the role of certain key parameters on the spread of asthma and to support the analytical results.

  18. Effect of Education on Asthma Control in Children: A Quasi- Experimental Study

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    Arash Kalantari

    2017-12-01

    Full Text Available Introduction: The prevalence of asthma has increased significantly in recent decades1 especially in lower socioeconomic groups and in minority populations. Because of the increasing prevalence of asthma among children in worldwide and Iran, the importance of timely control of the disease after its diagnosis and few studies on the effect of education on asthma control in Iran, the aim of this study was to investigate the effect of education on asthma control in children. Methods: In this quasi-experimental study, 104 Iranian children (6-14 years old with asthma referred to asthma and allergy clinic of Children's Medical Center in Tehran were studied via convenience sampling method. Recruitment was occurred between 2011 to 2014. Subjects randomly were divided into two equal groups of intervention and control. For intervention group, common education as well as special education in format of booklet, pamphlets, CD and group training sessions were applied every two weeks within the first two months of follow up and every two months then after. While, the control group received usual careResults: The means of FEV1/ FVC change, frequency of admission to the ED, hospitalization and absence from school and use of steroids were significantly different before and after education in the intervention group. While changes among measured parameters in the control group were not significantly different.Conclusion: The results of this study showed that specific education has significant helpful effect on asthma attack control in children.

  19. No audible wheezing: nuggets and conundrums from mouse asthma models.

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    Boyce, Joshua A; Austen, K Frank

    2005-06-20

    Mouse models of T helper type 2 (Th2) cell-biased pulmonary inflammation have elucidated mechanisms of sensitization, cell traffic, and induced airway hyperresponsiveness (AHR). Nonetheless, most mice lack intrinsic AHR, a central property of human asthma, and disparities persist regarding the contributions of eosinophils and mast cells and the sensitivity to induced AHR in the commonly used mouse strains. We suggest that these discordances, reflecting methodological and genetic differences, may be informative for understanding heterogeneity of human asthma.

  20. Stem cells in animal asthma models: a systematic review.

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    Srour, Nadim; Thébaud, Bernard

    2014-12-01

    Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. Control of asthma triggers in indoor air with air cleaners: a modeling analysis.

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    Myatt, Theodore A; Minegishi, Taeko; Allen, Joseph G; Macintosh, David L

    2008-08-06

    Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30-55% lower cat allergen levels, 90-99% lower risk of respiratory infection through the inhalation route of exposure, 90-98% lower environmental tobacco smoke (ETS) levels, and 50-75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.

  2. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes.

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    Zhang, J-H; Chen, Y-P; Yang, X; Li, C-Q

    2017-11-13

    Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3-4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

  3. [Modeling asthma evolution by a multi-state model].

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    Boudemaghe, T; Daurès, J P

    2000-06-01

    There are many scores for the evaluation of asthma. However, most do not take into account the evolutionary aspects of this illness. We propose a model for the clinical course of asthma by a homogeneous Markov model process based on data provided by the A.R.I.A. (Association de Recherche en Intelligence Artificielle dans le cadre de l'asthme et des maladies respiratoires). The criterion used is the activity of the illness during the month before consultation. The activity is divided into three levels: light (state 1), mild (state 2) and severe (state 3). The model allows the evaluation of the strength of transition between states. We found that strong intensities were implicated towards state 2 (lambda(12) and lambda(32)), less towards state 1 (lambda(21) and lambda(31)), and minimum towards state 3 (lambda(23)). This results in an equilibrium distribution essentially divided between state 1 and 2 (44.6% and 51.0% respectively) with a small proportion in state 3 (4.4%). In the future, the increasing amount of available data should permit the introduction of covariables, the distinction of subgroups and the implementation of clinical studies. The interest of this model falls within the domain of the quantification of the illness as well as the representation allowed thereof, while offering a formal framework for the clinical notion of time and evolution.

  4. Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats.

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    Abdel-Fattah, Maha M; Messiha, Basim A S; Salama, Abeer A A

    2015-01-01

    Calcium influx, inflammatory infiltration, cytokine production, immunoglobulin E activation and oxidative stress play coordinated roles in bronchial asthma pathogenesis. We aim to assess the protective effect of cinnarizine against experimentally induced bronchial asthma. Bronchial asthma was induced by ovalbumin sensitization and challenge. Rats were allocated into a normal control, an asthma control, a dexamethasone (standard) treatment, and 2 cinnarizine treatment groups. The respiratory functions tidal volume (TV) and peak expiratory flow rate (PEFR), the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-5 (IL-5) in lung tissue, the allergic immunoglobulin IgE in serum, the absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF), as well as the oxidative and nitrosative markers glutathione reduced (GSH) and superoxide dismutase (SOD) in lung tissue and nitric oxide end products (NOx) in BALF were assessed, followed by a histopathological study. Cinnarizine administration significantly restored TV, PEFR, TNF-α, IL-5, IgE, AEC, GSH, SOD and NOx values back to normal levels, and significantly decreased perivascular and peribronchiolar inflammatory scores. Cinnarizine may protect against experimental bronchial asthma. Suppressant effect of cinnarizine on pro-inflammatory cytokines release, IgE antibody production, eosinophil infiltration as well as oxidative and nitrosative stress may explain its anti-asthmatic potential. © 2015 S. Karger AG, Basel.

  5. Asthma: a comparison of animal models using stereological methods

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    D. M. Hyde

    2006-12-01

    Full Text Available Asthma is a worldwide health problem that affects 300 million people, as estimated by the World Health Organization. A key question in light of this statistic is: "what is the most appropriate laboratory animal model for human asthma?" The present authors used stereological methods to assess airways in adults and during post-natal development, and their response to inhaled allergens to compare rodents and nonhuman primates to responses in humans. An epithelial–mesenchymal trophic unit was defined in which all of the compartments interact with each other. Asthma manifests itself by altering not only the epithelial compartment but also other compartments (e.g. interstitial, vascular, immunological and nervous. All of these compartments show significant alteration in an airway generation-specific manner in rhesus monkeys but are limited to the proximal airways in mice. The rhesus monkey model shares many of the key features of human allergic asthma including the following: 1 allergen-specific immunoglobulin (IgE and skin-test positivity; 2 eosinophils and IgE+ cells in airways; 3 a T-helper type 2 cytokine profile in airways; 4 mucus cell hyperplasia; 5 subepithelial fibrosis; 6 basement membrane thickening; and 7 persistent baseline hyperreactivity to histamine or methacholine. In conclusion, the unique responses to inhaled allergens shown in rhesus monkeys make it the most appropriate animal model of human asthma.

  6. Dysregulation of metabolic pathways in a mouse model of allergic asthma.

    Science.gov (United States)

    Quinn, K D; Schedel, M; Nkrumah-Elie, Y; Joetham, A; Armstrong, M; Cruickshank-Quinn, C; Reisdorph, R; Gelfand, E W; Reisdorph, N

    2017-09-01

    Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed. In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10(-5) ), arginine and proline metabolism (P=1.12×10(-7) ), glycerophospholipid metabolism (P=1.3×10(-10) ), and the neurotrophin signaling pathway (P=7.0×10(-6) ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  7. Experimentally manipulated sleep duration in adolescents with asthma: Feasibility and preliminary findings.

    Science.gov (United States)

    Meltzer, Lisa J; Faino, Anna; Szefler, Stanley J; Strand, Matthew; Gelfand, Erwin W; Beebe, Dean W

    2015-12-01

    To examine the impact of sleep duration on lung function and asthma symptoms in adolescents. Ten adolescents with asthma (60% female, 60% Caucasian, mean age = 13.7 years, range 12-17) completed a 3-week randomized, cross-over sleep manipulation protocol. Following a week of self-selected sleep duration, adolescents were randomized to a five-night deficient sleep opportunity (6.5 hr in bed) or a healthy sleep opportunity (10 hr in bed) obtained by systematically changing bedtimes. Wake time remained consistent across all 3 weeks (including weekends). Daily reports of sleep patterns and asthma symptoms, actigraphy, and daily peak expiratory flow rates (PEFR), as well as weekly spirometry and exhaled nitric oxide were collected. Participants averaged 3.2 hr less sleep (P sleep condition versus the long sleep condition. Further, they had an 8.4% decrease overnight in PEFR (P = 0.007), and reported more asthma symptoms interfering with activities in the past 24 hr (P = 0.02) in the short sleep condition than the long sleep condition. No significant differences between experimental weeks were found for weekly spirometry or exhaled nitric oxide. This pilot study demonstrated the feasibility of a cross-over sleep manipulation protocol in adolescents with asthma. Since overnight decrease in PEFR is a marker of nocturnal asthma, and has been associated with the severity of daytime airflow limitation, these early-stage results suggest that shortened sleep duration may exacerbate adolescent asthma and associated functional impairments. © 2015 Wiley Periodicals, Inc.

  8. Mouse mast cell protease-6 and MHC are involved in the development of experimental asthma.

    Science.gov (United States)

    Cui, Yue; Dahlin, Joakim S; Feinstein, Ricardo; Bankova, Lora G; Xing, Wei; Shin, Kichul; Gurish, Michael F; Hallgren, Jenny

    2014-11-15

    Allergic asthma is a complex disease with a strong genetic component where mast cells play a major role by the release of proinflammatory mediators. In the mouse, mast cell protease-6 (mMCP-6) closely resembles the human version of mast cell tryptase, β-tryptase. The gene that encodes mMCP-6, Tpsb2, resides close by the H-2 complex (MHC gene) on chromosome 17. Thus, when the original mMCP-6 knockout mice were backcrossed to the BALB/c strain, these mice were carrying the 129/Sv haplotype of MHC (mMCP-6(-/-)/H-2bc). Further backcrossing yielded mMCP-6(-/-) mice with the BALB/c MHC locus. BALB/c mice were compared with mMCP-6(-/-) and mMCP-6(-/-)/H-2bc mice in a mouse model of experimental asthma. Although OVA-sensitized and challenged wild type mice displayed a striking airway hyperresponsiveness (AHR), mMCP-6(-/-) mice had less AHR that was comparable with that of mMCP-6(-/-)/H-2bc mice, suggesting that mMCP-6 is required for a full-blown AHR. The mMCP-6(-/-)/H-2bc mice had strikingly reduced lung inflammation, IgE responses, and Th2 cell responses upon sensitization and challenge, whereas the mMCP-6(-/-) mice responded similarly to the wild type mice but with a minor decrease in bronchoalveolar lavage eosinophils. These findings suggest that inflammatory Th2 responses are highly dependent on the MHC-haplotype and that they can develop essentially independently of mMCP-6, whereas mMCP-6 plays a key role in the development of AHR. Copyright © 2014 by The American Association of Immunologists, Inc.

  9. Mouse mast cell protease -6 and MHC are involved in the development of experimental asthma1

    Science.gov (United States)

    Feinstein, Ricardo; Bankova, Lora G.; Xing, Wei; Shin, Kichul; Gurish, Michael F.; Hallgren, Jenny

    2014-01-01

    Allergic asthma is a complex disease with a strong genetic component where mast cells play a major role by the release of pro-inflammatory mediators. In the mouse, mast cell protease-6 (mMCP-6) closely resembles the human version of mast cell tryptase, β-tryptase. The gene that encodes mMCP-6, Tpsb2, resides close by the H-2 complex (MHC gene) on chromosome 17. Thus, when the original mMCP-6 knockout mice were backcrossed to the BALB/c strain, these mice were carrying the 129/Sv haplotype of MHC (mMCP-6−/−/H-2bc). Further backcrossing yielded mMCP-6−/− mice with the BALB/c MHC locus. BALB/c mice were compared with mMCP-6−/− and mMCP-6−/−/H-2bc mice in a mouse model of experimental asthma. While OVA-sensitized and challenged wild type mice displayed a striking airway hyperresponsiveness (AHR), mMCP-6−/− mice had less AHR that was comparable to that of mMCP-6−/−/H-2bc mice, suggesting that mMCP-6 is required for a full-blown AHR. The mMCP-6−/−/H-2bc mice had strikingly reduced lung inflammation, IgE-responses and Th2 cell-responses upon sensitization and challenge, whereas the mMCP-6−/− mice responded similarly to the wild type mice but with a minor decrease in bronchoalveolar lavage (BAL) eosinophils. These findings suggest that inflammatory Th2-responses are highly dependent on the MHC-haplotype and that they can develop essentially independently of mMCP-6 while mMCP-6 plays a key role in the development of AHR. PMID:25320274

  10. Asthma Self-Management Model: Randomized Controlled Trial

    Science.gov (United States)

    Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

    2016-01-01

    Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

  11. Niflumic Acid Inhibits Goblet Cell Degranulation in a Guinea Pig Asthma Model

    Directory of Open Access Journals (Sweden)

    Mitsuko Kondo

    2012-01-01

    Conclusions: NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with goblet cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma.

  12. The healthy learner model for student chronic condition management--part II: the asthma initiative.

    Science.gov (United States)

    Erickson, Cecelia DuPlessis; Splett, Patricia L; Mullett, Sara Stoltzfus; Jensen, Charlotte; Belseth, Stephanie Bisson

    2006-12-01

    The Healthy Learner Asthma Initiative (HLAI) was designed as a comprehensive, school-community initiative to improve asthma management and produce healthy learners. National asthma guidelines were translated into components of asthma management in the school setting that defined performance expectations and lead to greater quality and consistency of asthma care. The HLAI incorporated evidence-based practice and introduced the role of the asthma resource nurse. Leadership, capacity building, and strong partnerships among school nurses, students, families, and health care providers were essential to the implementation and sustainability of the HLAI. Professional school nursing and evaluation were defined as key requisites to a successful initiative. Evaluation results indicated positive effects on nursing practice, fewer asthma visits to the health office, and better attendance among students who received asthma care in the school health office. The HLAI provided the basis for development of the Healthy Learner Model for Student Chronic Condition Management.

  13. Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells.

    Science.gov (United States)

    Terashita, Tomomi; Kobayashi, Kazuyuki; Nagano, Tatsuya; Kawa, Yoshitaka; Tamura, Daisuke; Nakata, Kyosuke; Yamamoto, Masatsugu; Tachihara, Motoko; Kamiryo, Hiroshi; Nishimura, Yoshihiro

    2016-11-09

    Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine the contribution of the signaling of S1P and S1PRs expressed in airway epithelial cells (ECs) to asthma responses in mice. Bronchial asthma was experimentally induced in BALB/c mice by ovalbumin (OVA) sensitization followed by an OVA inhalation challenge. The effects of S1PR antagonists on the development of asthma were analyzed 24 h after the OVA challenge. Immunohistological analysis revealed S1PR1-3 expression on mouse airway ECs. Quantitative real-time polymerase chain reaction demonstrated that S1P greatly stimulated the induction of CCL3 and TIMP2 mRNA in human airway ECs, i.e., BEAS-2B cells, in a dose-dependent manner. Pretreatment with the S1PR2 antagonist JTE013 inhibited the CCL3 gene expression in BEAS-2B cells. Immunohistological analysis also showed that the expression level of CCL3 was attenuated by JTE013 in asthmatic mice. Furthermore, JTE013 as well as anti-CCL3 antibody attenuated allergic responses. Intratracheal administration of JTE013 also attenuated eosinophilic reactions in bronchoalveolar lavage fluids. S1P induced transcription factor NFκB activation, while JTE013 greatly reduced the NFκB activation. JTE013 attenuated allergic airway reactions by regulating CCL3 production from bronchial ECs. The intratracheal administration of JTE013 may be a promising therapeutic strategy for bronchial asthma.

  14. Nonspecific airway reactivity in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Collie, D.D.; Wilder, J.A.; Bice, D.E.

    1995-12-01

    Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

  15. Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

    Science.gov (United States)

    Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

    2014-05-01

    New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (PmCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (PmCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (PmCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. A systematic review of predictive models for asthma development in children.

    Science.gov (United States)

    Luo, Gang; Nkoy, Flory L; Stone, Bryan L; Schmick, Darell; Johnson, Michael D

    2015-11-28

    Asthma is the most common pediatric chronic disease affecting 9.6 % of American children. Delay in asthma diagnosis is prevalent, resulting in suboptimal asthma management. To help avoid delay in asthma diagnosis and advance asthma prevention research, researchers have proposed various models to predict asthma development in children. This paper reviews these models. A systematic review was conducted through searching in PubMed, EMBASE, CINAHL, Scopus, the Cochrane Library, the ACM Digital Library, IEEE Xplore, and OpenGrey up to June 3, 2015. The literature on predictive models for asthma development in children was retrieved, with search results limited to human subjects and children (birth to 18 years). Two independent reviewers screened the literature, performed data extraction, and assessed article quality. The literature search returned 13,101 references in total. After manual review, 32 of these references were determined to be relevant and are discussed in the paper. We identify several limitations of existing predictive models for asthma development in children, and provide preliminary thoughts on how to address these limitations. Existing predictive models for asthma development in children have inadequate accuracy. Efforts to improve these models' performance are needed, but are limited by a lack of a gold standard for asthma development in children.

  17. Effect of Orem's Self-Care Model on Self-Esteem of Adolescents with Asthma Referred to an Asthma and Allergy Clinic in Isfahan.

    Science.gov (United States)

    Hemati, Zeinab; Mosaviasl, Fatemeh Sadat; Abasi, Samira; Ghazavi, Zohre; Kiani, Davood

    2015-01-01

    Acquisition of chronic diseases such as asthma leads to psychological, mental and physical complications in adolescents, and hence their self-esteem may be compromised. Therefore, the present study was conducted to assess the effect of Orem's self-care model on self-esteem of adolescents with asthma. This semi-experimental study enrolled 64 asthmatic adolescents referred to Shariati Hospital, Isfahan. Subjects were assigned to two groups of control and intervention consecutively. Then, the self-care training program was conducted according to Orem's self-care model in eight two-hour sessions based on self-care needs, and self-esteem was measured in the two groups prior to and two months after the last training session. The data were collected by a questionnaire of demographic characteristics and the Coopersmith Self-Esteem Inventories (CSEI) and analyzed by SPSS version 20. Independent t-test showed a significant difference in the mean score of self-esteem between the intervention and control groups after the training (Pself-esteem before and after the training in the intervention group (P0.05). Regarding the effect of Orem's self-care model on self-esteem of adolescents with asthma, we recommend the use of this model as a care intervention in healthcare centers to promote adolescents' health.

  18. A refined QSAR model for prediction of chemical asthma hazard.

    Science.gov (United States)

    Jarvis, J; Seed, M J; Stocks, S J; Agius, R M

    2015-11-01

    A previously developed quantitative structure-activity relationship (QSAR) model has been extern ally validated as a good predictor of chemical asthma hazard (sensitivity: 79-86%, specificity: 93-99%). To develop and validate a second version of this model. Learning dataset asthmagenic chemicals with molecular weight (MW) chemicals for which no reported case(s) of occupational asthma had been identified were selected at random from UK and US occupational exposure limit tables. MW banding was used in an attempt to categorically match the control group for MW distribution of the asthmagens. About 10% of chemicals in each MW category were excluded for use as an external validation set. An independent researcher utilized a logistic regression approach to compare the molecular descriptors present in asthmagens and controls. The resulting equation generated a hazard index (HI), with a value between zero and one, as an estimate of the probability that the chemical had asthmagenic potential. The HI was determined for each compound in the external validation set. The model development sets comprised 99 chemical asthmagens and 204 controls. The external validation showed that using a cut-point HI of 0.39, 9/10 asthmagenic (sensitivity: 90%) and 23/24 non-asthmagenic (specificity: 96%) compounds were correctly predicted. The new QSAR model showed a better receiver operating characteristic plot than the original. QSAR refinement by iteration has resulted in an improved model for the prediction of chemical asthma hazard. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. The Common Sense Model in early adolescents with asthma: longitudinal relations between illness perceptions, asthma control and emotional problems mediated by coping.

    Science.gov (United States)

    Tiggelman, Dana; van de Ven, Monique O M; van Schayck, Onno C P; Kleinjan, Marloes; Engels, Rutger C M E

    2014-10-01

    The present study examined the longitudinal relations between illness perceptions and asthma control and emotional problems (i.e., anxiety, depression, stress), respectively, in adolescents with asthma. Furthermore, the mediating effects of asthma-specific coping strategies on these relations were examined, as specified in the Common Sense Model (CSM). In 2011, 2012, and 2013, adolescents (aged 10-15) with asthma were visited at home (N=253) and completed questionnaires about their illness perceptions, asthma-specific coping strategies, asthma control, symptoms of anxiety and depression, and perceived stress. Path analyses were used to examine the direct relations of illness perceptions with asthma control and emotional problems and the mediating effects of coping strategies cross-sectionally and longitudinally. Perceptions of less perceived control and attributing more complaints to asthma were associated with better asthma control. Perceptions of more concern, less coherence, and increased influence of asthma on emotional well-being were associated with more emotional problems. Longitudinally, perceptions of more treatment control and fewer concerns predicted less emotional problems over time. More worrying mediated the cross-sectional relation between perceiving more concern about asthma and less asthma control and the longitudinal relation between perceiving more concern about asthma and more emotional problems. Illness perceptions were associated with asthma control and emotional problems; however, over time, illness perceptions only predicted changes in emotional problems. Most coping strategies did not mediate the relation between illness perceptions and outcomes. Interventions aimed to change illness perceptions in adolescents with asthma could decrease emotional problems. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Upper airway inflammation exacerbates bronchial hyperreactivity in mouse models of rhinosinusitis and allergic asthma.

    Science.gov (United States)

    Liang, Kai-Li; Jiang, Rong-San; Wang, Ren-Ching; Koo, Malcolm; Chen, Shyh-Chang; Huang, Wan-Chun; Yeh, Yueh-Chiao

    2013-07-01

    Recent studies have suggested that upper airway inflammation has a strong impact on lower airway diseases. The purpose of this study was to assess whether nasal inflammation could exacerbate allergic asthma in a mouse model. Mice were assigned to 4 groups: control (Cont), either rhinosinusitis (R) or allergic asthma (A) alone, and both rhinosinusitis and allergic asthma (R&A). Mice underwent induction of nasal inflammation (R and R&A) or sham surgery (Cont and A) on day 1. Mice in the A and R&A groups were sensitized to ovalbumin on days 1, 7, and 14, followed by aerosol challenge on days 18 to 20, whereas in the Cont and R groups only saline was administered. All mice were assessed for airway hyperresponsiveness (AHR) and were euthanized on day 21. The sera, bronchoalveolar lavage fluids (BALFs), and nasal and lung tissues were collected for further analyses. Histology findings confirmed upper and lower airway inflammation in experimental mice. Significantly increased AHR and total serum immunoglobulin E (IgE) were observed in the R&A group when compared with those of the Cont, R, and A groups. Responses to IgG2a induction were also found in sera and BALFs from mice with rhinosinusitis (R and R&A). Higher levels of interleukin 4 (IL-4) and IL-13, and increased eosinophilic inflammation were detected in BALFs and lung tissues from the experimental groups when compared with those from the Cont group. Our results confirm that upper airway inflammation could exacerbate allergic asthma, and provide support to the concept of "one airway, one disease. © 2013 ARS-AAOA, LLC.

  1. Models of experimental epilepsy

    Directory of Open Access Journals (Sweden)

    Fatih Ekici

    2011-03-01

    Full Text Available Epilepsy is the most common serious neurological conditionin the world, with an estimated prevalence of 1% ofthe population. A large number of experimental modelsof seizure and epilepsy have been developed. These experimentalmodels are elicited by chemical convulsants,electrical stimulation, genetic models, structural lesions,physical stimuli (cold, pressure, hyperthermia, electricalin animals. Well-characterized animal models may allowthe understanding of the basic mechanisms underlyingepileptogenesis (it refers to the alteration of a normalneuronal network into a hyperexcitable network in whichrecurrent, spontaneous seizures occur. Moreover, thesemodels might also prove useful in identifying novel therapeuticapproaches to treatment of epilepsy. J Clin ExpInvest 2011; 2(1: 118-123

  2. Anti-asthmatic activity of osthole in an ovalbumin-induced asthma murine model.

    Science.gov (United States)

    Wang, Jingjing; Fu, Yunhe; Wei, Zhengkai; He, Xuexiu; Shi, Mingyu; Kou, Jinhua; Zhou, Ershun; Liu, Weijian; Yang, Zhengtao; Guo, Changming

    2017-05-01

    Osthole, an active coumarin extracted from the dried fruits of Cnidium monnieri (L.) Cusson, is known to possess a variety of pharmacological activities. In the present study, we investigated and illuminated the mechanisms underlying the protective effects of osthole in an experimental model of allergic asthma. Our results show that osthole treatment significantly reduced the OVA-induced increase in serum IgE and inflammatory cytokines (IL-4, IL-5, IL-13) in bronchoalveolar lavage fluid (BALF), and decreased the recruitment of inflammatory cells in BALF and the lung. It also effectively attenuated goblet cell hyperplasia and mucus overproduction in lung tissue. In addition, western blot analysis demonstrated that osthole blocked NF-κB activation, which may be associated with a reduction in inflammatory cytokine production. These data suggest that osthole attenuated OVA-induced allergic asthma inflammation by inhibiting NF-κB activation. The present study identified the molecular mechanisms of action of osthole, which support the potential pharmaceutical application of osthole treatment for asthma and other airway inflammation disorders. Copyright © 2017. Published by Elsevier B.V.

  3. Pharmacological and pharmacokinetic studies with vitamin D-loaded nanoemulsions in asthma model.

    Science.gov (United States)

    Wei-hong, Tang; Min-chang, Guan; Zhen, Xu; Jie, Sun

    2014-06-01

    Vitamin D (VD) was studied for its anti-inflammatory activities with prepared VD-loaded nanoemulsions (VDNM) in ovalbumin-induced asthmatic mice in this paper. In this study, we prepared VDNM for the delivery of VD from the established composition of solid self-emulsifying drug delivery systems (sSEDDS) by spray-drying technique and evaluated its bioavailability (BA) and anti-inflammatory activities in experimental allergic asthma. After the mice were treated orally with VD or VDNM, the plasma 25(OH) D levels, polymorphonuclear cells, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), total antioxidant activity, and C3 and C4 complement protein levels were studied, respectively. Treatment with VDNM reduced MPO activity, oxidative stress, C3 protein level, O2(-) level as well as the production of IL-1β and TNF-α. Pharmacokinetic studies showed that a significant increase in the maximum concentration (Cmax) and AUC0→24 h were observed in VDNM group when compared with VD group (P asthma model. These data provided an important proof that VDNM might be a new potential therapy for the management of asthma in humans.

  4. Role of community pharmacists in asthma – Australian research highlighting pathways for future primary care models

    Directory of Open Access Journals (Sweden)

    Saini B

    2011-04-01

    Full Text Available Asthma is one of the most common chronic conditions affecting the Australian population. Amongst primary healthcare professionals, pharmacists are the most accessible and this places pharmacists in an excellent position to play a role in the management of asthma. Globally, trials of many community pharmacy-based asthma care models have provided evidence that pharmacist delivered interventions can improve clinical, humanistic and economic outcomes for asthma patients. In Australia, a decade of coordinated research efforts, in various aspects of asthma care, has culminated in the implementation trial of the Pharmacy Asthma Management Service (PAMS, a comprehensive disease management model. There has been research investigating asthma medication adherence through data mining, ways in which usual asthma care can be improved. Our research has focused on self-management education, inhaler technique interventions, spirometry trials, interprofessional models of care, and regional trials addressing the particular needs of rural communities. We have determined that inhaler technique education is a necessity and should be repeated if correct technique is to be maintained. We have identified this effectiveness of health promotion and health education, conducted within and outside the confines of the pharmacy, in public for a and settings such as schools, and established that this outreach role is particularly well received and increases the opportunity for people with asthma to engage in their asthma management. Our research has identified that asthma patients have needs which pharmacists delivering specialized models of care, can address. There is a lot of evidence for the effectiveness of asthma care by pharmacists, the future must involve integration of this role into primary care.

  5. Using structural equation modeling to understand child and parent perceptions of asthma quality of life.

    Science.gov (United States)

    Annett, Robert D; Turner, Charles; Brody, Janet L; Sedillo, Donna; Dalen, Jeanne

    2010-09-01

    Using structural equation modeling, test a conceptual model of associations between constructs predicting parent and child asthma quality of life. Children with a confirmed asthma diagnosis and their parents completed measures of health status and independently reported on psychological functioning, family functioning, and quality of life. Measurement and structural models for predicting parent and child quality of life provided a good fit of data to the conceptual model. Parent and child independent reports of quality of life are dependent upon family functioning and child psychological functioning. Long-term asthma symptom control is the only health status variable that impacts quality of life. With minor modifications, both parent and child data fit the conceptual model. Child psychological functioning and long-term asthma control jointly contribute to quality of life outcomes. Findings suggest that both acute and long-term asthma health status outcomes have different determinants.

  6. Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review.

    Science.gov (United States)

    Kianmeher, Majid; Ghorani, Vahideh; Boskabady, Mohammad Hosein

    2016-12-01

    Asthma is a chronic inflammatory disease of the airway with extensive airway remodeling. The ethical issues associated with the studies in asthmatic patients, required development of animal model of asthma. Animal models of asthma can provide valuable information on several features of asthma pathogenesis and treatment. Although these models cannot carry out all clinical features, they are valuable to understand mechanisms of the disease and curative access. Related articles were searched in different databases from September 1994 to April 2016 using; animal model of asthma, animal sensitization, allergen-induced asthma in animals terms. Although there are several reviews on this topic, in the present article, induction of animal model of asthma in different animals, various methods used for this purpose, measured parameters and research purposes were reviewed, which will help investigators to use the appropriate animal, methods, and evaluating parameters depending on their study design. In this study various method used for induction of animal model of asthma in different animals and measured parameters were described, which will help investigators to use the appropriate animal, method and evaluating parameters depending on their study design.

  7. Effect of mesenchymal stem cells on allergic asthma in mouse model

    Directory of Open Access Journals (Sweden)

    Reza Habibian

    2015-08-01

    Conclusion: In the present study, we demonstrated the inhibitory effect of MSCs on airway inflammation using mice model of allergic asthma. The mice were sensitized with OVA and compared to the results of dexamethasone administration. Our results demonstrated that administration of MSCs could be used as a potential therapeutic approach for the allergic asthma.

  8. An experimental examination of learned helplessness in older adolescents and young adults with long-standing asthma.

    Science.gov (United States)

    Chaney, J M; Mullins, L L; Uretsky, D L; Pace, T M; Werden, D; Hartman, V L

    1999-06-01

    To examine the effects of experimentally induced learned helplessness in older adolescents and young adults with long-standing asthma. Thirty-nine participants (18-24 years of age) with histories of long-standing asthma (AS) and an age-matched healthy cohort (HC) (N = 94) received either contingent or noncontingent feedback on an experimental task. Participants' anagram-solving performance was assessed following the experimental procedure. Participants also completed a measure of depression and pretest-posttest measures of mood, expectancy, and attributions related to experimental task performance. The AS participants demonstrated significantly greater problem-solving deficits following response-noncontingent feedback, compared to the HC group. Further, whereas both AS and HC participants made more internal performance attributions when given response-contingent feedback, only AS participants demonstrated a pattern of increased internal attributions (i.e., self-focus) following response-noncontingent failure. In addition, 21% of AS participants met DSM-IV criteria for major depression, compared to only 5% of the HC group. Individuals with long-standing asthma may be at increased risk for depression and for learned helplessness deficits, specifically impaired problem solving, in response to environmental noncontingency. Results are discussed in terms of both learned helplessness theory and perseverative self-focus conceptualizations of depression. The implications for both short- and long-term management of pediatric asthma are also discussed.

  9. Geospatial Modeling of Asthma Population in Relation to Air Pollution

    Science.gov (United States)

    Kethireddy, Swatantra R.; Tchounwou, Paul B.; Young, John H.; Luvall, Jeffrey C.; Alhamdan, Mohammad

    2013-01-01

    Current observations indicate that asthma is growing every year in the United States, specific reasons for this are not well understood. This study stems from an ongoing research effort to investigate the spatio-temporal behavior of asthma and its relatedness to air pollution. The association between environmental variables such as air quality and asthma related health issues over Mississippi State are investigated using Geographic Information Systems (GIS) tools and applications. Health data concerning asthma obtained from Mississippi State Department of Health (MSDH) for 9-year period of 2003-2011, and data of air pollutant concentrations (PM2.5) collected from USEPA web resources, and are analyzed geospatially to establish the impacts of air quality on human health specifically related to asthma. Disease mapping using geospatial techniques provides valuable insights into the spatial nature, variability, and association of asthma to air pollution. Asthma patient hospitalization data of Mississippi has been analyzed and mapped using quantitative Choropleth techniques in ArcGIS. Patients have been geocoded to their respective zip codes. Potential air pollutant sources of Interstate highways, Industries, and other land use data have been integrated in common geospatial platform to understand their adverse contribution on human health. Existing hospitals and emergency clinics are being injected into analysis to further understand their proximity and easy access to patient locations. At the current level of analysis and understanding, spatial distribution of Asthma is observed in the populations of Zip code regions in gulf coast, along the interstates of south, and in counties of Northeast Mississippi. It is also found that asthma is prevalent in most of the urban population. This GIS based project would be useful to make health risk assessment and provide information support to the administrators and decision makers for establishing satellite clinics in future.

  10. Role of eosinophilic airway inflammation in models of asthma

    Directory of Open Access Journals (Sweden)

    Lapa e Silva José R

    1997-01-01

    Full Text Available Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.

  11. Experimental Object-Oriented Modelling

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius

    and discuss techniques for handling and representing uncertainty when modelling in experimental system development. These techniques are centred on patterns and styles for handling uncertainty in object-oriented software architectures. Tools We present the Knight tool designed for collaborative modelling......This thesis examines object-oriented modelling in experimental system development. Object-oriented modelling aims at representing concepts and phenomena of a problem domain in terms of classes and objects. Experimental system development seeks active experimentation in a system development project...... through, e.g., technical prototyping and active user involvement. We introduce and examine “experimental object-oriented modelling” as the intersection of these practices. The contributions of this thesis are expected to be within three perspectives on models and modelling in experimental system...

  12. The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

    Science.gov (United States)

    Rojanasarot, Sirikan; Carlson, Angeline M

    2017-08-14

    The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

  13. Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations

    DEFF Research Database (Denmark)

    Silkoff, Philip E; Flavin, Susan; Gordon, Robert

    2017-01-01

    BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on...

  14. Forecasting peak asthma admissions in London: an application of quantile regression models

    Science.gov (United States)

    Soyiri, Ireneous N.; Reidpath, Daniel D.; Sarran, Christophe

    2013-07-01

    Asthma is a chronic condition of great public health concern globally. The associated morbidity, mortality and healthcare utilisation place an enormous burden on healthcare infrastructure and services. This study demonstrates a multistage quantile regression approach to predicting excess demand for health care services in the form of asthma daily admissions in London, using retrospective data from the Hospital Episode Statistics, weather and air quality. Trivariate quantile regression models (QRM) of asthma daily admissions were fitted to a 14-day range of lags of environmental factors, accounting for seasonality in a hold-in sample of the data. Representative lags were pooled to form multivariate predictive models, selected through a systematic backward stepwise reduction approach. Models were cross-validated using a hold-out sample of the data, and their respective root mean square error measures, sensitivity, specificity and predictive values compared. Two of the predictive models were able to detect extreme number of daily asthma admissions at sensitivity levels of 76 % and 62 %, as well as specificities of 66 % and 76 %. Their positive predictive values were slightly higher for the hold-out sample (29 % and 28 %) than for the hold-in model development sample (16 % and 18 %). QRMs can be used in multistage to select suitable variables to forecast extreme asthma events. The associations between asthma and environmental factors, including temperature, ozone and carbon monoxide can be exploited in predicting future events using QRMs.

  15. The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model

    Directory of Open Access Journals (Sweden)

    Fabian M Patricia

    2012-09-01

    Full Text Available Abstract Background In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. Methods We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%, which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Results Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. Conclusions We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens

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

    Science.gov (United States)

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

    2017-06-24

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

  17. A simulation model of building intervention impacts on indoor environmental quality, pediatric asthma, and costs.

    Science.gov (United States)

    Fabian, Maria Patricia; Adamkiewicz, Gary; Stout, Natasha Kay; Sandel, Megan; Levy, Jonathan Ian

    2014-01-01

    Although indoor environmental conditions can affect pediatric asthmatic patients, few studies have characterized the effect of building interventions on asthma-related outcomes. Simulation models can evaluate such complex systems but have not been applied in this context. We sought to evaluate the impact of building interventions on indoor environmental quality and pediatric asthma health care use, and to conduct cost comparisons between intervention and health care costs and energy savings. We applied our previously developed discrete event simulation model (DEM) to simulate the effect of environmental factors, medication compliance, seasonality, and medical history on (1) pollutant concentrations indoors and (2) asthma outcomes in low-income multifamily housing. We estimated health care use and costs at baseline and subsequent to interventions, and then compared health care costs with energy savings and intervention costs. Interventions, such as integrated pest management and repairing kitchen exhaust fans, led to 7% to 12% reductions in serious asthma events with 1- to 3-year payback periods. Weatherization efforts targeted solely toward tightening a building envelope led to 20% more serious asthma events, but bundling with repairing kitchen exhaust fans and eliminating indoor sources (eg, gas stoves or smokers) mitigated this effect. Our pediatric asthma model provides a tool to prioritize individual and bundled building interventions based on their effects on health and costs, highlighting the tradeoffs between weatherization, indoor air quality, and health. Our work bridges the gap between clinical and environmental health sciences by increasing physicians' understanding of the effect that home environmental changes can have on their patients' asthma. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  18. The effect of the training program on the quality of life in patients with asthma based on the Precede model in Ahvaz, Iran.

    Science.gov (United States)

    Nejad, Mina Motaghi; Nejad, Ghodratollah Shakeri; Tavakol, Heshmatollah; Cheraghi, Maria

    2017-06-01

    The aim of the study was to determine the effect of the training program based on the Precede model and its main components on improving the quality of life in patients with asthma. It was a randomized quasi-experimental study done on 120 patients with asthma who were referred to the Imam Khomeini hospital in Ahvaz who were selected using the convenience sampling method and were randomly divided into intervention and control groups. The data collection tool consisted of two questionnaires. The first questionnaire evaluated the quality of life in patients with asthma and the other one was developed by the researcher based on the structures of the Precede model. Training intervention was conducted during four sessions twice a week and each session was carried out for an hour based on the structures of the Precede model. In order to achieve the results, SPSS software, even t-test, and χ(2) were used. The results showed that after the training intervention in the experimental group, the mean scores of predisposing factors (p quality of life in two groups after the intervention (p quality of life of patients in the experimental group was improved after the training intervention. The design and implementation of the training program based on the Precede model can have a positive effect on the improvement of quality of life in patients with asthma.

  19. Phytochemical profiles and biological activity evaluation of Zanthoxylum bungeanum Maxim seed against asthma in murine models.

    Science.gov (United States)

    Tang, Weizhuo; Xie, Qiangmin; Guan, Jian; Jin, Saihong; Zhao, Yuqing

    2014-03-28

    Zanthoxylum bungeanum Maxim seed (ZBMS) has been used in Traditional Chinese Medicine (TCM) as an ingredient of polyherbal formulations for the treatment of inflammation and asthma. The aim of this study was to analyze the major composition and to evaluate the anti-asthma activity of ZBMS. Some murine models including acetylcholine/histamine-induced asthma, ovalbumin-induced airway inflammation, ear edema and toe swelling measurement, citric acid-induced cough, and anti-stress abilities were investigated to fully study the anti-asthma activity of ZBMS.GC chromatography was also performed to analyze the major fatty acid composition of ZBMS. The results demonstrated that the major fatty acid composition of ZBMS includes oleic acid (20.15%), linoleic acid (26.54%), and α-linolenic acid (30.57%), which was the leading component of ZBMS, and that the total fatty acid content of ZBMS was 77.27%. The murine models demonstrated that ZBMS displays a protective effect on guinea pig sensitization, a dose-dependent inhibition of the increases in RL and decreases in Cdyn, which resulted in the relief of auricle edema and toe swelling in mice and anti-stress activity. Our results validate the traditional use of ZBMS for the treatment of asthma and other inflammatory joint disorders, and suggest that ZBMS has potential as a new therapeutic agent for asthma management. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Cytogenetics and experimental models.

    Science.gov (United States)

    Toretsky, J A; Helman, L J

    1997-07-01

    The use of cytogenetics has led to significant improvement in the diagnoses and classification of sarcomas. Many of the major sarcomas have been to have characteristic tumor-specific chromosomal translocations that are currently used in the diagnosis of these tumors. In the past year, a subset of Ewing's family of tumors and myxoid liposarcomas, which lack one of the characteristic translocations, were found to carry related translocations. New technologies such as a spectral karyotyping will likely increase out ability to identify additional tumor-specific translocations. The emergence of genetic alterations as prognostic factors, as illustrated by Ewing's family of tumors, osteosarcoma, and p53 expression in soft tissue sarcomas in general, is discussed. The review concludes with laboratory applications derived from either tumor cytogenetic or gene function abnormalities that are related to tumor-specific translocations. It is anticipated that advances in diagnosis, prognosis, and modeling will translate into future therapeutic advances.

  1. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  2. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Chia-Rui Shen

    2015-11-01

    Full Text Available Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

  3. Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin-driven IL-9+and IL-13+type 2 innate lymphoid cell subpopulations.

    Science.gov (United States)

    Verma, Mukesh; Liu, Sucai; Michalec, Lidia; Sripada, Anand; Gorska, Magdalena M; Alam, Rafeul

    2017-11-10

    IL-33 plays an important role in the development of experimental asthma. We sought to study the role of the IL-33 receptor suppressor of tumorigenicity 2 (ST2) in the persistence of asthma in a mouse model. We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness by using flexiVent; inflammatory indices by using ELISA, histology, and real-time PCR; and type 2 innate lymphoid cells (ILC2s) in lung single-cell preparations by using flow cytometry. Airway hyperresponsiveness was increased in allergen-treated ST2 KO mice and comparable with that in allergen-treated wild-type control mice. Peribronchial and perivascular inflammation and mucus production were largely similar in both groups. Persistence of experimental asthma in ST2 KO mice was associated with an increase in levels of thymic stromal lymphopoietin (TSLP), IL-9, and IL-13, but not IL-5, in bronchoalveolar lavage fluid. Expectedly, ST2 deletion caused a reduction in IL-13 + CD4 T cells, forkhead box P3-positive regulatory T cells, and IL-5 + ILC2s. Unexpectedly, ST2 deletion led to an overall increase in innate lymphoid cells (CD45 + lin - CD25 + cells) and IL-13 + ILC2s, emergence of a TSLP receptor-positive IL-9 + ILC2 population, and an increase in intraepithelial mast cell numbers in the lung. An anti-TSLP antibody abrogated airway hyperresponsiveness, inflammation, and mucus production in allergen-treated ST2 KO mice. It also caused a reduction in innate lymphoid cell, ILC2, and IL-9 + and IL-13 + ILC2 numbers in the lung. Genetic deletion of the IL-33 receptor paradoxically increases TSLP production, which stimulates the emergence of IL-9 + and IL-13 + ILC2s and mast cells and leads to development of chronic experimental asthma. An anti-TSLP antibody abrogates all pathologic features of asthma in this model. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Epigenetics, asthma, and allergic diseases: a review of the latest advancements.

    Science.gov (United States)

    Lovinsky-Desir, Stephanie; Miller, Rachel L

    2012-06-01

    Environmental epigenetic regulation in asthma and allergic disease is an exciting area that has gained a great deal of scientific momentum in recent years. Environmental exposures, including prenatal maternal smoking, have been associated with asthma-related outcomes that may be explained by epigenetic regulation. In addition, several known allergy and asthma genes have been found to be susceptible to epigenetic regulation. We review the latest experimental and translational studies that have been published this past year in several areas, including 1) characterization of environmental asthma triggers that induce epigenetic changes, 2) characterization of allergic immune and regulatory pathways important to asthma that undergo epigenetic regulation, 3) evidence of active epigenetic regulation in asthma experimental models and the production of asthma biomarkers, 4) evidence of transmission of an asthma-related phenotype across multiple generations, and 5) "pharmaco-epigenetics." The field has certainly advanced significantly in the past year.

  5. The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma.

    Science.gov (United States)

    Liu, Chentao; Huang, Rong; Yao, Rujie; Yang, Aimei

    2017-10-01

    Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response. Asthmatic mice models were established with OVA challenge and treated with oral administration of Broncho-Vaxom (OM-85). Next, infiltrations of inflammatory cells including eosinophil and neutrophils were examined. Pulmonary tissues in asthmatic mice models were analyzed by hematoxylin and eosin (HE) staining. The levels of Th1/Th2-typed cytokines in bronchoalveolar lavage fluid (BALF) of asthmatic mice models were examined by enzyme-linked immunosorbent assay. Compared to control group, we found significant reduction of airway wall thickness, luminal stenosis, and mucus plug formation in asthmatic mice models after oral administration of OM-85. The infiltrations of eosinophil were also significantly decreased in BALF in asthmatic mice models. Oral administration of OM-85 was shown to suppress Th2-type cytokine levels. Our findings provide evidence that oral administration of OM-85 is capable of attenuating airway inflammation in asthmatic mice models. Oral administration of OM-85 may have a positive impact in terms of asthma severity.

  6. Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

    Science.gov (United States)

    Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

    2017-03-04

    Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. PEMFC modeling and experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, J.V.C. [Federal University of Parana (UFPR), Curitiba, PR (Brazil). Dept. of Mechanical Engineering], E-mail: jvargas@demec.ufpr.br; Ordonez, J.C.; Martins, L.S. [Florida State University, Tallahassee, FL (United States). Center for Advanced Power Systems], Emails: ordonez@caps.fsu.edu, martins@caps.fsu.edu

    2009-07-01

    In this paper, a simplified and comprehensive PEMFC mathematical model introduced in previous studies is experimentally validated. Numerical results are obtained for an existing set of commercial unit PEM fuel cells. The model accounts for pressure drops in the gas channels, and for temperature gradients with respect to space in the flow direction, that are investigated by direct infrared imaging, showing that even at low current operation such gradients are present in fuel cell operation, and therefore should be considered by a PEMFC model, since large coolant flow rates are limited due to induced high pressure drops in the cooling channels. The computed polarization and power curves are directly compared to the experimentally measured ones with good qualitative and quantitative agreement. The combination of accuracy and low computational time allow for the future utilization of the model as a reliable tool for PEMFC simulation, control, design and optimization purposes. (author)

  8. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  9. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model

    NARCIS (Netherlands)

    Vissers, Joost L. M.; van Esch, Betty C. A. M.; Hofman, Gerard A.; Kapsenberg, Martien L.; Weller, Frank R.; van Oosterhout, Antoon J. M.

    2004-01-01

    Background: Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma

  10. Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    previously associated with asthma validate this equine model for gene expression studies.

  11. Deficiency of KLF4 compromises the lung function in an acute mouse model of allergic asthma.

    Science.gov (United States)

    Nimpong, Jeanette A; Gebregziabher, Wintana; Singh, Udai P; Nagarkatti, Prakash; Nagarkatti, Mitzi; Hodge, Johnie; Liu, Chunming; Fan, Daping; Ai, Walden

    2017-11-04

    Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known. Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine and a key initiator of allergic airway inflammation. Given the fact that TSLP promotes Th2 cytokine production that increases MDSC differentiation into fibrocytes, we postulate that KLF4 regulates asthma in a TSLP-dependent manner. In this study, we utilized a model of allergic asthma with ovalbumin challenge (OVA). We found that upon OVA treatment the wild type mice had increased MDSC infiltration into the lung, up-regulation of KLF4 and TSLP gene expression, and higher levels of Th2 cytokines including IL4 and IL13. Consistently, lack of KLF4 expression in monocytes and lung epithelial cells resulted in decreased TSLP expression and lower levels of Th2 cytokines in mice, and fibrocyte generation was compromised. KLF4 deficiency in these cells also led to decreased airway hyperresponsiveness (AHR), a cardinal feature of asthma, as assessed by whole body plethysmography. Moreover, lung fibrosis as measured by trichome staining was attenuated and the population of CD45 + COL1A1+ fibrocytes was diminished in this setting. Together, our results suggest that KLF4 regulates asthma development in a TSLP- and fibrocyte-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. THE EXPERIMENTAL MODEL OF OSTEONECROSIS

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    G. I. Netylko

    2010-01-01

    Full Text Available The experimental investigation for the purpose of modeling of knee osteonecrosis were performed in 36 rats. The chronic renal insufficiency by means of left nephrectomy and electrocoagulation in 25% cortical substance of right kidney was induced before 6 months till experiment with subsequent introduction of 0,1% adrenalin solution and methylprednisolone in paraarticular structures. The results of experiment showed the polyetiologic feature of disease.

  13. The updated experimental proteinoid model

    Science.gov (United States)

    Fox, S. W.; Nakashima, T.; Przybylski, A.; Syren, R. M.

    1982-01-01

    The experimental proteinoid model includes new results indicating that polymers sufficiently rich in basic amino acid catalyze the synthesis of peptides from ATP and amino acids and of oligonucleotides from ATP. The need for simulation syntheses of amino acids yielding significant proportions of basic amino acids is now in focus. The modeled simultaneous protocellular synthesis of peptides and polynucleotides is part of a more comprehensive proposal for the origin of the coded genetic mechanism. The finding of membrane and action potentials in proteinoid microspheres, with or without added lecithin, is reported. The crucial nature of a nonrandom matrix for protocells is developed.

  14. Modeling of regional climate change effects on ground-level ozone and childhood asthma.

    Science.gov (United States)

    Sheffield, Perry E; Knowlton, Kim; Carr, Jessie L; Kinney, Patrick L

    2011-09-01

    The adverse respiratory effects of ground-level ozone are well established. Ozone is the air pollutant most consistently projected to increase under future climate change. To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s. This study assessed future numbers of asthma emergency department visits for children aged 0-17 years using (1) baseline New York City metropolitan area emergency department rates; (2) a dose-response relationship between ozone levels and pediatric asthma emergency department visits; and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010. In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0-17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger. The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes, such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

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    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  16. Using the Health Belief Model to Understand School Nurse Asthma Management

    Science.gov (United States)

    Quaranta, Judith E.; Spencer, Gale A.

    2015-01-01

    Ten million children in the United States have asthma. Since children are in school about 6 hr a day, school nurses are positioned to intervene and influence asthma outcomes. A descriptive correlational study was designed to investigate performance of school nurses' asthma management behaviors in relationship to asthma knowledge, asthma attitude,…

  17. Effects of a self-management asthma educational program in Taiwan based on PRECEDE-PROCEED model for parents with asthmatic children.

    Science.gov (United States)

    Chiang, Li-Chi; Huang, Jing-Long; Yeh, Kuo-Wei; Lu, Chang-Ming

    2004-04-01

    This study was conducted to evaluate the comparative effectiveness of two different asthma educational programs. One was self-management asthma education based on the PRECEDE-PROCEED model to change the influential factors based on a previous need assessment study in Taiwan. The other consisted of regular outpatient asthma education. The purposes were: 1) to compare differences in the asthma knowledge, self-efficacy, perceived effectiveness, children's cooperation, doctor-patient communication, and self-management behaviors in the experimental and control groups before education, and 2 weeks, 3 months, and 6 months after education; and 2) to compare differences in drug use, medication utilization, asthma severity, signs/symptoms of asthma, school absenteeism, and exercise ability before education, and 2 weeks, 3 months, and 6 months after education. Parents of asthmatic children were recruited from among outpatients of Chang Gung Children's Hospital, Taoyuan, Taiwan. They were grouped by registration number: those with even numbers were assigned to the experimental group, and those with odd numbers were assigned to the control group. Measurements were collected four times from all parents by means of a questionnaire and chart review. The General Linear Model: Repeat Measurement was used to compare variance differences. The following results were found. 1) Asthma knowledge, self-efficacy, perceived effectiveness, children's cooperation, and self-management behaviors significantly improved after the self-management asthma educational program based on PRECEDE-PROCEED. Except for perceived effectiveness, all variables still had good effectiveness after 6 months of follow-up. The experimental group was better than the control group in knowledge, children's cooperation, and self-management behaviors at the 3-month follow up, as well as in knowledge and children's cooperation at the 6-month follow-up. 2) In both the experimental and control groups, the educational program

  18. Asthma Basics

    Science.gov (United States)

    ... Giving Teens a Voice in Health Care Decisions Asthma KidsHealth > For Parents > Asthma Print A A A ... Should I Know? en español Asma What Is Asthma? Asthma is a condition that causes breathing problems. ...

  19. Effect of Orem’s Self-Care Model on Perceived Stress in Adolescents with Asthma Referring the Asthma and Allergy Clinic, Isfahan, 2014

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    Zeinab Hemati

    2016-07-01

    Full Text Available Background: Incidence of asthma in adolescents leads to variations in family status, roles and interaction with peers for them, which could be a source of stress and psychological tensions in them. Therefore, the present study was conducted to investigate the effect of Orem’s self-care model on perceived stress in adolescents with asthma. Methods: In this semi-experimental study conducted from April 2013 to February 2014, 64 asthmatic adolescents referring Shariati Hospital, Isfahan were enrolled by simple random sampling and the patients were assigned to two groups of control and intervention. Then, Orem’s self-care model-based training was implemented throughout eight sessions of two hours each and the Cohen Perceived Stress Scale was administered to both groups prior to and two months after the completion of the training. The data were analyzed by descriptive and analytical statistics consisting of paired t-test, independent t-test, Chi-square and Mann-Whitney using SPSS Version 20. Results: Mean age of the participants was 14.15±3.12 years in the intervention group and 15.21±3.09 years in the control groups. 68.8% and 59.4% of the participants were male in the intervention and control groups, respectively. Independent t-test indicated a significant difference in the mean scores of perceived stress in the intervention (25.46±5.31 and control groups (28.90±5.27 after the training. Also, the result of paired t-test indicated a significant difference in the mean score of perceived stress between before (29.18±5.27 and after (25.46±5.31 training. Conclusion: As the training based on Orem’s model had a positive effect on declining perceived stress in asthmatic adolescents, continuation of using these training interventions could contribute to ultimately achieving positive outcomes in health functions of these patients.

  20. Epithelial Ovarian Cancer Experimental Models

    Science.gov (United States)

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

  1. The effect of the training program on the quality of life in patients with asthma based on the Precede model in Ahvaz, Iran

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    Mina Motaghi Nejad

    2017-05-01

    Full Text Available Aim: The aim of the study was to determine the effect of the training program based on the Precede model and its main components on improving the quality of life in patients with asthma. Material and methods: It was a randomized quasi-experimental study done on 120 patients with asthma who were referred to the Imam Khomeini hospital in Ahvaz who were selected using the convenience sampling method and were randomly divided into intervention and control groups. The data collection tool consisted of two questionnaires. The first questionnaire evaluated the quality of life in patients with asthma and the other one was developed by the researcher based on the structures of the Precede model. Training intervention was conducted during four sessions twice a week and each session was carried out for an hour based on the structures of the Precede model. In order to achieve the results, SPSS software, even t-test, and 2 were used. Results: The results showed that after the training intervention in the experimental group, the mean scores of predisposing factors (p < 0.001, enabling factors, reinforcing factors and behavioral factors were significantly increased (p < 0.001 as compared to the control group. A significant difference was observed in the mean scores of quality of life in two groups after the intervention (p < 0.001, and the quality of life of patients in the experimental group was improved after the training intervention. Conclusions : The design and implementation of the training program based on the Precede model can have a positive effect on the improvement of quality of life in patients with asthma.

  2. Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

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    Melissa M. Bunting

    2013-01-01

    Full Text Available We investigated the role of interleukin-33 (IL-33 in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  3. Leukotriene receptor antagonist attenuated airway inflammation and hyperresponsiveness in a double-stranded RNA-induced asthma exacerbation model

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    Mariko Ujino

    2017-09-01

    Conclusions: This is the first report showing that LTRA functionally suppressed the pathophysiology of a virus-induced asthma exacerbation model, suggesting the importance of cysLTs as a potential treatment target.

  4. Bronchodilatory and anti-inflammatory properties of inhaled selective phosphodiesterase inhibitors in a guinea pig model of allergic asthma

    NARCIS (Netherlands)

    Santing, R.E; de Boer, J; Rohof, A.A B; van der Zee, N.M; Zaagsma, Hans

    2001-01-01

    In a guinea pig model of allergic asthma, we investigated the effects of the selective phosphodiesterase inhibitors rolipram (phosphodiesterase 4-selective), Org 9935 (phosphodiesterase 3-selective) and Org 20241 (dual phosphodiesterase 4/phosphodiesterase 3-selective), administered by aerosol

  5. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Larsson, Emanuel [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); University of Trieste, Trieste (Italy); Linkoeping University, SE-581 83 Linkoeping (Sweden); Tromba, Giuliana [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); Markus, Andrea M. [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Alves, Frauke [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Max Planck Institut for Experimental Medicine, Hermann-Rein-Strasse 3, Goettingen, Lower Saxony 37075 (Germany)

    2015-06-17

    Synchrotron inline phase-contrast computed tomography in combination with single-distance phase retrieval enables quantification of morphological alterations in lungs of mice with mild and severe experimental allergic airways disease in comparison with healthy controls. Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, ‘Elettra’, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

  6. The Common Sense Model in early adolescents with asthma: Longitudinal relations between illness perceptions, asthma control and emotional problems mediated by coping

    NARCIS (Netherlands)

    Tiggelman, D.; Ven, M.O.M. van de; Schayck, C.P. van; Kleinjan, M.; Engels, R.C.M.E.

    2014-01-01

    Objective: The present study examined the longitudinal relations between illness perceptions and asthma control and emotional problems (i.e., anxiety, depression, stress), respectively, in adolescents with asthma. Furthermore, the mediating effects of asthma-specific coping strategies on these

  7. Experimental animal models of osteonecrosis.

    Science.gov (United States)

    Fan, Meng; Peng, Jiang; Qin, Ling; Lu, Shibi

    2011-08-01

    Osteonecrosis (ON) or avascular necrosis (AVN) is a common bone metabolic disorder, mostly affecting femoral head. Although many biological, biophysical, and surgical methods have been tested to preserve the femoral head with ON, none has been proven fully satisfactory. It lacks consensus on an optimal approach for treatment. This is due, at least in part, to the lack of ability to systematically compare treatment efficacy using an ideal animal model that mimics full-range osteonecrosis of femoral head (ONFH) in humans with high incidence of joint collapse accompanied by reparative reaction adjacent to the necrotic bone in a reproducible and accessible way. A number of preclinical animal ON models have been established for testing potential efficacy of various modalities developed for prevention and treatment of ON before introduction into clinics for potential applications. This paper describes a number of different methods for creating animal experimental ON models. Advantages and disadvantages of such models are also discussed as reference for future research in battle against this important medical condition.

  8. Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma.

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    Ying Lei

    Full Text Available In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma.

  9. Therapeutic Effects of S-Petasin on Disease Models of Asthma and Peritonitis

    Science.gov (United States)

    Lee, Kyoung-Pil; Kang, Saeromi; Noh, Min-Soo; Park, Soo-Jin; Kim, Jung-Min; Chung, Hae Young; Je, Nam Kyung; Lee, Young-Geun; Choi, Young-Whan; Im, Dong-Soon

    2015-01-01

    To explore the anti-allergic and anti-inflammatory effects of extracts of Petasites genus, we studied the effects of s-petasin, a major sesquiterpene from Petasites formosanus (a butterbur species) on asthma and peritonitis models. In an ovalbumin-induced mouse asthma model, s-petasin significantly inhibited the accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar fluids. S-petasin inhibited the antigen-induced degranulation of β-hexosamidase but did not inhibit intracellular Ca2+ increase in RBL-2H3 mast cells. S-petasin inhibited the LPS induction of iNOS at the RNA and protein levels in mouse peritoneal macrophages. Furthermore, s-petasin inhibited the production of NO (the product of iNOS) in a concentration-dependent manner in the macrophages. Furthermore, in an LPS-induced mouse model of peritonitis, s-petasin significantly inhibited the accumulation of polymorpho nuclear and mononuclear leukocytes in peritoneal cavity. This study shows that s-petasin in Petasites genus has therapeutic effects on allergic and inflammatory diseases, such as, asthma and peritonitis through degranulation inhibition in mast cells, suppression of iNOS induction and production of NO in macrophages, and suppression of inflammatory cell accumulation. PMID:25593643

  10. Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model.

    Science.gov (United States)

    Li, Kai; Huang, En Ping; Su, Jin; Zhu, Ping; Lin, Jun; Luo, Shen Qiu; Yang, Cui Lan

    2018-01-27

    Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam3CSK4. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2. © 2018 S. Karger AG, Basel.

  11. Effect of nintedanib on airway inflammation and remodeling in a murine chronic asthma model.

    Science.gov (United States)

    Lee, Hwa Young; Hur, Jung; Kim, In Kyoung; Kang, Ji Young; Yoon, Hyoung Kyu; Lee, Sook Young; Kwon, Soon Suk; Kim, Young Kyoon; Rhee, Chin Kook

    Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area. The expression of growth factor receptors was analyzed in mice lung tissues. The OVA challenged group showed a significant increase in airway eosinophilic inflammation, elevated Th2 cytokines, AHR, and airway remodeling compared to those in the control group. The airway remodeling process, as evaluated by goblet cell hyperplasia, total lung collagen level, and airway smooth muscle area, was suppressed by nintedanib compared to that by OVA. Nintedanib effectively suppressed the phosphorylation of vascular endothelial growth factor/ platelet derived growth factor subunit2/fibroblast growth factor3 receptors in the mice lung. Nintedanib effectively ameliorated airway inflammation and remodeling in an OVA-induced chronic asthma model. These results suggest that nintedanib could be a new treatment agent targeting airway remodeling in patients with severe asthma.

  12. Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

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    Kang JY

    2013-10-01

    Full Text Available Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA for 1 month (n = 8–12 per group. We analyzed inflammatory cells and T-helper (Th2 cytokines in bronchoalveolar lavage (BAL fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old mice than in the young (6-week-old mice. Interleukin (IL 4 (IL-4 concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma

  13. Transcription factor RBP-J-mediated signalling regulates basophil immunoregulatory function in mouse asthma model.

    Science.gov (United States)

    Qu, Shuo-Yao; He, Ya-Long; Zhang, Jian; Wu, Chang-Gui

    2017-09-01

    Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b+ microbeads. The recombination signal binding protein J (RBP-J-/- ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J-/- BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma. © 2017 John Wiley & Sons Ltd.

  14. [Fine particulate matter estimated by mathematical model and hospitalizations for pneumonia and asthma in children].

    Science.gov (United States)

    César, Ana Cristina Gobbo; Nascimento, Luiz Fernando Costa; Mantovani, Katia Cristina Cota; Pompeo Vieira, Luciana Cristina

    2016-01-01

    To estimate the association between exposure to fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and hospitalizations for pneumonia and asthma in children. An ecological study of time series was performed, with daily indicators of hospitalization for pneumonia and asthma in children up to 10 years of age, living in Taubaté (SP) and estimated concentrations of PM2.5, between August 2011 and July 2012. A generalized additive model of Poisson regression was used to estimate the relative risk, with lag zero up to five days after exposure; the single pollutant model was adjusted by the apparent temperature, as defined from the temperature and relative air humidity, seasonality and weekday. The values of the relative risks for hospitalization for pneumonia and asthma were significant for lag 0 (RR=1.051, 95%CI; 1.016 to 1.088); lag 2 (RR=1.066, 95%CI: 1.023 to 1.113); lag 3 (RR=1.053, 95%CI: 1.015 to 1.092); lag 4 (RR=1.043, 95%CI: 1.004 to 1.088) and lag 5 (RR=1.061, 95%CI: 1.018 to 1.106). The increase of 5mcg/m(3) in PM2.5 contributes to increase the relative risk for hospitalization from 20.3 to 38.4 percentage points; however, the reduction of 5μg/m(3) in PM2.5 concentration results in 38 fewer hospital admissions. Exposure to PM2.5 was associated with hospitalizations for pneumonia and asthma in children younger than 10 years of age, showing the role of fine particulate matter in child health and providing subsidies for the implementation of preventive measures to decrease these outcomes. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  15. Fine particulate matter estimated by mathematical model and hospitalizations for pneumonia and asthma in children

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    Ana Cristina Gobbo César

    2016-03-01

    Full Text Available Abstract Objective: To estimate the association between exposure to fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5 and hospitalizations for pneumonia and asthma in children. Methods: An ecological study of time series was performed, with daily indicators of hospitalization for pneumonia and asthma in children up to 10 years of age, living in Taubaté (SP and estimated concentrations of PM2.5, between August 2011 and July 2012. A generalized additive model of Poisson regression was used to estimate the relative risk, with lag zero up to five days after exposure; the single pollutant model was adjusted by the apparent temperature, as defined from the temperature and relative air humidity, seasonality and weekday. Results: The values of the relative risks for hospitalization for pneumonia and asthma were significant for lag 0 (RR=1.051, 95%CI; 1.016 to 1.088; lag 2 (RR=1.066, 95%CI: 1.023 to 1.113; lag 3 (RR=1.053, 95%CI: 1.015 to 1.092; lag 4 (RR=1.043, 95%CI: 1.004 to 1.088 and lag 5 (RR=1.061, 95%CI: 1.018 to 1.106. The increase of 5mcg/m3 in PM2.5 contributes to increase the relative risk for hospitalization from 20.3 to 38.4 percentage points; however, the reduction of 5µg/m3 in PM2.5 concentration results in 38 fewer hospital admissions. Conclusions: Exposure to PM2.5 was associated with hospitalizations for pneumonia and asthma in children younger than 10 years of age, showing the role of fine particulate matter in child health and providing subsidies for the implementation of preventive measures to decrease these outcomes.

  16. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma

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    Nur Salme Suhana Shamshuddin

    2018-01-01

    Full Text Available Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v, 40% (v/v and 80% (v/v, dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05. In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05 reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  17. Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

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    Jing Wang

    2016-01-01

    Full Text Available Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

  18. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    Science.gov (United States)

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.

  19. Interconnection between nitric oxide formation and hypersensitivity parameters under guinea pig model of acute asthma with multiple challenges

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    O. O. Parilova

    2015-10-01

    Full Text Available An immunoregulatory role of nitric oxide (NO in the development of adaptive immune responses associated with allergic diseases is very important. The present study extended these observations by the examination of the reciprocal changes in characteristic immunologic parameters of the disease and NO level of bronchoalveolar lavage (BAL cells under guinea pig model of acute asthma with multiple challenges. Development of guinea pig Th2 mediated asthma was accompanied by increasing the level of allergic markers: ovalbumin (OVA specific IgG and IL-4. We demonstrated that the infiltrate of airway cells contributes to NO synthesis in the respiratory tract during allergic inflammation. The level of intracellular NO formation significantly correlated with plasma allergen specific IgG value in OVA-induced asthma. The presented data evidence that the elevated intracellular NO level in BAL fluid may reflect a nitrosative stress in respiratory tract in general, when allergic asthma exacerbation is present.

  20. Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma.

    Science.gov (United States)

    He, Qing; Liu, Linlin; Yang, Qiaoyu; Wang, Ailing; Chen, Shuo; Li, Ruiyun; Huang, Yi; Zhang, Guqin; Ding, Xuhong; Yu, Hongying; Hu, Suping; Nie, Hanxiang

    2017-12-01

    Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficiency could downregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from a mouse model of asthma. However, elevated activation of iNKT cells by α-galactosylceramide and adoptive transfer of iNKT cells could upregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from mouse models of asthma. Meanwhile, iNKT cells significantly influenced the function of LDCs, markedly enhancing Th2 responses in vivo and in vitro. In addition, iNKT cell can induce LDCs expression of CD206 and RELM-α, reflecting alternative activation of LDCs in a mouse model of asthma. α-Galactosylceramide treatment significantly enhanced expression of CD40L of lung iNKT cells from a mouse model of asthma, and the coculture experiment of LDCs with iNKT cells showed that the blockade of CD40L strongly suppressed surface maturation markers and proinflammatory cytokine production by LDCs. Our data suggest that iNKT cells can promote immunogenic maturation of LDCs to enhance Th2 responses in mouse models of asthma. Copyright © 2017 the American Physiological Society.

  1. Asthma education

    African Journals Online (AJOL)

    2011-01-01

    ). Allergy and Asthma Clinic, Red Cross War Memorial Hospital. Mike Levin runs a secondary level asthma/ allergy clinic and does a tertiary allergy session once a week, focusing on difficult asthma and food allergies. He has ...

  2. A model to predict short-time asthma morbidity: what could be the explanatory factors?

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    Minoo Habibi

    2015-10-01

    Full Text Available Background: There is an increase in the worldwide prevalence, morbidity and mortality of asthma. Therefore, study of the possible factors related to the burden of this disorder could help the health providers to introduce effective initiatives and reduce adverse consequences due to this condition. This study was designed to investigate any relationship between asthma morbidity with inhaler technique and other probable explanatory factors in asthmatic patients.Methods: An observational, cross-sectional study was designed in which asthmatic patients referring to the outpatient respiratory clinic of the Shaheed Labbafinezhad hospital were entered the study using a non-probability sampling method. Their demographic, socio-economic, medical and medication history, inhaler technique (using a 10-step check list, as well as short-term morbidity index (in the past 4 weeks using the Jone’s morbidity questionnaire were determined and recorded in organized data collection forms. These data were entered the Excel and SPSS (version 17.0 worksheets and analyzed using appropriate statistical tests. A step-by-step analysis method was used in order to find out any relationship between possible explanatory factors and the morbidity index of the patients. Results: 199 adult asthmatic patients (94 male and 105 female with mean ± SD age of 54.29 ±15.52 years enrolled the study. In the first step of data analysis only 5 factors out of 20 explanatory factors were eligible to be included in the multivariate analysis leading to the final predictive model. In the multivariate regression analysis, 2 out of 5 factors could remain in the final model, which were “history of systemic steroid usage” and “age” (p=0.007, r=0.32. So that, patients with a positive history of systemic steroid use and those with a younger age had higher asthma morbidity rate. Conclusion: The observed positive relationship between history of systemic steroid usage and asthma morbidity

  3. Modelling Drug Administration Regimes for Asthma: A Romanian Experience

    Science.gov (United States)

    Andras, Szilard; Szilagyi, Judit

    2010-01-01

    In this article, we present a modelling activity, which was a part of the project DQME II (Developing Quality in Mathematics Education, for more details see http://www.dqime.uni-dortmund.de) and some general observations regarding the maladjustments and rational errors arising in such type of activities.

  4. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma.

    Science.gov (United States)

    Secor, Eric R; Shah, Sonali J; Guernsey, Linda A; Schramm, Craig M; Thrall, Roger S

    2012-01-01

    Allergic asthma continues to increase despite new pharmacological advances for both acute treatment and chronic-disease management. Asthma is a multifactorial disease process with genetic, allergic, infectious, environmental, and dietary origins. Researchers are investigating the benefits of lifestyle changes and alternative asthma treatments, including the ability of bromelain to inhibit inflammation. Bromelain is a commonly used, proteolytically active pineapple extract. The present study intended to determine the ability of bromelain to reduce the inflammation of preexisting asthma via an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). The research team designed a study examining the effects of bromelain in a control group of mice that received phosphate buffered saline (PBS) only and in an intervention group that received bromelain in PBS. Setting The study took place in the Department of Immunology at the University of Connecticut's School of Medicine, Farmington. Intervention The research team sensitized female C57BL/6J mice with intraperitoneal OVA/alum and then challenged them with OVA aerosolization for 10 consecutive days. On day 4, the team began administering daily doses of PBS to the control group (n = 10) and bromelain (6mg/kg) in PBS to the bromelain (intervention) group (n = 10). The primary measures included bronchoalveolar lavage (BAL) cellular differential, cellular phenotype via flow cytometry, and lung histology. Additional outcomes included testing for serum cytokines and immunoglobulin. Bromelain treatment of AAD mice (bromelain group) resulted in significant anti-inflammatory activity as indicated by reduced BAL total leukocytes (P bromelain significantly reduced BAL CD4+ and CD8+ T cells without affecting cell numbers in the spleen or hilar lymph node. The study found decreased interleukins IL-4, IL-12, IL-17, as well as IFN-α in the serum of bromelain-treated animals. The results suggest that bromelain has a

  5. Effect of Rho-kinase inhibition on complexity of breathing pattern in a guinea pig model of asthma.

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    Saeed Pazhoohan

    Full Text Available Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.

  6. Effect of Rho-kinase inhibition on complexity of breathing pattern in a guinea pig model of asthma.

    Science.gov (United States)

    Pazhoohan, Saeed; Raoufy, Mohammad Reza; Javan, Mohammad; Hajizadeh, Sohrab

    2017-01-01

    Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols) prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.

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

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    N. A. Kamalaldin

    2017-01-01

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

  8. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies

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    Wagner James G

    2012-07-01

    Full Text Available Abstract Background Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5 are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. Methods We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs or filtered air for 8 h (7:00 AM - 3:00 PM. Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Results Similar CAPs mass concentrations were generated in Detroit (542 μg/m3 and Grand Rapids (519 μg/m3. Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase, eosinophils (90%, and total protein (300% compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Conclusions Despite inhalation exposure to the same mass concentration of urban PM2

  9. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies.

    Science.gov (United States)

    Wagner, James G; Morishita, Masako; Keeler, Gerald J; Harkema, Jack R

    2012-07-06

    Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5) are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs) or filtered air for 8 h (7:00 AM - 3:00 PM). Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF) and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Similar CAPs mass concentrations were generated in Detroit (542 μg/m3) and Grand Rapids (519 μg/m3). Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase), eosinophils (90%), and total protein (300%) compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Despite inhalation exposure to the same mass concentration of urban PM2.5, disparate health effects can be elicited in the airways of

  10. The effect of rhinovirus on airway inflammation in a murine asthma model

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    Eugene Kim

    2013-11-01

    Full Text Available Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF and the airway, to rhinovirus (RV infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df or phosphate buffered saline (PBS and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh in both the Df sensitized and challenged mice (Df mice and PBS-treated mice (PBS mice (P&lt;0.05. Airway eosinophil infiltration increased in Df mice after RV infection (P&lt;0.05. The levels of interleukin (IL 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES increased in response to RV infection in Df mice, but not in PBS mice (P&lt;0.05. The level of IL-10 significantly decreased following RV infection in Df mice (P&lt;0.05. Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

  11. Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-κB inhibition.

    Science.gov (United States)

    Huang, Chuan-Qi; Li, Wei; Wu, Bo; Chen, Wei-Ming; Chen, Li-Hong; Mo, Guan-Wen; Zhang, Qiu-Feng; Gong, Ling; Li, Jing; Zhang, Hong-Chao; Zhu, Hai-Mei; Zeng, Qing-Zhong

    2016-08-02

    Guang-Pheretima, the live form of the earthworm Pheretima aspergillum, is a traditional Chinese medicine commonly used for the treatment of asthma, cough, stroke, epilepsy and other diseases due to its anti-inflammatory, anti-asthmatic, anti-seizure, thrombolytic and diuretic properties. Although Guang-Pheretima is effective in the relief of asthma, its pharmacological activity and the underlying molecular mechanisms are not fully understood. Hence, we investigated the effects of a Pheretima aspergillum decoction (PAD) against inflammation in a model of ovalbumin (OVA)-induced asthma in BALB/c mice, as well as the nuclear factor-κB (NF-κB) pathway involved in this process. OVA was used to sensitize and challenge the airway of the mice, and PAD was administrated by gavage. We measured airway hyperresponsiveness (AHR) in the mice 24h following a final methacholine challenge with whole-body plethysmography. The bronchoalveolar lavage fluid (BALF), serum and pulmonary tissues were collected 48h after the last challenge. The levels of inflammatory factors and the related mRNAs were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. The number of differential inflammatory cells in the BALF was counted. Serum total and OVA-specific IgE levels were measured with ELISA. The activation of NF-κB signaling in the lung was detected by western blotting. In addition, the lung tissues were stained with hematoxylin and eosin or periodic acid Schiff stain for histopathological examination. PAD treatment significantly alleviated AHR in the asthmatic mice, decreased the mRNA and protein levels of IL-4, IL-5 and IL-13 and downregulated IgE. In addition, PAD treatment attenuated mucus secretion and infiltration of inflammatory cells in the lung while inhibiting the activation of NF-κB signaling. PAD effectively inhibited the activation of NF-κB signaling in the lungs of mice with OVA-induced asthma, and mitigated

  12. Different Nebulized Budesonide Dosing Regimens in a Mouse Model of Chronic Asthma

    Directory of Open Access Journals (Sweden)

    Pınar Uysal

    2016-12-01

    Full Text Available Objective: The aim of this study was to compare the effectiveness of different inhaled steroid regimens on the lungs and their potential side effects on the bone tissues in chronic asthma model. Materials and Methods: Thirty-five specific pathogen-free BALB/c mice were divided into five groups. The mice in all of the study groups except the control group were sensitized with chicken egg albumin. After sensitization, the mice in group 2 were treated with saline modeling twice daily, the mice in group 3 were treated with 250 mcg of nebulized budesonide twice daily, the mice in group 4 were treated with 500 mcg of budesonide once daily, and the mice in group 5 were treated with 1000 mcg of budesonide every other day for the last 14 days of the challenge period. After challenge, the mice were sacrificed and lung and tibia samples were histologically examined. Results: Pulmonary parameters, including subepithelial smooth muscle thickness, goblet cell count, mast cell count and epithelial thickness, were the lowest in group 5 compared to other groups (p0.01. Conclusion: The beneficial effect on lung tissue was highest in the treatment group receiving budesonide every other day (group 5 and no further measureable side effects on bone mineralization were observed in this group compared with the other treatment groups. Every-other-day treatment application seems to be the most effective regimen in chronic asthma model.

  13. Dose-response modelling of umeclidinium and fluticasone furoate/umeclidinium in asthma.

    Science.gov (United States)

    Yang, Shuying; Goyal, Navin; Beerahee, Misba; Trivedi, Roopa; Lee, Laurie; Pascoe, Steven

    2015-09-01

    In two dose-ranging crossover studies, the long-acting muscarinic antagonist umeclidinium (UMEC) was assessed as monotherapy in patients with asthma not treated with inhaled corticosteroids (ICS) (NCT01641692 [study 1]) and combined with the ICS fluticasone furoate (FF) in patients with asthma symptomatic on ICS (NCT01573624 [study 2]). The present study aimed to further characterise the UMEC dose-response relationship with change from baseline trough forced expiratory volume in one second (FEV1) (day 15). A model-based approach using non-linear mixed-effects analyses was used to assess data from studies 1 and 2. Within the Study 1 dose range, no significant dose-response was demonstrated. In study 2, the slope-intercept on log-dose model showed a mild dose-response, with a 10 % probability of a 0.075-L FEV1 improvement with FF/UMEC 100/250 mcg; period 1 data (with an absent carryover effect) indicated an 88 % probability of a 0.075-L FEV1 improvement. The model-based approach in study 2 identified FF/UMEC doses warranting further investigation.

  14. Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.

    Science.gov (United States)

    Hasegawa, Shunji; Wakiguchi, Hiroyuki; Okada, Seigo; Gui Kang, Yu; Fujii, Nao; Hasegawa, Masanari; Hasegawa, Hideki; Ainai, Akira; Atsuta, Ryo; Shirabe, Komei; Toda, Shoichi; Wakabayashi-Takahara, Midori; Morishima, Tsuneo; Ichiyama, Takashi

    2014-10-01

    Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. K(Ca3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma.

    Directory of Open Access Journals (Sweden)

    Joanne Van Der Velden

    Full Text Available The Ca(2+-activated K(+ channel K(Ca3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of K(Ca3.1 modifies experimental asthma in sheep.Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073, a selective inhibitor of the K(Ca3.1-channel, or vehicle alone (0.5% methylcellulose twice daily (orally. Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147. The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288. Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340. Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling.These findings suggest that K(Ca3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of K(Ca3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans.

  16. The effect of rupatadine on lung histopathology in a murine model of chronic asthma.

    Science.gov (United States)

    Tuncel, Tuba; Karaman, Meral; Firinci, Fatih; Uysal, Pinar; Kiray, Muge; Bagriyanik, Alper H; Yilmaz, Osman; Karaman, Ozkan; Uzuner, Nevin

    2013-03-01

    Rupatadine is a new second-generation antihistamine with H(1) receptor antagonist activity and platelet-activating factor antagonist properties. This study aimed to investigate the effect of rupatadine on histologic changes in the lungs in a murine model of chronic asthma. Thirty-five BALB/c mice were divided into five groups of seven mice each: group I (control), group II (placebo [saline]), group III (dexamethasone 1 mg · kg(-1)·d(-1)), group IV (rupatadine 3 mg·kg(-1) d(-1)), and group V (rupatadine 30 mg·kg(-1)·d(-1)). Groups II through V were sensitized and challenged with ovalbumin and treated once per day via the oral route (gavage). Animals were sacrificed 24 h after the last treatment was administered. Airway histopathology was evaluated using light and electron microscopy in all groups. There were no significant differences observed in any of the histologic parameters between groups II and IV. There were significantly thinner basement membrane, subepithelial smooth muscle layer, and epithelia were significantly thinner in group V than in group II (p Rupatadine had a beneficial effect on histologic changes in a chronic murine model of asthma.

  17. Control and minimization of allergenic plants impact on bronchial asthma morbidity, based on spatial-temporal data model

    Science.gov (United States)

    Vuzh, Tatyana Y.; Mokin, Vitaliy B.; Wójcik, Waldemar; Imanbek, Baglan

    2015-12-01

    Control and development of priority measures to minimize the impact of allergenic plants on the state of morbidity, caused by asthma are one of the most common and complex problems for public health in modern cities. Bronchial asthma in humans occurs because of aggregation of various factors, the nature of which varies in time and space. So, we should use spatial-temporal data model for formalization of this problem, but typical data formalization methods and data processing methods need to be improved, taking into consideration the peculiarities of impact, especially of allergenic plants and weather conditions on people in a city. The paper shows a new approach to unified in time and optimal by discretization in space data formalization, concerning the main factors that form the conditions for the emergence of bronchial asthma. The example of such analysis was given, which illustrated the efficiency of the proposed information model and the method of its processing.

  18. Airway hyperresponsiveness in asthma : lessons from in vitro model systems and animal models

    NARCIS (Netherlands)

    Meurs, H.; Gosens, R.; Zaagsma, J.

    Airway hyperresponsiveness (AHR) is a hallmark clinical symptom of asthma. At least two components of AHR have been identified: 1) baseline AHR, which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation; and 2) acute and variable AHR, which is

  19. Allergic asthma biomarkers using systems approaches

    Directory of Open Access Journals (Sweden)

    Gaurab eSircar

    2014-01-01

    Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

  20. NKT cells contribute to basal IL-4 production but are not required to induce experimental asthma.

    Directory of Open Access Journals (Sweden)

    Christopher G McKnight

    Full Text Available CD1d-deficiency results in a selective deletion of NKT cells in mice that is reported to prevent murine allergic airway disease (AAD. Because we find 2-3 fold lower basal IL-4 production in CD1d- mice than in wild-type (WT mice, we hypothesized that the contribution made by NKT cells to AAD would depend on the strength of the stimulus used to induce the disease. Consequently, we compared CD1d-deficient mice to WT mice in the development of AAD, using several models of disease induction that differed in the type and dose of allergen, the site of sensitization and the duration of immunization. Surprisingly we found equivalent allergic inflammation and airway disease in WT and CD1d- mice in all models investigated. Consistent with this, NKT cells constituted only ~2% of CD4+ T cells in the lungs of mice with AAD, and IL-4-transcribing NKT cells did not expand with disease induction. Concerned that the congenital absence of NKT cells might have caused a compensatory shift within the immune response, we administered an anti-CD1d monoclonal Ab (mAb to block NKT function before airway treatments, before or after systemic sensitization to antigen. Such Ab treatment did not affect disease severity. We suggest that the differences reported in the literature regarding the significance of NKT cells in the induction of allergic airway disease may have less to do with the methods used to study the disease and more to do with the animals themselves and/or the facilities used to house them.

  1. New model systems for experimental evolution.

    Science.gov (United States)

    Collins, Sinéad

    2013-07-01

    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  2. Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma.

    Science.gov (United States)

    Fu, Luo-Qin; Li, Ya-Li; Fu, Ai-Kun; Wu, Yan-Ping; Wang, Yuan-Yuan; Hu, Sheng-Lan; Li, Wei-Fen

    2017-10-01

    Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control). The authors determined that treatment with pidotimod exacerbated pulmonary inflammation as demonstrated by significantly increased eosinophil infiltration, dramatically elevated immunoglobulin E production, and enhanced T helper 2 response. Moreover, treatment failed to attenuate mucus production in lung tissue, and did not reduce OVA‑induced high levels of FIZZ1 and Arg1 expression in asthmatic mice. In contrast, administration of dexamethasone was efficient in alleviating allergic airway inflammation in OVA‑induced asthmatic mice. These data indicated that pidotimod as an immunotherapeutic agent should be used cautiously and the effectiveness for controlling allergic asthma needs further evaluation and research.

  3. Efficacy of parthenolide on lung histopathology in a murine model of asthma.

    Science.gov (United States)

    Arıkan-Ayyıldız, Z; Karaman, M; Özbal, S; Bağrıyanık, A; Yilmaz, O; Karaman, Ö; Uzuner, N

    Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  4. Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models

    Directory of Open Access Journals (Sweden)

    D. Betty Lew

    2017-01-01

    Full Text Available One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM remodeling effects. The mannose receptor (MR family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR and that mannan derived from Saccharomyces cerevisiae (SC-MN inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2 expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

  5. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Directory of Open Access Journals (Sweden)

    Jun Kurai

    Full Text Available An Asian dust storm (ADS contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil in asthma model mice.Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df, and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF were measured, and airway inflammation was examined histopathologically.Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles.These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  6. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Science.gov (United States)

    Kurai, Jun; Watanabe, Masanari; Tomita, Katsuyuki; Sano, Hiroyuki; Yamasaki, Hiroyuki Sano Akira; Yamasaki, Akira; Shimizu, Eiji

    2014-01-01

    An Asian dust storm (ADS) contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil) in asthma model mice. Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured, and airway inflammation was examined histopathologically. Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles. These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  7. Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic Asthma.

    Science.gov (United States)

    Brüggemann, T R; Ávila, L C M; Fortkamp, B; Greiffo, F R; Bobinski, F; Mazzardo-Martins, L; Martins, D F; Duarte, M M M F; Dafre, A; Santos, A R S; Silva, M D; Souza, L F; Vieira, R P; Hizume-Kunzler, D C

    2015-06-01

    In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming (non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48 h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (pswimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (pSwimming group when compared to all groups (pswimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (pswimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Accessible Modelling of Complexity in Health (AMoCH and associated data flows: asthma as an exemplar

    Directory of Open Access Journals (Sweden)

    Harshana Liyanage

    2016-04-01

    Full Text Available Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1 to describe the data and information flows in clinical practice to information scientists, (2 to compare health systems and care pathways, (3 to understand how clinical cases are recorded in record systems and (4 to model health care business models. Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain. Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar. Method The four steps in our process are: 1. Drawing a rich picture, following Checkland’s soft systems methodology; 2. Constructing data flow diagrams (DFDs; 3. Creating Unified Modelling Language (UML use case diagrams to describe the interaction of the key actors with the system; 4. Activity diagrams, either UML activity diagram or business process modelling notation diagram. Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding. Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of

  9. Accessible Modelling of Complexity in Health (AMoCH) and associated data flows: asthma as an exemplar.

    Science.gov (United States)

    Liyanage, Harshana; Luzi, Daniela; De Lusignan, Simon; Pecoraro, Fabrizio; McNulty, Richard; Tamburis, Oscar; Krause, Paul; Rigby, Michael; Blair, Mitch

    2016-04-18

    Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models.Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain.Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar.Method The four steps in our process are:1. Drawing a rich picture, following Checkland's soft systems methodology;2. Constructing data flow diagrams (DFDs);3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system;4. Activity diagrams, either UML activity diagram or business process modelling notation diagram.Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding.Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

  10. Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype.

    Science.gov (United States)

    Joshi, Radhika; Valdez, Daniel; Kim, Hosu; Eikenburg, Douglas C; Knoll, Brian J; Bond, Richard A

    2017-10-01

    Our previous studies suggested certain β-adrenoceptor blockers (β-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance. We tested the non-selective β-blockers, carvedilol and nadolol, in house dust mite (HDM) driven murine asthma models where drugs were administered both pre- and post-development of the asthma phenotype. We measured inflammation, mucous metaplasia, and airway hyper-responsiveness (AHR). We also measured the effects of the β-blockers on extracellular-signal regulated kinase (ERK 1/2) phosphorylation in lung homogenates. We show that nadolol, but not carvedilol, attenuated inflammation and mucous metaplasia, and had a moderate effect attenuating AHR. Following HDM exposure, ERK1/2 phosphorylation was elevated, but the level of phosphorylation was unaffected by β-blockers, suggesting ERK1/2 phosphorylation becomes dissociated from the asthma phenotype. Our findings in HDM models administering drugs both pre- and post-development of the asthma phenotype are consistent with previous results using ovalbumin models and show differential effects for nadolol and carvedilol on the asthma phenotype. Lastly, our data suggest that ERK1/2 phosphorylation may be involved in development of the asthma phenotype, but may have a limited role in maintaining the phenotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Population Pharmacokinetics Modeling of Inhaled Umeclidinium for Adult Patients with Asthma.

    Science.gov (United States)

    Yang, Shuying; Lee, Laurie; Pascoe, Steven

    2017-02-01

    Umeclidinium (UMEC; a long-acting anti-muscarinic) in combination with fluticasone furoate (an inhaled corticosteroid) is in development for asthma treatment. This secondary analysis aimed to develop a population pharmacokinetic model characterizing UMEC in adults with asthma, and evaluated the impact of covariates on pharmacokinetic parameters. Plasma concentration data from study NCT01641692 (assessing once-daily UMEC 15.6, 31.25, 62.5, 125, and 250 mcg, twice daily UMEC 15.6 and 31.25 mcg, and placebo) were analyzed using non-linear mixed-effect modeling in NONMEM ® . Full likelihood, including observed data and data below the quantification limit (treated as censored), was maximized. Study endpoints were population pharmacokinetics (including apparent inhaled clearance [CL/F] and apparent distribution volume in the central compartment [V c /F]) and derived pharmacokinetic parameters (area under the concentration-time curve [AUC] and maximum concentration [C max ] at steady-state). In total, 128 patients provided 3757 data points. The pharmacokinetics of UMEC were best described using a two-compartment model with intravenous bolus input, due to fast absorption following inhalation. CL/F was 257 L/h and V c /F was 804 L. Creatinine clearance was a significant covariate for CL/F, as were age and body weight for V c /F. AUC and C max increased with increasing UMEC dose (once-daily 15.6-250 mcg: AUC 0-24 median: 64.7-863 pg h/mL; C max median: 10.6-256 pg/mL). The final population pharmacokinetic model adequately described the data, demonstrating minimal creatinine clearance, age, and body weight effects on overall plasma UMEC pharmacokinetics and systemic exposure.

  12. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    Kristensen, Niels Rode; Madsen, Henrik; Jørgensen, Sten Bay

    2003-01-01

    unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance......A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  13. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance......A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  14. Effects of Inhalable Microparticles of Seonpyejeongcheon-Tang in an Asthma Mouse Model: - Effects of Microparticles of SJT.

    Science.gov (United States)

    Yang, Won-Kyung; Lee, Chul-Hwa; Kim, Min-Hee; Kim, Seung-Hyeong; Choi, Hae-Yoon; Yeo, Yoon; Park, Yang-Chun

    2016-12-01

    Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeongcheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT. SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% ± 6.4% and mass median aerodynamic diameter of 3.7 ± 0.3 μm). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

  15. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    Campos H.S.

    2006-01-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  16. Effects of Inhalable Microparticles of Seonpyejeongcheon-Tang in an Asthma Mouse Model - Effects of Microparticles of SJT -

    Directory of Open Access Journals (Sweden)

    Won-Kyung Yang

    2016-12-01

    Full Text Available Objectives: Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT consists of 12 herbs. It originated from Jeongcheon-tang (JT, also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Methods: Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA-induced asthma in comparison with orally-administered SJT. Results: SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% ± 6.4% and mass median aerodynamic diameter of 3.7 ± 0.3 μm. SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. Conclusion: This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

  17. Model refinement for offshore platforms: Experimental study

    Science.gov (United States)

    Zhang, Min; Chen, Zongli; Wu, Yanjian

    2017-08-01

    Offshore jacket platforms are widely used in offshore oil and gas exploitation. Finite element models of such structures need to have many degrees of freedom (DOFs) to represent the geometrical detail of complex structures, thereby leading to incompatibility in the number of DOFs of experimental models. To bring them both to the same order while ensuring that the essential eigen- properties of the refined model match those of experimental models, an extended model refinement procedure is presented in this paper. Vibration testing of an offshore jacket platform model is performed to validate the applicability of the proposed approach. A full-order finite element model of the platform is established and then tuned to meet the measured modal properties identified from the acceleration signals. Both model reduction and modal expansion methods are investigated, as well as various scenarios of sensor arrangements. Upon completion of the refinement, the updated jacket platform model matches the natural frequencies of the measured model well.

  18. Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model

    NARCIS (Netherlands)

    Loymans, Rik J. B.; Honkoop, Persijn J.; Termeer, Evelien H.; Snoeck-Stroband, Jiska B.; Assendelft, Willem J. J.; Schermer, Tjard R. J.; Chung, Kian Fan; Sousa, Ana R.; Sterk, Peter J.; Reddel, Helen K.; Sont, Jacob K.; ter Riet, Gerben

    2016-01-01

    Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. We used data from a 12-month primary care pragmatic

  19. Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model

    NARCIS (Netherlands)

    Loymans, R.J.; Honkoop, P.J.; Termeer, E.H.; Snoeck-Stroband, J.B.; Assendelft, W.J.J.; Schermer, T.R.J.; Chung, K.F.; Sousa, A.R.; Sterk, P.J.; Reddel, H.K.; Sont, J.K.; Riet, G. Ter

    2016-01-01

    BACKGROUND: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. METHODS: We used data from a 12-month

  20. Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Haim Bibi

    2014-01-01

    Conclusion: In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO.

  1. Experimental models of demyelination and remyelination.

    Science.gov (United States)

    Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

    2017-08-29

    Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. CONGESTIVE HEART FAILURE: EXPERIMENTAL MODEL

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    Antonio Francesco Corno

    2013-10-01

    Full Text Available INTRODUCTION.Surgically induced, combined volume and pressure overload has been used in rabbits to create a simplified and reproducible model of acute left ventricular (LV failure.MATERIALS AND METHODS.New Zealand white male rabbits (n=24, mean weight 3.1±0.2kg were randomly assigned to either the Control group (n=10 or to the Heart Failure group (HF, n=14. Animals in the Control group underwent sham procedures. Animals in the HF group underwent procedures to induce LV volume overload by inducing severe aortic valve regurgitation with aortic cusp disruption and pressure overload using an occlusive silver clip positioned around the pre-renal abdominal aorta.RESULTS.Following Procedure-1 (volume overload echocardiography confirmed severe aortic regurgitation in all animals in the HF group, with increased mean pulse pressure difference from 18±3mmHg to 38±3mmHg (P

  3. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells

    National Research Council Canada - National Science Library

    Arnold, Isabelle C; Dehzad, Nina; Reuter, Sebastian; Martin, Helen; Becher, Burkhard; Taube, Christian; Müller, Anne

    2011-01-01

    .... The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies...

  4. The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

    Directory of Open Access Journals (Sweden)

    Anna V Wiese

    Full Text Available C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1. Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs and monocyte-derived DCs (moDCs during the allergic effector phase using a floxed green fluorescent protein (GFP-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental

  5. Asthma Research

    Science.gov (United States)

    EPA is working to explore the role of common air pollutants in the development and exacerbation of asthma at different life stages as well as other environmental and genetic factors that might make a person more sensitive to developing asthma.

  6. Inhalation of honey reduces airway inflammation and histopathological changes in a rabbit model of ovalbumin-induced chronic asthma

    Science.gov (United States)

    2014-01-01

    Background Honey is widely used in folk medicine to treat cough, fever, and inflammation. In this study, the effect of aerosolised honey on airway tissues in a rabbit model of ovalbumin (OVA)-induced asthma was investigated. The ability of honey to act either as a rescuing agent in alleviating asthma-related symptoms or as a preventive agent to preclude the occurrence of asthma was also assessed. Methods Forty New Zealand white rabbits were sensitized twice with mixture of OVA and aluminium hydroxide on days 1 and 14. Honey treatments were given from day 23 to day 25 at two different doses (25% (v/v) and 50% (v/v) of honey diluted in sterile phosphate buffer saline. In the aerosolised honey as a rescue agent group, animals were euthanized on day 28; for the preventive group, animals were further exposed to aerosolised OVA for 3 days starting from day 28 and euthanized on day 31. The effects of honey on inflammatory cell response, airway inflammation, and goblet cell hyperplasia were assessed for each animal. Results Histopathological analyses revealed that aerosolised honey resulted in structural changes of the epithelium, mucosa, and submucosal regions of the airway that caused by the induction with OVA. Treatment with aerosolised honey has reduced the number of airway inflammatory cells present in bronchoalveolar lavage fluid and inhibited the goblet cell hyperplasia. Conclusion In this study, aerosolised honey was used to effectively treat and manage asthma in rabbits, and it could prove to be a promising treatment for asthma in humans. Future studies with a larger sample size and studies at the gene expression level are needed to better understand the mechanisms by which aerosolised honey reduces asthma symptoms. PMID:24886260

  7. Improving the physiological realism of experimental models.

    Science.gov (United States)

    Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

    2016-04-06

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

  8. Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma.

    Science.gov (United States)

    Liang, Zhengmin; Nie, Haiying; Xu, Yangfeng; Peng, Jianbo; Zeng, Yun; Wei, Yingyi; Wen, Xuemei; Qiu, Jiaming; Zhong, Weiting; Deng, Xuming; He, Jiakang

    2016-12-01

    Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma.

    Science.gov (United States)

    Xiao, Xiaojun; Zeng, Xiaowei; Zhang, Xinxin; Ma, Li; Liu, Xiaoyu; Yu, Haiqiong; Mei, Lin; Liu, Zhigang

    2013-01-01

    Pollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid) (PLGA) has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP)-loaded PLGA nanoparticles and the underlying mechanisms involved. A mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a) and cytokines, and observing histologic sections of lung tissue. The rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms. PLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH)3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed herein offer a promising avenue for specific immunotherapy in allergic asthma.

  10. A Group of Asthma Patients\\\\\\' Treatment Related Thoughts Based on Health Belief Model and Perception of Medication Success

    Directory of Open Access Journals (Sweden)

    Mesut Cimen

    2012-02-01

    Full Text Available Purpose: This study is a descriptive study which aims to determine the attitude and perceptions of asthma patients about their health and their opinion regarding the success of treatment. Method: The study is carried out without any sampling. The participants are 74 patients who were admitted in a public pulmonary disease clinic between April and June 2010. A revised version of Health Belief Model scale for asthma treatment and another scale, which was developed to determine the opinion and observations of patients regarding the success of treatment, are used for data collection. In addition to descriptive statistics, regression analysis, Mann-Whitney U and Kruskal Wallis tests are used in the data analysis. Findings: The mean score of attitudes and perceptions of asthma patients, which is defined with the Health Belief Model and which can affect their responsiveness to treatment, is found out 3,37(±0,38 and the attitude and perceptions of patients are positive. The mean value for success treatment is 2,35(±0,49. Since the treatment is deemed to be more successful as it gets closer to 1 hence it can be said that the opinion of asthma patients regarding the success of treatment is positive. In the study, it is found out that the participants have a high admission rate to hospitals and that there is no significant difference for socio-demographic characteristics in the positive attitude development and in their belief in the efficiency of the treatment that they are receiving, of which both are components of health belief model concept. The findings from regression analysis indicate that the duration of the asthma sickness and the number of people living in the household not only affect the perceptions and attitudes of patients that are investigated by health belief model, but also the effectiveness of the treatment and the number of admissions to the Emergency Room in the last 6 months. Conclusion: In order to prevent long-term complications

  11. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

    Directory of Open Access Journals (Sweden)

    Kayla G Kinker

    Full Text Available Levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1 and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR. ADMA levels in bronchoalveolar lavage fluid (BALF and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM. Airway inflammation was assessed by bronchoalveolar lavage (BAL total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses.

  12. Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma

    Science.gov (United States)

    De Sanctis, George T.; MacLean, James A.; Hamada, Kaoru; Mehta, Sanjay; Scott, Jeremy A.; Jiao, Aiping; Yandava, Chandri N.; Kobzik, Lester; Wolyniec, Walter W.; Fabian, Attila J.; Venugopal, Changaram S.; Grasemann, Hartmut; Huang, Paul L.; Drazen, Jeffrey M.

    1999-01-01

    Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma. PMID:10330441

  13. Antiasthmatic Effects of Hesperidin, a Potential Th2 Cytokine Antagonist, in a Mouse Model of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Seung-Hyung Kim

    2011-01-01

    Full Text Available Background and Objective. The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR, excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgE in vivo asthma model mice. Methods. In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma. Results. In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE. Conclusions. Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5, eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor.

  14. Antiasthmatic Effects of Hesperidin, a Potential Th2 Cytokine Antagonist, in a Mouse Model of Allergic Asthma

    Science.gov (United States)

    Kim, Seung-Hyung; Kim, Bok-Kyu; Lee, Young-Cheol

    2011-01-01

    Background and Objective. The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN) on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgE in vivo asthma model mice. Methods. In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma. Results. In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE. Conclusions. Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor. PMID:21772663

  15. Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

    Directory of Open Access Journals (Sweden)

    W. V. Kalina

    2004-01-01

    Full Text Available Respiratory syncytial virus (RSV, an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin on development of allergic asthma.

  16. A collagen IV matrikine inhibits neutrophil recruitment in a mouse model of asthma exacerbation

    NARCIS (Netherlands)

    Weckmann, M.; Nissen, G.; Lundig, L.; Burgess, J.K.; Holst, O.; Wegmann, M.; Kopp, M.V.

    2015-01-01

    Background: Increased neutrophilic infiltration of the airways is a key feature of acute asthma exacerbation, which may lead to prolonged hospital admissions and an enhanced rate of decline of lung function. The increase in asthma severity in this subpobulation of patients is thought to be partially

  17. Understanding Leadership: An Experimental-Experiential Model

    Science.gov (United States)

    Hole, George T.

    2014-01-01

    Books about leadership are dangerous to readers who fantasize about being leaders or apply leadership ideas as if they were proven formulas. As an antidote, I offer an experimental framework in which any leadership-management model can be tested to gain experiential understanding of the model. As a result one can gain reality-based insights about…

  18. Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma.

    Science.gov (United States)

    Herbert, C; Hettiaratchi, A; Webb, D C; Thomas, P S; Foster, P S; Kumar, R K

    2008-05-01

    In a mouse model of mild chronic asthma, both inflammation and remodelling can be suppressed by dexamethasone (a glucocorticoid) and roflumilast (a selective phosphodiesterase-4 inhibitor). To better understand the underlying molecular mechanisms, we investigated the effects of treatment on airway expression of inflammation-related cytokines, as well as on epithelial expression of growth factors. BALB/c mice systemically sensitized to ovalbumin were challenged with aerosolized antigen for 6 weeks and treated with roflumilast or dexamethasone during the final 2 weeks. Expression of mRNA, for a variety of cytokines and growth factors, was assessed in selectively dissected proximal airways or in airway epithelium obtained by laser capture microdissection. In the airway wall of vehicle-treated challenged animals, there was significantly elevated expression of mRNA for a variety of pro-inflammatory and T helper type 2 cytokines, as well as for IFN-gamma. All these cytokines were suppressed by dexamethasone. Treatment with roflumilast reduced expression of IL-17A, TNF-alpha, granulocyte-macrophage colony-stimulating factor and IL-6, but did not inhibit other cytokines. Both drugs suppressed the enhanced expression of mRNA for growth factors such as TGF-beta1 and FGF-2 in airway epithelium. Whereas dexamethasone non-specifically inhibits numerous mediators involved in inflammation and the immune response, roflumilast selectively inhibits a subset of pro-inflammatory cytokines and growth factors. These mediators and/or the cells that produce them may have critical roles in the pathogenesis of the lesions of chronic asthma.

  19. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    Directory of Open Access Journals (Sweden)

    P. Hemachandra Reddy

    2011-02-01

    Full Text Available Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma.

  20. Early risk factors for pubertal asthma.

    Science.gov (United States)

    Hovland, V; Riiser, A; Mowinckel, P; Carlsen, K-H; Lødrup Carlsen, K C

    2015-01-01

    Early life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before 2 years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities. Based on data from 550 adolescents in the prospective birth cohort 'Environment and Childhood Asthma' study, subjects were categorized by recurrent bronchial obstruction (rBO) 0-2 years, asthma 2-10 years, and pubertal asthma from 10 to 16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0-16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis (AR) from 10 to 16 years. Twenty-three common asthma risk factors identified by 2 years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype. In adjusted models, the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the firstborn child, and familial stress around birth. Pubertal asthma in remission was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond 4 months. Pubertal incident asthma was more common among firstborn children. All asthma phenotypes with allergic diseases were significantly associated with severity score, whereas familial perinatal stress increased the risk of asthma only. Asthma combined with AR was associated with parental asthma and being firstborn, whereas the risk of asthma with both atopic dermatitis and AR increased with higher paternal education, atopic dermatitis, being firstborn, and familial perinatal stress. Important early risk factors for pubertal asthma were early airways obstruction, parental rhinitis, being the firstborn child, and perinatal familial

  1. Correlated gamma-based hidden Markov model for the smart asthma management based on rescue inhaler usage.

    Science.gov (United States)

    Son, Junbo; Brennan, Patricia Flatley; Zhou, Shiyu

    2017-05-10

    Asthma is a very common chronic disease that affects a large portion of population in many nations. Driven by the fast development in sensor and mobile communication technology, a smart asthma management system has become available to continuously monitor the key health indicators of asthma patients. Such data provides opportunities for healthcare practitioners to examine patients not only in the clinic (on-site) but also outside of the clinic (off-site) in their daily life. In this paper, taking advantage from this data availability, we propose a correlated gamma-based hidden Markov model framework, which can reveal and highlight useful information from the rescue inhaler-usage profiles of individual patients for practitioners. The proposed method can provide diagnostic information about the asthma control status of individual patients and can help practitioners to make more informed therapeutic decisions accordingly. The proposed method is validated through both numerical study and case study based on real world data. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses.

    Science.gov (United States)

    Zhang, Zhonghua; Biagini Myers, Jocelyn M; Brandt, Eric B; Ryan, Patrick H; Lindsey, Mark; Mintz-Cole, Rachael A; Reponen, Tiina; Vesper, Stephen J; Forde, Frank; Ruff, Brandy; Bass, Stacey A; LeMasters, Grace K; Bernstein, David I; Lockey, James; Budelsky, Alison L; Khurana Hershey, Gurjit K

    2017-01-01

    Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. We sought to determine the mechanism by which fungi affect asthma development and severity. We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. We report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13(+)IL-17(+)CD4(+) double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc(-/-) mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. Our data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Modeling of Experimental Adsorption Isotherm Data

    Directory of Open Access Journals (Sweden)

    Xunjun Chen

    2015-01-01

    Full Text Available Adsorption is considered to be one of the most effective technologies widely used in global environmental protection areas. Modeling of experimental adsorption isotherm data is an essential way for predicting the mechanisms of adsorption, which will lead to an improvement in the area of adsorption science. In this paper, we employed three isotherm models, namely: Langmuir, Freundlich, and Dubinin-Radushkevich to correlate four sets of experimental adsorption isotherm data, which were obtained by batch tests in lab. The linearized and non-linearized isotherm models were compared and discussed. In order to determine the best fit isotherm model, the correlation coefficient (r2 and standard errors (S.E. for each parameter were used to evaluate the data. The modeling results showed that non-linear Langmuir model could fit the data better than others, with relatively higher r2 values and smaller S.E. The linear Langmuir model had the highest value of r2, however, the maximum adsorption capacities estimated from linear Langmuir model were deviated from the experimental data.

  4. Rhinoviruses, Allergic Inflammation, and Asthma

    Science.gov (United States)

    Gavala, Monica; Bertics, Paul J.; Gern, James E.

    2011-01-01

    Summary Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma. PMID:21682739

  5. Inhalation of concentrated PM2.5from Mexico City acts as an adjuvant in a guinea pig model of allergic asthma.

    Science.gov (United States)

    Falcon-Rodriguez, Carlos Iván; De Vizcaya-Ruiz, Andrea; Rosas-Pérez, Irma Aurora; Osornio-Vargas, Álvaro Román; Segura-Medina, Patricia

    2017-09-01

    Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 μg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and β-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway

  6. Experimental Concepts for Testing Seismic Hazard Models

    Science.gov (United States)

    Marzocchi, W.; Jordan, T. H.

    2015-12-01

    Seismic hazard analysis is the primary interface through which useful information about earthquake rupture and wave propagation is delivered to society. To account for the randomness (aleatory variability) and limited knowledge (epistemic uncertainty) of these natural processes, seismologists must formulate and test hazard models using the concepts of probability. In this presentation, we will address the scientific objections that have been raised over the years against probabilistic seismic hazard analysis (PSHA). Owing to the paucity of observations, we must rely on expert opinion to quantify the epistemic uncertainties of PSHA models (e.g., in the weighting of individual models from logic-tree ensembles of plausible models). The main theoretical issue is a frequentist critique: subjectivity is immeasurable; ergo, PSHA models cannot be objectively tested against data; ergo, they are fundamentally unscientific. We have argued (PNAS, 111, 11973-11978) that the Bayesian subjectivity required for casting epistemic uncertainties can be bridged with the frequentist objectivity needed for pure significance testing through "experimental concepts." An experimental concept specifies collections of data, observed and not yet observed, that are judged to be exchangeable (i.e., with a joint distribution independent of the data ordering) when conditioned on a set of explanatory variables. We illustrate, through concrete examples, experimental concepts useful in the testing of PSHA models for ontological errors in the presence of aleatory variability and epistemic uncertainty. In particular, we describe experimental concepts that lead to exchangeable binary sequences that are statistically independent but not identically distributed, showing how the Bayesian concept of exchangeability generalizes the frequentist concept of experimental repeatability. We also address the issue of testing PSHA models using spatially correlated data.

  7. Oral Bromelain Attenuates Inflammation in an Ovalbumin-Induced Murine Model of Asthma

    Directory of Open Access Journals (Sweden)

    Eric R. Secor

    2008-01-01

    Full Text Available Bromelain, a widely used pineapple extract with cysteine protease activity, has been shown to have immunomodulatory effects in a variety of immune system models. The purpose of the present study was to determine the effects of orally administered bromelain in an ovalbumin (OVA-induced murine model of acute allergic airway disease (AAD. To establish AAD, female C57BL/6J mice were sensitized with intraperitoneal (i.p. OVA/alum and then challenged with OVA aerosols for 3 days. Mice were gavaged with either (phosphate buffered salinePBS or 200 mg/kg bromelain in PBS, twice daily for four consecutive days, beginning 1 day prior to OVA aerosol challenge. Airway reactivity and methacholine sensitivity, bronchoalveolar lavage (BAL cellular differential, Th2 cytokines IL-5 and IL-13, and lung histology were compared between treatment groups. Oral bromelain-treatment of AAD mice demonstrated therapeutic efficacy as evidenced by decreased methacholine sensitivity (P ≤ 0.01, reduction in BAL eosinophils (P ≤ 0.02 and IL-13 concentrations (P ≤ 0.04 as compared with PBS controls. In addition, oral bromelain significantly reduced BAL CD19+ B cells (P ≤ 0.0001 and CD8+ T cells (P ≤ 0.0001 in AAD mice when compared with controls. These results suggest that oral treatment with bromelain had a beneficial therapeutic effect in this murine model of asthma and bromelain may also be effective in human conditions.

  8. Cloud-based Predictive Modeling System and its Application to Asthma Readmission Prediction.

    Science.gov (United States)

    Chen, Robert; Su, Hang; Khalilia, Mohammed; Lin, Sizhe; Peng, Yue; Davis, Tod; Hirsh, Daniel A; Searles, Elizabeth; Tejedor-Sojo, Javier; Thompson, Michael; Sun, Jimeng

    The predictive modeling process is time consuming and requires clinical researchers to handle complex electronic health record (EHR) data in restricted computational environments. To address this problem, we implemented a cloud-based predictive modeling system via a hybrid setup combining a secure private server with the Amazon Web Services (AWS) Elastic MapReduce platform. EHR data is preprocessed on a private server and the resulting de-identified event sequences are hosted on AWS. Based on user-specified modeling configurations, an on-demand web service launches a cluster of Elastic Compute 2 (EC2) instances on AWS to perform feature selection and classification algorithms in a distributed fashion. Afterwards, the secure private server aggregates results and displays them via interactive visualization. We tested the system on a pediatric asthma readmission task on a de-identified EHR dataset of 2,967 patients. We conduct a larger scale experiment on the CMS Linkable 2008-2010 Medicare Data Entrepreneurs' Synthetic Public Use File dataset of 2 million patients, which achieves over 25-fold speedup compared to sequential execution.

  9. [Effects of milkvetch root on neuro-endocrino-immune network in asthma model rat].

    Science.gov (United States)

    Dong, Jing-cheng; Zhao, Fu-dong; Xie, Jin-yu

    2007-07-01

    To study the change and the effect of milkvetch root (MR) on neuro-endocrino-immune (NEI) network related indexes in repeated asthmatic attack model rats. Rats were randomly divided into five groups: the normal group (A), the model group (B), and the three treated groups (C, D, E) treated with low, medium and high dose of the MR by gastrogavage. The corticotropin releasing hormone (CRH) mRNA expression in hypothalamus was tested by Realtime-PCR, serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected with radioimmunoassay, serum IL-6, IL-4, IFN-gamma determined with enzyme-linked immunosorbent assay, and the lung tissue pathology was examined by hematoxylin and eosin staining. As compared with the normal group, in the rats 3 weeks after modeling, CRH mRNA expression, blood IFN-gamma and plasma ACTH were unchanged, serum level of CORT raised significantly (P<0.05), IL-6 and IL-4 showed an increasing trend but without significance. Low dose of MR could promote the production of serum CORT, and hight dose of MR could down-regulate the concentrations of IL-4 and IL-6 (P<0.01). No significant difference was found in comparison of pathological changes of lung tissue among the groups. Rats suffered from repeated asthmatic attack have some disorders in indexes of NEI, MR could enhance the function of hypothalamic-pituitary-adrenal cortex axis and adjust the balance of Th1 and Th2 cytokines to alleviate the inflammation of asthma.

  10. A novel statistical model for analyzing data of a systematic review generates optimal cutoff values for fractional exhaled nitric oxide for asthma diagnosis.

    Science.gov (United States)

    Schneider, Antonius; Linde, Klaus; Reitsma, Johannes B; Steinhauser, Susanne; Rücker, Gerta

    2017-12-01

    Measurement of fractional exhaled nitric oxide (FENO) might substitute bronchial provocation for diagnosing asthma. However, optimal FENO thresholds for diagnosing asthma remain unclear. We reanalyzed data collected for a systematic review investigating the diagnostic accuracy of FENO measurement to exploit all available thresholds under consideration of pretest probabilities using a newly developed statistical model. One hundred and fifty data sets for a total of 53 different cutoffs extracted from 26 studies with 4,518 participants were analyzed with the multiple thresholds model. This model allows identifying thresholds at which the test is likely to perform best. Diagnosing asthma might only be possible in a meaningful manner when the pretest probability of asthma is at least 30%. In that case, FENO > 50 ppb leads to a positive predictive value of 0.76 [95% confidence interval (CI): 0.29-0.96]. Excluding asthma might only be possible, when the pretest probability of asthma is 30% at maximum. Then, FENO asthma with FENO measurement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Experimental deep brain stimulation in animal models.

    Science.gov (United States)

    Tan, Sonny Kh; Vlamings, Rinske; Lim, Leewei; Sesia, Thibault; Janssen, Marcus Lf; Steinbusch, Harry Wm; Visser-Vandewalle, Veerle; Temel, Yasin

    2010-10-01

    DEEP BRAIN STIMULATION (DBS) as a therapy in neurological and psychiatric disorders is widely applied in the field of functional and stereotactic neurosurgery. In this respect, experimental DBS in animal models is performed to evaluate new indications and new technology. In this article, we review our experience with the concept of experimental DBS, including its development and validation. An electrode construction was developed using clinical principles to perform DBS unilaterally or bilaterally in freely moving rats. The stimulation parameters were adjusted for the rat using current density calculations. We performed validation studies in 2 animal models: a rat model of Parkinson's disease (bilateral 6-hydroxydopamine infusion in the striatum) and a rat model of Huntington's disease (transgenic rats). The effects of DBS were evaluated in different behavioral tasks measuring motor and cognitive functions. The electrode construction developed allows experimental DBS to be performed in freely moving rats. With the current setup, electrodes are placed in the target in 70% to 95% of the cases. Using a rat model, we showed that bilateral DBS of the subthalamic nucleus improves parkinsonian motor disability, but can induce behavioral side effects, similar to the clinical situation. In addition, we showed that DBS of the globus pallidus can improve motor and cognitive symptoms in a rat model of Huntington's disease. Nevertheless, during the process of the development and validation of experimental DBS, we encountered specific problems. These are discussed in detail. Experimental DBS in freely moving animals is an adequate tool to explore new indications for DBS and to refine DBS technology.

  12. Prospects of experimentally reachable beyond Standard Model ...

    Indian Academy of Sciences (India)

    2016-01-06

    Jan 6, 2016 ... Home; Journals; Pramana – Journal of Physics; Volume 86; Issue 2. Prospects of experimentally reachable beyond Standard Model physics in inverse see-saw motivated SO(10) GUT. Ram Lal Awasthi. Special: Supersymmetric Unified Theories and Higgs Physics Volume 86 Issue 2 February 2016 pp 223- ...

  13. Prospects of experimentally reachable beyond Standard Model ...

    Indian Academy of Sciences (India)

    2016-01-06

    Jan 6, 2016 ... also fit perfectly in the model framework. Despite the fact that SM has unravelled the gauge origin of fundamental forces and the structure of Universe while successfully confronting numerous experimental tests, it has various limitations. For a good summary on its excellencies and compulsions see [1], and.

  14. Changes in lung sounds during asthma progression in a guinea pig model

    Directory of Open Access Journals (Sweden)

    Chizu Habukawa

    2016-10-01

    Conclusions: Lung sound intensity in the middle frequency range from 501 to 1000 Hz correlated with peripheral airway wall thickness. Inspiratory sound intensity appeared to be an indicator of morphological changes in small airways in asthma.

  15. Novel drug targets for asthma and COPD : Lessons learned from in vitro and in vivo models

    NARCIS (Netherlands)

    Baker, Katie E.; Bonvini, Sara J.; Donovan, Chantal; Foong, Rachel E.; Han, Bing; Jha, Aruni; Shaifta, Yasin; Smit, Marieke; Johnson, Jill R.; Moir, Lyn M.

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as beta-agonists and glucocorticoids, may be effective at reducing symptoms, they

  16. Electrochemical desalination of bricks - Experimental and modeling

    DEFF Research Database (Denmark)

    Skibsted, Gry; Ottosen, Lisbeth M.; Jensen, Pernille Erland

    2015-01-01

    Chlorides, nitrates and sulfates play an important role in the salt-decay of porous materials in buildings and monuments. Electrochemical desalination is a technology able to remove salts from such porous materials in order to stop or prevent the decay. In this paper, experimental and numerical......-contaminated bricks with respect to the monovalent ions is discussed. Comparison between the experimental and the simulation results showed that the proposed numerical model is able to predict electrochemical desalination treatments with remarkable accuracy, and it can be used as a predictive tool...

  17. Rosmarinic Acid Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma.

    Science.gov (United States)

    Liang, Zhengmin; Xu, Yangfeng; Wen, Xuemei; Nie, Haiying; Hu, Tingjun; Yang, Xiaofeng; Chu, Xiao; Yang, Jian; Deng, Xuming; He, Jiakang

    2016-06-13

    Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with ovalbumin (Ova) were pretreated with RA (5, 10 or 20 mg/kg) at 1 h before Ova challenge. The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF), significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR) compared with the control Ova-induced mice. Histological analyses showed that RA substantially decreased the number of inflammatory cells and mucus hypersecretion in the airway. In addition, our results suggested that the protective effects of RA might be mediated by the suppression of ERK, JNK and p38 phosphorylation and activation of nuclear factor-κB (NF-κB). Furthermore, RA pretreatment resulted in a noticeable reduction in AMCase, CCL11, CCR3, Ym2 and E-selectin mRNA expression in lung tissues. These findings suggest that RA may effectively delay the progression of airway inflammation.

  18. Rosmarinic Acid Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma

    Directory of Open Access Journals (Sweden)

    Zhengmin Liang

    2016-06-01

    Full Text Available Rosmarinic acid (RA has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with ovalbumin (Ova were pretreated with RA (5, 10 or 20 mg/kg at 1 h before Ova challenge. The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF, significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR compared with the control Ova-induced mice. Histological analyses showed that RA substantially decreased the number of inflammatory cells and mucus hypersecretion in the airway. In addition, our results suggested that the protective effects of RA might be mediated by the suppression of ERK, JNK and p38 phosphorylation and activation of nuclear factor-κB (NF-κB. Furthermore, RA pretreatment resulted in a noticeable reduction in AMCase, CCL11, CCR3, Ym2 and E-selectin mRNA expression in lung tissues. These findings suggest that RA may effectively delay the progression of airway inflammation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-22

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

  20. Experimental Animal Models in Periodontology: A Review

    Science.gov (United States)

    Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre

    2010-01-01

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and primates have been used for modeling human periodontal diseases and treatments. However, both the anatomy and physiopathology of animals are different from those of humans, making difficult the evaluation of new therapies. Experimental models have been developed in order to reproduce major periodontal diseases (gingivitis, periodontitis), their pathogenesis and to investigate new surgical techniques. The aim of this review is to define the most pertinent animal models for periodontal research depending on the hypothesis and expected results. PMID:20556202

  1. The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma.

    Science.gov (United States)

    Shakeri, Farzaneh; Soukhtanloo, Mohammad; Boskabady, Mohammad Hossein

    2017-02-01

    The effects of Curcuma longa (C. longa) and curcumin on total and differential WBC count and oxidant, antioxidant biomarkers, in rat model of asthma were evaluated. Total and differential WBC count in the blood, NO2, NO3, MDA, SOD, CAT and thiol levels in serum were examined in control, asthma, Asthmatic rats treated with C. longa (0.75, 1.50, and 3.00 mg/ml), curcumin (0.15, 0.30, and 0.60 mg/ml), and dexamethasone (1.25 μg/ml) rats. Total and most differential WBC count, NO2, NO3 and MDA were increased but lymphocytes, SOD, CAT and thiol were decreased in asthmatic animals compared to controls (Plonga and curcumin compared to asthmatic group (Plonga and curcumin (Plonga extract and its constituent curcumin in animal model of asthma was observed which suggest a therapeutic potential for the plant and its constituent on asthma.

  2. The role of trait mindfulness in quality of life and asthma control among adolescents with asthma.

    Science.gov (United States)

    Cillessen, Linda; van de Ven, Monique O; Karremans, Johan C

    2017-08-01

    The current study focused on the role of trait mindfulness in asthma-related quality of life (QoL) and asthma control in adolescent asthma patients. Furthermore, potential underlying mechanisms (general and asthma-specific stress) of this relationship were investigated. In this cross-sectional study, questionnaire data of 94 adolescents with asthma that were prescribed daily asthma medication were included. Two Structural Equation Models (SEMs), a direct model and an indirect model, were tested. We found that trait mindfulness was directly related to asthma-related QoL, but not to asthma control. The relationship between trait mindfulness and asthma-related QoL was explained by asthma-specific, but not by general stress. Furthermore, an indirect relation from mindfulness to asthma control via asthma-specific stress was found. Cross-sectional evidence for a relation between mindfulness and asthma-related QoL is found. These findings may point to the possibility that an intervention aimed at increasing mindfulness could be a promising tool to improve asthma-related QoL in adolescents via a decrease in asthma-specific stress. Copyright © 2017. Published by Elsevier Inc.

  3. Severe Asthma

    Science.gov (United States)

    Erzurum, Serpil C.; Bleecker, Eugene R.; Calhoun, William J.; Castro, Mario; Comhair, Suzy A. A.; Chung, Kian Fan; Curran-Everett, Douglas; Dweik, Raed A.; Fain, Sean B.; Fitzpatrick, Anne M.; Gaston, Benjamin M.; Israel, Elliot; Hastie, Annette; Hoffman, Eric A.; Holguin, Fernando; Levy, Bruce D.; Meyers, Deborah A.; Moore, Wendy C.; Peters, Stephen P.; Sorkness, Ronald L.; Teague, W. Gerald; Wenzel, Sally E.; Busse, William W.

    2012-01-01

    The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure–function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies. PMID:22095547

  4. Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma.

    Science.gov (United States)

    Gu, Wen; Cui, Rong; Ding, Tao; Li, Xiaoming; Peng, Juan; Xu, Weiguo; Han, Fengfeng; Guo, Xuejun

    2017-04-01

    Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma. Ovalbumin (OVA)-sensitized and challenged mice were treated with simvastatin and sacrificed. The autophagy-related proteins Atg5, LC3B and Beclin1 were quantified, as well as the autophagy flux in bronchial smooth muscle cells (BSMCs). The relationship between airway inflammation and the autophagic process was investigated. We show that simvastatin treatment mediates activation of autophagy in BSMCs, which is correlated with airway inflammation and airway remodelling in mouse models of asthma. Simvastatin increases autophagy-related protein Atg5, LC3B and Beclin1 expression and autophagosome formation in lung tissue. Simvastatin-induced autophagy is associated with increased interferon-gamma (IFN-γ) and decreased IL-4, IL-5 and IL-13 cytokines production in BSMCs, as well as reversed extracellular matrix (ECM) deposition. In contrast, autophagy inhibitor 3-methyladenine (3-MA) eliminates the therapeutic effect of simvastatin. These findings demonstrate that simvastatin inhibits airway inflammation and airway remodelling through an activated autophagic process in BSMCs. We propose a crucial function of autophagy in statin-based therapeutic approaches in asthma. © 2016 Asian Pacific Society of Respirology.

  5. Experimental superficial candidiasis on tissue models.

    Science.gov (United States)

    Jayatilake, J A M S; Samaranayake, L P

    2010-07-01

    Candida species are common pathogens causing superficial mycoses primarily affecting the mucosa and the skin in humans. Crucial steps during pathogenesis of superficial candidiasis comprise fungal adhesion, colonisation and subsequent penetration of the respective tissues. Exploring these pathological events and perhaps fungal and tissue responses towards drug treatment is imperative in the management of this infection. Unfortunately, pathological biopsies of superficial candidiasis do not exhibit the early changes in the host-pathogen interaction as the tissues are already invaded by the fungi. In vivo experimental assessments of pathological processes of superficial candidiasis are also limited because of the difficulties in providing reproducible and comparable conditions in the host environment. Conversely, in vitro models have helped studying fungal-host interactions under more defined and controlled conditions. Some common in vitro models used to simulate superficial candidiasis are chick chorioallantoic membrane, mucosal explants and single layer or multiple layer cell cultures. Interestingly, these experimental approaches share advantages as well as disadvantages when compared with in vivo conditions. Hence, this review intends to discuss about the experimental superficial candidiasis produced in various tissue models and their advantages as well as disadvantages with a particular reference to further improvement of validity and reliability of such experiments.

  6. Seclazone Reactor Modeling And Experimental Validation

    Energy Technology Data Exchange (ETDEWEB)

    Osinga, T. [ETH-Zuerich (Switzerland); Olalde, G. [CNRS Odeillo (France); Steinfeld, A. [PSI and ETHZ (Switzerland)

    2005-03-01

    A numerical model is formulated for the SOLZINC solar chemical reactor for the production of Zn by carbothermal reduction of ZnO. The model involves solving, by the finite-volume technique, a 1D unsteady state energy equation that couples heat transfer to the chemical kinetics for a shrinking packed bed exposed to thermal radiation. Validation is accomplished by comparison with experimentally measured temperature profiles and Zn production rates as a function of time, obtained for a 5-kW solar reactor tested at PSI's solar furnace. (author)

  7. Beyond the standard model, experimental summary

    CERN Document Server

    McPherson, R A

    2003-01-01

    An overview of experimental results in searches for physics beyond the Standard Model is presented. It is impossible to cover all topics in this field, so a set of examples is used to highlight the scope and breadth of the results. Selected topics include searches for compositeness, flavour changing neutral currents, SUSY, exotic Higgs particles, low scale gravity in extra dimensions, and non commutative geometry. Current results are presented from the LEP, Tevatron Run I, and HERA I experiments. No convincing evidence for physics beyond the Standard Model has been observed. Prospects for ongoing and upcoming experiments are discussed. (40 refs).

  8. Experimental in Vivo Models of Candidiasis

    Directory of Open Access Journals (Sweden)

    Esther Segal

    2018-02-01

    Full Text Available Candidiasis is a multifaceted fungal disease including mucosal-cutaneous, visceral, and disseminated infections caused by yeast species of the genus Candida. Candida infections are among the most common human mycoses. Candida species are the third to fourth most common isolates from bloodstream infections in neutropenic or immunocompromised hospitalized patients. The mucosal-cutaneous forms—particularly vaginal infections—have a high prevalence. Vaginitis caused by Candida species is the second most common vaginal infection. Hence, candidiasis is a major subject for research, including experimental in vivo models to study pathogenesis, prevention, or therapy of the disease. The following review article will focus on various experimental in vivo models in different laboratory animals, such as mammals (mice, rats, rabbits, the fruit fly–Drosophila melanogaster, the larvae of the moth Galleria mellonella, or the free-living nematode Caenorhabditis elegans. The review will describe the induction of the different clinical forms of candidiasis in the various models and the validity of such models in mimicking the human clinical situations. The use of such models for the assessment of antifungal drugs, evaluation of potential vaccines to protect before candidiasis, exploration of Candida virulence factors, and comparison of pathogenicity of different Candida species will be included in the review. All of the above will be reported as based on published studies of numerous investigators as well as on the research of the author and his group.

  9. Endometriose: modelo experimental em ratas Endometriosis: experimental model in rats

    Directory of Open Access Journals (Sweden)

    Eduardo Schor

    1999-06-01

    Full Text Available Objetivo: divulgar a metodologia da indução de endometriose experimental em animais de laboratório. Método: utilizamos ratas albinas, virgens, adultas de aproximadamente três meses de idade, que foram inicialmente anestesiadas pelo éter etílico. Aberta a cavidade abdominal, identificamos os cornos uterinos e retiramos um fragmento de aproximadamente 4 cm do corno uterino direito. Esse fragmento foi mergulhado em solução fisiológica e sob lupa estereoscópica foi separado o endométrio do miométrio e feitos retângulos de aproximadamente 4 por 5 mm. Esses foram fixados por meio de fio de sutura, sobre vasos sangüíneos visíveis a olho nu, na parede lateral do abdômen, tomando-se sempre o cuidado de manter a porção do endométrio livre voltada para a luz da cavidade abdominal. Após 21 dias os animais foram novamente operados para verificarmos o tamanho dos implantes e para retirada do endométrio ectópico para análise histológica. Resultados: macroscopicamente observamos crescimento significativo dos implantes endometriais. Ao exame microscópico pudemos observar a presença de epitélio glandular e estroma semelhantes ao do endométrio tópico. Conclusões: o modelo utilizado reproduz a doença, em ratas, sendo método auxiliar de valia para estudar esta afecção, principalmente a ação de medicamentos sobre esses implantes.Purpose: to demonstrate the experimental endometriosis induction in animals. Method: we used adult female Wistar rats weighing 200 - 250 g anesthetized with ethyl ether to open the abdominal cavity. After identifying the uterine horns, we removed an approximately 4 cm fragment from the right uterine horn. This fragment was placed in physiological saline and, with the aid of a stereoscopic magnifying glass, the endometrium was separated from the myometrium and cut into rectangles of approximately 4 x 5 mm. These rectangles were fastened to the lateral abdominal wall near great blood vessels, taking care

  10. Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma.

    Science.gov (United States)

    Rogerio, Alexandre P; Fontanari, Caroline; Borducchi, Erica; Keller, Alexandre C; Russo, Momtchilo; Soares, Edson G; Albuquerque, Deijanira A; Faccioli, Lúcia H

    2008-02-02

    We have shown that the ethanolic extract of Lafoensia pacari inhibits eosinophilic inflammation induced by Toxocara canis infection, and that ellagic acid is the secondary metabolite responsible for the anti-eosinophilic activity seen in a model of beta-glucan peritonitis. In the present study, we investigated the preventive and curative effects of L. pacari extract and ellagic acid on allergic lung inflammation using a murine model of ovalbumin-induced asthma. In bronchoalveolar lavage fluid, preventive (22-day) treatment with L. pacari (200 mg/kg) and ellagic acid (10 mg/kg) inhibited neutrophil counts (by 75% and 57%) and eosinophil counts (by 78% and 68%). L. pacari reduced IL-4 and IL-13 levels (by 67% and 73%), whereas ellagic acid reduced IL-4, IL-5 and IL-13 (by 67%, 88% and 85%). To investigate curative anti-inflammatory effects, we treated mice daily with ellagic acid (0.1, 1, or 10 mg/kg), also treating selected mice with L. pacari (200 mg/kg) from day 18 to day 22. The highest ellagic acid dose reduced neutrophil and eosinophil numbers (by 59% and 82%), inhibited IL-4, IL-5, and IL-13 (by 62%, 61%, and 49%). Neither L. pacari nor ellagic acid suppressed ovalbumin-induced airway hyperresponsiveness or cysteinyl leukotriene synthesis in lung homogenates. In mice treated with ellagic acid (10 mg/kg) or L. pacari (200 mg/kg) at 10 min after the second ovalbumin challenge, eosinophil numbers were 53% and 69% lower, respectively. Cytokine levels were unaffected by this treatment. L. pacari and ellagic acid are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.

  11. An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Chang-Min Lee

    Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

  12. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  13. Nonlinear hierarchical modeling of experimental infection data.

    Science.gov (United States)

    Singleton, Michael D; Breheny, Patrick J

    2016-08-01

    In this paper, we propose a nonlinear hierarchical model (NLHM) for analyzing longitudinal experimental infection (EI) data. The NLHM offers several improvements over commonly used alternatives such as repeated measures analysis of variance (RM-ANOVA) and the linear mixed model (LMM). It enables comparison of relevant biological properties of the course of infection including peak intensity, duration and time to peak, rather than simply comparing mean responses at each observation time. We illustrate the practical benefits of this model and the insights it yields using data from experimental infection studies on equine arteritis virus. Finally, we demonstrate via simulation studies that the NLHM substantially reduces bias and improves the power to detect differences in relevant features of the infection response between two populations. For example, to detect a 20% difference in response duration between two groups (n=15) in which the peak time and peak intensity were identical, the RM-ANOVA test had a power of just 11%, and LMM a power of just 12%. By comparison, the nonlinear model we propose had a power of 58% in the same scenario, while controlling the Type I error rate better than the other two methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Models for Experimental High Density Housing

    Science.gov (United States)

    Bradecki, Tomasz; Swoboda, Julia; Nowak, Katarzyna; Dziechciarz, Klaudia

    2017-10-01

    The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio - housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.

  15. Modeling of Experimental Atherosclerotic Plaque Delamination.

    Science.gov (United States)

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations.

  16. Puerarin Attenuates Ovalbumin-Induced Lung Inflammation and Hemostatic Unbalance in Rat Asthma Model

    Directory of Open Access Journals (Sweden)

    Feng Dong

    2014-01-01

    Full Text Available Aim. We aimed to investigate and evaluate the preventive activity of puerarin on the ovalbumin-induced asthma rat model. Materials and Methods. Male Wistar rats were sensitized intraperitoneally on days 0, 7, and 14 and challenged to ovalbumin intratracheally on day 21. Groups of sensitized rats were treated randomly either with placebo, puerarin, dexamethasone, or puerarin combined with dexamethasone, from days 15 to 20. Inflammatory markers, including cell counts in bronchoalveolar lavage fluid (BALF, inflammatory cytokines, histopathology, and coagulation parameters, such as coagulation tests and the activity of coagulation factors, were analyzed. Results. Puerarin significantly inhibited the recruitment of inflammatory cells in BALF and lung tissue. At the same time, the release of IL-4, IL-10, and IFN-γ in serum and the expression of mRNAs in lung tissue homogenate were changed by puerarin. Administration of puerarin also effectively rectified the coagulation disorder in asthmatic rats, such as prothrombin time (PT (P<0.01, thrombin time (TT (P<0.05, fibrinogen (FIB (P<0.01,the activity of factor II (FII (P<0.01, the activity of factor V (FV (P<0.05, the activity of factor VII (FVII (P<0.05, the activity of factor X (FX (P<0.05, the activity of factor VIII (FVIII (P<0.01, the activity of factor IX (FIX (P<0.05, and the activity of factor XII (FXII (P<0.05. Conclusions. Our results provide a clue that puerarin was useful for the preventive of allergic airway disease in rodents.

  17. A biological model to explain the association between human rhinovirus respiratory infections and bronchial asthma.

    Science.gov (United States)

    Bianco, A; Spiteri, M A

    1998-02-01

    Human rhinoviruses (HRVs) are a frequent cause or upper respiratory tract infections in children and adults, and can exacerbate existing pulmonary disease. The major group of HRV attach to the receptor intercellular adhesion molecule (ICAM)-1, which is expressed on many cell types including epithelial cells. To study the influence of biological mediators on ICAM-1 expression, and consequently HRV attachment and infection, we have established an in vitro model system to evaluate the effects or pre-exposure to different cytokines on surface expression of ICAM-1 of uninfected and HRV-14-infected epithelial cells. The results of our studies show that the cytokines interleukin (IL)-1 beta, IL-8 and tumour necrosing factor (TNF)alpha increased ICAM-1 expression on epithelial cells. Epithelial cells infected with live HRV-14 displayed a significant upregulation of ICAM-1 compared to baseline. In contrast, interferon (IFN)gamma, whilst increasing the level of ICAM-1 expression on uninfected cells, induced a marked persistent downregulation of ICAM-1 expression on HRV-infected epithelial cells. In addition, IFN gamma appeared to completely override the ICAM-1 upregulation induced by IL-1 beta, IL-8 and TNF alpha, during HRV infection. We have further demonstrated that type 2 T-helper cell (Th2)-associated cytokines, predominantly IL-13, induce a marked upregulation or epithelial cell surface ICAM-1, thus increasing cellular binding sites for HRV attachment. As the airway mucosa or asthmatic subjects is predominantly infiltrated by activated type 2 T-helper cells with a simultaneous decrease of type 1 T-helper cells, our observations could explain the increased susceptibility to human rhinovirus infection observed in asthma.

  18. Individual-level socioeconomic status is associated with worse asthma morbidity in patients with asthma

    Directory of Open Access Journals (Sweden)

    Bouchard Anne

    2009-12-01

    Full Text Available Abstract Background Low socioeconomic status (SES has been linked to higher morbidity in patients with chronic diseases, but may be particularly relevant to asthma, as asthmatics of lower SES may have higher exposures to indoor (e.g., cockroaches, tobacco smoke and outdoor (e.g., urban pollution allergens, thus increasing risk for exacerbations. Methods This study assessed associations between adult SES (measured according to educational level and asthma morbidity, including asthma control; asthma-related emergency health service use; asthma self-efficacy, and asthma-related quality of life, in a Canadian cohort of 781 adult asthmatics. All patients underwent a sociodemographic and medical history interview and pulmonary function testing on the day of their asthma clinic visit, and completed a battery of questionnaires (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Asthma Self-Efficacy Scale. General Linear Models assessed associations between SES and each morbidity measure. Results Lower SES was associated with worse asthma control (F = 11.63, p Conclusions Results suggest that lower SES (measured according to education level, is associated with several indices of worse asthma morbidity, particularly worse asthma control, in adult asthmatics independent of disease severity. Results are consistent with previous studies linking lower SES to worse asthma in children, and add asthma to the list of chronic diseases affected by individual-level SES.

  19. Superficial tension: experimental model with simple materials

    Directory of Open Access Journals (Sweden)

    Tintori Ferreira, María Alejandra

    2012-09-01

    Full Text Available In this work appears a didactic offer based on an experimental activity using materials of very low cost, orientated to achieving that the student understand and interpret the phenomenon of superficial tension together with the importance of the modeling in sciences. It has as principal aim of education bring the student over to the mechanics of the static fluids and the intermolecular forces, combining scientific contents with questions near to the student what provides an additional motivation to the reflection of the scientific investigation.

  20. The importance of genetic influences in asthma

    NARCIS (Netherlands)

    Los, H; Koppelman, GH; Postma, DS

    1999-01-01

    Asthma is a complex genetic disorder in which the mode of inheritance is not known. Many segregation studies suggest that a major gene could be involved in asthma, but until now different genetic models have been obtained, Twin studies, too, have shown evidence for genetic influences in asthma, but

  1. Socioeconomic factors associated with asthma prevalence and ...

    African Journals Online (AJOL)

    studies corroborate a 'stress hypothesis' for asthma, whereby greater life stress increases the likelihood of asthma onset and frequent exacerbations. No studies have tested this type of socioeconomic risk model for childhood asthma in southern Africa, however, despite high rates of violence, poverty and psychological ...

  2. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Directory of Open Access Journals (Sweden)

    Francieli Vuolo

    2015-01-01

    Full Text Available Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA. In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p. and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

  3. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Science.gov (United States)

    Vuolo, Francieli; Petronilho, Fabricia; Sonai, Beatriz; Ritter, Cristiane; Hallak, Jaime E. C.; Zuardi, Antonio Waldo; Crippa, José A.; Dal-Pizzol, Felipe

    2015-01-01

    Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma. PMID:26101464

  4. Cost-effectiveness of primary prevention of paediatric asthma: a decision-analytic model

    NARCIS (Netherlands)

    Ramos, G. Feljandro P.; van Asselt, Antoinette D. I.; Kuiper, Sandra; Severens, Johan L.; Maas, Tanja; Dompeling, Edward; Knottnerus, J. André; van Schayck, Onno C. P.

    2013-01-01

    Background: Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention

  5. Muscle injury: review of experimental models.

    Science.gov (United States)

    Souza, Jaqueline de; Gottfried, Carmem

    2013-12-01

    Skeletal muscle is the most abundant tissue in the human body. Its main characteristic is the capacity to regenerate after injury independent of the cause of injury through a process called inflammatory response. Mechanical injuries are the most common type of the skeletal muscle injuries and are classified into one of three areas strain, contusion, and laceration. First, this review aims to describe and compare the main experimental methods that replicate the mechanical muscle injuries. There are several ways to replicate each kind of mechanical injury; there are, however, specific characteristics that must be taken into account when choosing the most appropriate model for the experiment. Finally, this review discusses the context of mechanical injury considering types, variability of methods, and the ability to reproduce injury models. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma.

    Science.gov (United States)

    Yang, Xia; Lv, Jian-Ning; Li, Hui; Jiao, Bo; Zhang, Qiu-Hong; Zhang, Yong; Zhang, Jie; Liu, Yan-Qin; Zhang, Ming; Shan, Hu; Zhang, Jin-Zhao; Wu, Run-Miao; Li, Ya-Li

    2017-05-01

    Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3β and β-catenin was detected by Western Blot. Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs. Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.

  7. Diagnosing Asthma

    Science.gov (United States)

    ... Ribbon Commands Skip to main content Turn off Animations Turn on Animations Our Sponsors Log in | Register Menu Log in | ... were tried and if they helped Any family history of allergies or asthma It is very important ...

  8. Occupational Asthma

    Science.gov (United States)

    ... the enzymes of the bacteria Bacillus subtilis, while bakers may develop an allergy and occupational asthma symptoms ... counts Continuing education center Find an allergist / immunologist Journals Login / My membership Search your symptoms Shop the ...

  9. Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in a murine model of neutrophilic asthma.

    Science.gov (United States)

    Guo, Qinyue; Li, Huixia; Liu, Jiali; Xu, Lin; Yang, Lan; Sun, Zhongmin; Zhou, Bo

    2017-03-01

    Endoplasmic reticulum (ER) stress has been considered to be an important regulator of airway inflammation in the pathogenesis of bronchial asthma, but the mechanism of ER stress involved in neutrophilic asthma remain not fully understood. Tunicamycin is a mixture of homologous nucleoside antibiotics, which is used to induce ER stress. In the present study, Tunicamycin was administered to mouse bronchial epithelial cells and a neutrophilic asthma model (OVALPS-OVA mice), and ER stress indicators and inflammatory cytokines were measured by Western blotting and Elisa. Tunicamycin not only induced ER stress in mouse bronchial epithelial cells, but also increased expression of inflammation indicators such as IL-6, IL-8, and TNF-α via PERK-ATF4-CHOP signaling. Additionally, the phosphorylation of PERK and the expression levels of ATF4 and CHOP proteins and inflammatory cytokines (IL-6, IL-8 and TNF-α) were elevated in the lung tissue of OVALPS-OVA mice. Administering tunicamycin further increased protein expression levels of ER stress indicators and inflammatory cytokines, and resulted in more severe asthma phenotypes in OVALPS-OVA mice, suggesting that PERK-ATF4-CHOP signaling is associated with airway inflammation in neutrophil-dominant asthma. These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma.

  10. Organ models in wound ballistics: experimental study.

    Science.gov (United States)

    Ozer, Mustafa Tahir; Oğünç, Gökhan; Eryilmaz, Mehmet; Yiğit, Taner; Menteş, Mustafa Oner; Dakak, Mehmet; Uzar, Ali Ihsan; Oner, Köksal

    2007-01-01

    Effects of various types and diameters of guns and related treatment principles are different. Our study was performed to experimentally demonstrate the effects of different gunshots in body tissues. 9x19 mm hand-gun and 7.62x51 mm G-3 infantry rifle were used in the study. Injury models were created through hand-gun and rifle shootings at isolated soft tissue, lower extremity, liver and intestine tissue simulants made of ballistic candle. High-speed cameras were used to capture 1000 frames per second. Images were examined and wound mechanisms were evaluated. It was observed that the colon content distributed more within the surrounding tissues by the rifle shootings comparing with hand-gun shootings and could be an infection source due to the large size of the cavity in the colon. Especially when the bullets hitting the bone were investigated, it was seen that much more tissue injury occurs with high speed bullets due to bullet deformation and fragmentation. However, no significant difference was found between the effect of hand-gun and rifle bullets passing through the extremity without hitting the bone. To know the type of the gun that caused the injury and its characteristics will allow to estimate severity and size of the injury before the treatment and to focus on different alternatives of treatment. Therefore, use of appropriate models is required in experimental studies.

  11. Do Allergies Cause Asthma?

    Science.gov (United States)

    ... Voice in Health Care Decisions Do Allergies Cause Asthma? KidsHealth > For Parents > Do Allergies Cause Asthma? Print ... son la causa del asma? Do Allergies Cause Asthma? Allergies don't cause asthma. But kids who ...

  12. Asthma Medications and Pregnancy

    Science.gov (United States)

    ... Associated Conditions Asthma & Pregnancy Asthma & Pregnancy: Medications Asthma & Pregnancy: Medications Make an Appointment Refer a Patient Ask ... mother and child. Making Decisions about Medication During Pregnancy It is important that your asthma be controlled ...

  13. Asthma and dental caries.

    Science.gov (United States)

    Matthews, Joseph

    2012-06-01

    Medline, government reports and conference proceedings were searched. Case-control, cohort or cross sectional studies were included if they provided relevant and applicable quantitative information on the relation between asthma and caries, had an independent study population and adequate definitions of asthma and caries and appropriate measurement of caries. Data were extracted independently by two reviewers and quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Fixed- and random-effects models were used for the analyses. Heterogeneity and publication bias were evaluated. Eighteen articles were included; 11 provided information on primary dentition and 15 on permanent dentition. Random-effects models showed a significant association between asthma and caries for both primary and permanent dentition, the odds ratios being 2.73 (95% CI: 1.61, 4.64) and 2.04 (95% CI: 1.44, 2.89), respectively. Evidence from this analysis suggests that asthma doubles the risk of caries in both primary and permanent dentition. Publication bias diagnostics and simulation suggested possible overestimation of the summary odds ratio for permanent dentition but not for primary dentition. Physicians and dentists should recommend preventive measures against caries for people with asthma.

  14. Experimental Basis for IED Particle Model

    Science.gov (United States)

    Zheng-Johansson, J.

    2009-05-01

    The internally electrodynamic (IED) particle model is built on three experimental facts: a) electric charges present in all matter particles, b) an accelerated charge generates electromagnetic (EM) waves by Maxwell's equations and Planck energy equation, and c) source motion gives Doppler effect. A set of well-kwon basic particle equations have been predicted based on first-principles solutions for IED particle (e.g. arxiv:0812.3951, J Phys CS128, 012019, 2008); the equations are long experimentally validated. A critical review of the key experiments suggests that the IED process underlies these equations not just sufficiently but also necessarily. E.g.: 1) A free IED electron solution is a plane wave ψ= Ce^i(kdX-φT) requisite for producing the diffraction fringe in a Davisson-Germer experiment, and of also all basic point-like attributes facilitated by a linear momentum kd and the model structure. It needs not further be a wave packet which produces not a diffraction fringe. 2)The radial partial EM waves, hence the total ψ, of an IED electron will, on both EM theory and experiment basis -not by assumption, enter two slits at the same time, as is requisite for an electron to interfere with itself as shown in double slit experiments. 3) On annihilation, an electron converts (from mass m) to a radiation energy φ without an acceleration which is externally observable and yet requisite by EM theory. So a charge oscillation of frequency φ and its EM waves must regularly present internal of a normal electron, whence the IED model.

  15. Diet and Asthma: Vitamins and Methyl Donors

    Science.gov (United States)

    Han, Yueh-Ying; Blatter, Josh; Brehm, John M.; Forno, Erick; Litonjua, Augusto A; Celedón, Juan C.

    2014-01-01

    SUMMARY Dietary changes may partly explain the high burden of asthma in industrialized nations. Experimental studies have motivated a significant number of observational studies of the relation between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. Because observational studies are susceptible to several sources of bias, well-conducted randomized controlled trials (RCTs) remain the “gold standard” to determine whether a vitamin or nutrient has an effect on asthma. Evidence from observational studies and/or relatively few RCTs most strongly justify ongoing and future RCTs of: 1) vitamin D to prevent or treat asthma, 2) choline supplementation as adjuvant treatment for asthma, and 3) vitamin E to prevent the detrimental effects of air pollution in subjects with asthma. At this time, there is insufficient evidence to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma. PMID:24461761

  16. Aerosolized montelukast polymeric particles-an alternative to oral montelukast-alleviate symptoms of asthma in a rodent model.

    Science.gov (United States)

    Patel, Brijeshkumar; Gupta, Nilesh; Ahsan, Fakhrul

    2014-11-01

    Cysteinyl leukotrienes (CysLTs) propagate inflammatory reactions that result from allergen exposure in asthma. Montelukast, a CysLT type-1 receptor antagonist, disrupts mediator-receptor interactions and minimizes inflammatory response. In this study, we have evaluated anti-asthmatic efficacy of inhalable montelukast-loaded large porous particulate formulations in ovalbumin-induced rat airway inflammation model that mimics asthma. The anti-inflammatory effects of a montelukast-loaded formulation were investigated in rats by measuring the total protein content, levels of injury markers and number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). The histopathological studies assessed the morphological and structural changes that occur in asthmatic lungs. Animals were also challenged with methacholine to examine the airway hyper-reactivity. Compared with healthy animals, asthmatic animals showed a 3.8- and 4.77-fold increase in the protein content and number of inflammatory cells in BALF, respectively. Intratracheal montelukast particles reduced the protein content by 3.3-fold and the number of inflammatory cells by 2.62-fold. Also, montelukast particles reduced the lactate dehydrogenase (LDH) and myeloperoxidase (MPO) levels by a 4.87- and 6.8-fold in BALF, respectively. Montelukast particles reduced the airway wall thickness by 2.5-fold compared with untreated asthmatic lungs. Further, particulate formulation protected the lungs against methacholine-induced bronchial provocation (p montelukast alleviated allergen-induced inflammatory response in an animal model and prevented histological changes associated with asthma. Thus montelukast-loaded large porous polylactic acid (PLA) particles could be an aerosolized delivery approach for administration of currently available oral montelukast.

  17. Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma.

    Science.gov (United States)

    Skappak, Christopher; Ilarraza, Ramses; Wu, Ying-Qi; Drake, Matthew G; Adamko, Darryl J

    2017-01-01

    Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.

  18. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  19. A human experimental model of episodic pain

    DEFF Research Database (Denmark)

    Petrini, Laura; Hennings, Kristian; Li, Xi

    2014-01-01

    were subjected to 45 min of intense painful cutaneous electrical stimulation (episodic pain session), using a stimulus paradigm that in animals has been shown to induce long-term potentiation. These electrical stimulations produced a verbal pain rating of approximately 85 on a 0-100 verbal rating scale......An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants...... (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused...

  20. What Works for Asthma Education Programs: Lessons from Experimental Evaluations of Social Programs and Interventions for Children. Fact Sheet. Publication #2012-01

    Science.gov (United States)

    Chrisler, Alison

    2012-01-01

    Asthma is a chronic respiratory disease that affects millions of children and adolescents each year. In 2009, 7.1 million children ages 0 to 17 years were reported to have asthma. Unfortunately, when children and teens are unable to manage and cope with their disease, it can compromise their physical, academic, and social development. Therefore,…

  1. Experimental validation of model Hortel Whillier; Validacion experimental del model de Hottel-Whillier

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez Munoz, F.; Cejudo Lopez, J. M.; Carrillo andres, A.

    2010-07-01

    Comparing the results of testing of a commercial flat-plate solar collector with a detailed implementation model of Hottel Whillier fin and tube. The validation procedure is based on comparing experimental and theoretical curves and more likely uncertainty bands. the model correctly predicts the end of profits and underestimates the 5% of losses, although a sensitivity analysis shows that this result is not attributable to the model itself but to the inputs with which it was implemented. The model has difficulty differentiating between the terms of linear and quadratic losses that appear in the quadratic fit curve. (Author) 1 refs.

  2. Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma.

    Science.gov (United States)

    de Azevedo, Bruna Cestari; de Freitas Morel, Lucas Junqueira; Carmona, Fábio; Cunha, Thiago Mattar; Contini, Silvia Helena Taleb; Delprete, Piero Giuseppe; Ramalho, Fernando Silva; Crevelin, Eduardo; Bertoni, Bianca Waléria; de Castro França, Suzelei; de Carvalho Borges, Marcos; Pereira, Ana Maria Soares

    2018-02-09

    Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200mgkg -1 , respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200mgkg -1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100mgkg -1 respectively. The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine

  3. 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.

  4. Is influenza vaccination in asthma helpful?

    Science.gov (United States)

    Bueving, Herman J; Thomas, Siep; Wouden, Johannes C van der

    2005-02-01

    Influenza infections are frequently involved in asthma exacerbations. During influenza epidemics substantial excess morbidity due to respiratory tract complications is reported in all age categories as well as excess mortality among the elderly. Vaccines are available for protection against influenza. Worldwide, vaccination is advised and considered a quality point for asthma care. However, the protective effect of influenza vaccination in patients with asthma is still disputed. In order to establish the current state of affairs we reviewed the recent literature on the protective effect of influenza vaccination and its usefulness in patients with asthma. Several studies were found addressing influenza and the protective aspects of vaccination. They discussed the incidence, the adverse effects of vaccination, the coverage of influenza vaccination among patients with asthma and the effectiveness of the vaccine. Influenza vaccination can safely be used in patients with asthma. Allegations that vaccination could provoke asthma exacerbations are convincingly invalidated by previous and recent research. Although patients with asthma are one of the major target groups for immunization, vaccine coverage in all age categories remains low. So far, no unequivocal beneficial effect of influenza vaccination in patients with asthma was found in observational and experimental studies in the sense of reduction of asthma exacerbations and other complications. Recent studies confirm these negative findings. More long-term randomized, placebo-controlled studies, focusing on influenza- proven illness in patients with asthma, are needed to address the question of how helpful influenza vaccination is in these patients.

  5. Effects of Anethole in Nociception Experimental Models

    Directory of Open Access Journals (Sweden)

    Alessandra Mileni Versuti Ritter

    2014-01-01

    Full Text Available This study investigated the antinociceptive activity of anethole (anethole 1-methoxy-4-benzene (1-propenyl, major compound of the essential oil of star anise (Illicium verum, in different experimental models of nociception. The animals were pretreated with anethole (62.5, 125, 250, and 500 mg/kg one hour before the experiments. To eliminate a possible sedative effect of anethole, the open field test was conducted. Anethole (62.5, 125, 250, and 500 mg/kg showed an antinociceptive effect in the writhing model induced by acetic acid, in the second phase of the formalin test (125 and 250 mg/kg in the test of glutamate (62.5, 125, and 250 mg/kg, and expresses pain induced by ACF (250 mg/kg. In contrast, anethole was not able to increase the latency time on the hot plate and decrease the number of flinches during the initial phase of the formalin test in any of the doses tested. It was also demonstrated that anethole has no association with sedative effects. Therefore, these data showed that anethole, at all used doses, has no sedative effect and has an antinociceptive effect. This effect may be due to a decrease in the production/release of inflammatory mediators.

  6. Tendon healing in vivo. An experimental model.

    Science.gov (United States)

    Abrahamsson, S O; Lundborg, G; Lohmander, L S

    1989-01-01

    Flexor tendon segments were incubated in a diffusion chamber in the subcutis of rabbits. Tendons incubated up to 6 weeks in the diffusion chamber showed proliferating and migrating cells from the epitenon cell layer as well as viable endotenon cells. Explants frozen in liquid nitrogen prior to incubation showed no signs of extrinsic cell contamination and remained non-viable indicating that no cell penetration occurred through the Millipore filter and that cell division seen in non-frozen and incubated tendons was an expression of intrinsic cellular proliferative capacity of the tendon. In tendon segments incubated in chambers for three weeks, collagen synthesis was reduced by 50% and the rate of cell proliferation measured as 3H-thymidine incorporation, was 15 times that of native tendons. Frozen and incubated tendons showed only traces of remaining matrix synthesis or cell proliferation. With this experimental model we have histologically and biochemically shown that tendons may survive and heal while the nutrition exclusively could be based on diffusion and the tendons have an intrinsic capacity of healing. The described model enables further studies on tendon healing and its regulation.

  7. Regulation of hypothalamic-pituitary-adrenal axis activity and immunologic function contributed to the anti-inflammatory effect of acupuncture in the OVA-induced murine asthma model.

    Science.gov (United States)

    Wei, Ying; Dong, Ming; Zhong, Ling; Liu, Jiaqi; Luo, Qingli; Lv, Yubao; Mo, Shuming; Sun, Jing; Liu, Feng; Xu, Fei; Yan, Chen; Dong, Jingcheng

    2017-01-01

    Asthma is a complex inflammatory disease of the airways and acupuncture is one of the effective therapies widely used to treat asthma in China. The aim of the study was to evaluate the regulatory role of acupuncture in airway inflammation and the hypothalamic-pituitary-adrenal (HPA) axis activity in OVA-induced murine asthma model. Our results demonstrated that acupuncture was effective in suppression of AHR, inhibition of total leukocyte, neutrophil, lymphocyte and eosinophil counts in BALF, attenuation of airway inflammation and TNF-α, IL-1β, IL-5 and eotaxin secretion. Furthermore, the HPA axis activity was also regulated by acupuncture, which included promotion of adrenocorticotropic hormone and cortisol secretion in the plasma. Our findings revealed that acupuncture could attenuate airway inflammation and regulate HPA axis and immunologic function in the OVA-induced murine asthma model, which may provide support to better understand the contribution of acupuncture to the regulation of airway inflammation and HPA axis activity in asthma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Experimental models for Murray’s law

    Science.gov (United States)

    Akita, Dai; Kunita, Itsuki; Fricker, Mark D.; Kuroda, Shigeru; Sato, Katsuhiko; Nakagaki, Toshiyuki

    2017-01-01

    Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized vein-network when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53-3.29, consistent with predictions from Murray’s law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall.

  9. Death due to asthma

    Directory of Open Access Journals (Sweden)

    Albert L. Sheffer

    1996-01-01

    Full Text Available The prevalence and fatality rate of asthma have increased worldwide. Underdiagnosis and undertreatment of asthma are central to the occurrence of fatal asthma. Atopy is the principal risk factor associated with asthma. However, consideration of the epidemiologic, physiologic, pharmacologic, pathologic and clinical parameters of asthma assessment may provide valuable insight into death due to asthma. Psychologic and socioeconomic factors may further aggravate the asthma status. Ethnic minorities are at increased risk of asthma. The perception of dyspnea may be blunted in asthma sufferers. Slow-onset fatal asthma may be associated with submucosal eosinophilic, whereas sudden-onset may be associated with submucosal neutrophilia. Fatal asthma occurs in patients abusing regular |32-agonist therapy. Peak flow assessment often provides insight into asthma deterioration prior to signs of respiratory distress. Markers of risk of death due to asthma further identify the fatality-prone asthma patient.

  10. Vitamin E and D regulation of allergic asthma immunopathogenesis

    OpenAIRE

    Cook-Mills, Joan M.; Avila, Pedro C

    2014-01-01

    Asthma occurs as complex interactions of the environmental and genetics. Clinical studies and animal models of asthma indicate dietary factors such as vitamin E and vitamin D as protective for asthma risk. In this review, we discuss opposing regulatory functions of tocopherol isoforms of vitamin E and regulatory functions of vitamin D in asthma and how the variation in global prevalence of asthma may be explained, at least in part, by these dietary components.

  11. Death due to asthma

    OpenAIRE

    Sheffer, Albert L.

    1996-01-01

    The prevalence and fatality rate of asthma have increased worldwide. Underdiagnosis and undertreatment of asthma are central to the occurrence of fatal asthma. Atopy is the principal risk factor associated with asthma. However, consideration of the epidemiologic, physiologic, pharmacologic, pathologic and clinical parameters of asthma assessment may provide valuable insight into death due to asthma. Psychologic and socioeconomic factors may further aggravate the asthma status. Ethnic minoriti...

  12. Indicators of asthma control among students in a rural, school-based asthma management program.

    Science.gov (United States)

    Rasberry, Catherine N; Cheung, Karen; Buckley, Rebekah; Dunville, Richard; Daniels, Brandy; Cook, Deborah; Robin, Leah; Dean, Blair

    2014-10-01

    The evaluation sought to determine if a comprehensive, school-based asthma management program in a small, rural school district helped students improve asthma control. To determine if students in the asthma program demonstrated better asthma control than students in a comparison school district, the evaluation team used a quasi-experimental, cross-sectional design and administered questionnaires assessing asthma control (which included FEV1 measurement) to 456 students with asthma in the intervention and comparison districts. Data were analyzed for differences in asthma control between students in the two districts. To determine if students in the intervention experienced increased asthma control between baseline and follow-up, the evaluation team used a one-group retrospective design. Program records for 323 students were analyzed for differences in percent of predicted forced expiratory volume in one second (FEV1) between baseline and follow-up. Students with asthma in the intervention district exhibited significantly better asthma control than students with asthma in the comparison district. Percent of predicted FEV1 did not change significantly between baseline and follow-up for the intervention participants; however, post hoc analyses revealed students with poorly controlled asthma at baseline had significantly higher FEV1 scores at follow-up, and students with well-controlled asthma at baseline had significantly lower FEV1 scores at follow-up. Findings suggest that the comprehensive school-based program led to improvements in asthma control for students with poorly controlled asthma at baseline, and school-based programs need mechanisms for tracking students with initially well-controlled asthma to ensure they maintain control.

  13. The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model

    Directory of Open Access Journals (Sweden)

    Chih-Che Lin

    2014-01-01

    Full Text Available Serine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT, gabexate mesilate (FOY, and ulinastatin (UTI on a long-term challenged mouse model of chronic asthma are unclear. BALB/c mice (6 mice/group were intratracheally inoculated with five doses of Dermatophagoides pteronyssinus (Der p; 50 μL, 1 mg/mL at one-week intervals. Therapeutic doses of FUT (0.0625 mg/kg, FOY (20 mg/kg, or UTI (10,000 U/kg were, respectively, injected intraperitoneally into these mice. Control mice received sterile PBS. At 3 days after the last challenge, mice were sacrificed to assess airway hyperresponsiveness (AHR, remodeling, and inflammation; lung histological features; and cytokine expression profiles. Compared with untreated controls, mice treated with FUT, FOY, and UTI had decreased AHR and goblet cell hyperplasia, decreased eosinophil and neutrophil infiltration, decreased Der p-induced IL-4 levels in serum and IL-5, IL-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid, and inhibited nuclear factor (NF-κB activity in lung tissues. The serine protease inhibitors FUT, FOY, and UTI have potential therapeutic benefits for treating asthma by downregulating Th2 cytokines and Th17 cell function and inhibiting NF-κB activation in lung tissue.

  14. In vivo micro-CT assessment of airway remodeling in a flexible OVA-sensitized murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Mathieu Lederlin

    Full Text Available Airway remodeling is a major pathological feature of asthma. Up to now, its quantification still requires invasive methods. In this study, we aimed at determining whether in vivo micro-computed tomography (micro-CT is able to demonstrate allergen-induced airway remodeling in a flexible mouse model of asthma. Sixty Balb/c mice were challenged intranasally with ovalbumin or saline at 3 different endpoints (Days 35, 75, and 110. All mice underwent plethysmography at baseline and just prior to respiratory-gated micro-CT. Mice were then sacrificed to assess bronchoalveolar lavage and lung histology. From micro-CT images (voxel size = 46×46×46 µm, the numerical values of total lung attenuation, peribronchial attenuation (PBA, and PBA normalized by total lung attenuation were extracted. Each parameter was compared between OVA and control mice and correlation coefficients were calculated between micro-CT and histological data. As compared to control animals, ovalbumin-sensitized mice exhibited inflammation alone (Day 35, remodeling alone (Day 110 or both inflammation and remodeling (Day 75. Normalized PBA was significantly greater in mice exhibiting bronchial remodeling either alone or in combination with inflammation. Normalized PBA correlated with various remodeling markers such as bronchial smooth muscle size or peribronchial fibrosis. These findings suggest that micro-CT may help monitor remodeling non-invasively in asthmatic mice when testing new drugs targeting airway remodeling in pre-clinical studies.

  15. Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model of ovalbumin induced chronic asthma.

    Science.gov (United States)

    Shin, In Sik; Jeon, Woo Young; Shin, Hyeun Kyoo; Lee, Mee Young

    2013-11-01

    Montelukast, a leukotriene receptor antagonist, is used commercially as a maintenance treatment for asthma and to relieve allergic symptoms. In this study, we evaluated the protective effects of montelukast against the airway inflammation and fibrosis using a murine model of ovalbumin (OVA) induced chronic asthma. The animals received OVA challenge three times a week for 4 weeks. Montelukast (30 mg/kg) was administrated orally once a day for 4 weeks. The administration of montelukast caused a reduction in elevated interleukin (IL)-4, IL-13, eotaxin, immunoglobulin (Ig), inflammatory cell infiltration into the airways, and mucus production after repeated OVA challenges. To investigate the antifibrotic mechanism of montelukast, we examined the expression of profibrotic mediators, including vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and Smad3 proteins in the lung tissue using western blotting and immunohistochemistry. The administration of montelukast reduced the overexpression of profibrotic proteins in the lung tissue, which was confirmed by immnunohistochemistry. These results are consistent with a histopathological examination of lung tissue with Masson's trichrome stain. In conclusion, the administration of montelukast reduced airway inflammation and pulmonary fibrosis by reducing the release of Th2 cytokines and the expression of VEGF, TGF-β1/Smad3 in the lung tissue. © 2013.

  16. Differential Effects of Rapamycin and Dexamethasone in Mouse Models of Established Allergic Asthma

    Science.gov (United States)

    Mushaben, Elizabeth M.; Brandt, Eric B.; Hershey, Gurjit K. Khurana; Le Cras, Timothy D.

    2013-01-01

    The mammalian target of rapamycin (mTOR) plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM)-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections) and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4–6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR), inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established. PMID:23349887

  17. Flavonoids and Asthma

    Science.gov (United States)

    Tanaka, Toshio; Takahashi, Ryo

    2013-01-01

    Asthma is a chronic disease, characterized by airway inflammation, airflow limitation, hyper-reactivity and airway remodeling. It is believed that asthma is caused by the interaction between genetic and environmental factors. The prevalence of allergic diseases, including asthma, has increased worldwide during the past two decades. Although the precise reasons that have caused this increase remain unknown, dietary change is thought to be one of the environmental factors. Flavonoids, which are polyphenolic plant secondary metabolites ubiquitously present in vegetables, fruits and beverages, possess antioxidant and anti-allergic traits, as well as immune-modulating activities. Flavonoids are powerful antioxidants and anti-allergic nutrients that inhibit the release of chemical mediators, synthesis of Th2 type cytokines, such as interleukin (IL)-4 and IL-13, and CD40 ligand expression by high-affinity immunoglobulin E (IgE) receptor-expressing cells, such as mast cells and basophils. They also inhibit IL-4-induced signal transduction and affect the differentiation of naïve CD4+ T cells into effector T-cells through their inhibitory effect on the activation of the aryl hydrocarbon receptor. Various studies of flavonoids in asthmatic animal models have demonstrated their beneficial effects. The results of several epidemiological studies suggest that an increase in flavonoid intake is beneficial for asthma. Moreover, clinical trials of flavonoids have shown their ameliorative effects on symptoms related to asthma. However, these human studies are currently limited; further validation is required to clarify whether an appropriate intake of flavonoids may constitute dietary treatment and for part of a preventive strategy for asthma. PMID:23752494

  18. Long-term control medication use and asthma control status among children and adults with asthma.

    Science.gov (United States)

    Zahran, Hatice S; Bailey, Cathy M; Qin, Xiaoting; Johnson, Carol

    2017-12-01

    Uncontrolled asthma decreases quality of life and increases health care use. Most people with asthma need daily use of long-term control (LTC) medications for asthma symptoms and to prevent asthma attacks. Ongoing assessment of a person's level of asthma control and medication use is important in determining the effectiveness of current treatment to decrease the frequency and intensity of symptoms and functional limitations. To assess the use of LTC medication among children and adults with current asthma and identify contributing factors for LTC medication use. We used the 2006-2010 Behavioral Risk Factor Surveillance System (BRFSS) child and adult Asthma Call-back Survey (ACBS) data to assess the level of asthma control and LTC medication use. Asthma control was classified as well controlled and uncontrolled using guideline-based measures. We used multivariable logistic regression models to identify contributing factors for LTC medication use and having uncontrolled asthma. Among persons with current asthma, 46.0% of children and 41.5% of adults were taking LTC medications and 38.4% of children and 50.0% of adults had uncontrolled asthma. Among children who had uncontrolled asthma (38.4%), 24.1% were taking LTC medications and 14.3% were not taking LTC medications. Among adults who had uncontrolled asthma (50.0%), 26.7% were taking LTC medications and 23.3% were not taking LTC medications. Using BRFSS ACBS data to assess the level of asthma control and LTC medication use can identify subpopulations of persons with asthma who receive suboptimal treatment, for which better asthma-related medical treatment and management are needed.

  19. Asthma - children

    Science.gov (United States)

    ... BS, Burks AW, et al, eds. Middleton's Allergy Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 53. Lugogo N, Que LG, Gilstrap DL, Kraft M. Asthma: clinical diagnosis and management. In: Broaddus VC, Mason RJ, Ernst JD, et ...

  20. Childhood asthma

    African Journals Online (AJOL)

    atopy, night cough, exercise-induced cough and/or wheeze and seasonal variation in symptoms. Epidemiology. Asthma is on the increase in both the developed and developing countries of the world. In South Africa, its prevalence in children in Cape Town (measured by exercise challenge) was only three per cent in 1979.

  1. Childhood asthma

    African Journals Online (AJOL)

    prevalence in children in Cape Town (measured by exercise challenge) was only three per ... mortality among the five to 34-year-old age group, and fifth for asthma ... clouded by differences in terminology used by respondents, depending on ...

  2. MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase?mediated suppression of histone deacetylase 2

    OpenAIRE

    Kim, RY; Horvat, JC; Pinkerton, JW; Starkey, MR; Essilfie, AT; Mayall, JR; Nair, PM; Hansbro, NG; Jones, B; Haw, TJ; Sunkara, KP; Nguyen, TH; Jarnicki, AG; Keely, S; Mattes, J

    2016-01-01

    BACKGROUND: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The?mechanisms...

  3. Effect of 1,25-Dihydroxy Vitamin D3 on the Expression of Interleukin-17 and -21 in an Asthma Mice Model

    Directory of Open Access Journals (Sweden)

    RJ Lin

    2015-09-01

    Full Text Available Objective: To explore the effect of 1,25-dihydroxy vitamin D3 (1,25(OH2D3 on the expression of interleukin (IL-17 and IL-21 in asthma by establishing an asthma mice model. Methods: Forty female Kunming mice were randomly divided into normal control group (group A, n = 10, asthma group (group B, n = 10, 1,25(OH2D3 intervention group (group C, n = 10 and dexamethasone treatment group (group D, n = 10. Asthma mice model was established and subsequently treated with different intervention. The airway lesions in mice were observed and the serum IL-17, IL-21 and immunoglobulin E (IgE levels were determined using the enzyme-linked immunosorbent assay (ELISA method. Immunohistochemical method was used to detect the expression of IL-17 and IL-21 in lung tissues. Results:Serum IL-17 and IgE levels in groups B, C and D were remarkably higher than those in group A, especially in group B (F = 31.276, 18.677, p < 0.01. However, serum IL-21 level in group A was the highest, significantly higher than the other three groups (F = 22.406, p < 0.01. Immunohistochemical test revealed that the expression of IL-17 in group B was significantly higher than that in groups A, C and D, while IL-21 was strongly expressed in groups A and D but weakly expressed in group B. Conclusion: In the pathogenesis of asthma, 1,25(OH2D3 intervention can reduce the expression of IL-17 but elevate the expression of IL-21, suggesting it has a certain effect on asthma.

  4. Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

  5. Strain Differences in a Murine Model of Air Pollutant-induced Nonatopic Asthma and Rhinitis.

    Science.gov (United States)

    Harkema, Jack R; Hotchkiss, Lucas A; Vetter, Nicholas A; Jackson-Humbles, Daven N; Lewandowski, Ryan P; Wagner, James G

    2017-01-01

    Ozone is an irritating gas found in photochemical smog. Epidemiological associations have been made between the onset of asthma and childhood exposures to increasing levels of ambient ozone (i.e., air pollutant-induced nonatopic asthma). Individuals, however, vary in their susceptibility to this outdoor air pollutant, which may be due, in part, to their genetic makeup. The present study was designed to test the hypothesis that there are murine strain-dependent differences in pulmonary and nasal pathologic responses to repeated ozone exposures. C57BL/6NTac and BALB/cNTac mice were exposed to 0 or 0.8 ppm ozone, 4 hr/day, for 9 consecutive weekdays. In both strains of mice, ozone induced eosinophilic inflammation and mucous cell metaplasia in the nasal and pulmonary airways. Lungs of ozone-exposed C57BL/6NTac mice, however, had greater eosinophilic inflammation, mucous cell metaplasia, and expression of genes related to type 2 immunity and airway mucus hypersecretion, as compared to similarly exposed BALB/cNTac mice. Ozone-exposed C57BL/6NTac mice also had greater eosinophilic rhinitis but a similar degree of mucous cell metaplasia in nasal epithelium, as ozone-exposed BALB/cNTac mice. These findings suggest that nonatopic individuals may differ in their inflammatory and epithelial responses to repeated ozone exposures that are due, in part, to genetic factors.

  6. Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma.

    Science.gov (United States)

    Klaßen, Carina; Karabinskaya, Anna; Dejager, Lien; Vettorazzi, Sabine; Van Moorleghem, Justine; Lühder, Fred; Meijsing, Sebastiaan H; Tuckermann, Jan P; Bohnenberger, Hanibal; Libert, Claude; Reichardt, Holger M

    2017-07-01

    Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to modulate gene expression in airway epithelial cells coincided with its potency to resolve AAI supports a crucial role for transcriptional regulation by the GR in this cell type. Taken together, we identified an unknown mode of GC action in the treatment of allergic asthma that might help to develop more specific therapies in the future. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. The effects of early allergen/endotoxin exposure on subsequent allergic airway inflammation to allergen in mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Yeong-Ho Rha

    2010-04-01

    Full Text Available Purpose : Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR in mouse model of asthma. Methods : Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA, LPS or 1.0 μg LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; P values for significance were set to 0.05. Results : Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion : These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic

  8. Exercise-Induced Asthma

    Science.gov (United States)

    ... January 2014 More on this topic for: Parents Kids Teens Can Kids and Teens With Asthma Play Sports? Asthma Center When to Go to the ER if Your Child Has Asthma Kids and Exercise Asthma Triggers Word! Exercise-Induced Asthma ...

  9. Injury Based on Its Study in Experimental Models

    Directory of Open Access Journals (Sweden)

    M. Mendes-Braz

    2012-01-01

    Full Text Available The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered.

  10. Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma

    NARCIS (Netherlands)

    van Oosterhout, A. J.; van Esch, B.; Hofman, G.; Hofstra, C. L.; van Ark, I.; Nijkamp, F. P.; Kapsenberg, M. L.; Savelkoul, H. F.; Weller, F. R.

    1998-01-01

    In the present study, we investigated whether allergen immunotherapy is effective in a murine model with immunologic and pathophysiologic features reminiscent of allergic asthma. Ovalbumin-sensitized mice received increasing (1 microgram to 1 mg) subcutaneous doses of ovalbumin twice a week for 8 wk

  11. Biomass thermochemical gasification: Experimental studies and modeling

    Science.gov (United States)

    Kumar, Ajay

    The overall goals of this research were to study the biomass thermochemical gasification using experimental and modeling techniques, and to evaluate the cost of industrial gas production and combined heat and power generation. This dissertation includes an extensive review of progresses in biomass thermochemical gasification. Product gases from biomass gasification can be converted to biopower, biofuels and chemicals. However, for its viable commercial applications, the study summarizes the technical challenges in the gasification and downstream processing of product gas. Corn stover and dried distillers grains with solubles (DDGS), a non-fermentable byproduct of ethanol production, were used as the biomass feedstocks. One of the objectives was to determine selected physical and chemical properties of corn stover related to thermochemical conversion. The parameters of the reaction kinetics for weight loss were obtained. The next objective was to investigate the effects of temperature, steam to biomass ratio and equivalence ratio on gas composition and efficiencies. DDGS gasification was performed on a lab-scale fluidized-bed gasifier with steam and air as fluidizing and oxidizing agents. Increasing the temperature resulted in increases in hydrogen and methane contents and efficiencies. A model was developed to simulate the performance of a lab-scale gasifier using Aspen Plus(TM) software. Mass balance, energy balance and minimization of Gibbs free energy were applied for the gasification to determine the product gas composition. The final objective was to optimize the process by maximizing the net energy efficiency, and to estimate the cost of industrial gas, and combined heat and power (CHP) at a biomass feedrate of 2000 kg/h. The selling price of gas was estimated to be 11.49/GJ for corn stover, and 13.08/GJ for DDGS. For CHP generation, the electrical and net efficiencies were 37 and 86%, respectively for corn stover, and 34 and 78%, respectively for DDGS. For

  12. Fuzzy model to estimate the number of hospitalizations for asthma and pneumonia under the effects of air pollution.

    Science.gov (United States)

    Chaves, Luciano Eustáquio; Nascimento, Luiz Fernando Costa; Rizol, Paloma Maria Silva Rocha

    2017-06-22

    Predict the number of hospitalizations for asthma and pneumonia associated with exposure to air pollutants in the city of São José dos Campos, São Paulo State. This is a computational model using fuzzy logic based on Mamdani's inference method. For the fuzzification of the input variables of particulate matter, ozone, sulfur dioxide and apparent temperature, we considered two relevancy functions for each variable with the linguistic approach: good and bad. For the output variable number of hospitalizations for asthma and pneumonia, we considered five relevancy functions: very low, low, medium, high and very high. DATASUS was our source for the number of hospitalizations in the year 2007 and the result provided by the model was correlated with the actual data of hospitalization with lag from zero to two days. The accuracy of the model was estimated by the ROC curve for each pollutant and in those lags. In the year of 2007, 1,710 hospitalizations by pneumonia and asthma were recorded in São José dos Campos, State of São Paulo, with a daily average of 4.9 hospitalizations (SD = 2.9). The model output data showed positive and significant correlation (r = 0.38) with the actual data; the accuracies evaluated for the model were higher for sulfur dioxide in lag 0 and 2 and for particulate matter in lag 1. Fuzzy modeling proved accurate for the pollutant exposure effects and hospitalization for pneumonia and asthma approach. Prever o número de internações por asma e pneumonia associadas à exposição a poluentes do ar no município em São José dos Campos, estado de São Paulo. Trata-se de um modelo computacional que utiliza a lógica fuzzy baseado na técnica de inferência de Mamdani. Para a fuzzificação das variáveis de entrada material particulado, ozônio, dióxido de enxofre e temperatura aparente foram consideradas duas funções de pertinência para cada variável com abordagem linguísticas: bom e ruim. Para a variável de saída número interna

  13. PMWS: Experimental model and co-infections

    DEFF Research Database (Denmark)

    Allan, G. M.; McNeilly, F.; Ellis, J

    2004-01-01

    and pneumonia and typical histological lesions include lymphocytic depletion and multinucleated giant cell formation in lymph nodes, degeneration and necrosis of hepatocytes, and multifocal lymphohistocytic interstitial pneumonia. This communication will review the results of experimental infections...

  14. Effect of relaxation-breathing training on anxiety and asthma signs/symptoms of children with moderate-to-severe asthma: a randomized controlled trial.

    Science.gov (United States)

    Chiang, Li-Chi; Ma, Wei-Fen; Huang, Jing-Long; Tseng, Li-Feng; Hsueh, Kai-Chung

    2009-08-01

    Emotional stress triggers and exacerbates asthma in children. Reducing anxiety in adults by relaxation-breathing techniques has been shown in clinical trials to produce good asthma outcomes. However, more evidence is needed on using this intervention with asthmatic children. To evaluate the effectiveness of combined self-management and relaxation-breathing training for children with moderate-to-severe asthma compared to self-management-only training. Two-group experimental design. Pediatric outpatient clinic of a medical center in central Taiwan. Participants were 48 children, ages 6-14 years, with moderate-to-severe asthma and their parents. Participants were randomly assigned to an experimental or comparison group and matched by gender, age, and asthma severity. Both groups participated in an asthma self-management program. Children in the experimental group were also given 30 min of training in a relaxation-breathing technique and a CD for home practice. Data on anxiety levels, self-perceived health status, asthma signs/symptoms, peak expiratory flow rate, and medication use were collected at baseline and at the end of the 12-week intervention. Effects of group, time, and group-time interaction were analyzed using the Mixed Model in SPSS (12.0). Anxiety (especially state anxiety) was significantly lower for children in the experimental group than in the comparison group. Differences in the other four physiological variables were also noted between pre- and post-intervention, but these changes did not differ significantly between groups. A combination of self-management and relaxation-breathing training can reduce anxiety, thus improving asthmatic children's health. These results can serve as an evidence base for psychological nursing practice with asthmatic children.

  15. Allergies, asthma, and molds

    Science.gov (United States)

    Reactive airway - mold; Bronchial asthma - mold; Triggers - mold; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. Mold is a common trigger. When your asthma or allergies become worse due to mold, you are ...

  16. Asthma Triggers: Gain Control

    Science.gov (United States)

    ... asthma. Dogs, cats, rodents (including hamsters and guinea pigs) and other warm-blooded mammals can trigger asthma ... Page Contact Us to ask a question, provide feedback, or report a problem. Asthma Indoor Air Quality ...

  17. Dynamic vehicle model for handling performance using experimental data

    Directory of Open Access Journals (Sweden)

    SangDo Na

    2015-11-01

    Full Text Available An analytical vehicle model is essential for the development of vehicle design and performance. Various vehicle models have different complexities, assumptions and limitations depending on the type of vehicle analysis. An accurate full vehicle model is essential in representing the behaviour of the vehicle in order to estimate vehicle dynamic system performance such as ride comfort and handling. An experimental vehicle model is developed in this article, which employs experimental kinematic and compliance data measured between the wheel and chassis. From these data, a vehicle model, which includes dynamic effects due to vehicle geometry changes, has been developed. The experimental vehicle model was validated using an instrumented experimental vehicle and data such as a step change steering input. This article shows a process to develop and validate an experimental vehicle model to enhance the accuracy of handling performance, which comes from precise suspension model measured by experimental data of a vehicle. The experimental force data obtained from a suspension parameter measuring device are employed for a precise modelling of the steering and handling response. The steering system is modelled by a lumped model, with stiffness coefficients defined and identified by comparing steering stiffness obtained by the measured data. The outputs, specifically the yaw rate and lateral acceleration of the vehicle, are verified by experimental results.

  18. Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model.

    Science.gov (United States)

    Ozkars, M Y; Keskin, O; Tokur, M; Ulasli, M; Gogebakan, B; Ciralik, H; Kucukosmanoglu, E; Demirel, C; Oztuzcu, S; Kahraman, H

    2017-11-27

    Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  19. A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model.

    Directory of Open Access Journals (Sweden)

    Daniel J Fullen

    Full Text Available Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose.A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London.In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics.ClinicalTrials.gov NCT02522832.

  20. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

    NARCIS (Netherlands)

    Valstar, D.L.; Schijf, M.A.; Nijkamp, F.P.; Storm, G.; Arts, J.H.E.; Kuper, C.F.; Bloksma, N.; Henricks, P.A.J.

    2006-01-01

    Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In

  1. What Is Asthma?

    Science.gov (United States)

    ... Asthma Awareness National Asthma Awards Federal and Partner Organizations Public Service Announcements & Multimedia Main menu Environmental Topics Air Bed Bugs Chemicals and Toxics Environmental ...

  2. Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

    Directory of Open Access Journals (Sweden)

    Amatullah Hajera

    2011-02-01

    Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

  3. Comparing predictions made by a prediction model, clinical score, and physicians: pediatric asthma exacerbations in the emergency department.

    Science.gov (United States)

    Farion, K J; Wilk, S; Michalowski, W; O'Sullivan, D; Sayyad-Shirabad, J

    2013-01-01

    Asthma exacerbations are one of the most common medical reasons for children to be brought to the hospital emergency department (ED). Various prediction models have been proposed to support diagnosis of exacerbations and evaluation of their severity. First, to evaluate prediction models constructed from data using machine learning techniques and to select the best performing model. Second, to compare predictions from the selected model with predictions from the Pediatric Respiratory Assessment Measure (PRAM) score, and predictions made by ED physicians. A two-phase study conducted in the ED of an academic pediatric hospital. In phase 1 data collected prospectively using paper forms was used to construct and evaluate five prediction models, and the best performing model was selected. In phase 2 data collected prospectively using a mobile system was used to compare the predictions of the selected prediction model with those from PRAM and ED physicians. Area under the receiver operating characteristic curve and accuracy in phase 1; accuracy, sensitivity, specificity, positive and negative predictive values in phase 2. In phase 1 prediction models were derived from a data set of 240 patients and evaluated using 10-fold cross validation. A naive Bayes (NB) model demonstrated the best performance and it was selected for phase 2. Evaluation in phase 2 was conducted on data from 82 patients. Predictions made by the NB model were less accurate than the PRAM score and physicians (accuracy of 70.7%, 73.2% and 78.0% respectively), however, according to McNemar's test it is not possible to conclude that the differences between predictions are statistically significant. Both the PRAM score and the NB model were less accurate than physicians. The NB model can handle incomplete patient data and as such may complement the PRAM score. However, it requires further research to improve its accuracy.

  4. Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma.

    Science.gov (United States)

    Ennis, D P; Cassidy, J P; Mahon, B P

    2004-09-01

    It has been proposed that T helper (Th)2-driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter-regulation can protect against allergic asthma. To test whether Th1-inducing infection with Bordetella pertussis protects against allergic asthma using well-characterized murine models. Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well-characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function. We demonstrate that OVA sensitization does not affect the development of B. pertussis-specific immune responses dominated by IgG2a and IFN-gamma and does not impair Th1-mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA-specific IgE. The pattern of cytokine responses, in particular OVA-specific IL-5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL-10 and IL-13 levels were enhanced in OVA-stimulated spleen cell cultures and in lavage fluid from infected co-sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper-reactivity to methacholine exposure. Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper-reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.

  5. Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model.

    Science.gov (United States)

    Lee, Yueh-Lun; Lee, Lin-Wen; Su, Chen-Yao; Hsiao, George; Yang, Yi-Yuan; Leu, Sy-Jye; Shieh, Ying-Hua; Burnouf, Thierry

    2013-09-01

    Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-β1 (TGF-β1) content, PCLs may exert immunosuppressive and anti-inflammatory functions. PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-β in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-β1 was used as control. PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-β-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice. S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates. © 2013 American Association of Blood Banks.

  6. Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma.

    Science.gov (United States)

    Kim, Yun-Ho; Choi, Yean-Jung; Lee, Eun-Jung; Kang, Min-Kyung; Park, Sin-Hye; Kim, Dong Yeon; Oh, Hyeongjoo; Park, Sang-Jae; Kang, Young-Hee

    2017-12-01

    Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. This study employed 2 µg/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 µg/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ≥ 50 mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

  7. Investigation of anti-asthmatic potential of dried fruits of Vitis vinifera L. in animal model of bronchial asthma.

    Science.gov (United States)

    Arora, Poonam; Ansari, S H; Najmi, Abul Kalam; Anjum, Varisha; Ahmad, Sayeed

    2016-01-01

    Fruits of Vitis vinifera L., commonly known as grapes, are largely consumed worldwide because of their high nutritional and medicinal benefits. The present study investigated effects of V. vinifera fruits in ovalbumin-induced animal model of bronchial asthma. Male wistar rats (except group 1) were sensitized with allergen (ovalbumin, 40 mg/rat + aluminum hydroxide, 2 mg/rat). Groups of sensitized animals were treated orally with either vehicle (0.4 mL/kg), standard dexamethasone (2.5 mg/kg) or alcoholic extract of V. vinifera dried fruits (31 and 42.5 mg/kg) from day 1 to 28 (n = 6 for all groups). Inflammatory markers including cell counts, cytokines such as interleukin (IL)-4, IL-5, IL-1β, tumor necrosis factor, immunoglobulin E (IgE), leukotrienes and nitrite levels in both blood/serum and bronchoalveolar fluid were analysed. Breathing rate and tidal volume as lung function parameters were examined by spirometer. Lung tissues were studied for histamine content and histopathology. Treatment of sensitized animals with dexamethasone or two doses of V. vinifera fruits extract inhibited recruitment of inflammatory cytokines, IgE, nitrites and circulating cells particularly eosinophils in blood/serum and bronchoalveolar fluid (p vinifera fruits extract treatment also normalized lung functions and histamine levels compared to ovalbumin-sensitized controls (p vinifera fruits in allergic asthma possibly related to its ability to inhibit cellular response and subsequent production of inflammatory cytokines.

  8. Experimental comparison of models for ultrafast impact ionization is silicon

    DEFF Research Database (Denmark)

    Tarekegne, Abebe Tilahun; Iwaszczuk, Krzysztof; Jepsen, Peter Uhd

    2016-01-01

    We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses....

  9. From bedside to bench to clinic trials: identifying new treatments for severe asthma

    Directory of Open Access Journals (Sweden)

    Amarjit Mishra

    2013-07-01

    Full Text Available Asthmatics with a severe form of the disease are frequently refractory to standard medications such as inhaled corticosteroids, underlining the need for new treatments to prevent the occurrence of potentially life-threatening episodes. A major obstacle in the development of new treatments for severe asthma is the heterogeneous pathogenesis of the disease, which involves multiple mechanisms and cell types. Furthermore, new therapies might need to be targeted to subgroups of patients whose disease pathogenesis is mediated by a specific pathway. One approach to solving the challenge of developing new treatments for severe asthma is to use experimental mouse models of asthma to address clinically relevant questions regarding disease pathogenesis. The mechanistic insights gained from mouse studies can be translated back to the clinic as potential treatment approaches that require evaluation in clinical trials to validate their effectiveness and safety in human subjects. Here, we will review how mouse models have advanced our understanding of severe asthma pathogenesis. Mouse studies have helped us to uncover the underlying inflammatory mechanisms (mediated by multiple immune cell types that produce Th1, Th2 or Th17 cytokines and non-inflammatory pathways, in addition to shedding light on asthma that is associated with obesity or steroid unresponsiveness. We propose that the strategy of using mouse models to address clinically relevant questions remains an attractive and productive research approach for identifying mechanistic pathways that can be developed into novel treatments for severe asthma.

  10. The Effects of Proresolution of Ellagic Acid in an Experimental Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Claudiney de Freitas Alves

    2013-01-01

    Full Text Available Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF, the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO activity, and P-selectin expression, but not activator protein 1 (AP-1 and nuclear factor kappa B (NF-κB pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation.

  11. Studies on experimental models used for nutritional and biological ...

    African Journals Online (AJOL)

    The anatomical location for a successful implantation in order to reduce complications to the hearest minimum has been suggested . The maintenance of the implanted cannulae for the purpose of keeping the modified experimental model in perfect health is discussed. Key Words: Experimental Models, Nutritional Biological ...

  12. Occupational asthma caused by samba (Triplochiton scleroxylon) wood dust in a professional maker of wooden models of airplanes: a case study.

    Science.gov (United States)

    Krawczyk-Szulc, Patrycja; Wiszniewska, Marta; Pałczyński, Cezary; Nowakowska-Świrta, Ewa; Kozak, Anna; Walusiak-Skorupa, Jolanta

    2014-06-01

    Wood dust is a known occupational allergen that may induce, in exposed workers, respiratory diseases including asthma and allergic rhinitis. Samba (obeche, Triplochiton scleroxylon) is a tropical tree, which grows in West Africa, therefore, Polish workers are rarely exposed to it. This paper describes a case of occupational asthma caused by samba wood dust. The patient with suspicion of occupational asthma due to wood dust was examined at the Department of Occupational Diseases and Clinical Toxicology in the Nofer Institute of Occupational Medicine. Clinical evaluation included: analysis of occupational history, skin prick tests (SPT) to common and occupational allergens, determination of serum specific IgE to occupational allergens, serial spirometry measurements, metacholine challenge test and specific inhalation challenge test with samba dust SPT and specific serum IgE assessment revealed sensitization to common and occupational allergens including samba. Spirometry measurements showed mild obstruction. Metacholine challenge test revealed a high level of bronchial hyperactivity. Specific inhalation challenge test was positive and cellular changes in nasal lavage and induced sputum confirmed allergic reaction to samba. IgE mediated allergy to samba wood dust was confirmed. This case report presents the first documented occupational asthma and rhinitis due to samba wood dust in wooden airplanes model maker in Poland.

  13. Vitamin D in asthma and future perspectives

    Directory of Open Access Journals (Sweden)

    Huang H

    2013-09-01

    Full Text Available Haidong Huang,1 Konstantinos Porpodis,2 Paul Zarogoulidis,2,3 Kalliopi Domvri,2 Paschalina Giouleka,2 Antonis Papaiwannou,2 Stella Primikyri,2 Efi Mylonaki,2 Dionysis Spyratos,2 Wolfgang Hohenforst-Schmidt,4 Ioannis Kioumis,2 Konstantinos Zarogoulidis2 1Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 2Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg–Essen, Essen, Germany; 4II Medical Clinic, “Coburg” Hospital, University of Würzburg, Coburg, Germany Abstract: Humans have the ability to synthesize vitamin D during the action of ultraviolet (UV radiation upon the skin. Apart from the regulation of calcium and phosphate metabolism, another critical role for vitamin D in immunity and respiratory health has been revealed, since vitamin D receptors have also been found in other body cells. The term “vitamin D insufficiency” has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with a wide range of pulmonary diseases, including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. This review focuses on the controversial relationship between vitamin D and asthma. Also, it has been found that different gene polymorphisms of the vitamin D receptor have variable associations with asthma. Other studies investigated the vitamin D receptor signaling pathway in vitro or in experimental animal models and showed either a beneficial or a negative effect of vitamin D in asthma. Furthermore, a range of epidemiological studies has also suggested that vitamin D insufficiency is associated with low lung function. In the future, clinical trials in different asthmatic

  14. Improving the physiological realism of experimental models

    NARCIS (Netherlands)

    Vinnakota, Kalyan C.; Cha, Chae Y.; Rorsman, Patrik; Balaban, Robert S.; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A.; Jeneson, Jeroen A. L.

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these

  15. Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

    Science.gov (United States)

    Wei, Da-Zhen; Guo, Xian-Yang; Lin, Li-Na; Lin, Meng-Xiang; Gong, Yu-Qiang; Ying, Bin-Yu; Huang, Ming-Yuan

    2016-12-01

    Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

  16. Asthma-like airway inflammation and responses in a rat model of atopic dermatitis induced by neonatal capsaicin treatment

    Directory of Open Access Journals (Sweden)

    Han RT

    2017-05-01

    Full Text Available Rafael Taeho Han,1,2 Sewon Kim,3 Kyungmin Choi,1,2 Hyeonseok Jwa,1,2 JaeHee Lee,1,2 Hye Young Kim,1,2 Hee Jin Kim,4 Hang-Rae Kim,5 Seung Keun Back,6 Heung Sik Na1,2 1Neuroscience Research Institute, 2Department of Physiology, 3Department of Microbiology, College of Medicine, Korea University, Seoul, 4Division of Biological Science and Technology, Science and Technology College, Yonsei University Wonju Campus, Wonju, 5Department of Anatomy, College of Medicine, Seoul National University, Seoul, 6Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea Abstract: Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment. Here, we investigated whether our model also showed asthmatic changes, with the aim of expanding our AD model into an atopic march model. First, we confirmed that capsaicin treatment (50 mg/kg within 24 h after birth induced dermatitis and scratching behaviors until 6 weeks of age. After that, the mRNA expression of Th1 and Th2 cytokines, such as IFN-γ and TNF-α, and IL-4, IL-5, and IL-13, respectively, was quantified with quantitative real-time polymerase chain reaction in the skin and the lungs. The number of total cells and eosinophils was counted in bronchoalveolar lavage (BAL fluid. The levels of IgE in the serum and BAL fluid were determined with enzyme-linked immunosorbent assay. Paraffin-embedded sections (4 μm were stained with hematoxylin/eosin to analyze the morphology of the lung and the airway

  17. Experimental Diabetes Mellitus in Different Animal Models

    Directory of Open Access Journals (Sweden)

    Amin Al-awar

    2016-01-01

    Full Text Available Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

  18. Experimental model to induce obesity in rats

    National Research Council Canada - National Science Library

    Vinicius Von Diemen; Eduardo Neubarth Trindade; Manoel Roberto Maciel Trindade

    2006-01-01

    .... Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH...

  19. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  20. Experimental model of arteriovenous malformation in vitro using biological grafts

    Directory of Open Access Journals (Sweden)

    Sandu Aurelia Mihaela

    2015-06-01

    Full Text Available Introduction: Brain arteriovenous malformations (AVMs represent a serious health problem all around the world. Experimental models help to better understand the pathophysiology of these lesions. Experiment: We performed an experimental model of AVM using biological grafts, arteries and veins harvested from chicken wings at the elbow joint. We used 14 vessels and we performed 20 end-to-end anastomoses to create a nidus with a single feeding artery and a single draining vein. The system was irrigated with colored solution. The experiment was done according with law in force regarding experimental research activity. Conclusions: Experimental models allow us to understand the hemodynamics and predict the outcome of brain AVMs in humans. This experimental model is a useful tool in understanding the hemodynamic properties of brain AVMs. It is very useful in vascular anastomosis training

  1. An experimental comparison of modelling techniques for speaker ...

    Indian Academy of Sciences (India)

    Most of the existing modelling techniques for the speaker recognition task make an implicit assumption of sufficient data for speaker modelling and hence may lead to poor modelling under limited data condition. The present work gives an experimental evaluation of the modelling techniques like Crisp Vector Quantization ...

  2. How Variability in Clinical Phenotypes Should Guide Research into Disease Mechanisms in Asthma

    Science.gov (United States)

    Adcock, Ian M.

    2013-01-01

    Asthma is increasingly being considered as a collection of different phenotypes that present with intermittent wheezing. Unbiased approaches to classifying asthma have led to the identification of distinct phenotypes based on age of onset of disease, atopic state, disease severity or activity, degree of chronic airflow obstruction, and sputum eosinophilia. Linking phenotypes to known disease mechanism is likely to be more fruitful in determining the potential targets necessary for successful therapies of specific endotypes. A “Th2-high expression” signature from the epithelium of patients with asthma identifies a subset of patients with high eosinophilia and good therapeutic responsiveness to corticosteroids. Other characteristic traits of asthma include noneosinophilic asthma, corticosteroid insensitivity, obesity-associated, and exacerbation-prone. Further progress into asthma mechanisms will be driven by unbiased data integration of multiscale data sets from omics technologies with those phenotypic characteristics and by using mathematical modeling. This will lead to the discovery of new pathways and their integration into endotypes and also set up further hypothesis-driven research. Continued iteration through experimentation or modeling will be needed to refine the phenotypes that relate to outcomes and also delineate specific treatments for specific phenotypes. PMID:24313760

  3. Asthma and obesity

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ali, Zarqa; Nilas, Lisbeth

    2012-01-01

    Obesity is a major health problem, and obesity is associated with a high incidence of asthma and poor asthma control. The aim of the present paper is to systematically review the current knowledge of the effect on overall asthma control of weight reduction in overweight and obese adults with asthma....

  4. Hysteretic behavior of a belt tensioner: modeling and experimental investigation

    OpenAIRE

    Michon, Guilhem; Manin, Lionel; Dufour, Regis

    2005-01-01

    In this paper we describe the modeling of the hysteretic behavior of belt tensioners. An initial experimental device is composed only of the tensioner by using forcing frequencies, preloads and deflection amplitudes. It permits the identification of the parameters of the restoring force model used. Comparison of the measured and predicted force deflection loops of the tensioner subjected to large deflections permits preliminary validation of the model.The second experimental device consists o...

  5. Yoga for asthma

    Directory of Open Access Journals (Sweden)

    Zu-Yao Yang

    outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardized mean difference (SMD with 95% CI. For dichotomous outcomes, we used risk ratio (RR with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder. There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants, improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants, and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in

  6. The integrated care of asthma in Switzerland (INCAS)-study: Patients' perspective of received asthma care and their interest in asthma education.

    Science.gov (United States)

    Dürr, Selina; Hersberger, Kurt E; Zeller, Andreas; Scheuzger, Jonas; Miedinger, David; Gregoriano, Claudia; Leuppi, Jörg D; Steurer-Stey, Claudia

    2016-11-01

    For successful long-term asthma care, self-management education is a cornerstone. Little is known about associations between patients' interest in education, asthma control and care delivery. We compared patients' characteristics, asthma control and patients' perspective about asthma care in subjects with and without interest in asthma education. Moreover, we assessed reasons, why patients denied participating in asthma education. Baseline data of 223 patients with asthma (age 43 ± 12 years, 38% male, 58% non-smokers, 13% current smokers), who participated in a multicentre longitudinal controlled study, are reported. At baseline, patients completed the Asthma Control Test (ACT), the Patient Assessment Chronic Illness Care questionnaire (PACIC 5A) and stated their interest in an asthma education programme. Overall, 34% of all participants showed uncontrolled asthma. One hundred and twenty-five (56%) patients were interested in education. Compared to patients without interest, they were characterised by male gender (p = 0.013), worse asthma control (p < 0.001), and perception of lower quality of chronic asthma care delivery, in particular lower self-management support (p < 0.001). Main reasons for rejecting asthma education were having sufficient asthma knowledge, having only mild asthma, receiving adequate medical support and lack of time. More than half of the patients were interested in asthma education. Interest was associated with worse asthma control and lower receipt of care according to the Chronic Care Model. Considering these aspects, this approach may help to improve care quality and allow targeting interventions to those patients who are interested in becoming active participants in their care and who might benefit most.

  7. Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study

    DEFF Research Database (Denmark)

    Lange, Peter; Çolak, Yunus; Ingebrigtsen, Truls Sylvan

    2016-01-01

    focus on individuals with asthma-COPD overlap. METHODS: We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those...... mixed-effects model. FINDINGS: We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma......·004) than in healthy never-smokers. INTERPRETATION: Prognosis of individuals with asthma-COPD overlap is poor and seems to be affected by the age of recognition of asthma, being worst in those with late asthma onset (after 40 years of age). Such patients should be followed up closely to prevent fast lung...

  8. Asthma exacerbation prediction: recent insights.

    Science.gov (United States)

    Fleming, Louise

    2018-04-01

    Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.

  9. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

    Directory of Open Access Journals (Sweden)

    Alicja Pacholewska

    Full Text Available Recurrent airway obstruction (RAO is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs. We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

  10. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model.

    Science.gov (United States)

    Espinoza, Julia; Montaño, Luis M; Perusquía, Mercedes

    2013-11-01

    Primates secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA); in humans, its levels are low during childhood and start declining after the fourth decade. It has been postulated that the progressive decline in DHEA levels may be related with the severity of asthma associated with age. To determine whether DHEA may regulate the airway smooth muscle (ASM) activity, isolated tracheal rings with and without epithelium from male guinea pigs were isometrically recorded to characterize the response of ASM to DHEA at different concentrations on KCl- and carbachol (CCh)-induced contraction as well as on ovalbumin (OVA)-induced contraction in sensitized guinea pigs. Additionally, we used barometric plethysmography in sensitized guinea pigs in order to compare changes of the lung resistance increased by the antigen challenge to OVA in the absence and presence of different doses of DHEA. DHEA concentration-dependently abolished the contraction to KCl, CCh and OVA, and no differences were found in preparations with and without epithelium. DHEA-induced relaxation was not modified by the suppression of protein synthesis or transcription, pharmacological inhibition of nitric oxide (NO) synthase, nor by antagonist of β2-adrenergic receptors or an inhibitor of the 3β-HSD enzyme. Likewise, Ca(2+)-induced contraction in Ca(2+)-free depolarized tissues was antagonized by DHEA, and the contraction to the L-type voltage-dependent calcium channel activator (Bay K 8644) was inhibited by DHEA. Furthermore, DHEA prevented OVA-induced increases in lung resistance. These results indicate that DHEA-induced relaxation in ASM is a nongenomic (membrane) action and is not produced after its bioconversion. The data suggest that DHEA-induced relaxation is an epithelium- and NO-independent mechanism that involves a blockade of voltage-dependent calcium channels and possible non-selective cation channels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Experimental Measurement, Analysis and Modelling of Dependency ...

    African Journals Online (AJOL)

    We propose a direct method of measurement of the total emissivity of opaque samples on a range of temperature around the ambient one. The method rests on the modulation of the temperature of the sample and the infra-red signal processing resulting from the surface of the sample we model the total emissivity obtained ...

  12. New experimental model for training in videosurgery Novo modelo experimental para treinamento em videocirurgia

    Directory of Open Access Journals (Sweden)

    Danilo Malta Batista

    2012-10-01

    Full Text Available PURPOSE: To develop a new experimental model of lower cost for training in videosurgery. METHODS: This project was performed at the Nucleus of Experimental Surgery of the Bahiana School of Medicine and Public Health, based on previous models described in the literature and under the supervision of the full professor of Operative Technique and Experimental Surgery II. It was made a model cube-shaped, made of wood, with holes distributed in various locations, rubber stoppers for the holes and lined externally with carpet, and internally with laminate. RESULTS: The new experimental model is of low cost and reproduces quite faithfully several videosurgical procedures. CONCLUSION: Medical schools interested in the subject may adopt the new model for training in videosurgery without the need of high costs for making and using these models.OBJETIVO: Desenvolver um novo modelo experimental de baixo custo para treinamento em videocirurgia MÉTODOS: Este projeto foi conduzido no Núcleo de Cirurgia Experimental da Escola Bahiana de Medicina e Saúde Pública, baseado em modelos prévios descritos na literatura e sob a supervisão do professor titular de Técnica Operatória e Cirurgia Experimental II. Foi feito um modelo em formato de cubo, de madeira, com furos distribuídos em vários locais, tampas de borracha para os orifícios e forrado externamente com carpete e internamente com laminado. RESULTADOS: O novo modelo experimental desenvolvido é de baixo custo e reproduz de forma bastante fiel diversos procedimentos videocirúrgicos. CONCLUSÃO: Faculdades médicas interessadas no tema poderão adotar o novo modelo para o treinamento em videocirurgia sem que sejam necessários gastos elevados para a confecção e o uso desses modelos.

  13. Different experimental approaches in modelling cataractogenesis

    Science.gov (United States)

    Kyselova, Zuzana

    2010-01-01

    Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed. PMID:21217865

  14. Experimentally testing the standard cosmological model

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, D.N. (Chicago Univ., IL (USA) Fermi National Accelerator Lab., Batavia, IL (USA))

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, {Omega}{sub b}, remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that {Omega}{sub b} {approximately} 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming {Omega}{sub total} = 1) and the need for dark baryonic matter, since {Omega}{sub visible} < {Omega}{sub b}. Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M{sub x} {approx gt} 20 GeV and an interaction weaker than the Z{sup 0} coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for {nu}-masses may imply that the {nu}{sub {tau}} is a good hot dark matter candidate. 73 refs., 5 figs.

  15. Tesla coil theoretical model and experimental verification

    OpenAIRE

    Voitkans, Janis; Voitkans, Arnis

    2014-01-01

    Abstract – In this paper a theoretical model of a Tesla coil operation is proposed. Tesla coil is described as a long line with distributed parameters in a single-wired format, where the line voltage is measured against electrically neutral space. It is shown that equivalent two-wired scheme can be found for a single-wired scheme and already known long line theory can be applied to a Tesla coil. Formulas for calculation of voltage in a Tesla coil by coordinate and calculation of resonance fre...

  16. Mathematical Models and the Experimental Analysis of Behavior

    Science.gov (United States)

    Mazur, James E.

    2006-01-01

    The use of mathematical models in the experimental analysis of behavior has increased over the years, and they offer several advantages. Mathematical models require theorists to be precise and unambiguous, often allowing comparisons of competing theories that sound similar when stated in words. Sometimes different mathematical models may make…

  17. Health-related quality of life in childhood bronchial asthma

    African Journals Online (AJOL)

    EL-HAKIM

    worldwide.1. In Egypt, the prevalence of asthma among school children in the Nile Delta region is about. 7.7%.2 Asthma is relatively common in Egypt, and probably under diagnosed ... and adolescent HRQoL is not only to capture the individual perspective, but ..... Egypt: the models of asthma, type 1 diabetes, epilepsy, and ...

  18. The effect of Cordia platythyrsa on various experimental models of ...

    African Journals Online (AJOL)

    The effect of Cordia platythyrsa on various experimental models of pain and carrageenan induced inflammation. Benedicta N Nkeh-Chungag, Eugene J Ndebia, Joseph T Mbafor, Lonwabo A Dotwana, OO Oyedeji, Jehu E Iputo ...

  19. Microplasticity of MMC. Experimental results and modelling

    Energy Technology Data Exchange (ETDEWEB)

    Maire, E. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Lormand, G. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Gobin, P.F. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Fougeres, R. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France))

    1993-11-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.).

  20. Experimental investigation of a flapping wing model

    Energy Technology Data Exchange (ETDEWEB)

    Hubel, Tatjana Y.; Tropea, Cameron [Technische Universitaet Darmstadt, Fachgebiet Stroemungslehre und Aerodynamik, Darmstadt (Germany)

    2009-05-15

    The main objective of this research study was to investigate the aerodynamic forces of an avian flapping wing model system. The model size and the flow conditions were chosen to approximate the flight of a goose. Direct force measurements, using a three-component balance, and PIV flow field measurements parallel and perpendicular to the oncoming flow, were performed in a wind tunnel at Reynolds numbers between 28,000 and 141,000 (3-15 m/s), throughout a range of reduced frequencies between 0.04 and 0.20. The appropriateness of quasi-steady assumptions used to compare 2D, time-averaged particle image velocimetry (PIV) measurements in the wake with direct force measurements was evaluated. The vertical force coefficient for flapping wings was typically significantly higher than the maximum coefficient of the fixed wing, implying the influence of unsteady effects, such as delayed stall, even at low reduced frequencies. This puts the validity of the quasi-steady assumption into question. The (local) change in circulation over the wing beat cycle and the circulation distribution along the wingspan were obtained from the measurements in the tip and transverse vortex planes. Flow separation could be observed in the distribution of the circulation, and while the circulation derived from the wake measurements failed to agree exactly with the absolute value of the circulation, the change in circulation over the wing beat cycle was in excellent agreement for low and moderate reduced frequencies. The comparison between the PIV measurements in the two perpendicular planes and the direct force balance measurements, show that within certain limitations the wake visualization is a powerful tool to gain insight into force generation and the flow behavior on flapping wings over the wing beat cycle. (orig.)

  1. Vitamin D deficiency and adult asthma exacerbations.

    Science.gov (United States)

    Salas, Natalie Mariam; Luo, Li; Harkins, Michelle S

    2014-11-01

    There is growing evidence indicating a connection between vitamin D deficiency and the severity of asthma exacerbations. This study seeks to assess the relationship between vitamin D deficiency and the number and severity of asthma exacerbation in adults. A retrospective analysis was conducted in 92 patients being treated for asthma at the University of New Mexico Adult Asthma Clinic. Serum 25-hydroxyvitamin D3 levels were analyzed in adults with mild to severe persistent asthma. Using multi-variant modeling, the relationship was examined between serum vitamin D levels and the odds of asthma exacerbations ranging in severity from moderate to severe over the span of five years. This study demonstrates that vitamin D sufficiency was significantly associated with a decreased total number of asthma exacerbations (incidence rate ratio [IRR]: 0.61, 95% confidence interval [CI]: 0.44-0.84, p = 0.002), decreased total severe asthma exacerbations (IRR: 0.41, 95% CI: 0.24-0.72, p = 0.002) and decreased emergency room visits (IRR: 0.42, 95% CI: 0.20-0.88, p = 0.023). Vitamin D deficiency may be linked to the risk of severe asthma exacerbations in adults.

  2. Genetic and environmental influence on asthma

    DEFF Research Database (Denmark)

    Skadhauge, L.R.; Christensen, Kaare; Kyvik, Kirsten Ohm

    1999-01-01

    The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from...... the Danish Twin Register. The cumulative incidence of asthma was 6.2% in the pooled sample. The data showed a decreasing cumulative incidence with age for males, but no sex or zygosity difference was observed. Substantially higher concordance rates, odds ratios and correlations for asthma were estimated...... in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age...

  3. TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma.

    Science.gov (United States)

    Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O; Al-Harbi, Mohammed M; Ahmad, Sheikh F

    2016-04-01

    Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Statistical approach for uncertainty quantification of experimental modal model parameters

    DEFF Research Database (Denmark)

    Luczak, M.; Peeters, B.; Kahsin, M.

    2014-01-01

    . This paper aims at a systematic approach for uncertainty quantification of the parameters of the modal models estimated from experimentally obtained data. Statistical analysis of modal parameters is implemented to derive an assessment of the entire modal model uncertainty measure. Investigated structures...... estimates obtained from vibration experiments. Modal testing results are influenced by numerous factors introducing uncertainty to the measurement results. Different experimental techniques applied to the same test item or testing numerous nominally identical specimens yields different test results...

  5. Artificial neural network approach for selection of susceptible single nucleotide polymorphisms and construction of prediction model on childhood allergic asthma

    Directory of Open Access Journals (Sweden)

    Kobayashi Takeshi

    2004-09-01

    Full Text Available Abstract Background Screening of various gene markers such as single nucleotide polymorphism (SNP and correlation between these markers and development of multifactorial disease have previously been studied. Here, we propose a susceptible marker-selectable artificial neural network (ANN for predicting development of allergic disease. Results To predict development of childhood allergic asthma (CAA and select susceptible SNPs, we used an ANN with a parameter decreasing method (PDM to analyze 25 SNPs of 17 genes in 344 Japanese people, and select 10 susceptible SNPs of CAA. The accuracy of the ANN model with 10 SNPs was 97.7% for learning data and 74.4% for evaluation data. Important combinations were determined by effective combination value (ECV defined in the present paper. Effective 2-SNP or 3-SNP combinations were found to be concentrated among the 10 selected SNPs. Conclusion ANN can reliably select SNP combinations that are associated with CAA. Thus, the ANN can be used to characterize development of complex diseases caused by multiple factors. This is the first report of automatic selection of SNPs related to development of multifactorial disease from SNP data of more than 300 patients.

  6. Airway remodeling in a mouse asthma model assessed by in-vivo respiratory-gated micro-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lederlin, Mathieu; Montaudon, Michel [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); Ozier, Annaig; Begueret, Hugues; Ousova, Olga; Marthan, Roger; Berger, Patrick [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); Laurent, Francois [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); CHU de Bordeaux, Hopital du Haut-Leveque, Hopital Cardiologique, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France)

    2010-01-15

    The aim of our study was to evaluate the feasibility of non-invasive respiratory-gated micro-computed tomography (micro-CT) for assessment of airway remodelling in a mouse asthma model. Six female BALB/c mice were challenged intranasally with ovalbumin. A control group of six mice received saline inhalation. All mice underwent plethysmographic study and micro-CT. For each mouse, peribronchial attenuation values of 12 bronchi were measured, from which a peribronchial density index (PBDI) was computed. Mice were then sacrificed and lungs examined histologically. Final analysis involved 10 out of 12 mice. Agreement of measurements across observers and over time was very good (intraclass correlation coefficients: 0.94-0.98). There was a significant difference in PBDI between asthmatic and control mice (-210 vs. -338.9 HU, P=0.008). PBDI values were correlated to bronchial muscle area (r=0.72, P=0.018). This study shows that respiratory-gated micro-CT may allow non-invasive monitoring of bronchial remodelling in asthmatic mice and evaluation of innovative treatment effects. (orig.)

  7. Bidirectional Interactions between Antigen-bearing Respiratory Tract Dendritic Cells (DCs) and T Cells Precede the Late Phase Reaction in Experimental Asthma

    OpenAIRE

    Huh, Joong C.; Strickland, Deborah H.; Jahnsen, Frode L.; Turner, Debra J.; Thomas, Jenny A.; Napoli, Sylvia; Tobagus, Iriani; Stumbles, Philip A.; Sly, Peter D.; Holt, Patrick G.

    2003-01-01

    The airway mucosal response to allergen in asthma involves influx of activated T helper type 2 cells and eosinophils, transient airflow obstruction, and airways hyperresponsiveness (AHR). The mechanism(s) underlying transient T cell activation during this inflammatory response is unclear. We present evidence that this response is regulated via bidirectional interactions between airway mucosal dendritic cells (AMDC) and T memory cells. After aerosol challenge, resident AMDC acquire antigen and...

  8. In silico simulations of experimental protocols for cardiac modeling.

    Science.gov (United States)

    Carro, Jesus; Rodriguez, Jose Felix; Pueyo, Esther

    2014-01-01

    A mathematical model of the AP involves the sum of different transmembrane ionic currents and the balance of intracellular ionic concentrations. To each ionic current corresponds an equation involving several effects. There are a number of model parameters that must be identified using specific experimental protocols in which the effects are considered as independent. However, when the model complexity grows, the interaction between effects becomes increasingly important. Therefore, model parameters identified considering the different effects as independent might be misleading. In this work, a novel methodology consisting in performing in silico simulations of the experimental protocol and then comparing experimental and simulated outcomes is proposed for parameter model identification and validation. The potential of the methodology is demonstrated by validating voltage-dependent L-type calcium current (ICaL) inactivation in recently proposed human ventricular AP models with different formulations. Our results show large differences between ICaL inactivation as calculated from the model equation and ICaL inactivation from the in silico simulations due to the interaction between effects and/or to the experimental protocol. Our results suggest that, when proposing any new model formulation, consistency between such formulation and the corresponding experimental data that is aimed at being reproduced needs to be first verified considering all involved factors.

  9. 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

  10. Obesity and Asthma

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is more prevalent in obese compared with normal weight subjects. Our aim has been to review current knowledge of the impact of obesity on asthma severity, asthma control, and response to therapy.Several studies have shown that overweight and obesity is associated with more severe asthma...... and impaired quality of life compared with normal weight individuals. Furthermore, obesity is associated with poorer asthma control, as assessed by asthma control questionnaires, limitations in daily activities, breathlessness and wheezing, use of rescue medication, unscheduled doctor visits, emergency...... department visits, and hospitalizations for acute asthma. Studies of the impact of a high body mass index (BMI) on response to asthma therapy have, however, revealed conflicting results. Most studies show that overweight and obesity is associated with less favorable response to asthma therapy with regard...

  11. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  12. Smoking and Asthma (For Teens)

    Science.gov (United States)

    ... Personal Plan Hot Topics Flu Facts Arrhythmias Abuse Smoking and Asthma KidsHealth > For Teens > Smoking and Asthma ... A en español Fumar y el asma Does Smoking Make Asthma Worse? Yes. If you have asthma, ...

  13. AVE 0991, a non-peptide mimic of angiotensin-(1–7) effects, attenuates pulmonary remodelling in a model of chronic asthma

    Science.gov (United States)

    Rodrigues-Machado, M G; Magalhães, G S; Cardoso, J A; Kangussu, L M; Murari, A; Caliari, M V; Oliveira, M L; Cara, D C; Noviello, M L M; Marques, F D; Pereira, J M; Lautner, R Q; Santos, R A S; Campagnole-Santos, M J

    2013-01-01

    BACKGROUND AND PURPOSE AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1–7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation. EXPERIMENTAL APPROACH We used BALB/c mice (6–8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 μg·mouse−1, i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg−1·per day, s.c.) or saline (100 μL·kg−1·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates. KEY RESULTS Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs. CONCLUSIONS AND IMPLICATIONS AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1–7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma. PMID:23889691

  14. Modeling long-term effects attributed to nitrogen dioxide (NO2) and sulfur dioxide (SO2) exposure on asthma morbidity in a nationwide cohort in Israel.

    Science.gov (United States)

    Greenberg, N; Carel, R S; Derazne, E; Tiktinsky, A; Tzur, D; Portnov, B A

    2017-01-01

    Studies have provided extensive documentation that acutely elevated environmental exposures contribute to chronic health problems. However, only attention has been paid to the effects of modificate of exposure assessment methods in environmental health investigations, leading to uncertainty and gaps in our understanding of exposure- and dose-response relationships. The goal of the present study was to evaluate whether average or peak concentration exerts a greater influence on asthma outcome, and which of the exposure models may better explain various physiological responses generated by nitrogen dioxide (NO2) or sulfur dioxide (SO2) air pollutants. The effects of annual NO2 and SO2 exposures on asthma prevalence were determined in 137,040 17-year-old males in Israel, who underwent standard health examinations before induction to military service during 1999-2008. Three alternative models of cumulative exposure were used: arithmetic mean level (AM), average peak concentration (APC), and total number of air pollution exposure episodes (NEP). Air pollution data for NO2 and SO2 levels were linked to the residence of each subject and asthma prevalence was predicted using bivariate logistic regression. There was significant increased risk for asthma occurrence attributed to NO2 exposure in all models with the highest correlations demonstrated using the APC model. Data suggested that exposure-response is better correlated with NO2 peak concentration than with average exposure concentration in subjects with asthma. For SO2, there was a weaker but still significant exposure response association in all models. These differences may be related to differences in physiological responses including effects on different regions of the airways following exposure to these pollutants. NO2, which is poorly soluble in water, penetrates deep into the bronchial tree, producing asthmatic manifestations such as inflammation and increased mucus production as a result of high gaseous

  15. Selective p38α mitogen-activated protein kinase inhibitor attenuates lung inflammation and fibrosis in IL-13 transgenic mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Jing Ying Ma

    2008-11-01

    Full Text Available Jing Ying Ma1, Satyanarayana Medicherla1, Irene Kerr, Ruban Mangadu, Andrew A Protter, Linda S Higgins1Scios Inc, Fremont, CA, USA 1Jing Ying Ma and Satyanarayana Medicherla contributed equally to this workAbstract: p38 Mitogen-activated protein kinase (MAPK plays a critical role in the activation of inflammatory cells. We investigated the anti-inflammatory effects of a p38α-selective MAPK inhibitor (SD-282 in a mouse transgenic (CC10:IL-13 asthma model. The CC-10-driven over-expression of IL-13 in the mouse lung/airway has been shown to result in a remarkable phenotype recatitulating many features of asthma and characterized by eosinophilic and mononuclear inflammation, with airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot–Leyden-like crystal, and airway sub-epitheilial fibrosis. Here we show how activated p38 MAPK can be observed in the lungs at the onset of asthma ie, around 8 weeks of age in both female and male mice. We also show that administration of a p38α MAPK selective inhibitor, SD-282 at 30 or 90 mg/kg, twice a day for a period of four weeks beginning at the onset of asthma, significantly reduced the inflammation (p < 0.001; hyperplasia of airway epithelium (p < 0.05; goblet cell metaplasia and mucus hypersecretion (p < 0.001 and reduced lung remodeling and fibrosis (p < 0.01, alleviating the severity of lung damage as measured by a composite score (p < 0.05. Furthermore, SD-282 significantly reduced activated p38 MAPK in the lymphocytes and epithelial cells (p < 0.001. Simultaneously, identical studies were conducted with an anti-fibrotic TGFβR1 kinase inhibitor (SD-208 which demonstrated anti-fibrotic but not anti-inflammatory properties. These findings suggest that the p38α-selective MAPK inhibitor may have dual therapeutic potential in attenuating both the inflammatory component and the fibrotic component of asthma and other Th2

  16. The use of Alloxan and Streptozotocin in Experimental Diabetes Models

    Directory of Open Access Journals (Sweden)

    Zehra Kurçer

    2012-06-01

    Full Text Available Diabetes is a chronic metabolic disease which leads to several acute and chronic complications, morbidity and mortality, and decreased lifespan and quality of life. Therefore, in research studies that aim to enlighten the pathogenesis of diabetes and investigate possible treatment strategies, experimental animal models of diabetes provide many advantages to the investigator. Models of diabetes obtained by chemical induction, diet, surgical manipulations or combination thereof and also new genetically modified animal models are some of the experimental models. Alloxan and streptozotocin (STZ, which are toxic glucose analogues that preferentially accumulate in pancreatic beta cells, are widely used toxic agents to induce experimental diabetes in animals. This review gives an overview on the use of alloxan and STZ to induce chemical diabetes models with reference to their mechanisms, utilizable doses, advantages and disadvantages in diabetes research. Turk Jem 2012; 16: 34-40

  17. Vitamin D, asthma prevalence and asthma exacerbations: a large adult population-based study.

    Science.gov (United States)

    Confino-Cohen, R; Brufman, I; Goldberg, A; Feldman, B S

    2014-12-01

    The impact of low vitamin D status on asthma, asthma morbidity and control is unclear. We aimed to investigate in adults the associations between serum 25-hydroxyvitamin D level and prevalent asthma as well as asthma exacerbations. A cohort of Israeli adults aged 22-50 years with documented vitamin D status were extracted from Clalit Health Services (HMO) between July 1, 2008 and July 1, 2012. Among this population, those with physician-diagnosed asthma and asthma exacerbations were identified. Asthma exacerbations were defined as any of the following: prescription for oral corticosteroids, >5 prescriptions for short acting beta agonists and more than four visits to a physician for asthma. Logistic regression models assessed the associations between vitamin D and both asthma and asthma exacerbations. Approximately 308 000 members with at least one vitamin D measurement were included in the cohort. Among them, 6.9% (21 237) had physician-diagnosed asthma vs 5.7% in the general population. Serum 25-OHD levels across both groups were similar. However, among those with vitamin D deficiency, the odds of having an exacerbation were 25% greater compared to those with levels in the normal range. This association remained significant after controlling for known confounders. While there was no significant association between vitamin D status and physician-diagnosed asthma, there was a strong association with asthma exacerbations. The presented evidence supports vitamin D screening in the subgroup of asthmatics that are uncontrolled and experience recurrent exacerbations. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Design and Implementation of an Experimental Segway Model

    Science.gov (United States)

    Younis, Wael; Abdelati, Mohammed

    2009-03-01

    The segway is the first transportation product to stand, balance, and move in the same way we do. It is a truly 21st-century idea. The aim of this research is to study the theory behind building segway vehicles based on the stabilization of an inverted pendulum. An experimental model has been designed and implemented through this study. The model has been tested for its balance by running a Proportional Derivative (PD) algorithm on a microprocessor chip. The model has been identified in order to serve as an educational experimental platform for segways.

  19. Experimental and modeling studies of mass transfer in ...

    African Journals Online (AJOL)

    Gaining a better understanding of mass transfer problems in encapsulated cell systems and in tissue engineering requires both experimental investigations and mathematical modelling. Specific mass transfer studies are reviewed including oxygen transfer in immobilised animal cell culture systems, modelling of ...

  20. Asthma and obesity.

    Science.gov (United States)

    Boulet, L-P

    2013-01-01

    The prevalence and incidence of asthma have increased among obese children and adults, particularly among women. Obesity seems to be a predisposing factor for the development of asthma, but the underlying mechanisms of its influence are still uncertain. Various hypotheses have been proposed to explain the link between obesity and asthma such as a common genetic predisposition, developmental changes, altered lung mechanics, the presence of a systemic inflammatory process, and an increased prevalence of associated comorbid conditions. Over-diagnosis of asthma does not seem to be more frequent in obese compared to non-obese subjects, but the added effects of obesity on respiratory symptoms can affect asthma control assessment. Obesity can make asthma more difficult to control and is associated with a reduced beneficial effect of asthma medications. This could be due to a change in asthma phenotype, particularly evidenced as a less eosinophilic type of airway inflammation combined to the added effects of changes in lung mechanics. Weight loss is associated with a universal improvement of asthma and should be part of asthma management in the obese patient. Additional research should be conducted to better determine how obesity influences the development and clinical expression of asthma, establish the optimal management of asthma in this population and determine how obesity affects long-term asthma outcomes in these patients. © 2012 Blackwell Publishing Ltd.

  1. Allergy in severe asthma.

    Science.gov (United States)

    Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

    2017-02-01

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. For Parents of Children with Asthma

    Science.gov (United States)

    ... Asthma > Managing Asthma For Parents of Children with Asthma Your Child's Asthma: A Parent's Guide to Better Breathing This step- ... health considerations you should keep in mind. Diagnosing Asthma in Young Children Most children who have asthma ...

  3. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Asthma among Persons with Current Asthma Asthma and Obesity Percentage of People with Asthma who Smoke Insurance ... Asthma Resources for Professionals National Asthma Control Program America Breathing Easier Guide for State Programs Interventions Community ...

  4. Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Kim Seung-Hyung

    2012-03-01

    Full Text Available Abstract Background Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2 cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF is a fruit of Cornus officinalis Sieb. Et. Zucc. (Cornaceae and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmatic effects of CF and their underlying mechanism, we examined the influence of CF on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA by intraperitoneal (i.p., intratracheal (i.t. injections and intranasal (i.n. inhalation of OVA. We investigated the effect of CF on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, and OVA-specific immunoglobulin E (IgE production. Results The CF-treated groups showed suppressed eosinophil infiltration, allergic airway inflammation, and AHR via reduced production of interleuin (IL -5, IL-13, and OVA-specific IgE. Conclusions Our data suggest that the therapeutic effects of CF in asthma are mediated by reduced production of Th2 cytokines (IL-5, eotaxin, and OVA-specific IgE and reduced eosinophil infiltration.

  5. Evaluation of propolis, honey, and royal jelly in amelioration of peripheral blood leukocytes and lung inflammation in mouse conalbumin-induced asthma model.

    Science.gov (United States)

    El-Aidy, Waleed K; Ebeid, Ahmad A; Sallam, Abd El-Raouf M; Muhammad, Ibrahim E; Abbas, Ayman T; Kamal, M A; Sohrab, Sayed Sartaj

    2015-11-01

    Bee products have been used since ancient times to treat many diseases, including respiratory ailments. The present study aimed to examine the modulatory effect of honey, royal jelly, and propolis extract on peripheral blood leukocytes and lung inflammation in a mouse conalbumin-induced asthma model. The mice in group I were not sensitised or treated; they were kept as controls. The mice in group II were sensitised and challenged with conalbumin. Twenty-four hours after the first challenge with antigen, the mice in group III received 0.5 mg/kg of dexamethasone intraperitoneally per day for 18 consecutive days and kept as positive controls. The mice in groups IV, V, and VI received 650, 1000, and 30 mg/kg of honey, royal jelly, and propolis (aqueous and ethanolic extract), respectively, once per day for 18 consecutive days. Blood was collected from all of the mice for white blood cell differentiation, and the lungs were removed for histopathological studies. The groups treated with propolis extract exhibited considerable ameliorative effects against asthma, which might be explained by the flavonoids and phenolics found in propolis, which might have antioxidative effects. Otherwise, the sensitised and honey- or royal jelly-treated groups exhibited an increased incidence of asthma cascade events due to increased inflammatory cells. These results might be due to the immunostimulatory and vasodilatory effects of royal jelly and honey, which are antagonistic to bronchial asthma cases. Histopathological examination revealed that the sensitised treated propolis extract groups had significant decreases in inflammatory scores compared with other treatments and the sensitised untreated group. These results confirmed the previous data of peripheral blood cells.

  6. Using an experimental model for the study of therapeutic touch.

    Science.gov (United States)

    dos Santos, Daniella Soares; Marta, Ilda Estéfani Ribeiro; Cárnio, Evelin Capellari; de Quadros, Andreza Urba; Cunha, Thiago Mattar; de Carvalho, Emilia Campos

    2013-02-01

    to verify whether the Paw Edema Model can be used in investigations about the effects of Therapeutic Touch on inflammation by measuring the variables pain, edema and neutrophil migration. this is a pilot and experimental study, involving ten male mice of the same genetic strain and divided into experimental and control group, submitted to the chemical induction of local inflammation in the right back paw. The experimental group received a daily administration of Therapeutic Touch for 15 minutes during three days. the data showed statistically significant differences in the nociceptive threshold and in the paw circumference of the animals from the experimental group on the second day of the experiment. the experiment model involving animals can contribute to study the effects of Therapeutic Touch on inflammation, and adjustments are suggested in the treatment duration, number of sessions and experiment duration.

  7. Linking Experimental Characterization and Computational Modeling in Microstructural Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Demirel, Melik Cumhar [Univ. of Pittsburgh, PA (United States)

    2002-06-01

    It is known that by controlling microstructural development, desirable properties of materials can be achieved. The main objective of our research is to understand and control interface dominated material properties, and finally, to verify experimental results with computer simulations. In order to accomplish this objective, we studied the grain growth in detail with experimental techniques and computational simulations. We obtained 5170-grain data from an Aluminum-film (120μm thick) with a columnar grain structure from the Electron Backscattered Diffraction (EBSD) measurements. Experimentally obtained starting microstructure and grain boundary properties are input for the three-dimensional grain growth simulation. In the computational model, minimization of the interface energy is the driving force for the grain boundary motion. The computed evolved microstructure is compared with the final experimental microstructure, after annealing at 550 ºC. Two different measures were introduced as methods of comparing experimental and computed microstructures. Modeling with anisotropic mobility explains a significant amount of mismatch between experiment and isotropic modeling. We have shown that isotropic modeling has very little predictive value. Microstructural evolution in columnar Aluminum foils can be correctly modeled with anisotropic parameters. We observed a strong similarity between grain growth experiments and anisotropic three-dimensional simulations.

  8. Development of a fault test experimental facility model using Matlab

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Iraci Martinez; Moraes, Davi Almeida, E-mail: martinez@ipen.br, E-mail: dmoraes@dk8.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The Fault Test Experimental Facility was developed to simulate a PWR nuclear power plant and is instrumented with temperature, level and pressure sensors. The Fault Test Experimental Facility can be operated to generate normal and fault data, and these failures can be added initially small, and their magnitude being increasing gradually. This work presents the Fault Test Experimental Facility model developed using the Matlab GUIDE (Graphical User Interface Development Environment) toolbox that consists of a set of functions designed to create interfaces in an easy and fast way. The system model is based on the mass and energy inventory balance equations. Physical as well as operational aspects are taken into consideration. The interface layout looks like a process flowchart and the user can set the input variables. Besides the normal operation conditions, there is the possibility to choose a faulty variable from a list. The program also allows the user to set the noise level for the input variables. Using the model, data were generated for different operational conditions, both under normal and fault conditions with different noise levels added to the input variables. Data generated by the model will be compared with Fault Test Experimental Facility data. The Fault Test Experimental Facility theoretical model results will be used for the development of a Monitoring and Fault Detection System. (author)

  9. Linking Experimental Characterization and Computational Modeling in Microstructural Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Demirel, Melik Cumhur [Univ. of California, Berkeley, CA (United States)

    2002-06-01

    It is known that by controlling microstructural development, desirable properties of materials can be achieved. The main objective of our research is to understand and control interface dominated material properties, and finally, to verify experimental results with computer simulations. In order to accomplish this objective, we studied the grain growth in detail with experimental techniques and computational simulations. We obtained 5170-grain data from an Aluminum-film (120μm thick) with a columnar grain structure from the Electron Backscattered Diffraction (EBSD) measurements. Experimentally obtained starting microstructure and grain boundary properties are input for the three-dimensional grain growth simulation. In the computational model, minimization of the interface energy is the driving force for the grain boundary motion. The computed evolved microstructure is compared with the final experimental microstructure, after annealing at 550 ºC. Two different measures were introduced as methods of comparing experimental and computed microstructures. Modeling with anisotropic mobility explains a significant amount of mismatch between experiment and isotropic modeling. We have shown that isotropic modeling has very little predictive value. Microstructural evolution in columnar Aluminum foils can be correctly modeled with anisotropic parameters. We observed a strong similarity

  10. What is Asthma?

    Medline Plus

    Full Text Available ... Lung Association 104 COPD Awareness Month: Connecting with Social Support American Lung Association ... Asthma - Duration: 3:36. Nucleus Medical Media 658,979 views 3:36 What is asthma. ...

  11. Obesity, adipokines and asthma

    National Research Council Canada - National Science Library

    Jartti, T; Saarikoski, L; Jartti, L; Lisinen, I; Jula, A; Huupponen, R; Viikari, J; Raitakari, O. T

    2009-01-01

    .... Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma. Methods...

  12. What is Asthma?

    Medline Plus

    Full Text Available ... Lung Association 139 Barbara Tie talks about Alpha 1-caused COPD American Lung Association 140 Judy Pruitt ... American Lung Association 182 Asthma - Theresa Moore PSA 1 American Lung Association 183 Asthma Walk PSA American ...

  13. Exercise-induced asthma

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000036.htm Exercise-induced asthma To use the sharing features on this page, ... such as running, basketball, or soccer. Use Your Asthma Medicine Before you Exercise Take your short-acting, ...

  14. Allergies, asthma, and pollen

    Science.gov (United States)

    Reactive airway - pollen; Bronchial asthma - pollen; Triggers - pollen; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. It is important to know your triggers because avoiding them is your first step toward feeling better. ...

  15. What is Asthma?

    Medline Plus

    Full Text Available ... Clubs American Lung Association 146 Angela Abel on exercise and COPD American Lung Association 147 American Lung ... 40 Types of Asthma - Duration: 11:38. Affinity Health Plan 6,222 views 11:38 Asthma Tech - ...

  16. Smoking and asthma

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000504.htm Smoking and asthma To use the sharing features on ... your allergies or asthma worse are called triggers. Smoking is a trigger for many people who have ...

  17. Asthma - child - discharge

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000001.htm Asthma - child - discharge To use the sharing features on this ... care for your child. Take Charge of Your Child's Asthma at Home Make sure you know the ...

  18. Psychopathology in difficult asthma

    NARCIS (Netherlands)

    Prins, L.C.; van Son, M.J.M.; Keimpema, A.R.; van Ranst, D; Pommer, A; Meijer, J.W.; Pop, V.J.M.

    2015-01-01

    OBJECTIVE: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed

  19. Oxidative stress biomarkers and asthma characteristics in adults of the EGEA study.

    Science.gov (United States)

    Andrianjafimasy, Miora; Zerimech, Farid; Akiki, Zeina; Huyvaert, Helene; Le Moual, Nicole; Siroux, Valérie; Matran, Régis; Dumas, Orianne; Nadif, Rachel

    2017-12-01

    Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression. Copyright ©ERS 2017.

  20. Experimental-analytical method of technological processes modeling in education

    OpenAIRE

    Efremov German I.; Geller Julia A.

    2016-01-01

    The article considers general modeling techniques used in the study in education at different stages. The classification of different types of models and main stages of the simulation are considered. It is shown that in the course “Process of simulation” for technical areas of the Universities required the category of “Experimental-analytical simulation method”. For example, a new textbook for bachelors “Modeling of chemical-technological processes” shows that the section facilitates the comp...

  1. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model

    National Research Council Canada - National Science Library

    Tracey L. Bonfield; Mary Koloze; Donald P. Lennon; Brandon Zuchowski; Sung Eun Yang; Arnold I. Caplan

    2010-01-01

    .... host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases...

  2. LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction.

    Science.gov (United States)

    Chen, Xi; Li, Xiao-Ming; Gu, Wen; Wang, Di; Chen, Yi; Guo, Xue-Jun

    2017-03-01

    Low expression of linker for activation of T cells (LAT) is observed in asthma. LAT and its downstream regulator, phospholipase C-gamma 1 (PLC-γ1) play important roles in the T cell antigen receptor signaling pathway, and their interaction is associated with CD4 + cell polarization. Here, we investigated whether LAT can alleviate the imbalance among CD4 + cell subgroups and the possible mechanism. An ovalbumin-induced allergic asthma mouse model was established and LAT plasmid was delivered. The pathological changes in lung were evaluated by hematoxylin and eosin and periodic acid-Schiff staining. The typical cytokines released by T helper 2 (Th2) and regulatory T (Treg) cells were measured using enzyme-linked immunosorbent assay and the number of Th1, Th2, and Treg cells were determined using flow cytometry. Lung CD4 + T cells were isolated by magnetic isolation. The mRNA expression of LAT and PLC-γ1 was determined by real-time PCR. Co-Immunoprecipitation was performed to confirm the interaction between LAT and PLC-γ1. The protein expression of LAT, PLC-γ1 and corresponding downstream signaling factors were determined by western blotting. The delivery of LAT DNA to the lung could suppress an overactive Th2 response by decreasing allergic response and Th2 cytokine secretion, and by increasing Treg cytokine secretion. The Th2/Treg imbalance in lung and decreased phosphorylated PLC-γ1 expression in lung CD4 + T cells were rectified by LAT DNA delivery. Excessive activation of the Raf-MEK-ERK and PI3K-AKT-CREB pathways after asthma is attenuated by LAT. The site-specific delivery of LAT DNA to the lung could suppress an overactive Th2 response and rectify the Th2/Treg imbalance in asthmatic mouse model. LAT-PLC-γ1 interaction may contribute to LAT activity in vivo and LAT protects against asthma partly via Raf-MEK-ERK and PI3K-AKT-CREB pathways. The delivery of LAT DNA could offer a novel and safe strategy for asthma prevention. Copyright © 2016 Elsevier B

  3. Maternal body mass index in early pregnancy and offspring asthma, rhinitis and eczema up to 16 years of age.

    Science.gov (United States)

    Ekström, S; Magnusson, J; Kull, I; Lind, T; Almqvist, C; Melén, E; Bergström, A

    2015-01-01

    Maternal obesity has been linked to offspring asthma; however, other allergy-related diseases, as well as the association beyond early school age, are largely unstudied. To examine the associations between maternal body mass index (BMI) in pregnancy and offspring asthma, rhinitis, eczema and sensitization up to 16 years of age. A total of 3294 children from the Swedish birth cohort BAMSE were included in the analyses. Maternal BMI was assessed around week 10 in pregnancy. Information on asthma, rhinitis, eczema, lifestyle factors and environmental exposures was obtained by parental questionnaires at 1, 2, 4, 8, 12 and 16 years. Sensitization was defined from IgE levels of inhalant allergens at 4, 8 and 16 years in a subsample of 2850 children. Generalized estimated equation models were used to analyse the associations between maternal BMI and the outcomes at 1-16 years. Maternal BMI was positively associated with overall risk of asthma up to age of 16 years (adj OR per 5 kg/m(2) increase: 1.23; 95% CI 1.07-1.40 for prevalent asthma) excluding underweight mothers. In contrast, no significant associations were found for rhinitis, eczema or sensitization. The association with asthma was restricted to obese, rather than overweight mothers, but was attenuated when adjusting for overweight in the offspring. A causal inference test at 16 years further indicated that the child's own overweight is a mediator in the suggested association between maternal BMI and offspring asthma at 16 years. Maternal BMI is associated with an increased risk of asthma, but not rhinitis, eczema or sensitization; however, overweight in the offspring seems to have a mediating role. Prevention strategies of maternal pre-pregnancy and childhood obesity might be important to reduce the prevalence of childhood asthma. 2014 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

  4. Epigenome-modifying tools in asthma

    Science.gov (United States)

    Brook, Peter O; Perry, Mark M; Adcock, Ian M; Durham, Andrew L

    2015-01-01

    Asthma is a chronic disease which causes recurrent breathlessness affecting 300 million people worldwide of whom 250,000 die annually. The epigenome is a set of heritable modifications and tags that affect the genome without changing the intrinsic DNA sequence. These marks include DNA methylation, modifications to histone proteins around which DNA is wrapped and expression of noncoding RNA. Alterations in all of these processes have been reported in patients with asthma. In some cases these differences are linked to disease severity and susceptibility and may account for the limited value of genetic studies in asthma. Animal models of asthma suggest that epigenetic modifications and processes are linked to asthma and may be tractable targets for therapeutic intervention. PMID:26479310

  5. Experimental Validation of a Dynamic Model for Lightweight Robots

    Directory of Open Access Journals (Sweden)

    Alessandro Gasparetto

    2013-03-01

    Full Text Available Nowadays, one of the main topics in robotics research is dynamic performance improvement by means of a lightening of the overall system structure. The effective motion and control of these lightweight robotic systems occurs with the use of suitable motion planning and control process. In order to do so, model-based approaches can be adopted by exploiting accurate dynamic models that take into account the inertial and elastic terms that are usually neglected in a heavy rigid link configuration. In this paper, an effective method for modelling spatial lightweight industrial robots based on an Equivalent Rigid Link System approach is considered from an experimental validation perspective. A dynamic simulator implementing the formulation is used and an experimental test-bench is set-up. Experimental tests are carried out with a benchmark L-shape mechanism.

  6. Obesity and asthma

    DEFF Research Database (Denmark)

    Ali, Zarqa; Ulrik, Charlotte Suppli

    2013-01-01

    Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed...... association between obesity and asthma....

  7. Allergy in severe asthma

    NARCIS (Netherlands)

    Del Giacco, Stefano R.; Bakirtas, A.; Bel, E.; Custovic, A.; Diamant, Z.; Hamelmann, E.; Heffler, E.; Kalayci, O.; Saglani, S.; Sergejeva, S.; Seys, S.; Simpson, A.; Bjermer, Leif

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps

  8. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  9. Pre-birth origins of allergy and asthma.

    Science.gov (United States)

    Gatford, K L; Wooldridge, A L; Kind, K L; Bischof, R; Clifton, V L

    2017-09-01

    Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A systematic review of animal models for experimental neuroma.

    Science.gov (United States)

    Toia, Francesca; Giesen, Thomas; Giovanoli, Pietro; Calcagni, Maurizio

    2015-10-01

    Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be defined. Experimental research still plays a major role, but - although numerous neuroma models have been proposed on different animals - there is still no single model recognised as being the reference. Several models show advantages over the others in specific aspects of neuroma physiopathology, prevention or treatment, making it unlikely that a single model could be of reference. A reproducible and standardised model of peripheral neuroma would allow better comparison of results from different studies. We present a systematic review of the literature on experimental in vivo models, analysing advantages and disadvantages, specific features and indications, with the goal of providing suggestions to help their standardisation. Published models greatly differ in the animal and the nerve employed, the mechanisms of nerve injury and the evaluation methods. Specific experimental models exist for terminal neuromas and neuromas in continuity (NIC). The rat is the most widely employed animal, the rabbit being the second most popular model. NIC models are more actively researched, but it is more difficult to generate such studies in a reproducible manner. Nerve transection is considered the best method to cause terminal neuromas, whereas partial transection is the best method to cause NIC. Traditional histomorphology is the historical gold-standard evaluation method, but immunolabelling, reverse transcriptase-polymerase chain reaction (RT-PCR) and proteomics are gaining increasing popularity. Computerised gait analysis is the gold standard for motor-recovery evaluation, whereas mechanical testing of allodynia and hyperalgesia reproducibly assesses sensory recovery. This review summarises current knowledge on experimental neuroma models, and it provides a useful tool for defining experimental protocols

  11. Experimental modeling of injectivity loss; Modelagem experimental da perda de injetividade

    Energy Technology Data Exchange (ETDEWEB)

    Bonato, Adriano Jose do Amaral Mello; Silva, Pedro Glauto de Farias e; Gomes, Vanessa Limeira Azevedo; Santos, Adriano dos [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2012-07-01

    Produced water reinjection, suspended particles are retained in the porous media causing formation damage and injectivity decline. In general the retention of the particles occurs near the side of injection, this fact occurs in most cases, due to the size exclusion. The modeling of filtration and the consequent formation damage is essential to the project management of water injection in oil reservoirs. Thus, mathematical models are studied to better predict the distribution of particles throughout the porous media and determine the parameters of adjustment to injectivity decline. Among these models, there is the classic model which consists in determining these parameters (coefficient of filtration and formation damage). The methodology used in modeling is given from the equations the mass conservation, kinetic particle retention, the modified Darcy equation and the function formation damage. This study aimed to improve experimental modeling, including development of software for acquisition and processing of experimental data, considering the variable number of pressure measurements along the sample. The software was developed using the Labview 2011 platform and allows the determination of relevant parameters to predict injectivity loss in water injection wells. Furthermore, based on the traditional model of filtration in porous media (including depth filtration and formation of the external plaster), the software was applied to predict injectivity loss in addition to the properties of the grout. Finally, the classical models for transporting suspensions and damage to the formation were observed. (author)

  12. Contact Modelling in Resistance Welding, Part II: Experimental Validation

    DEFF Research Database (Denmark)

    Song, Quanfeng; Zhang, Wenqi; Bay, Niels

    2006-01-01

    Contact algorithms in resistance welding presented in the previous paper are experimentally validated in the present paper. In order to verify the mechanical contact algorithm, two types of experiments, i.e. sandwich upsetting of circular, cylindrical specimens and compression tests of discs...... with a solid ring projection towards a flat ring, are carried out at room temperature. The complete algorithm, involving not only the mechanical model but also the thermal and electrical models, is validated by projection welding experiments. The experimental results are in satisfactory agreement...... with the simulation prediction, showing the validity of the algorithm....

  13. 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

  14. Team Modelling: Review of Experimental Scenarios and Computational Models

    Science.gov (United States)

    2006-09-01

    designed to be) Yes Yes No Yes (Model individuals, or sub-teams - groups of individuals.) 19 C3TRACE* (Command, Control, and Communicatio ...radar sensors, satellites, c2 structures, jammers, communicatio ns networks and devices, and fire support) Depends (EADSIM normally models at

  15. Asthma during pregnancy: the experiences, concerns and views of pregnant women with asthma.

    Science.gov (United States)

    Lim, Angelina S; Stewart, Kay; Abramson, Michael J; Ryan, Kath; George, Johnson

    2012-06-01

    To investigate how pregnant women manage their asthma during pregnancy and factors influencing their behavior. In-depth interviews (telephone or face-to-face) with a purposive sample of 23 asthmatic women at various stages of pregnancy and with varying severity of asthma. Five major themes were discerned relating to health behavior of pregnant women with asthma. Many of the participants decreased or discontinued their asthma medications themselves and refrained from taking doses when necessary during pregnancy without consulting their doctors. Reasons behind their decisions revolved around lack of support and information about what to do, concerns about the safety of the medications, past experiences, and desire for an "all natural" pregnancy. Asthma monitoring during pregnancy was seen as a low priority for some women and their doctors. Communication between pregnant women and health professionals regarding asthma management was poor. The health behavior of pregnant women with asthma could be explained using the Health Beliefs Model. Pregnant women are not well supported in managing asthma during pregnancy, despite being concerned about outcomes. Interventions, education, and more support are warranted and wanted by pregnant women with asthma to optimize pregnancy and neonatal outcomes.

  16. Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes.

    Science.gov (United States)

    Dixon, Anne E; Poynter, Matthew E

    2016-05-01

    The majority of patients with severe or difficult-to-control asthma in the United States are obese. Epidemiological studies have clearly established that obese patients tend to have worse asthma control and increased hospitalizations and do not respond to standard controller therapy as well as lean patients with asthma. Less clear are the mechanistic underpinnings for the striking clinical differences between lean and obese patients with asthma. Because obesity is principally a disorder of metabolism and energy regulation, processes fundamental to the function of every cell and system within the body, it is not surprising that it affects the respiratory system; it is perhaps surprising that it has taken so long to appreciate how dysfunctional metabolism and energy regulation lead to severe airway disease. Although early investigations focused on identifying a common factor in obesity that could promote airway disease, an appreciation has emerged that the asthma of obesity is a manifestation of multiple anomalies related to obesity affecting all the different pathways that cause asthma, and likely also to de novo airway dysfunction. Consequently, all the phenotypes of asthma currently recognized in lean patients (which are profoundly modified by obesity), as well as those unique to one's obesity endotype, likely contribute to obese asthma in a particular individual. This perspective reviews what we have learned from clinical studies and animal models about the phenotypes of asthma in obesity, which show how specific aspects of obesity and altered metabolism might lead to de novo airway disease and profoundly modify existing airway disease.

  17. Epigenetic Mechanisms in Asthma.

    Science.gov (United States)

    DeVries, Avery; Vercelli, Donata

    2016-03-01

    Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood, but the underlying pathogenetic mechanisms are poorly understood. Because epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories, their contribution to asthma and allergy pathogenesis is under active investigation. DNA methylation signatures associated with concurrent disease and with the development of asthma during childhood asthma have been identified, but their significance is not easily interpretable. On the other hand, the characterization of early epigenetic predictors of asthma points to a potential role of epigenetic mechanisms in regulating the inception of, and the susceptibility to, this disease.

  18. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  19. Modeling and experimentation of a positioning system of SMA wires

    Science.gov (United States)

    Lei, KinFong; Yam, Yeung

    2000-06-01

    This work reports two modeling and control attempts performed on a positioning system comprising of linking SMA wires and an overlooking video system for on-line measurements. The first attempt takes the model by Ikuta and identifies experimentally the parameters of the SMA wire. The identified single wire model is then extended to a system of two SMA wires joining together at their tips, based upon which open loop position control of the linkage is then conducted. The approach, however, becomes too complicated when more SMA wires are involved. The second attempt utilizes a neuro-fuzzy based approach for positioning control of a linkage point joining together four SMA wires. The second approach involves four ANFIS neuro-networks with hybrid learning algorithm trained to model the currents to the SMA wires as functions of present and target positions of the linkage point. Experimentation for both the two-wires and four-wires system yield quite satisfactory performance.

  20. Experimental bounds on collapse models from gravitational wave detectors

    Science.gov (United States)

    Carlesso, Matteo; Bassi, Angelo; Falferi, Paolo; Vinante, Andrea

    2016-12-01

    Wave function collapse models postulate a fundamental breakdown of the quantum superposition principle at the macroscale. Therefore, experimental tests of collapse models are also fundamental tests of quantum mechanics. Here, we compute the upper bounds on the collapse parameters, which can be inferred by the gravitational wave detectors LIGO, LISA Pathfinder, and AURIGA. We consider the most widely used collapse model, the continuous spontaneous localization (CSL) model. We show that these experiments exclude a huge portion of the CSL parameter space, the strongest bound being set by the recently launched space mission LISA Pathfinder. We also rule out a proposal for quantum-gravity-induced decoherence.

  1. Experimental model in rat for sentinel node biopsy

    Directory of Open Access Journals (Sweden)

    Oliveira Filho Renato Santos de

    2003-01-01

    Full Text Available Although sentinel node procedure has been used world wide, there are many aspects to be defined and better standardized. This study address if the experimental model in rats is appropriate for sentinel node biopsy. In this model, the lymph nodes are showed by lymphoscintigraphy, they are dyed by patent blue and identified by intraoperative gamma probe detection. It isn?t necessary to use magnification for the procedure. The model demonstrated that sentinel node biopsy in rats is feasible. So, besides allowing researches in this field, the model is useful for training and diffusing this technique.

  2. Experimental Analysis and Model Validation of an Opaque Ventilated Facade

    DEFF Research Database (Denmark)

    López, F. Peci; Jensen, Rasmus Lund; Heiselberg, Per

    2012-01-01

    Natural ventilation is a convenient way of reducing energy consumption in buildings. In this study an experimental module of an opaque ventilated façade (OVF) was built and tested for assessing its potential of supplying free ventilation and air preheating for the building. A numerical model was ...

  3. Experimental model of capsular contracture in silicone implants

    Directory of Open Access Journals (Sweden)

    Bastos Érika Malheiros

    2003-01-01

    Full Text Available The breast implant procedure is one of the most performed into Plastic Surgery and the contracture that occurs the capsule formed around the breast implants one of most frequent complication. We describe here one experimental model of capsule contracture in rats.

  4. Sciara as an experimental model for studies on the evolutionary ...

    Indian Academy of Sciences (India)

    Sciara as an experimental model for studies on the evolutionary relationships between the zygotic, maternal and environmental primary signals for sexual development. Lucas Sánchez. Review Article Volume ... Lucas Sánchez1. Centro de Investigaciones Biol´ogicas (C. S. I. C.), Ramiro de Maeztu 9, 28040 Madrid, Spain ...

  5. Novel sensors for food inspection modelling, fabrication and experimentation

    CERN Document Server

    Abdul Rahman, Mohd Syaifudin; Yu, Pak-Lam

    2014-01-01

    This book addresses presents recent developments of novel planar interdigital sensors for food inspection. It covers the fundamentals of sensors, their design, modelling and simulations, fabrications, characterizations, experimental investigations and analyses. This book will be useful for the engineers and researchers especially higher undergraduate, postgraduate students as well as practitioners working on the development of Electromagnetic Sensors.

  6. numerical and numerical and experimental modeling of the static

    African Journals Online (AJOL)

    eobe

    recommendation for subsequent experiments and analysis of these types of structural elements. In this paper a report of numerical and experimental modeling of the static response of thin-walled reinforced concrete box girder bridges is given. The work is executed to verify the validity of a software developed by the authors ...

  7. An Interactive Multimedia Based Instruction in Experimental Modelling

    DEFF Research Database (Denmark)

    Knudsen, Morten; Nielsen, J.N.; Østergaard, J.

    1997-01-01

    A CD-ROM based interactive multimedia instruction in experimental modelling for Danish Engineering School teachers is described. The content is based on a new sensitivity approach for direct estimation of physical parameters in linear and nonlinear dynamic systems. The presentation is inspired...

  8. Pruning Chinese trees : an experimental and modelling approach

    NARCIS (Netherlands)

    Zeng, Bo

    2001-01-01

    Pruning of trees, in which some branches are removed from the lower crown of a tree, has been extensively used in China in silvicultural management for many purposes. With an experimental and modelling approach, the effects of pruning on tree growth and on the harvest of plant material were studied.

  9. [Establishment and evaluation of experimental sepsis mouse model].

    Science.gov (United States)

    Wang, Li-Yan; Xu, Ruo-Nan; Han, Gen-Cheng; Wang, Ren-Xi; Chen, Guo-Jiang; Xiao, He; Hou, Chun-Mei; Shen, Bei-Fen; Li, Yan

    2010-06-01

    After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.

  10. Obesity and asthma.

    Science.gov (United States)

    Gibson, Peter G

    2013-12-01

    There is a global epidemic of asthma and obesity that is concentrated in Westernized and developed countries. A causal association in some people with asthma is suggested by observations that obesity precedes the onset of asthma and that bariatric surgery for morbid obesity can resolve asthma. The obese asthma phenotype features poor asthma control, limited response to corticosteroids, and an exaggeration of the physiological effects of obesity on lung function, which includes a reduction in expiratory reserve volume and airway closure occurring during tidal breathing. Obesity has important implications for asthma treatment. Increasing corticosteroid doses based on poor asthma control, as currently recommended in guidelines, may lead to overtreatment with corticosteroids in obese asthma. Enhanced bronchodilation, particularly of the small airways, may reduce the component of airway closure due to increased bronchomotor tone and suggests that greater emphasis should be placed on long-acting bronchodilators in obese asthma. The societal implications of this are important: with increasing obesity there will be increasing asthma from obesity, and the need to identify successful individual and societal weight-control strategies becomes a key goal.

  11. Obesity and asthma

    DEFF Research Database (Denmark)

    Sivapalan, Pradeesh; Diamant, Zuzana; Ulrik, Charlotte Suppli

    2015-01-01

    PURPOSE OF REVIEW: Obesity has significant impact on asthma incidence and manifestations. The purpose of the review is to discuss recent observations regarding the association between obesity and asthma focusing on underlying mechanisms, clinical presentation, response to therapy and effect...... of weight reduction. RECENT FINDINGS: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities...... have been linked to both obesity and asthma, and may, therefore, contribute to the obese-asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma. SUMMARY: Compared with normal-weight patients, obese...

  12. Patient's adherence in asthma.

    Science.gov (United States)

    Gillisen, Adrian

    2007-11-01

    Nonadherence in asthma treatment results in increasing mortality, morbidity, and it is associated with increasing treatment costs. In asthma, adherence rates are often below 50%. Understanding of the needs and behaviors of asthma patients as well as treatment barriers to comply with asthma guidelines is important in developing programs to promote adherence. This article presents information on common types of nonadherence in asthma patients, the causes, and it reviews the literature on interventions to overcome these factors to maximize adherence rates. Although several interventions are effective in improving medication adherence in asthma, only few significantly enhance adherence rates and clinical outcomes of these patients. An improvement in treatment adherence is a complex task, requiring asthma self-management, education programs coupled with educational reinforcements, simplifying treatment planes and applications forms. Good communications skills among clinicians and patient education are also central for improving adherence. Methods to overcoming physician barriers ensure consistency in implementing guideline recommendations in practice.

  13. Effects of Radix Adenophorae and Cyclosporine A on an OVA-Induced Murine Model of Asthma by Suppressing to T Cells Activity, Eosinophilia, and Bronchial Hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    Seong-Soo Roh

    2008-01-01

    Full Text Available The present study is performed to investigate the inhibitory effects of Radix Adenophorae extract (RAE on ovalbumin-induced asthma murine model. To study the anti-inflammatory and antiasthmatic effects of RAE, we examined the development of pulmonary eosinophilic inflammation and inhibitory effects of T cells in murine by RAE and cyclosporine A (CsA. We examined determination of airway hyperresponsiveness, flow cytometric analysis (FACS, enzyme-linked immunosorbent assay (ELISA, quantitative real time (PCR, hematoxylin-eosin staining, and Masson trichrome staining in lung tissue, lung weight, total cells, and eosinophil numbers in lung tissue. We demonstrated how RAE suppressed development on inflammation and decreased airway damage.

  14. Impact of Maternal Lifetime Interpersonal Trauma on Children's Asthma: Mediation Through Maternal Active Asthma During Pregnancy.

    Science.gov (United States)

    Brunst, Kelly J; Rosa, Maria José; Jara, Calvin; Lipton, Lianna R; Lee, Alison; Coull, Brent A; Wright, Rosalind J

    2017-01-01

    Traumatic stressors, including child abuse and/or interpersonal violence over a woman's lifecourse, can affect the health of her children. This study examines the associations between maternal lifetime interpersonal trauma (IPT) and children's asthma by age 6 years (n = 857). Pregnant women completed the Revised Conflict Tactics Scale; IPT exposure was categorized as unexposed (55%), early (childhood and/or teen years only, 25%), late (adulthood and/or index pregnancy, 7%), and chronic (early and late, 13%). Clinician-diagnosed asthma in children was reported by mothers at each follow-up visit until the child reached age 6 years. We examined the effects of maternal IPT categories and child's asthma using logistic regression. Using structural equation models, we also examined indirect relationships between maternal chronic IPT and child asthma operating through active asthma in pregnancy, prepregnancy BMI, prenatal smoking, and/or increased exposure to other adverse life events or environmental toxins prenatally. Effect modification by the child's sex was examined. Mothers were primarily Hispanic (55%) or black (30%) with less than high school education (62%). In logistic regression models, chronic maternal IPT (compared with unexposed) was associated with asthma in boys (odds ratio = 2.87, 95% confidence interval = 1.48-5.57) but not girls (odds ratio = 0.69, 95% confidence interval = 0.23-2.12; pinteraction = .042). In structural equation models, chronic IPT was associated with maternal active asthma in pregnancy (β = 0.59, p mediated through active maternal asthma in pregnancy.

  15. Asthma and subjective sleep disordered breathing in a large cohort of urban adolescents.

    Science.gov (United States)

    Zandieh, Stephanie O; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M; Bruzzese, Jean-Marie

    2017-01-02

    Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. 12% reported SDB symptoms. Older and bi-racial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma.

  16. Systematic integration of experimental data and models in systems biology

    Directory of Open Access Journals (Sweden)

    Simeonidis Evangelos

    2010-11-01

    Full Text Available Abstract Background The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Results Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML. A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Conclusions Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  17. Asthma education for school staff.

    Science.gov (United States)

    Kew, Kayleigh M; Carr, Robin; Donovan, Tim; Gordon, Morris

    2017-04-12

    Teachers and school staff should be competent in managing asthma in schools. Demonstrated low levels of asthma knowledge mean that staff may not know how best to protect a child with asthma in their care, or may fail to take appropriate action in the event of a serious attack. Education about asthma could help to improve this knowledge and lead to better asthma outcomes for children. To assess the effectiveness and safety of asthma education programmes for school staff, and to identify content and attributes underpinning them. We conducted the most recent searches on 29 November 2016. We included randomised controlled trials comparing an intervention to educate school staff about asthma versus a control group. We included studies reported as full text, those published as abstract only and unpublished data. At least two review authors screened the searches, extracted outcome data and intervention characteristics from included studies and assessed risk of bias. Primary outcomes for the quantitative synthesis were emergency department (ED) or hospital visits, mortality and asthma control; we graded the main results and presented evidence in a 'Summary of findings' table. We planned a qualitative synthesis of intervention characteristics, but study authors were unable to provide the necessary information.We analysed dichotomous data as odds ratios, and continuous data as mean differences or standardised mean differences, all with a random-effects model. We assessed clinical, methodological and statistical heterogeneity when performing meta-analyses, and we narratively described skewed data. Five cluster-RCTs of 111 schools met the review eligibility criteria. Investigators measured outcomes in participating staff and often in children or parents, most often at between 1 and 12 months.All interventions were educational programmes but duration, content and delivery varied; some involved elements of training for pupils or primary care providers. We noted risk of selection

  18. Theories linguistiques, modeles informatiques, experimentation psycholinguistique (Linguistic Theories, Information-Processing Models, Psycholinguistic Experimentation)

    Science.gov (United States)

    Dubois, Daniele

    1975-01-01

    Delineates and elaborates upon the underlying psychological postulates in linguistic and information-processing models, and shows the interdependence of psycholinguistics and linguistic analysis. (Text is in French.) (DB)

  19. Lung dendritic cells undergo maturation and polarization towards a T helper type 2-stimulating phenotype in a mouse model of asthma: Role of nerve growth factor.

    Science.gov (United States)

    Qin, Qingwu; Wang, Zhan; Pan, Pinhua; Cao, Zu; Xia, Qing; Tan, Hongyi; Hu, Chengping

    2014-11-01

    Nerve growth factor (NGF) and dendritic cells (DCs) have been hypothesized to modulate T cell responses in a mouse model of asthma. However, whether NGF plays a role in regulating the maturation and polarization of lung DCs remains unclear. In the present study, the effect of NGF inhibition on the maturation and phenotype of lung DCs was investigated in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and subsequently received anti-NGF treatment. At 24 h following the last challenge, airway responsiveness and inflammation were examined. The concentrations of NGF, interferon (IFN)-γ and interleukin (IL)-4 were analyzed. In addition, maturation and CD103 expression in the lung DCs were investigated. Anti-NGF treatment was found to significantly reduce airway hyperreactivity and inflammation in asthmatic mice. In addition, a subdued T helper 2 (Th2) response was observed, characterized by the downregulation of IL-4 and the upregulation of IFN-γ. Furthermore, the expression of the DC surface molecules, CD80, CD86 and major histocompatibility complex class II, as well as the proportion of lung CD103(+) DCs, decreased in the OVA-sensitized and challenged mice. The proportion of lung CD103(+) DCs also exhibited a positive correlation with the levels of plasma NGF in the mice. These results may provide an explanation for the role of NGF in amplifying the Th2 response in allergic diseases. Therefore, NGF may promote the maturation and polarization towards a Th2-stimulating phenotype of activated DCs, contributing to an amplification of the Th2 response in asthma.

  20. Lactobacillus gasseri suppresses Th17 pro-inflammatory response and attenuates allergen-induced airway inflammation in a mouse model of allergic asthma.

    Science.gov (United States)

    Jan, Ren-Long; Yeh, Kung-Chih; Hsieh, Miao-Hsi; Lin, Yen-Lin; Kao, Hui-Fang; Li, Pi-Hsueh; Chang, Yuh-Shin; Wang, Jiu-Yao

    2012-07-14

    Probiotics are normal inhabitants of the gastrointestinal tract of man and are widely considered to exert a number of beneficial effects in many diseases. But the mechanism by which they modulate the immune system is poorly understood. The present study was planned to explore the anti-allergic effect of Lactobacillus gasseri on a mouse model of allergic asthma. Dermatophoides pteronyssinus (Der p) sensitised and challenged BALB/c mice were orally administered via oral administration with three different doses of L. gasseri (low, 1 × 10(6) colony-forming units (CFU); medium, 2 × 10(6) CFU; high, 4 × 10(6) CFU), in 700 μl of PBS daily, starting from 2 weeks before Der p sensitisation for 4 weeks. After the allergen challenge, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage (BAL) fluids and splenocytes culture were assessed. Our results showed that oral administration of a high dose of L. gasseri (4 × 10(6) CFU) decreased airway responsiveness to methacholine, attenuated the influx of inflammatory cells to the airways and reduced the levels of TNF-α, thymus and activation-regulated chemokine (TARC) and IL-17A in BAL fluids of Der p-sensitised and -challenged mice. Moreover, L. gasseri decreased IL-17A production in transforming growth factor-α and IL-6 stimulated splenocytes and cell numbers of IL-17 producing alveolar macrophages in L. gasseri-treated mice as compared to non-treated, Der p-sensitised and -challenged mice. In conclusion, oral administration with L. gasseri can attenuate major characteristics of allergen-induced airway inflammation and IL-17 pro-inflammatory immune response in a mouse model of allergic asthma, which may have clinical implication in the preventive or therapeutic potential in allergic asthma.

  1. Optimization of Regression Models of Experimental Data Using Confirmation Points

    Science.gov (United States)

    Ulbrich, N.

    2010-01-01

    A new search metric is discussed that may be used to better assess the predictive capability of different math term combinations during the optimization of a regression model of experimental data. The new search metric can be determined for each tested math term combination if the given experimental data set is split into two subsets. The first subset consists of data points that are only used to determine the coefficients of the regression model. The second subset consists of confirmation points that are exclusively used to test the regression model. The new search metric value is assigned after comparing two values that describe the quality of the fit of each subset. The first value is the standard deviation of the PRESS residuals of the data points. The second value is the standard deviation of the response residuals of the confirmation points. The greater of the two values is used as the new search metric value. This choice guarantees that both standard deviations are always less or equal to the value that is used during the optimization. Experimental data from the calibration of a wind tunnel strain-gage balance is used to illustrate the application of the new search metric. The new search metric ultimately generates an optimized regression model that was already tested at regression model independent confirmation points before it is ever used to predict an unknown response from a set of regressors.

  2. Thermal conductivity of microporous layers: Analytical modeling and experimental validation

    Science.gov (United States)

    Andisheh-Tadbir, Mehdi; Kjeang, Erik; Bahrami, Majid

    2015-11-01

    A new compact relationship is developed for the thermal conductivity of the microporous layer (MPL) used in polymer electrolyte fuel cells as a function of pore size distribution, porosity, and compression pressure. The proposed model is successfully validated against experimental data obtained from a transient plane source thermal constants analyzer. The thermal conductivities of carbon paper samples with and without MPL were measured as a function of load (1-6 bars) and the MPL thermal conductivity was found between 0.13 and 0.17 W m-1 K-1. The proposed analytical model predicts the experimental thermal conductivities within 5%. A correlation generated from the analytical model was used in a multi objective genetic algorithm to predict the pore size distribution and porosity for an MPL with optimized thermal conductivity and mass diffusivity. The results suggest that an optimized MPL, in terms of heat and mass transfer coefficients, has an average pore size of 122 nm and 63% porosity.

  3. A systematic review of prion therapeutics in experimental models.

    Science.gov (United States)

    Trevitt, Clare R; Collinge, John

    2006-09-01

    Prion diseases are transmissible, invariably fatal, neurodegenerative diseases which include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy and scrapie in animals. A large number of putative treatments have been studied in experimental models over the past 30 years, with at best modest disease-modifying effects. The arrival of variant CJD in the UK in the 1990s has intensified the search for effective therapeutic agents, using an increasing number of animal, cellular and in vitro models with some recent promising proof of principle studies. Here, for the first time, we present a comprehensive systematic, rather than selective, review of published data on experimental approaches to prion therapeutics to provide a scientific resource for informing future therapeutics research, both in laboratory models and in clinical studies.

  4. Experimental validation of the multiphase extended Leblond's model

    Science.gov (United States)

    Weisz-Patrault, Daniel

    2017-10-01

    Transformation induced plasticity is a crucial contribution of the simulation of several forming processes involving phase transitions under mechanical loads, resulting in large irreversible strain even though the applied stress is under the yield stress. One of the most elegant and widely used models is based on analytic homogenization procedures and has been proposed by Leblond et al. [1-4]. Very recently, a simple extension of the Leblond's model has been developed by Weisz-Patrault [8]. Several product phases are taken into account and several assumptions are relaxed in order to extend the applicability of the model. The present contribution compares experimental tests with numerical computations, in order to discuss the validity of the developed theory. Thus, experimental results extracted from the existing literature are analyzed. Results show a good agreement between measurements and theoretical computations.

  5. Regression Model Optimization for the Analysis of Experimental Data

    Science.gov (United States)

    Ulbrich, N.

    2009-01-01

    A candidate math model search algorithm was developed at Ames Research Center that determines a recommended math model for the multivariate regression analysis of experimental data. The search algorithm is applicable to classical regression analysis problems as well as wind tunnel strain gage balance calibration analysis applications. The algorithm compares the predictive capability of different regression models using the standard deviation of the PRESS residuals of the responses as a search metric. This search metric is minimized during the search. Singular value decomposition is used during the search to reject math models that lead to a singular solution of the regression analysis problem. Two threshold dependent constraints are also applied. The first constraint rejects math models with insignificant terms. The second constraint rejects math models with near-linear dependencies between terms. The math term hierarchy rule may also be applied as an optional constraint during or after the candidate math model search. The final term selection of the recommended math model depends on the regressor and response values of the data set, the user s function class combination choice, the user s constraint selections, and the result of the search metric minimization. A frequently used regression analysis example from the literature is used to illustrate the application of the search algorithm to experimental data.

  6. Dynamic Modeling of Wind Turbine Gearboxes and Experimental Validation

    DEFF Research Database (Denmark)

    Pedersen, Rune

    is presented. The model takes into account the effects of load and applied grinding corrections. The results are verified by comparing to simulated and experimental results reported in the existing literature. Using gear data loosely based on a 1 MW wind turbine gearbox, the gear mesh stiffness is expanded...... analysis in relation to gear dynamics. A multibody model of two complete 2.3MWwind turbine gearboxes mounted back-to-back in a test rig is built. The mean values of the proposed gear mesh stiffnesses are included. The model is validated by comparing with calculated and measured eigenfrequencies and mode...

  7. Experimental validation of a Bayesian model of visual acuity.

    LENUS (Irish Health Repository)

    Dalimier, Eugénie

    2009-01-01

    Based on standard procedures used in optometry clinics, we compare measurements of visual acuity for 10 subjects (11 eyes tested) in the presence of natural ocular aberrations and different degrees of induced defocus, with the predictions given by a Bayesian model customized with aberrometric data of the eye. The absolute predictions of the model, without any adjustment, show good agreement with the experimental data, in terms of correlation and absolute error. The efficiency of the model is discussed in comparison with image quality metrics and other customized visual process models. An analysis of the importance and customization of each stage of the model is also given; it stresses the potential high predictive power from precise modeling of ocular and neural transfer functions.

  8. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...... hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r......TMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain...

  9. Experimental-analytical method of technological processes modeling in education

    Directory of Open Access Journals (Sweden)

    Efremov German I.

    2016-01-01

    Full Text Available The article considers general modeling techniques used in the study in education at different stages. The classification of different types of models and main stages of the simulation are considered. It is shown that in the course “Process of simulation” for technical areas of the Universities required the category of “Experimental-analytical simulation method”. For example, a new textbook for bachelors “Modeling of chemical-technological processes” shows that the section facilitates the compilation of process models in general; gives the possibility of studying the process at different levels; describes the nonlinear properties of the simulation objects, and to obtain refined adjustment of the model according to the experiment. The use of models of high accuracy can improve the quality of education.

  10. Experimental Evaluation of Equivalent-Fluid Models for Melamine Foam

    Science.gov (United States)

    Allen, Albert R.; Schiller, Noah H.

    2016-01-01

    Melamine foam is a soft porous material commonly used in noise control applications. Many models exist to represent porous materials at various levels of fidelity. This work focuses on rigid frame equivalent fluid models, which represent the foam as a fluid with a complex speed of sound and density. There are several empirical models available to determine these frequency dependent parameters based on an estimate of the material flow resistivity. Alternatively, these properties can be experimentally educed using an impedance tube setup. Since vibroacoustic models are generally sensitive to these properties, this paper assesses the accuracy of several empirical models relative to impedance tube measurements collected with melamine foam samples. Diffuse field sound absorption measurements collected using large test articles in a laboratory are also compared with absorption predictions determined using model-based and measured foam properties. Melamine foam slabs of various thicknesses are considered.

  11. [Epigenetics in allergic diseases and asthma].

    Science.gov (United States)

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. [Association between unplanned pregnancy and adolescence onset asthma].

    Science.gov (United States)

    Vázquez-Nava, Francisco; Gil-Lara, Bertoldo; Cruz-Torres, Leoncio; Vázquez-Rodríguez, Carlos F; Vázquez-Rodríguez, Eliza M; Felizardo-Ávalos, Jorge; Llanes-Castillo, Arturo; Córdova-Fernández, José A

    2013-01-01

    The association between asthma and pregnancy has been documented previously. The relationship between unplanned pregnancy and onset asthma in adolescence has not been studied. To determine the association between unplanned pregnancy and adolescence onset asthma. A cross-sectional study was done gathering information about asthma, unplanned pregnancy, family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years. Asthma diagnosis was established through a selfquestionnaire based on the International Study of Asthma and Allergy in Childhood. Odds ratios for asthma were determined using logistic regression model and chi-squared test. Mean age of the participants was 16.37 ± 1.93 years. The prevalence of active smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the pregnant adolescents (785), 59.5% reported had planned not to have a child before pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma was 5.4%. The age of initiation of asthma in the adolescence was 14.75 ± 1.60 years. The analysis showed that unplanned pregnancy has a slight risk for the development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05; p=0.000). Unplanned pregnancy, family atopy, active smoking and smoking friends are associated with the onset-asthma in the adolescence.

  13. Raw Cow's Milk Prevents the Development of Airway Inflammation in a Murine House Dust Mite-Induced Asthma Model.

    Science.gov (United States)

    Abbring, Suzanne; Verheijden, Kim A T; Diks, Mara A P; Leusink-Muis, Athea; Hols, Gert; Baars, Ton; Garssen, Johan; van Esch, Betty C A M

    2017-01-01

    Epidemiological studies show an inverse relation between raw cow's milk consumption and the development of asthma. This protective effect seems to be abolished by milk processing. However, evidence for a causal relationship is lacking, and direct comparisons between raw and processed milk are hardly studied. Therefore, this study investigated the preventive capacity of raw and heated raw milk on the development of house dust mite (HDM)-induced allergic asthma in mice. Six- to seven-week-old male BALB/c mice were intranasally (i.n.) sensitized with 1 µg HDM or PBS on day 0, followed by an i.n. challenge with 10 µg HDM or PBS on days 7-11. In addition, mice were fed 0.5 mL raw cow's milk, heated raw cow's milk, or PBS three times a week throughout the study, starting 1 day before sensitization. On day 14, airway hyperresponsiveness (AHR) in response to increasing doses of methacholine was measured to assess lung function. Bronchoalveolar lavage fluid (BALF) and lungs were furthermore collected to study the extent of airway inflammation. Raw milk prevented both HDM-induced AHR and pulmonary eosinophilic inflammation, whereas heated raw milk did not. Both milk types suppressed the Th2-polarizing chemokine CCL17 in lung homogenates and reduced lung Th2 and Th17 cell frequency. IL-4 and IL-13 production after ex vivo restimulation of lung T cells with HDM was also reduced by both milk types. However, local IL-5 and IL-13 concentrations were only suppressed by raw milk. These findings support the asthma-protective capacity of raw cow's milk and show the importance of reduced local type 2 cytokine levels. Heated raw milk did not show an asthma-protective effect, which indicates the involvement of heat-sensitive components. Besides causal evidence, this study provides the basis for further mechanistic studies.

  14. [Therapeutic effects of histone deacetylase inhibitor givinostat on air inflammation and high airway resistance in a murine asthma model].

    Science.gov (United States)

    Su, X M; Ren, Y; Kong, L F; Kang, J

    2017-02-01

    Objective: To investigate the therapeutic effects of givinostat, a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation, airway remodeling and airway hyperresponsiveness (AHR). Methods: BALB/C mice were randomly divided into control group, asthma group, dexamethasone group and givinostat group (n=12 per group). AHR was assessed. Total cell numbers and differential counts, interleukin-4(IL-4), interleukin-5(IL-5) and interferon-γ (IFNγ) levels in the bronchoalveolar lavage fluid (BALF) were measured in the above 4 groups. The pathology of lung tissue was evaluated. Immunohistochemical (IHC) staining and Western blot were used to detect α smooth muscle actin(α-SMA) and transforming growth factor-β1(TGFβ1). Results: Compared with the asthma only group, givinostat treatment relieved airway resistance (2.96±1.01 vs 6.50±0.79, P0.05] was enhanced in BALF. Inflammatory cell infiltration around the airway was reduced, with decreased inflammatory cell score[(1.60±0.69)points vs (3.40±0.68) points, P<0.01] and inflammatory cell number (111.65±31.41 vs 601.25±186.85, P<0.01). The goblet cell metaplasia [(26.36±2.33)% vs (57.21±11.56)%] and collagen deposition area [(52.77±7.58)μm(2)/μm vs (111.81±12.40)μm(2)/μm] were obviously reduced (P<0.01). The expressions of α-SMA and TGFβ1 in the lung tissue were both significantly decreased (P<0.01). Conclusion: Givinostat treatment can reduce airway inflammation, airway remodeling and airway hyperresponsiveness in chronic asthma. Its effect is comparable to that of glucocorticoid hormone treatment.

  15. Astragalus polysaccharide modulates ER stress response in an OVA-LPS induced murine model of severe asthma.

    Science.gov (United States)

    Lu, Yuan; Xing, Qiong-Qiong; Xu, Jian-Ya; Ding, Dou; Zhao, Xia

    2016-12-01

    Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) and the protein levels of IL13RA and IL17RA. APS also inhibits the activation of unfolded protein response by decreasing the levels of ER stress markers such as C/EBP homologous protein (CHOP), which was associated with a reduction of PERK phosphorylation. Moreover, APS substantially blocks the nuclear translocation of ATF6 and NF-κB p65. Interestingly, we observed that APS markedly suppresses mucus hypersecretion by decreasing the levels of mucin (MUC) 5AC and MUC5B, which might be due to inhibition of goblet cells differentiation by suppressing the expression of IRE1β-correlated genes. In summary, APS can have potential pharmaceutical application in treatment of severe asthma. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Yupingfeng San Inhibits NLRP3 Inflammasome to Attenuate the Inflammatory Response in Asthma Mice

    Directory of Open Access Journals (Sweden)

    Xue Liu

    2017-12-01

    Full Text Available Yupingfeng San (YPFS is a representative Traditional Chinese Medicine (TCM formula with accepted therapeutic effect on Asthma. However, its action mechanism is still obscure. In this study, we used network pharmacology to explore potential mechanism of YPFS on asthma. Nucleotide-binding oligomerization domain (NOD-like receptor pathway was shown to be the top one shared signaling pathway associated with both YPFS and asthma. In addition, NOD-like receptor family pyrin domain-containing 3 (NLRP3 inflammasome was treated as target protein in the process of YPFS regulating asthma. Further, experimental validation was done by using LPS-stimulated U937 cells and ovalbumin (OVA-sensitized BALB/c mice model. In vitro experiments showed that YPFS significantly decreased the production of TNF-α and IL-6, as well as both mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in LPS-stimulated U937 cells. In vivo experiment indicated that YPFS treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. Moreover, YPFS treatment remarkably decreased the mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in lung tissue of asthmatic mice. In conclusion, these results demonstrated that YPFS could inhibit NLRP3 inflammasome components to attenuate the inflammatory response in asthma.

  17. Sibship and self-esteem in children with asthma

    Directory of Open Access Journals (Sweden)

    Concetta Polizzi

    2016-06-01

    Full Text Available This study has explored the valence of sibship that may empower the self-esteem of children with asthma at the interpersonal, environmental control competence, emotionality management, and body-image levels. It has been assumed that the relationship between siblings may have a moderating effect on the negative impact that asthma has on child’s development. Seventy children suffering from chronic asthma have been involved: 40 children with siblings (experimental group and 30 sibling-free children (control group. The children with asthma have exhibited higher levels of self-esteem in comparison with the sibling-free children. The results of the study, at the clinical significance level, highlight how meaningful could be the involvement of healthy siblings to support the development, and to ease the compliance of children suffering from asthma. The outcomes have confirmed the supportive valence of sibship for the self-esteem of the children with asthma.

  18. Sibship and Self-esteem in Children with Asthma.

    Science.gov (United States)

    Polizzi, Concetta; Fontana, Valentina; Carollo, Antonio; Bono, Alessandra; Burgio, Sofia; Perricone, Giovanna

    2016-06-15

    This study has explored the valence of sibship that may empower the self-esteem of children with asthma at the interpersonal, environmental control competence, emotionality management, and body-image levels. It has been assumed that the relationship between siblings may have a moderating effect on the negative impact that asthma has on child's development. Seventy children suffering from chronic asthma have been involved: 40 children with siblings (experimental group) and 30 sibling-free children (control group). The children with asthma have exhibited higher levels of self-esteem in comparison with the sibling-free children. The results of the study, at the clinical significance level, highlight how meaningful could be the involvement of healthy siblings to support the development, and to ease the compliance of children suffering from asthma. The outcomes have confirmed the supportive valence of sibship for the self-esteem of the children with asthma.

  19. Transvaginal ultrasound ovarian diathermy: sheep as an experimental model

    Directory of Open Access Journals (Sweden)

    Pimentel Anita M

    2012-01-01

    Full Text Available Abstract Background Some techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model. Findings An experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale and 3.41 cm2 ± 0,64 (Suffolk. From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path. Conclusions This is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.

  20. Beta-2 adrenergic receptors increase TREG cell suppression in an OVA-induced allergic asthma mouse model when mice are moderate aerobically exercised.

    Science.gov (United States)

    Dugger, Kari J; Chrisman, Taylor; Sayner, Sarah L; Chastain, Parker; Watson, Kacie; Estes, Robert

    2018-02-17

    The potency of T regulatory (TREG) cells to inhibit T helper (Th)-driven immune cell responses has been linked to increased intracellular cyclic-AMP (cAMP) levels of TREG cells. In an ovalbumin (OVA)-driven allergic asthma mouse model, moderate aerobic exercise increases TREG cell function in a contact-dependent manner that leads to a significant reduction in chronic inflammation and restoration of lung function. However, the mechanism, whereby exercise increases TREG function, remains unknown and was the focus of these investigations. Exercise can communicate with TREG cells by their expression of β2-adrenergic receptors (β2-AR). Activation of these receptors results in an increase in intracellular levels of cyclic-AMP, potentially creating a potent inhibitor of Th cell responses. For the allergic asthma model, female wildtype BALB/c mice were challenged with OVA, and exercised (13.5 m/min for 45 min) 3×/week for 4 weeks. TREG cells were isolated from all mouse asthma/exercise groups, including β2-AR -/- mice, to test suppressive function and intracellular cAMP levels. In these studies, cAMP levels were increased in TREG cells isolated from exercised mice. When β2-AR expression was absent on TREG cells, cAMP levels were significantly decreased. Correlatively, their suppressive function was compromised. Next, TREG cells from all mouse groups were tested for suppressive function after treatment with either a pharmaceutical β2-adrenergic agonist or an effector-specific cAMP analogue. These experiments showed TREG cell function was increased when treated with either a β2-adrenergic agonist or effector-specific cAMP analogue. Finally, female wildtype BALB/c mice were antibody-depleted of CD25 + CD4 + TREG cells (anti-CD25). Twenty-four hours after TREG depletion, either β2-AR -/- or wildtype TREG cells were adoptively transferred. Recipient mice underwent the asthma/exercise protocols. β2-AR -/- TREG cells isolated from these mice showed no increase in

  1. Ultrashort-TE MRI longitudinal study and characterization of a chronic model of asthma in mice: inflammation and bronchial remodeling assessment.

    Science.gov (United States)

    Bianchi, Andrea; Ozier, Annaïg; Ousova, Olga; Raffard, Gérard; Crémillieux, Yannick

    2013-11-01

    Asthma is a chronic disease characterized by bronchial hyperresponsiveness (BHR), bronchial inflammation and remodeling. The great improvements in (1)H MRI ultrashort-TE (UTE) sequences in the last decade have allowed lung images with high-resolution and good signal-to-noise ratio to be obtained in parenchymal tissues. In this article, we present a UTE (1)H MRI high-resolution study of a chronic model of asthma in mice with the aim to longitudinally assess the main features of asthma using a fully noninvasive approach. Balb/c mice (n = 6) were sensitized with ovalbumin over a period of 75 days. The control group (n = 3) received normal saline on the same days. MRI acquisitions were performed on days 0, 38 and 78 to study the inflammatory volumes and bronchial remodeling (peribronchial signal intensity index, PBSI). Plethysmographic studies were performed on days 0, 39 and 79 to assess BHR to methacholine using the enhanced pause (Penh) ratio. The average inflammatory volume measured by MRI in the ovalbumin group (15.6 ± 2.4 μL) was increased significantly relative to control mice (-0.3 ± 0.7 μL) on day 38. The inflammatory volume was larger (34.2 ± 3.1 μL) on day 78 in the ovalbumin group. PBSI was significantly higher in the ovalbumin group on day 78 (1.53 ± 0.08) relative to the control group (1.16 ± 0.10), but not on day 38. After sensitization, asthmatic mice presented BHR to methacholine on days 39 and 79. Penh ratios correlated significantly with the inflammatory volume on day 39 and with the PBSI on day 79. This study shows, for the first time, that high-resolution UTE (1)H MRI of the lungs may allow the noninvasive quantification of peribronchial eosinophilic inflammation with airways occlusion by mucus and of bronchial remodeling in a murine asthma model that correlates with functional parameters. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Numerical modeling of experimental human fibrous cap delamination.

    Science.gov (United States)

    Leng, Xiaochang; Davis, Lindsey A; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2016-06-01

    Fibrous cap delamination is a critical process during the rupture of atherosclerotic plaque, which often leads to severe life-threatening clinical consequences such as myocardial infarction or stroke. In this study a finite element modeling and simulation approach is presented that enables the study of fibrous cap delamination experiments for the purpose of understanding the fibrous cap delamination process. A cohesive zone model (CZM) approach is applied to simulate delamination of the fibrous cap from the underlying plaque tissue. A viscoelastic anisotropic (VA) model for the bulk arterial material behavior is extended from existing studies so that the hysteresis phenomenon observed in the fibrous cap delamination experiments can be captured. A finite element model is developed for the fibrous cap delamination experiments, in which arterial layers (including the fibrous cap and the underlying plaque tissue) are represented by solid elements based on the VA model and the fibrous cap-underlying plaque tissue interface is characterized by interfacial CZM elements. In the CZM, the delamination process is governed by an exponential traction-separation law which utilizes critical energy release rates obtained directly from the fibrous cap delamination experiments. A set of VA model parameter values and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with one set of experimental measurements. Using this set of parameter values, simulation predictions for other sets of experimental measurements are obtained and good agreement between simulation predictions and experimental measurements is observed. Results of this study demonstrate the applicability of the viscoelastic anisotropic model and the CZM approach for the simulation of diseased arterial tissue failure processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Dietary patterns and asthma prevalence, incidence and control.

    Science.gov (United States)

    Barros, R; Moreira, A; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Lopes, C; Severo, M; Moreira, P

    2015-11-01

    The increased asthma prevalence in westernized societies has been suggested to be related to environment exposures and lifestyle changes, particularly diet. We aimed to explore the association between dietary patterns and asthma prevalence, incidence and control in a nationally representative population. Data from 32,644 adults, 53% female, from the 4th Portuguese National Health Survey were analysed. Prevalence of asthma was 5.3%; 'current asthma', defined by asthma symptoms within previous year, 3.5%; 'current medicated asthma' defined by use of asthma medication within previous year, 3.0%; 'current severe asthma' defined by emergency visit because of asthma within previous year, 1.4%; and 'incident asthma', 0.2%. Dietary patterns (DP) were identified by latent trait models based on dietary intake. Unconditional logistic regression models were performed to analyse association between DP and asthma. Age, gender, education, family income, proxy reporting information, smoking, body mass index and physical activity level were analysed as confounders. Two of the five identified DP were associated with asthma: 'high fat, sugar and salt' DP (positively correlated with pastry, chocolate and sweet desserts, candies, salty snacks, chips, fruit juices, soft drinks and alcoholic beverages consumption at snacks) was associated with asthma prevalence (OR = 1.13, 95% CI = 1.03, 1.24) and current severe asthma (OR = 1.23, 95% CI = 1.03, 1.48), while 'fish, fruit and vegetables' DP (positively correlated with fish, vegetables and fruit intake at meals) was negatively associated with current (OR = 0.84, 95% CI = 0.73, 0.98), and current medicated asthma (OR = 0.84, 95% CI = 0.72, 0.98), after adjustment for confounders. Our results suggest a protective association between 'fish, vegetables and fruit' DP and current asthma and current medicated asthma, and a detrimental association between 'high fat, sugar and salt' DP and severe asthma prevalence, further supporting the rational

  4. Justicia procumbens Extract (DW2008) Selectively Suppresses Th2 Cytokines in Splenocytes and Ameliorates Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

    Science.gov (United States)

    Youm, Jihyun; Lee, Hyunyong; Chang, Hwan Bong; Jeon, Jihyun; Yoon, Mi Hee; Woo, Ji Young; Choi, Min-Soo; Hwang, Yunha; Seong, Seungkyoo; Na, Kyuheum; Yoon, Joobyoung

    2017-01-01

    DW2008 is an anhydrous ethanol extract of Justicia procumbens produced by Dong-Wha Pharmaceutical, Inc., Co. as a candidate anti-asthmatic drug. In this study, DW2008 selectively reduced T helper 2 (Th2) cytokines in mouse splenocytes and ameliorated ovalbumin-induced airway inflammation by downregulating pulmonary infiltration of differential inflammatory cells and Th2 cytokines more than a decoction or ethanol extract of J. procumbens did in a mouse asthma model. DW2008 also significantly inhibited airway hyperresponsiveness and reduced the thickness of the airway epithelium. HPLC analysis showed that the major peaks (justicidin A and B) of DW2008 were higher than those of the other extracts. Justicidin A and B significantly suppressed Th2 cytokine levels in mouse spleen cells and exhibited a protective effect in ovalbumin-induced airway inflammation. Our findings indicate that DW2008 effectively inhibits allergic airway inflammatory reactions and airway hyperresponsiveness in a mouse model of asthma, suggesting its potential as an anti-asthmatic agent.

  5. Target Soil Impact Verification: Experimental Testing and Kayenta Constitutive Modeling.

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Scott Thomas [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Flint, Gregory Mark [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Dewers, Thomas [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Newell, Pania [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    This report details experimental testing and constitutive modeling of sandy soil deformation under quasi - static conditions. This is driven by the need to understand constitutive response of soil to target/component behavior upon impact . An experimental and constitutive modeling program was followed to determine elastic - plastic properties and a compressional failure envelope of dry soil . One hydrostatic, one unconfined compressive stress (UCS), nine axisymmetric compression (ACS) , and one uniaxial strain (US) test were conducted at room temperature . Elastic moduli, assuming isotropy, are determined from unload/reload loops and final unloading for all tests pre - failure and increase monotonically with mean stress. Very little modulus degradation was discernable from elastic results even when exposed to mean stresses above 200 MPa . The failure envelope and initial yield surface were determined from peak stresses and observed onset of plastic yielding from all test results. Soil elasto - plastic behavior is described using the Brannon et al. (2009) Kayenta constitutive model. As a validation exercise, the ACS - parameterized Kayenta model is used to predict response of the soil material under uniaxial strain loading. The resulting parameterized and validated Kayenta model is of high quality and suitable for modeling sandy soil deformation under a range of conditions, including that for impact prediction.

  6. Experimental Damage Identification of a Model Reticulated Shell

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2017-04-01

    Full Text Available The damage identification of a reticulated shell is a challenging task, facing various difficulties, such as the large number of degrees of freedom (DOFs, the phenomenon of modal localization and transition, and low modeling accuracy. Based on structural vibration responses, the damage identification of a reticulated shell was studied. At first, the auto-regressive (AR time series model was established based on the acceleration responses of the reticulated shell. According to the changes in the coefficients of the AR model between the damaged conditions and the undamaged condition, the damage of the reticulated shell can be detected. In addition, the damage sensitive factors were determined based on the coefficients of the AR model. With the damage sensitive factors as the inputs and the damage positions as the outputs, back-propagation neural networks (BPNNs were then established and were trained using the Levenberg–Marquardt algorithm (L–M algorithm. The locations of the damages can be predicted by the back-propagation neural networks. At last, according to the experimental scheme of single-point excitation and multi-point responses, the impact experiments on a K6 shell model with a scale of 1/10 were conducted. The experimental results verified the efficiency of the proposed damage identification method based on the AR time series model and back-propagation neural networks. The proposed damage identification method can ensure the safety of the practical engineering to some extent.

  7. Biomechanics of epithelial cell islands analyzed by modeling and experimentation

    CERN Document Server

    Coburn, Luke; Noppe, Adrian; Caldwell, Benjamin J; Moussa, Elliott; Yap, Chloe; Priya, Rashmi; Lobaskin, Vladimir; Roberts, Anthony P; Yap, Alpha S; Neufeld, Zoltan; Gomez, Guillermo A

    2016-01-01

    We generated a new computational approach to analyze the biomechanics of epithelial cell islands that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of protrusions (and traction forces) that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions (and monolayer stress) is not homogeneous across the island. Instead it is higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Moreover, our approach has the minimal elements necessary to reproduce mechanical crosstalk between both cell-cell and cell substrate adhesion systems. We found that an i...

  8. Numerical modeling of nitrogen oxide emission and experimental verification

    Directory of Open Access Journals (Sweden)

    Szecowka Lech

    2003-12-01

    Full Text Available The results of nitrogen reduction in combustion process with application of primary method are presented in paper. The reduction of NOx emission, by the recirculation of combustion gasses, staging of fuel and of air was investigated, and than the reduction of NOx emission by simultaneous usage of the mentioned above primary method with pulsatory disturbances.The investigations contain numerical modeling of NOx reduction and experimental verification of obtained numerical calculation results.

  9. Epidural blood patch: A study on an experimental model

    OpenAIRE

    S K Sengupta

    2013-01-01

    Aim: Epidural blood patch has been used to treat spinal headache with varying success. An experimental model was designed to ascertain whether an epidural blood patch can be used to seal the needle puncture sites in dural repair. Materials and Methods: Bovine dura was secured to the lower end of an open-ended calibrated plastic cylinder. Multiple interrupted stitches were applied over a 02 cm length of the dura without any incision. The cylinder was filled with colored saline gradually with t...

  10. Monitoring asthma in childhood

    Directory of Open Access Journals (Sweden)

    Karin C. Lødrup Carlsen

    2015-06-01

    Full Text Available The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. However, to date there is limited evidence on how to monitor patients with asthma. Childhood asthma introduces specific challenges in terms of deciding what, when, how often, by whom and in whom different assessments of asthma should be performed. The age of the child, the fluctuating course of asthma severity, variability in clinical presentation, exacerbations, comorbidities, socioeconomic and psychosocial factors, and environmental exposures may all influence disease activity and, hence, monitoring strategies. These factors will be addressed in herein. We identified large knowledge gaps in the effects of different monitoring strategies in children with asthma. Studies into monitoring strategies are urgently needed, preferably in collaborative paediatric studies across countries and healthcare systems.

  11. Tobaksrygning og asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2002-01-01

    Cigarette smoking is a well-known health hazard, probably not least for patients suffering from asthma. This review gives a short overview of the effects of passive and active smoking on the inception and outcome with of longitudinal changes in the lung function and mortality of patients...... with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke, especially maternal smoking in children, may be a significant risk factor for asthma. Such exposure in patients with established asthma is not only associated with more severe symptoms......, but also with a poorer quality of life, reduced lung function, and increased utilisation of health care including hospital admissions. Active smoking does not appear to be a significant risk factor for asthma, but is associated with a worse outcome with regard to both longitudinal changes in lung function...

  12. Asthma in the Elderly

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2009-01-01

    Full Text Available Bronchial asthma is a common problem with enormous medical and economics impacts. It is an inflammatory disease of the airways associated with intermittent episodes of bronchospasm. Asthma is not uncommon in the elderly patients. Prevalence of asthma is similar in older and younger adults. Asthma in the elderly patient is underdiagnosed because of false perceptions by both patient and physician. The high incidence of comorbid conditions in the elderly patient makes the diagnosis and management more difficult. Correct diagnosis is demonstrated with spirometry. The goals of asthma treatment are to achieve and maintain control of symptoms and to prevent development of irreversible airflow limitation. Asthma drugs are preferably inhaled because this route minimizes systemic absorption and, thus, improves the ratio of the therapeutic benefit to the potential side-effects in elderly patients.

  13. Asthma and obesity

    DEFF Research Database (Denmark)

    Ulrik, Charlotte S

    2016-01-01

    PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight...... reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness...... reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma....

  14. Late-Onset Asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2017-01-01

    , to objectively confirm asthma. If necessary, a trial of oral or inhaled corticosteroid might be necessary. Asthma can be diagnosed when increased airflow variability is identified in a symptomatic patient, and if the patient does not have a history of exposure, primarily smoking, known to cause chronic...... obstructive pulmonary disease, the diagnosis is asthma even if the patient does not have fully reversible airflow obstruction. Pharmacological therapy in patients with late-onset asthma follows international guidelines, including treatment with the lowest effective dose of inhaled corticosteroid to minimize...... the risk of systemic effects. However, most recommendations are based on extrapolation from findings in younger patients. Comorbidities are very common in patients with late-onset asthma and need to be taken into account in the management of the disease. In conclusion, late-onset asthma is poorly...

  15. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... please visit this page: About CDC.gov . Asthma Learn How to Control Asthma Asthma and Severe Weather ... Working on Asthma Follow @CDCasthma on Twitter to learn more about helping people with asthma live healthier ...

  16. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view ...

  17. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler ... ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view ...

  18. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I ...

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... among Children Asthma-related Missed School Days among Children aged 5–17 Years Asthma Severity among Adults with Current Asthma Asthma Severity among Children with Current Asthma Overuse of quick-relief medication ...

  20. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I ...

  1. Prematurity, atopy, and childhood asthma in Puerto Ricans.

    Science.gov (United States)

    Rosas-Salazar, Christian; Ramratnam, Sima K; Brehm, John M; Han, Yueh-Ying; Boutaoui, Nadia; Forno, Erick; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

    2014-02-01

    Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. We sought to examine whether prematurity is associated with asthma in Puerto Rican children. We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Risk of herpes zoster in children with asthma.

    Science.gov (United States)

    Wi, Chung-Il; Kim, Bong-Seong; Mehra, Sonia; Yawn, Barbara P; Park, Miguel A; Juhn, Young J

    2015-01-01

    There is literature that indicates the association of asthma with an increased risk of common and serious microbial infections. We recently reported an increased risk of vaccine-preventable diseases, e.g., herpes zoster (HZ) among children with asthma, defined by predetermined asthma criteria. Little is known about whether this association is persistent if the asthma status is defined by different asthma criteria, e.g., the Asthma Predictive Index, given the heterogeneity of asthma. To assess the consistency of the association between asthma and the risk of HZ in children. This is a population-based case-control study based on all pediatric patients with HZ between 1996 and 2001 in Olmsted County, Minnesota, and 1:1 age- and sex-matched controls without a history of HZ who were enrolled in our previous study. The original Asthma Predictive Index criteria was operationalized by two or more wheezing episodes in a year for the first 3 years of life plus one of the major (physician-diagnosed asthma for a parent or physician-diagnosed eczema for a patient) or two of the minor criteria (physician-diagnosed allergic rhinitis for a patient, wheezing apart from cold, or eosinophilia [≥4%]). Data were fit to traditional logistic regression models to calculate odds ratios and 95% confident intervals. Of the original cohort (n = 554), 95 (17%) did not meet the enrollment criteria for this study, which left 459. Of the 221 patients, 53% were female, with a mean (standard deviation) age of 9.7 ± 4.2 years. The risk of HZ was increased in children with asthma defined by the API controlling for a varicella vaccine history and atopic status (adjusted odds ratio 2.56 [95% confidence interval, 1.08-6.56]). The association between asthma and increased risk of HZ in children and adolescents is consistent, independent of asthma definitions. Asthma might be an important clinical condition to be considered in HZ vaccine studies.

  3. Race and asthma control in the pediatric population of Hawaii.

    Science.gov (United States)

    Wu, Brian H; Cabana, Michael D; Hilton, Joan F; Ly, Ngoc P

    2011-05-01

    The racially unique population of Hawaii has one of the highest prevalences of childhood asthma in America. We estimate the prevalence of impaired asthma control among asthmatic children in Hawaii and determine which factors are associated with impaired control. We analyzed data from 477 asthmatic children living in Hawaii participating in the 2006-2008 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Surveys. Impaired asthma control was modeled after 2007 National Asthma Education and Prevention Program guidelines. Univariate and multivariate analyses were used to identify factors associated with impaired asthma control. Children (53.8%) with asthma were either part or full Native Hawaiian/Pacific Islander. While 35.6% of asthmatic children met criteria for impaired asthma control, being part or full Native Hawaiian/Pacific Islander was not associated with impaired control. Only 31.1% of children with impaired control reported the use of inhaled corticosteroids despite >80% having had a routine checkup for asthma in the past year and receipt of asthma education from a healthcare provider. A large proportion of asthmatic children in Hawaii have impaired asthma control that does not appear to be associated with race but may be associated with inadequate pharmacologic therapy. While a significant percentage reported receiving routine asthma care and asthma education, a minority reported using inhaled corticosteroids. Reasons for this discrepancy between asthma assessment and treatment are unclear. However, additional education on part of the physician, community, and healthcare system are likely to improve management and reduce morbidity in this population. Copyright © 2010 Wiley-Liss, Inc.

  4. Experimental model of heterotopic ossification in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Zotz, T.G.G. [Escola Politécnica, Programa de Pós-Graduação em Tecnologia em Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, PR (Brazil); Paula, J.B. de [Médico,Doutor em Engenharia Biomédica, Curitiba, PR (Brazil); Moser, A.D.L. [Escola Politécnica, Programa de Pós-Graduação em Tecnologia em Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, PR (Brazil)

    2012-04-05

    Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats.

  5. Amplified energy harvester from footsteps: design, modeling, and experimental analysis

    Science.gov (United States)

    Wang, Ya; Chen, Wusi; Guzman, Plinio; Zuo, Lei

    2014-04-01

    This paper presents the design, modeling and experimental analysis of an amplified footstep energy harvester. With the unique design of amplified piezoelectric stack harvester the kinetic energy generated by footsteps can be effectively captured and converted into usable DC power that could potentially be used to power many electric devices, such as smart phones, sensors, monitoring cameras, etc. This doormat-like energy harvester can be used in crowded places such as train stations, malls, concerts, airport escalator/elevator/stairs entrances, or anywhere large group of people walk. The harvested energy provides an alternative renewable green power to replace power requirement from grids, which run on highly polluting and global-warming-inducing fossil fuels. In this paper, two modeling approaches are compared to calculate power output. The first method is derived from the single degree of freedom (SDOF) constitutive equations, and then a correction factor is applied onto the resulting electromechanically coupled equations of motion. The second approach is to derive the coupled equations of motion with Hamilton's principle and the constitutive equations, and then formulate it with the finite element method (FEM). Experimental testing results are presented to validate modeling approaches. Simulation results from both approaches agree very well with experimental results where percentage errors are 2.09% for FEM and 4.31% for SDOF.

  6. Experimental model of cutaneous radiation injury in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

    2013-07-01

    Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

  7. Ionospheric topside models compared with experimental electron density profiles

    Directory of Open Access Journals (Sweden)

    S. M. Radicella

    2005-06-01

    Full Text Available Recently an increasing number of topside electron density profiles has been made available to the scientific community on the Internet. These data are important for ionospheric modeling purposes, since the experimental information on the electron density above the ionosphere maximum of ionization is very scarce. The present work compares NeQuick and IRI models with the topside electron density profiles available in the databases of the ISIS2, IK19 and Cosmos 1809 satellites. Experimental electron content from the F2 peak up to satellite height and electron densities at fixed heights above the peak have been compared under a wide range of different conditions. The analysis performed points out the behavior of the models and the improvements needed to be assessed to have a better reproduction of the experimental results. NeQuick topside is a modified Epstein layer, with thickness parameter determined by an empirical relation. It appears that its performance is strongly affected by this parameter, indicating the need for improvements of its formulation. IRI topside is based on Booker's approach to consider two parts with constant height gradients. It appears that this formulation leads to an overestimation of the electron density in the upper part of the profiles, and overestimation of TEC.

  8. CFD modeling of pharmaceutical isolators with experimental verification of airflow.

    Science.gov (United States)

    Nayan, N; Akay, H U; Walsh, M R; Bell, W V; Troyer, G L; Dukes, R E; Mohan, P

    2007-01-01

    Computational fluid dynamics (CFD) models have been developed to predict the airflow in a transfer isolator using a commercial CFD code. In order to assess the ability of the CFD approach in predicting the flow inside an isolator, hot wire anemometry measurements and a novel experimental flow visualization technique consisting of helium-filled glycerin bubbles were used. The results obtained have been shown to agree well with the experiments and show that CFD can be used to model barrier systems and isolators with practical fidelity. This indicates that CFD can and should be used to support the design, testing, and operation of barrier systems and isolators.

  9. Contact drying: a review of experimental and mechanistic modeling approaches.

    Science.gov (United States)

    Sahni, Ekneet Kaur; Chaudhuri, Bodhisattwa

    2012-09-15

    Drying is one of the most complex unit operations with simultaneous heat and mass transfer. The contact drying process is also not well understood as several physical phenomena occur concurrently. This paper reviews current experimental and modeling approaches employed towards a better understanding of the contact drying operation. Additionally, an overview of some fundamental aspects relating to contact drying is provided. A brief discussion of some model extensions such as incorporation of noncontact forces, interstitial fluids and attrition rate is also presented. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Severe Asthma in Children.

    Science.gov (United States)

    Chipps, Bradley E; Parikh, Neil G; Maharaj, Sheena K

    2017-04-01

    The aim of this study is to characterize, diagnose, evaluate, and treat severe childhood asthma. Understanding the occurrence of the physiologic and clinical presentations of childhood severe asthma, the treatment and response may be predicted by biomarkers, but the patient's response is highly variable. The onset of severe asthma occurs early and is primarily predicted by severity of viral infection and coexistence of the atopic state.

  11. Pneumatic Adaptive Absorber: Mathematical Modelling with Experimental Verification

    Directory of Open Access Journals (Sweden)

    Grzegorz Mikułowski

    2016-01-01

    Full Text Available Many of mechanical energy absorbers utilized in engineering structures are hydraulic dampers, since they are simple and highly efficient and have favourable volume to load capacity ratio. However, there exist fields of applications where a threat of toxic contamination with the hydraulic fluid contents must be avoided, for example, food or pharmacy industries. A solution here can be a Pneumatic Adaptive Absorber (PAA, which is characterized by a high dissipation efficiency and an inactive medium. In order to properly analyse the characteristics of a PAA, an adequate mathematical model is required. This paper proposes a concept for mathematical modelling of a PAA with experimental verification. The PAA is considered as a piston-cylinder device with a controllable valve incorporated inside the piston. The objective of this paper is to describe a thermodynamic model of a double chamber cylinder with gas migration between the inner volumes of the device. The specific situation considered here is that the process cannot be defined as polytropic, characterized by constant in time thermodynamic coefficients. Instead, the coefficients of the proposed model are updated during the analysis. The results of the experimental research reveal that the proposed mathematical model is able to accurately reflect the physical behaviour of the fabricated demonstrator of the shock absorber.

  12. Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects : an observational study

    NARCIS (Netherlands)

    Majoor, Christof J.; van de Pol, Marianne A.; Kamphuisen, Pieter W.; Meijers, Joost C.M.; Molenkamp, Richard; Wolthers, Katja C.; van der Poll, Tom; Nieuwland, Rienk; Johnston, Sebastian L.; Sterk, Peter J.; Bel, Elisabeth H.D.; Lutter, Rene; van der Sluijs, Koenraad F.

    2014-01-01

    Background: Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.

  13. Experimental models in vaccine research: malaria and leishmaniasis

    Directory of Open Access Journals (Sweden)

    C. Teixeira

    2013-02-01

    Full Text Available Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis.

  14. Experimental models in vaccine research: malaria and leishmaniasis.

    Science.gov (United States)

    Teixeira, C; Gomes, R

    2013-02-01

    Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis.

  15. Linking obesity and asthma.

    Science.gov (United States)

    Sutherland, E Rand

    2014-04-01

    A growing body of literature suggests that obesity has a significant impact on asthma risk, phenotype, and prognosis. Epidemiological studies have clearly demonstrated that asthma is more likely to occur in obese patients, and health status is impaired in obese individuals with asthma, with obese asthmatics experiencing more symptoms, worse quality of life, increased healthcare use, and increased asthma severity. However, obesity has well-described effects on lung function and mechanics that can lead to symptoms of dyspnea without causing the pathophysiologic changes of asthma. Adding to the challenges of evaluating this association, some studies have failed to demonstrate a robust relationship between obesity and traditional biomarkers of airway inflammation in adult asthmatics, leading to the conclusion that obesity does not necessarily worsen airway inflammation in asthma. In this regard, emerging data suggest that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may have a direct impact on the response of obese asthmatics to asthma therapies, most notably inhaled glucocorticoids. This article will review selected aspects of the contributions of obesity-related airway and systemic inflammation to asthma, with a focus on the impact of obesity as a modifier of risk, prognosis, and therapeutic response in asthma. © 2014 New York Academy of Sciences.

  16. Asthma in the Elderly.

    Science.gov (United States)

    Braman, Sidney S

    2017-11-01

    The older population has seen the greatest increase in the prevalence of current asthma in recent years. Asthma may begin at any age and when it occurs at an advanced as opposed to a young age, it is often nonatopic, severe, and unremitting. Unfortunately, geriatric-specific guidelines are not available for the diagnosis and treatment of asthma. However, with objective monitoring, avoidance of asthma triggers, appropriate pharmacotherapy, and patient education, the disease can be managed successfully. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Asthma among mink workers

    DEFF Research Database (Denmark)

    Grøntved, Berit; Carstensen, Ole; Petersen, Rolf

    2014-01-01

    We report two cases of asthma among mink workers. The first case is about a mink farmer who had asthma that was difficult to treat. In the medical history there was no clear relation to work, and no conclusive work relation with peak flow monitoring. He had a positive histamine release test to mink...... urine. The second case is about a mink farm worker, who had an asthma attack when handling mink furs. Peak flow monitoring showed a clear relation to this work, but there were no signs of allergy. We conclude that these two cases suggest an increased risk of asthma among mink workers....

  18. Experimental model of cultured keratinocytes Modelo experimental de cultura de queratinócitos

    Directory of Open Access Journals (Sweden)

    Alfredo Gragnani

    2003-01-01

    Full Text Available The bioengineering research is essential in the development of ideal combination of biomaterials and cultured cells to produce the permanent wound coverage. The experimental model of cultured keratinocytes presents all steps of the culture, since the isolation of the keratinocytes, preparation of the human acellular dermis, preparation of the composite skin graft and their elevation to the air-liquid interface. The research in cultured keratinocytes model advances in two main ways: 1. optimization of the methods in vitro to the skin cells culture and proliferation and 2. developing biomaterials that present similar skin properties.A pesquisa em bioengenharia é primordial no desenvolvimento da combinação ideal de biomateriais e células cultivadas para produzir a cobertura definitiva das lesões. O modelo experimental da cultura de queratinócitos apresenta toda as etapas do cultivo, desde o isolamento dos queratinócitos, preparação da derme acelular humana, do enxerto composto e da sua elevação à interface ar-líquido. A pesquisa em modelo de cultura de queratinócitos desenvolve-se em duas vias principais: 1. otimização dos métodos in vitro para cultivo e proliferação de células da pele e 2. desenvolvimento de biomateriais que mimetizem as propriedades da pele.

  19. A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma.

    Science.gov (United States)

    Morel, Lucas Junqueira de Freitas; Azevedo, Bruna Cestari de; Carmona, Fábio; Contini, Silvia Helena Taleb; Teles, Aristônio Magalhães; Ramalho, Fernando Silva; Bertoni, Bianca Waléria; França, Suzelei de Castro; Borges, Marcos de Carvalho; Pereira, Ana Maria Soares

    2017-02-23

    Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg-1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg-1 of extract, which provided 0.745, 4.22 and 4.30mgkg-1day-1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (Pasthma, thereby supporting the ethnopharmacological uses of the plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. DMFC anode polarization: Experimental analysis and model validation

    Energy Technology Data Exchange (ETDEWEB)

    Casalegno, A.; Marchesi, R. [Dipartimento di Energetica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2008-01-03

    Anode two-phase flow has an important influence on DMFC performance and methanol crossover. In order to elucidate two-phase flow influence on anode performance, in this work, anode polarization is investigated combining experimental and modelling approach. A systematic experimental analysis of operating conditions influence on anode polarization is presented. Hysteresis due to operating condition is observed; experimental results suggest that it arises from methanol accumulation and has to be considered in evaluating DMFC performances and measurements reproducibility. A model of DMFC anode polarization is presented and utilised as tool to investigate anode two-phase flow. The proposed analysis permits one to produce a confident interpretation of the main involved phenomena. In particular, it confirms that methanol electro-oxidation kinetics is weakly dependent on methanol concentration and that methanol transport in gas phase produces an important contribution in anode feeding. Moreover, it emphasises the possibility to optimise anode flow rate in order to improve DMFC performance and reduce methanol crossover. (author)

  1. Of mice and men: modelling post-stroke depression experimentally

    Science.gov (United States)

    Kronenberg, G; Gertz, K; Heinz, A; Endres, M

    2014-01-01

    At least one-third of stroke survivors suffer from depression. The development of comorbid depression after stroke is clinically highly significant because post-stroke depression is associated with increased mortality, slows recovery and leads to worse functional outcomes. Here, we review the evidence that post-stroke depression can be effectively modelled in experimental rodents via a variety of approaches. This opens an exciting new window onto the neurobiology of depression and permits probing potential underlying mechanisms such as disturbed cellular plasticity, neuroendocrine dysregulation, neuroinflammation, and neurodegeneration in a novel context. From the point of view of translational stroke research, extending the scope of experimental investigations beyond the study of short-term end points and, in particular, acute lesion size, may help improve the relevance of preclinical results to human disease. Furthermore, accumulating evidence from both clinical and experimental studies offers the tantalizing prospect of 5-hydroxytryptaminergic antidepressants as the first pharmacological therapy for stroke that would be available during the subacute and chronic phases of recovery. Interdisciplinary neuropsychiatric research will be called on to dissect the mechanisms underpinning the beneficial effects of antidepressants on stroke recovery. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24838087

  2. Analytical modeling and experimental characterization of chemotaxis in Serratia marcescens

    Science.gov (United States)

    Zhuang, Jiang; Wei, Guopeng; Wright Carlsen, Rika; Edwards, Matthew R.; Marculescu, Radu; Bogdan, Paul; Sitti, Metin

    2014-05-01

    This paper presents a modeling and experimental framework to characterize the chemotaxis of Serratia marcescens (S. marcescens) relying on two-dimensional and three-dimensional tracking of individual bacteria. Previous studies mainly characterized bacterial chemotaxis based on population density analysis. Instead, this study focuses on single-cell tracking and measuring the chemotactic drift velocity VC from the biased tumble rate of individual bacteria on exposure to a concentration gradient of l-aspartate. The chemotactic response of S. marcescens is quantified over a range of concentration gradients (10-3 to 5 mM/mm) and average concentrations (0.5×10-3 to 2.5 mM). Through the analysis of a large number of bacterial swimming trajectories, the tumble rate is found to have a significant bias with respect to the swimming direction. We also verify the relative gradient sensing mechanism in the chemotaxis of S. marcescens by measuring the change of VC with the average concentration and the gradient. The applied full pathway model with fitted parameters matches the experimental data. Finally, we show that our measurements based on individual bacteria lead to the determination of the motility coefficient μ (7.25×10-6 cm2/s) of a population. The experimental characterization and simulation results for the chemotaxis of this bacterial species contribute towards using S. marcescens in chemically controlled biohybrid systems.

  3. [Pathogenetic and clinical aspects of diisocyanate asthma].

    Science.gov (United States)

    Swierczyńska-Machura, Dominika; Pałczyński, Cezary

    2012-01-01

    Diisocyanates are currently the most common cause of occupational asthma in industrialized countries, where its prevalence ranges from less than 5% to 15%. They are mainly used in the production of polyurethane foam, plastic packagings, laminates and polyurethane paints. The diagnosis of diisocyanate asthma is often problematic due to the lack of simple diagnostic or screening tests, uncertainty of underlying mechanisms, and a multitude of other potential occupational and environmental causes of asthma. At present, only a specific standardized challenge test with diisocyanates in concentrations not exceeding the adopted hygiene standards has been found to show a real diagnostic value. The diisocyanate-inducedsensitization, is associated with the recruitment of CD4 T lymphocytes to the lungs and the production of Th2-type cytokines, including IL-4, IL-5 and IL-13. However, clinical studies have suggested that an immunological response to diisocyanates may involve both Th1 and Th2 cells. The development of animal models has been instrumental in furthering the understanding of the pathogenesis of many diseases, including bronchial asthma. Murine models of diisocyanate-induced asthma have proved to be the most useful. Mouse models offer distinct advantages of a better-defined genome than that of guinea pigs or rats and the availability of antibody reagents and transgenic strains to investigate detailed mechanistic pathways. A better understanding of the immunopathogenesis of diisocyanate asthma will hopefully lead to early markers of sensitization and asthma, as well as to a profound comprehension of exposure and host risk factors, both of them should greatly facilitate the development of much-needed diagnostic and preventive strategies for diisocyanate asthma.

  4. An experimental and modeling study of diethyl carbonate oxidation

    KAUST Repository

    Nakamura, Hisashi

    2015-04-01

    Diethyl carbonate (DEC) is an attractive biofuel that can be used to displace petroleum-derived diesel fuel, thereby reducing CO2 and particulate emissions from diesel engines. A better understanding of DEC combustion characteristics is needed to facilitate its use in internal combustion engines. Toward this goal, ignition delay times for DEC were measured at conditions relevant to internal combustion engines using a rapid compression machine (RCM) and a shock tube. The experimental conditions investigated covered a wide range of temperatures (660-1300K), a pressure of 30bar, and equivalence ratios of 0.5, 1.0 and 2.0 in air. To provide further understanding of the intermediates formed in DEC oxidation, species concentrations were measured in a jet-stirred reactor at 10atm over a temperature range of 500-1200K and at equivalence ratios of 0.5, 1.0 and 2.0. These experimental measurements were used to aid the development and validation of a chemical kinetic model for DEC.The experimental results for ignition in the RCM showed near negative temperature coefficient (NTC) behavior. Six-membered alkylperoxy radical (RO˙2) isomerizations are conventionally thought to initiate low-temperature branching reactions responsible for NTC behavior, but DEC has no such possible 6- and 7-membered ring isomerizations. However, its molecular structure allows for 5-, 8- and 9-membered ring RO˙2 isomerizations. To provide accurate rate constants for these ring structures, ab initio computations for RO˙2⇌Q˙OOH isomerization reactions were performed. These new RO˙2 isomerization rate constants have been implemented in a chemical kinetic model for DEC oxidation. The model simulations have been compared with ignition delay times measured in the RCM near the NTC region. Results of the simulation were also compared with experimental results for ignition in the high-temperature region and for species concentrations in the jet-stirred reactor. Chemical kinetic insights into the

  5. Experimental validation of Swy-2 clay standard's PHREEQC model

    Science.gov (United States)

    Szabó, Zsuzsanna; Hegyfalvi, Csaba; Freiler, Ágnes; Udvardi, Beatrix; Kónya, Péter; Székely, Edit; Falus, György

    2017-04-01

    One of the challenges of the present century is to limit the greenhouse gas emissions for the mitigation of climate change which is possible for example by a transitional technology, CCS (Carbon Capture and Storage) and, among others, by the increase of nuclear proportion in the energy mix. Clay minerals are considered to be responsible for the low permeability and sealing capacity of caprocks sealing off stored CO2 and they are also the main constituents of bentonite in high level radioactive waste disposal facilities. The understanding of clay behaviour in these deep geological environments is possible through laboratory batch experiments of well-known standards and coupled geochemical models. Such experimentally validated models are scarce even though they allow deriving more precise long-term predictions of mineral reactions and rock and bentonite degradation underground and, therefore, ensuring the safety of the above technologies and increase their public acceptance. This ongoing work aims to create a kinetic geochemical model of Na-montmorillonite standard Swy-2 in the widely used PHREEQC code, supported by solution and mineral composition results from batch experiments. Several four days experiments have been carried out in 1:35 rock:water ratio at atmospheric conditions, and with inert and CO2 supercritical phase at 100 bar and 80 ⁰C relevant for the potential Hungarian CO2 reservoir complex. Solution samples have been taken during and after experiments and their compositions were measured by ICP-OES. The treated solid phase has been analysed by XRD and ATR-FTIR and compared to in-parallel measured references (dried Swy-2). Kinetic geochemical modelling of the experimental conditions has been performed by PHREEQC version 3 using equations and kinetic rate parameters from the USGS report of Palandri and Kharaka (2004). The visualization of experimental and numerous modelling results has been automatized by R. Experiments and models show very fast

  6. Experimental validation of solid rocket motor damping models

    Science.gov (United States)

    Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

    2017-12-01

    In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe

  7. Experimental limits from ATLAS on Standard Model Higgs production.

    CERN Multimedia

    ATLAS, collaboration

    2012-01-01

    Experimental limits from ATLAS on Standard Model Higgs production in the mass range 110-600 GeV. The solid curve reflects the observed experimental limits for the production of a Higgs of each possible mass value (horizontal axis). The region for which the solid curve dips below the horizontal line at the value of 1 is excluded with a 95% confidence level (CL). The dashed curve shows the expected limit in the absence of the Higgs boson, based on simulations. The green and yellow bands correspond (respectively) to 68%, and 95% confidence level regions from the expected limits. Higgs masses in the narrow range 123-130 GeV are the only masses not excluded at 95% CL

  8. Experimentally supported mathematical modeling of continuous baking processes

    DEFF Research Database (Denmark)

    Stenby Andresen, Mette

    The scope of the PhD project was to increase knowledge on the process-to-product interactions in continuous tunnel ovens. The work has focused on five main objectives. These objectives cover development of new experimental equipment for pilot plant baking experiments, mathematical modeling of heat...... and mass transfer in a butter cookie product, and evaluation of quality assessment methods. The pilot plant oven is a special batch oven designed to emulate continuous convection tunnel oven baking. The design, construction, and validation of the oven has been part of the project and is described...... in this thesis. The oven was successfully validated against a 10 m tunnel oven. Besides the ability to emulate the baking conditions in a tunnel oven, the new batch oven is designed and constructed for experimental research work. In the design options to follow the product continuously (especially weight...

  9. Nitrosative events in atopic asthma pathogenesis

    Directory of Open Access Journals (Sweden)

    Parilova O. O.

    2015-12-01

    Full Text Available The correlation between high exhaled nitric oxide levels and eosinophilic-mediated airway inflammation in patients with atopic asthma has been well documented. This generates prerequisites that a regulatory feedback mechanism exists between them. Therefore, the paper briefly describes evidence implementing biosynthesis, enzyme structural features, expression regulation of its isoforms and effects of nitric oxide, which have helped elucidate molecular mechanisms by which nitric oxide selectively promotes asthma exacerbation. In previous study we have demonstrated that airway infiltrate of immune cells contributes to NO synthesis in the respiratory tract during allergic inflammation under guinea pig model of acute asthma with multiple challenges. On the basis of these findings the authors posits that nitric oxide represents an additional signal of the induction of Th2 subset response and be considerably involved in the complex network of immune regulation distinctive for atopic asthma phenotype.

  10. Nutrition and Asthma

    Directory of Open Access Journals (Sweden)

    Gupta K

    2007-01-01

    Full Text Available Increase in the asthma prevalence in many countries over the recent decades, highlights the need for a greater understanding of the risk factors for asthma. Be-cause asthma is the result of interaction between genetic and environmental fac-tors, increasing prevalence is certainly the result of changes in environmental fac-tors because of process of wesernization. That is the reason for higher prevalence in countries where a traditional to a westernized lifestyle occurred earlier. This increasing prevalence has affected both rural and urban communities, suggesting that local environmental factors such as exposure to allergens or industrial air pol-lutions are not the sole cause. In the last few years, nutrition has represented an important conditioning factor of many cardiovascular, gastrointestinal and chronic pulmonary diseases. So it has been hypothesized that dietary constituents influence the immune system and thus, may also be actively involved in the onset of asthma and other allergic diseases. Dietary constituents can play beneficial as well as det-rimental role in asthma. The possible role of diet in the development of asthma can be described as follows: first, a food allergen can cause asthma. Second, there is role of breast-feeding for prevention of asthma later in life. Third, a low intake of antioxidative dietary constituents might be a risk factor for asthma. Moreover, role of cations such as sodium, potassium and magnesium has been described in development of asthma. Finally, intake of fatty acids specially the role of omega-3 and omega-6 fatty acids play important role in cause of asthma.

  11. Continuum damage modeling through theoretical and experimental pressure limit formulas

    Directory of Open Access Journals (Sweden)

    Fatima Majid

    2018-01-01

    Full Text Available In this paper, we developed a mathematical modeling to represent the damage of thermoplastic pipes. On the one hand, we adapted the theories of the rupture pressure to fit the High Density Polyethylene (HDPE case. Indeed, the theories for calculating the rupture pressure are multiple, designed originally for steels and alloys. For polymer materials, we have found that these theories can be adapted using a coefficient related to the nature of the studied material. The HDPE is characterized by two important values of pressure, deduced from the ductile form of the internal pressures evolution until burst. For this reason, we have designed an alpha coefficient taking into account these two pressures and giving a good approximation of the evolution of the experimental burst pressures through the theoretically corrected ones, using Faupel㒒s pressure formula. Then, we can deduce the evolution of the theoretical damage using the calculated pressures. On the other hand, two other mathematical models were undertaken. The first one has given rise to an adaptive model referring to an expression of the pressure as a function of the life fraction, the characteristic pressures and the critical life fraction. The second model represents a continuum damage model incorporating the pressure equations as a function of the life fraction and based on the burst pressure�s static damage model. These models represent important tools for industrials to assess the failure of thermoplastic pipes and proceed quick checks

  12. Short note: the experimental geopotential model XGM2016

    Science.gov (United States)

    Pail, R.; Fecher, T.; Barnes, D.; Factor, J. F.; Holmes, S. A.; Gruber, T.; Zingerle, P.

    2017-10-01

    As a precursor study for the upcoming combined Earth Gravitational Model 2020 (EGM2020), the Experimental Gravity Field Model XGM2016, parameterized as a spherical harmonic series up to degree and order 719, is computed. XGM2016 shares the same combination methodology as its predecessor model GOCO05c (Fecher et al. in Surv Geophys 38(3): 571-590, 2017. doi: 10.1007/s10712-016-9406-y). The main difference between these models is that XGM2016 is supported by an improved terrestrial data set of 15^' × 15^' gravity anomaly area-means provided by the United States National Geospatial-Intelligence Agency (NGA), resulting in significant upgrades compared to existing combined gravity field models, especially in continental areas such as South America, Africa, parts of Asia, and Antarctica. A combination strategy of relative regional weighting provides for improved performance in near-coastal ocean regions, including regions where the altimetric data are mostly unchanged from previous models. Comparing cumulative height anomalies, from both EGM2008 and XGM2016 at degree/order 719, yields differences of 26 cm in Africa and 40 cm in South America. These differences result from including additional information of satellite data, as well as from the improved ground data in these regions. XGM2016 also yields a smoother Mean Dynamic Topography with significantly reduced artifacts, which indicates an improved modeling of the ocean areas.

  13. Experimental validation of mathematical model for small air compressor

    Directory of Open Access Journals (Sweden)

    Tuhovčák Ján

    2017-01-01

    Full Text Available Development process of reciprocating compressors can be simplified by using simulation tools. Modelling of a compressor requires a trade-off between computational effort and accuracy of desired results. This paper presents experimental validation of the simulation tool, which can be used to predict compressor behaviour under different working conditions. The mathematical model provides fast results with very good accuracy, however the model must be calibrated for a certain type of compressor. Small air compressor was used to validate an in-house simulation tool, which is based on mass and energy conservation in a control volume. The simulation tool calculates pressure and temperature history inside the cylinder, valve characteristics, mass flow and heat losses during the cycle of the compressor. A test bench for the compressor consisted of pressure sensors on both discharge and suction side, temperature sensor on discharge side and flow meter with calorimetric principle sensor.

  14. A two-Higgs-doublet model facing experimental hints

    Directory of Open Access Journals (Sweden)

    Crivellin Andreas

    2016-01-01

    Full Text Available Physics beyond the Standard Model has so far eluded our experimental probes. Nevertheless, a number of interesting anomalies have accumulated that can be taken as hints towards new physics: BaBar, Belle, and LHCb have found deviations of approximately 3:8σ in B → Dτν and B → D*τν; the anomalous magnetic moment of the muon differs by about 3σ from the theoretic prediction; the branching ratio for τ → μνν is about 2σ above the Standard Model expectation; and CMS and ATLAS found hints for a non-zero decay rate of h → μτ at 2.6σ. Here we consider these processes within a lepton-specific two-Higgs doublet model with additional non-standard Yukawa couplings and show how (and which of these excesses can be accommodated.

  15. Comparison of mixed layer models predictions with experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Faggian, P.; Riva, G.M. [CISE Spa, Divisione Ambiente, Segrate (Italy); Brusasca, G. [ENEL Spa, CRAM, Milano (Italy)

    1997-10-01

    The temporal evolution of the PBL vertical structure for a North Italian rural site, situated within relatively large agricultural fields and almost flat terrain, has been investigated during the period 22-28 June 1993 by experimental and modellistic point of view. In particular, the results about a sunny day (June 22) and a cloudy day (June 25) are presented in this paper. Three schemes to estimate mixing layer depth have been compared, i.e. Holzworth (1967), Carson (1973) and Gryning-Batchvarova models (1990), which use standard meteorological observations. To estimate their degree of accuracy, model outputs were analyzed considering radio-sounding meteorological profiles and stability atmospheric classification criteria. Besides, the mixed layer depths prediction were compared with the estimated values obtained by a simple box model, whose input requires hourly measures of air concentrations and ground flux of {sup 222}Rn. (LN)

  16. Asthma control and productivity loss in those with work-related asthma: A population-based study.

    Science.gov (United States)

    Wong, Alyson; Tavakoli, Hamid; Sadatsafavi, Mohsen; Carlsten, Chris; FitzGerald, J Mark

    2017-06-01

    In Canada, asthma is the third leading cause of work loss, yet little is known about the associated productivity loss. The goal of this study was to look at the relationship between asthma control and productivity loss, particularly contrasting those with work-related asthma (WRA) and non-work-related asthma (NWRA). A population-based random sample of adults with asthma in British Columbia, Canada, was prospectively recruited. Asthma control was graded according to Global Initiative for Asthma classification, while productivity loss and presence of WRA was assessed using questionnaires. Ordinal regression models were then used to associate WRA with asthma control. Generalized linear models were applied to estimate the average productivity loss associated with different levels of asthma control among those with WRA and NWRA. The study included 300 employed adults. Sixty (20%) had WRA. The odds of being controlled were significantly lower in those with WRA (OR = 0.23, 95% CI: 0.09, 0.56; P productivity loss due to presenteeism ($659.1 [95% CI: 12.9, 1581.5; P = 0.04]), but not absenteeism ($88.7 [95% CI: -86.5, 279.6; P = 0.35]), when compared to those with NWRA and uncontrolled asthma. There was no significant difference when a similar comparison was made for those with controlled or partially controlled asthma. WRA is associated with worse asthma control and increased productivity loss. Presenteeism makes a significant contribution to productivity loss and should be considered when evaluating the overall economic burden of asthma, particularly WRA.

  17. Behavior problems and prevalence of asthma symptoms among Brazilian children.

    Science.gov (United States)

    Feitosa, Caroline A; Santos, Darci N; Barreto do Carmo, Maria B; Santos, Letícia M; Teles, Carlos A S; Rodrigues, Laura C; Barreto, Mauricio L

    2011-09-01

    Asthma is the most common chronic disease in childhood and has been designated a public health problem due to the increase in its prevalence in recent decades, the amount of health service expenditure it absorbs and an absence of consensus about its etiology. The relationships among psychosocial factors and the occurrence, symptomatology, and severity of asthma have recently been considered. There is still controversy about the association between asthma and a child's mental health, since the pathways through which this relationship is established are complex and not well researched. This study aims to investigate whether behavior problems are associated with the prevalence of asthma symptoms in a large urban center in Latin America. It is a cross-section study of 869 children between 6 and 12 years old, residents of Salvador, Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC) instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior Checklist (CBCL) was employed to evaluate behavioral problems. 19.26% (n=212) of the children presented symptoms of asthma. 35% were classified as having clinical behavioral problems. Poisson's robust regression model demonstrated a statistically significant association between the presence of behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% CI: 1.10-1.85). These results suggest an association between behavioral problems and pediatric asthma, and support the inclusion of mental health care in the provision of services for asthma morbidity. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Evaluation of the effects of the family-centered empowerment model on the nutrition style and physical activity of patients with asthma

    Directory of Open Access Journals (Sweden)

    Gholam Hossein Mahmoudi Rad

    2016-02-01

    Full Text Available Background: As the most prevalent chronic disease, asthma is associated with restrictions in the diet and physical activity of the patients. Patient empowerment and family support are the methods of choice for adapting to these limitations. This study aimed to evaluate the effects of the family-centered empowerment model on the nutrition style and physical activity of asthmatic patients. Methods: This clinical trial was conducted on 70 patients with asthma referring to a hospital in Zabol, Iran in 2015. Samples were selected via randomized convenience sampling and divided into two groups of intervention and control. Family-centered empowerment model was implemented in the intervention group in five educational sessions (45 min each twice a week. Data were collected using a researcher-made nutritional assessment scale and Beck’s physical activity questionnaire during four stages before the intervention, as well as one week, one month and three months after the intervention. Data analysis was performed in SPSS version 16 using descriptive statistics, Chi-square, repeated measures ANOVA, Friedman’s test, independent t-test, and Mann-Whitney U test. Results: Mean score of nutrition style significantly increased from 44.59±2.43 to 26.74±6.25 in the intervention group after the training sessions (P<0.001. Moreover, a significant increase was observed in the mean score of physical activity after the intervention (24.06±3.27 compared to before the intervention (31.20±3.06 (P<0.001. This difference was significant between the groups, with the exception of a one-month interval after the intervention (P<0.05. Conclusion: According to the results of this study, implementation of the family-centered empowerment model significantly improved the nutrition style and physical activity of asthmatic patients. Therefore, it is recommended that this model be employed by nurses in different hospital wards.

  19. Evaluation of Algebraic Reynolds Stress Model Assumptions Using Experimental Data

    Science.gov (United States)

    Jyoti, B.; Ewing, D.; Matovic, D.

    1996-11-01

    The accuracy of Rodi's ASM assumption is examined by evaluating the terms in Reynolds stress transport equation and their modelled counterparts. The basic model assumption: Dτ_ij/Dt + partial T_ijl/partial xl = (τ_ij/k )(Dk/Dt + partial Tl /partial xl ) (Rodi( Rodi W., ZAMM.), 56, pp. 219-221, 1976.), can also be broken into two stronger assumptions: Da_ij/Dt = 0 and (2) partial T_ijl/partial xl = (τ_ij/k )(partial Tl /partial xl ) (e.g. Taulbee( Taulbee D. B., Phys. of Fluids), 4(11), pp. 2555-2561, 1992.). Fu et al( Fu S., Huang P.G., Launder B.E. & Leschziner M.A., J. Fluid Eng.), 110(2), pp. 216-221., 1988 examined the accuracy of Rodi's assumption using the results of RSM calculation of axisymmetric jets. Since the RSM results did not accurately predict the experimental results either, it may be useful to examine the basic ASM model assumptions using experimental data. The database of Hussein, Capp and George( Hussein H., Capp S. & George W., J.F.M.), 258, pp.31-75., 1994. is sufficiently detailed to evaluate the terms of Reynolds stress transport equations individually, thus allowing both Rodi's and the stronger assumptions to be tested. For this flow assumption (1) is well satisfied for all the components (including \\overlineuv); however, assumption (2) does not seem as well satisfied.

  20. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    Science.gov (United States)

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. Hepatoprotective activity of Musa paradisiaca on experimental animal models.

    Science.gov (United States)

    Nirmala, M; Girija, K; Lakshman, K; Divya, T

    2012-01-01

    To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

  2. A comprehensive experimental and modeling study of 2-methylbutanol combustion

    KAUST Repository

    Park, Sungwoo

    2015-05-01

    2-Methylbutanol (2-methyl-1-butanol) is one of several next-generation biofuels that can be used as an alternative fuel or blending component for combustion engines. This paper presents new experimental data for 2-methylbutanol, including ignition delay times in a high-pressure shock tube and premixed laminar flame speeds in a constant volume combustion vessel. Shock tube ignition delay times were measured for 2-methylbutanol/air mixtures at three equivalence ratios, temperatures ranging from 750 to 1250. K, and at nominal pressures near 20 and 40. bar. Laminar flame speed data were obtained using the spherically propagating premixed flame configuration at pressures of 1, 2, and 5. bar. A detailed chemical kinetic model for 2-methylbutanol oxidation was developed including high- and low-temperature chemistry based on previous modeling studies on butanol and pentanol isomers. The proposed model was tested against new and existing experimental data at pressures of 1-40. atm, temperatures of 740-1636. K, equivalence ratios of 0.25-2.0. Reaction path and sensitivity analyses were conducted for identifying key reactions at various combustion conditions, and to obtain better understanding of the combustion characteristics of larger alcohols.

  3. Inhibitory effect of Zanthoxylum bungeanum seed oil on ovalbumin‑induced lung inflammation in a murine model of asthma.

    Science.gov (United States)

    Wang, Jun-Qin; Li, Xiao-Wei; Liu, Mingyi; Wang, Sheng-Chun; Cao, Zeng-Fa

    2016-05-01

    The present study aimed to investigate the therapeutic efficacy of Zanthoxylum bungeanum seed oil (Z. seed oil) to alleviate airway inflammation in asthmatic mice. The asthmatic mice were treated with vehicle, ovalbumin (OVA), or OVA + Z. seed oil (2 g/kg) for between 24 h and 14 days. Following treatment, inflammatory cell infiltration and pulmonary tissue damage were assessed by hematoxylin and eosin staining, and immunohistochemistry. The expression levels of pro‑inflammatory cytokines, chemokines, adhesion molecules and mitogen activated protein kinase signaling proteins were measured by enzyme‑linked immunosorbent assays, reverse transcription quantitative‑polymerase chain reaction and western blot analysis. In asthmatic mice, administration of Z. seed oil attenuated lung tissue injury and airway remodeling, and inhibited the infiltration of leukocytes and eosinophils into the airway by reducing the expression levels of inflammatory cytokines and chemokines compared with OVA‑treated mice (P<0.05). Z. seed oil also reduced the levels of inflammatory chemokine and adhesion molecules via downregulation of extracellular signal‑regulated kinase and activation of c‑JUN N‑terminal kinase in the Z. seed‑treated mice compared with OVA‑treated mice (P<0.05). Thus, data from the present study indicates that Z. seed oil can suppress pulmonary inflammation and tissue injury during asthma, and suggests that it may be used to effectively treat allergen‑induced asthma.

  4. Elevated leukocyte phosphodiesterase as a basis for depressed cyclic adenosine monophosphate responses in the Basenji greyhound dog model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S.C.; Hanifin, J.M.; Holden, C.A.; Thompson, W.J.; Hirshman, C.A.

    1985-08-01

    The BG dog manifests various characteristics of human asthma, including airway hyperreactivity to low concentrations of methacholine. Studies have suggested that airway hyperreactivity in asthma is related to inadequate intracellular cAMP responses. The authors studied cAMP characteristics in MNL from 19 BG and 14 mongrel dogs. beta-Adrenergic receptors were assessed by /sup 125/I CYP in the presence and absence of propranolol. The responses of cAMP to ISO were measured by radioimmunoassay. Adenylate cyclase activity was determined in homogenized MNL preparations by cAMP generation. PDE activity was quantitated by radioenzyme assay. Mongrel dog leukocyte ISO-stimulated cAMP levels doubled, whereas there were negligible increases in MNL from BG dogs. Basal PDE levels were higher in BG dogs than in mongrel dogs. The PDE inhibitor Ro 20-1724 restored ISO-stimulated cAMP responses in MNL of BG dogs. Adenylate cyclase activity was not lower in MNL homogenates from BG dogs than in mongrel dogs. Cells from both BG and mongrel dogs demonstrated similar receptor numbers and affinities of saturable, specific beta-adrenergic binding over a 10 pM to 400 pM range. The results suggest that depressed cAMP responses in BG dogs are due to high PDE activity rather than to a defect in the beta-adrenergic receptor adenylate cyclase system.

  5. What is Asthma?

    Medline Plus

    Full Text Available ... Lung Association 104 COPD Awareness Month: Connecting with Social Support American Lung Association 105 Ohio Cares about ... 7:59 Asthma - Duration: 3:36. Nucleus Medical Media 658,979 views 3:36 What is asthma. ...

  6. Traveling and Asthma

    Science.gov (United States)

    ... Stress How Cliques Make Kids Feel Left Out Traveling and Asthma KidsHealth > For Kids > Traveling and Asthma Print A A A en español ... handy at all times. So if you're traveling by car, keep them where you can get ...

  7. A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ and Type 2 Inflammation (IL-5 and IL-13

    Directory of Open Access Journals (Sweden)

    Trevor T. Hansel

    2017-05-01

    Conclusions: Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation.

  8. Assessment of asthma control using asthma control test in chest ...

    African Journals Online (AJOL)

    ... CI 1.06-3.47) and obesity (OR 1.81; 1.01-3.27). Conclusion: Asthma remains poorly controlled in a large proportion of asthma patients under specialist care in Cameroon. Educational programs for asthma patients targeting women and based on weight loss for obese patients may help in improving the control of asthma.

  9. Advances in pediatric asthma in 2013: coordinating asthma care.

    Science.gov (United States)

    Szefler, Stanley J

    2014-03-01

    Last year's "Advances in pediatric asthma: moving toward asthma prevention" concluded that "We are well on our way to creating a pathway around wellness in asthma care and also to utilize new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma." This year's summary will focus on recent advances in pediatric asthma on prenatal and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding potential therapeutic targets for altering the course of asthma in children, as indicated in Journal of Allergy and Clinical Immunology publications in 2013 and early 2014. Recent reports continue to shed light on methods to understand factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention, as well as new immunomodulators. It will now be important to carefully assess risk factors for the development of asthma, as well as the risk for asthma exacerbations, and to improve the way we communicate this information in the health care system. This will allow parents, primary care physicians, specialists, and provider systems to more effectively intervene in altering the course of asthma and to further reduce asthma morbidity and mortality. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. Model reduction for experimental thermal characterization of a holding furnace

    Science.gov (United States)

    Loussouarn, Thomas; Maillet, Denis; Remy, Benjamin; Dan, Diane

    2017-09-01

    Vacuum holding induction furnaces are used for the manufacturing of turbine blades by loss wax foundry process. The control of solidification parameters is a key factor for the manufacturing of these parts. The definition of the structure of a reduced heat transfer model with experimental identification through an estimation of its parameters is required here. Internal sensors outputs, together with this model, can be used for assessing the thermal state of the furnace through an inverse approach, for a better control. Here, an axisymmetric furnace and its load have been numerically modelled using FlexPDE, a finite elements code. The internal induction heat source as well as the transient radiative transfer inside the furnace are calculated through this detailed model. A reduced lumped body model has been constructed to represent the numerical furnace. The model reduction and the estimation of the parameters of the lumped body have been made using a Levenberg-Marquardt least squares minimization algorithm, using two synthetic temperature signals with a further validation test.

  11. Experimental models of sepsis and septic shock: an overview

    Directory of Open Access Journals (Sweden)

    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  12. Effects of pediatric asthma care coordination in underserved communities on parent perceptions of care and asthma-management confidence.

    Science.gov (United States)

    Janevic, Mary R; Baptist, Alan P; Bryant-Stephens, Tyra; Lara, Marielena; Persky, Victoria; Ramos-Valencia, Gilberto; Uyeda, Kimberly; Hazan, Rebecca; Garrity, Ashley; Malveaux, Floyd J

    2017-06-01

    Disparities by race and socioeconomic status persist in pediatric asthma morbidity, mortality, and treatment. Improving parent/provider communication and parents' asthma-management confidence may result in better asthma control in vulnerable populations. The Merck Childhood Asthma Network, Inc. funded an initiative to implement medical-social care coordination to improve asthma outcomes at sites in four low-income, urban communities (Los Angeles, CA; Philadelphia, PA; Chicago, IL; and San Juan, PR.) As part of a cross-site evaluation of this effort, pre- post-program changes in parents' reports of asthma care and management were assessed. Across sites, 805 parents or other caregivers responded to a baseline survey that was repeated one year later following their child's participation in care coordination. Parents' asthma-management confidence, as well as their perceptions of provider access, trust, and communication, were measured with Likert scales. Linear mixed models were used to assess improvement in these variables, across and within sites, adjusting for sociodemographics. Pooled across sites, the adjusted mean estimate for all outcomes showed a significant improvement (p asthma care coordination, as implemented variously in diverse settings, was associated with improvement in parents' perceptions of asthma care and self-reported asthma-management knowledge and confidence. This positive impact on parents may help sustain care coordination's impact on children.

  13. CFD Modeling and Experimental Validation of a Solar Still

    Directory of Open Access Journals (Sweden)

    Mahmood Tahir

    2017-01-01

    Full Text Available Earth is the densest planet of the solar system with total area of 510.072 million square Km. Over 71.68% of this area is covered with water leaving a scant area of 28.32% for human to inhabit. The fresh water accounts for only 2.5% of the total volume and the rest is the brackish water. Presently, the world is facing chief problem of lack of potable water. This issue can be addressed by converting brackish water into potable through a solar distillation process and solar still is specially assigned for this purpose. Efficiency of a solar still explicitly depends on its design parameters, such as wall material, chamber depth, width and slope of the zcondensing surface. This study was aimed at investigating the solar still parameters using CFD modeling and experimental validation. The simulation data of ANSYS-FLUENT was compared with actual experimental data. A close agreement among the simulated and experimental results was seen in the presented work. It reveals that ANSYS-FLUENT is a potent tool to analyse the efficiency of the new designs of the solar distillation systems.

  14. Experimental model for creation of carotid artery aneurysms in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hyun; Han, Moon Hee; Yu, In Kyu; Lee, Sang Hyun; Chang, Kee Hyun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-11-01

    To describe the detailed technique for producing experimental carotid aneurysms in dogs and the success rate, cause of failure and remedy, based on our experience. Fourteen male dogs weighing 12-15kg were anesthetized with inhalation of 1-2% halothane and 50% nitrous oxide. Each surgical procedure was performed under sterile condition with the aid of an operating microscope. A paramidline incision 7-8cm in length was made parallel to and medial to the external jugular vein in the dog's neck. The external jugular vein was harvested as a 1cm vein pouch by ligation and division of the proximal and distal ends. The ipsilateral common carotid artery was exposed and clamped at both ends by a vascular clamp. A 5-mm long elliptical arteriotomy was made at the mid portion of the artery, and then end to side anastomosis between the artery and vein sac was performed by using interrupted 7-0 monofilament prolene sutures. Carotid arteriography or Doppler sonography was performed 1-6 weeks after aneurysm construction. Twenty experimental aneurysms were constructed, and 17 aneurysms were patent on follow up study, but one dog with two aneurysms died from hemorrhagic pneumonia 17 days after surgery. The overall patency rate was 75%. We demonstrated the feasibility of creating experimental aneurysm models in the dog and expect that the technique presented will help to avoid failure in the construction of aneurysms.

  15. Plasma transferred arc welding—modeling and experimental optimization

    Science.gov (United States)

    Wilden, J.; Bergmann, J. P.; Frank, H.

    2006-12-01

    Plasma transferred arc (PTA) welded coatings are used to improve surface properties of mechanical parts. Advantages are the high reliability of the process and the low dilution of substrate and coating material. Processing of surfaces by PTA welding is restricted at the time to flat horizontal position. Furthermore, industry is interested in the development of strategies for coating with PTA in constraint position as complex three-dimensional (3D) parts could be then easily processed as well. Under commercial aspects, the process design can be optimized to increase process efficiency and to reduce heat input during the welding process. Process optimization involves the determination of guidelines for PTA welding in constraint positions as well. Modeling the process gives an alternative to reduce the experimental effort to optimize the welding process. Results of simulation studies of the PTA welding process are given in the present work. It will be shown that coating conditions can be optimized by varying plasma gas flow, heat input and heat flow, process speed, or powder injection with regard to welding in constraint positions. The defined controlling of the PTA welding allows modification of process management with less experimental effort and to develop coating strategies for processing in different positions. In experimental investigations, the developed coating strategies are confirmed by producing PTA coatings in constraint position as well as complex 3D parts.

  16. Diurnal temperature range and childhood asthma: a time-series study

    OpenAIRE

    Xu, Zhiwei; Huang, Cunrui; SU, HONG; Turner, Lyle R.; Qiao, Zhen; Tong, Shilu

    2013-01-01

    Background Hot and cold temperatures have been associated with childhood asthma. However, the relationship between daily temperature variation and childhood asthma is not well understood. This study aimed to examine the relationship between diurnal temperature range (DTR) and childhood asthma. Methods A Poisson generalized linear model combined with a distributed lag non-linear model was used to examine the relationship between DTR and emergency department admissions for childhood asthma in B...

  17. Genetics of asthma

    DEFF Research Database (Denmark)

    Thomsen, Simon F

    2015-01-01

    Asthma runs in families, and children of asthmatic parents are at increased risk of asthma. Prediction of disease risk is pivotal for the clinician when counselling atopic families. However, this is not always an easy task bearing in mind the vast and ever-increasing knowledge about asthma genetics....... The advent of new genotyping technologies has made it possible to sequence in great detail the human genome for asthma-associated variants, and accordingly, recent decades have witnessed an explosion in the number of rare and common variants associated with disease risk. This review presents an overview...... of methods and advances in asthma genetics in an attempt to help the clinician keep track of the most important knowledge in the field....

  18. Fertility outcomes in asthma

    DEFF Research Database (Denmark)

    Gade, Elisabeth Juul; Thomsen, Simon Francis; Lindenberg, Svend

    2016-01-01

    of fertility treatments, and the number of successful pregnancies differ significantly between women with unexplained infertility with and without asthma.245 women with unexplained infertility (aged 23-45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. 96...... women entering the study had either a former doctor's diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended.The likelihood...... pregnancies during fertility treatment, 39.6 versus 60.4% (p=0.002). Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women (interaction between age and asthma on time to pregnancy, p=0.001). Female asthmatics had a longer time to pregnancy and less often...

  19. Risk Assessment and Community Participation Model for Environmental Asthma Management in an Elementary Public School: A Case Study in Puerto Rico

    OpenAIRE

    Alberto Rivera-Rentas; Samarys Seguinot-Medina

    2006-01-01

    Asthma is a rapidly growing chronic disease in the general population of the world, mostly in children. Puerto Ricans have the highest prevalence of children with asthma among the Hispanic community in the US and its territories. Asthma and air quality are becoming a significant and potentially costly public health issue in Puerto Rico. The CDC has reported that in Puerto Rico, 320,350 adults have asthma and this number represents 11.5% of the island adult population. The north east municipal...

  20. An efficient approach to bioconversion kinetic model generation based on automated microscale experimentation integrated with model driven experimental design

    DEFF Research Database (Denmark)

    Chen, B. H.; Micheletti, M.; Baganz, F.

    2009-01-01

    design. It incorporates a model driven approach to the experimental design that minimises the number of experiments to be performed, while still generating accurate values of kinetic parameters. The approach has been illustrated with the transketolase mediated asymmetric synthesis of L......Reliable models of enzyme kinetics are required for the effective design of bioconversion processes. Kinetic expressions of the enzyme-catalysed reaction rate however, are frequently complex and establishing accurate values of kinetic parameters normally requires a large number of experiments....... These can be both time consuming and expensive when working with the types of non-natural chiral intermediates important in pharmaceutical syntheses. This paper presents ail automated microscale approach to the rapid and cost effective generation of reliable kinetic models useful for bioconversion process...

  1. Relationships among obesity, physical activity and sedentary behavior in young adolescents with and without lifetime asthma.

    Science.gov (United States)

    Groth, Susan W; Rhee, Hyekyun; Kitzman, Harriet

    2016-01-01

    To examine the inter-relationships among body mass index (BMI), physical activity, sedentary behavior and gender in urban, low-income, primarily African American young adolescents with or without lifetime asthma. Data were collected in 2002-2004 from 626 12-year old adolescents who were children of women who participated in the New Mother's Study in Memphis, TN (1990-1991). Adolescents with and without asthma were compared on BMI, physical activity and sedentary behavior. Multiple linear regression models were used to examine the association of asthma, gender and BMI with physical activity and sedentary behavior. Complete data were available for 545 adolescents. Eleven percent of adolescents had lifetime asthma. Asthma and gender were associated with high-intensity physical activity (p asthma participated in less physical activity and girls participated less than boys. Gender was associated with sedentary behavior (p asthma had a higher BMI than girls without asthma (p = 0.027). Boys with asthma were less physically active than boys without asthma (p asthma are less physically active than those without asthma and girls are less active than boys. Clinicians who provide care for adolescents with asthma are encouraged to assess physical activity/sedentary behavior and provide guidance that promotes active lifestyles. A longitudinal study is needed to shed light on the unique contribution of asthma separated from the effects of overweight/obesity on physical activity and sedentary behaviors.

  2. A DIDATIC EXPERIENCE IN BIOCHEMISTRY LABWORKS: THEORETICALVERSUS EXPERIMENTAL MODEL

    Directory of Open Access Journals (Sweden)

    B.C Rossi-Rodrigues

    2008-05-01

    Full Text Available Biochemistry labworks are fundamental to both the instrumentation and  for  the  establishment of important concepts. The labworks of Basic  Biochemistry  (BB280 for Biology students at UNICAMP have gone through several  improvements. The labworks are  now  structured  from simple  activities to more complex ones, and aimed  to  the student’s  autonomy  development  in the experiments planning and execution  over  the teaching  semester. The first practical activity is on buffer systems, and   it is based  on  the confrontation of a theoretical model with the  lab experiments results.  First of all, the students  simulate  a Titration  in  a computational environment, where students lay a theoretical model from their knowledge. In the theoretical model the buffer parameters are set according to the teacher instructions, and the experiment conditions are also set and tested.  The simulation results are used for planning  the experiment and to compare with the experimental ones.  After having the simulations concluded and having the experiment planned the students  perform  the  in lab  Titration with the parameters established in the simulation. The results obtained by students are presented in a report. We analyzed the reports from 76 BB280’s students in 2007(night class and day class. The students identified as the main causes of the discrepancy between theoretical and experimental data: 1 experimental errors, related to the lack of technical skill 2 limitation of equipment used 3 unexpected behavior of the substances  used. In addition to the theoretical content related to  labwork, the confrontation between the  simulation and experimentation provided the students with ability  to identify the main aspects of which can influence the quality of the data obtained.

  3. Astrocyte regulation of sleep circuits: experimental and modeling perspectives

    Directory of Open Access Journals (Sweden)

    Tommaso eFellin

    2012-08-01

    Full Text Available Integrated within neural circuits, astrocytes have recently been shown to modulate brain rhythms thought to mediate sleep function. Experimental evidence suggests that local impact of astrocytes on single synapses translates into global modulation of neuronal networks and behavior. We discuss these findings in the context of current conceptual models of sleep generation and function, each of which have historically focused on neural mechanisms. We highlight the implications and the challenges introduced by these results from a conceptual and computational perspective. We further provide modeling directions on how these data might extend our knowledge of astrocytic properties and sleep function. Given our evolving understanding of how local cellular activities during sleep lead to functional outcomes for the brain, further mechanistic and theoretical understanding of astrocytic contribution to these dynamics will undoubtedly be of great basic and translational benefit.

  4. An experimental and modeling study of n-octanol combustion

    KAUST Repository

    Cai, Liming

    2015-01-01

    This study presents the first investigation on the combustion chemistry of n-octanol, a long chain alcohol. Ignition delay times were determined experimentally in a high-pressure shock tube, and stable species concentration profiles were obtained in a jet stirred reactor for a range of initial conditions. A detailed kinetic model was developed to describe the oxidation of n-octanol at both low and high temperatures, and the model shows good agreement with the present dataset. The fuel\\'s combustion characteristics are compared to those of n-alkanes and to short chain alcohols to illustrate the effects of the hydroxyl moiety and the carbon chain length on important combustion properties. Finally, the results are discussed in detail. © 2014 The Combustion Institute.

  5. Experimental studies and modeling on concentration polarization in forward osmosis.

    Science.gov (United States)

    Qin, Jian-Jun; Chen, Sijie; Oo, Maung Htun; Kekre, Kiran A; Cornelissen, Emile R; Ruiken, Chris J

    2010-01-01

    Concentration polarization (CP) is an important issue in forward osmosis (FO) processes and it is believed that the coupled effect of dilutive internal CP (DICP) and concentrative external CP (CECP) limits FO flux. The objective of this study was to distinguish individual contribution of different types of DICP and CECP via modeling and to validate it by pilot studies. The influence of DICP/CECP on FO flux has been investigated in this study. The CP model presented in this work was derived from a previous study and evaluated by bench-scale FO experiments. Experiments were conducted with drinking water as the feed and NaCl/MgSO(4) as draw solutions at different concentrations and velocities. Modeling results indicated that DICP contributed to a flux reduction by 99.9% for 0.5 M NaCl as a draw solution although the flow pattern of both feed and draw solutions was turbulent. DICP could be improved via selection of the draw solution. The modeling results were well fit with the experimental data. It was concluded that the model could be used for selection of the draw solution and prediction of water flux under similar situation. A draw solution with greater diffusion coefficient or a thinner substrate of an asymmetric FO membrane resulted in a higher flux.

  6. Immunology and Homeopathy. 3. Experimental Studies on Animal Models

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2006-01-01

    Full Text Available A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials.

  7. Maternal hypothyroidism: An overview of current experimental models.

    Science.gov (United States)

    Ghanbari, Mahboubeh; Ghasemi, Asghar

    2017-10-15