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Sheep lung airway

Yanan Li, Zhongjia Jiang, Di Xue, Guangcun Deng, Min Li, Xiaoming Liu, Yujiong Wang
BACKGROUND: Mycoplasma ovipneumoniae (M. ovipneumoniae) is a species of Mycoplasma bacteria that specifically infects sheep and goat, causing ovine infectious pleuropneumonia. However, the mechanism underlying the pathogen-host interaction between M. ovipneumoniae and airway epithelial cells is unknown. METHODS: A primary air-liquid interface (ALI) epithelial culture model generated from the bronchial epithelial cells of Ningxia Tan sheep (ovis aries) was employed to explore the potential mechanism of M...
2016: BMC Microbiology
Rebecca Y Petersen, Emily Royse, Matthew W Kemp, Yuichiro Miura, Andres Noe, Alan H Jobe, Noah H Hillman
BACKGROUND: Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. OBJECTIVE: To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. METHODS: The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized...
2016: PloS One
Nicole Deptula, Emily Royse, Matthew W Kemp, Yuichiro Miura, Suhas G Kallapur, Alan H Jobe, Noah H Hillman
Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Joanne Van der Velden, Louise M Harkness, Donna M Barker, Garry J Barcham, Cathryn L Ugalde, Emmanuel Koumoundouros, Heidi Bao, Louise A Organ, Ana Tokanovic, Janette K Burgess, Kenneth J Snibson
Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep...
2016: Scientific Reports
Lauren E McClain, Marcus G Davey, Phillip W Zoltick, Maria P Limberis, Alan W Flake, William H Peranteau
PURPOSE: Successful in utero or perinatal gene therapy for congenital lung diseases, such as cystic fibrosis and surfactant protein deficiency, requires identifying clinically relevant viral vectors that efficiently transduce airway epithelial cells. The purpose of the current preclinical large animal study was to evaluate lung epithelium transduction of adeno-associated viral (AAV) vector serotypes following intratracheal delivery. METHODS: Six different AAV vector serotypes (AAV1, AAV5, AAV6, AAV8, AAV9, and AAVrh10) expressing the green fluorescent protein (GFP) as the transgene were injected into the right upper lobe of perinatal sheep via bronchoscopy...
June 2016: Journal of Pediatric Surgery
Laura Glendinning, Steven Wright, Jolinda Pollock, Peter Tennant, David Collie, Gerry McLachlan
UNLABELLED: Sequencing technologies have recently facilitated the characterization of bacterial communities present in lungs during health and disease. However, there is currently a dearth of information concerning the variability of such data in health both between and within subjects. This study seeks to examine such variability using healthy adult sheep as our model system. Protected specimen brush samples were collected from three spatially disparate segmental bronchi of six adult sheep (age, 20 months) on three occasions (day 0, 1 month, and 3 months)...
June 1, 2016: Applied and Environmental Microbiology
Erin V McGillick, Sandra Orgeig, Janna L Morrison
Inhibition of hypoxia signalling leads to respiratory distress syndrome (RDS), whereas administration of vascular endothelial growth factor (VEGF), the most widely characterized hypoxia responsive factor, protects from RDS. In the lung of the chronically hypoxaemic placentally restricted (PR) fetus, there is altered regulation of hypoxia signalling. This leads to reduced surfactant maturation in late gestation and provides evidence for the increased risk of RDS in growth restricted neonates at birth. We evaluated the effect of recombinant human VEGF administration with respect to bypassing the endogenous regulation of hypoxia signalling in the lung of the normally grown and PR sheep fetus...
March 1, 2016: Journal of Physiology
Bahar Liravi, David Piedrafita, Gary Nguyen, Robert J Bischof
BACKGROUND: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma...
2015: BMC Pulmonary Medicine
Vicki L Clifton, Timothy J M Moss, Amy L Wooldridge, Kathryn L Gatford, Bahar Liravi, Dasom Kim, Beverly S Muhlhausler, Janna L Morrison, Andrew Davies, Robert De Matteo, Megan J Wallace, Robert J Bischof
Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation...
March 1, 2016: Journal of Physiology
Alan W Cuthbert, Meena Murthy, Alexander P S Darlington
The mechanisms that lay behind the low-level secretions from airway submucosal glands and the surface epithelium in the absence of external innervation have been investigated in small areas (1.0-1.5 cm(2)) of mucosa from sheep tracheas, freshly collected from a local abattoir. Glandular secretion was measured by an optical method while short circuit current was used as a measure of surface secretion. Activation of neurones in the intrinsic nerve net by veratrine alkaloids caused an immediate increase in both glandular secretion and short circuit current, both effects being blocked by the addition of tetrodotoxin...
June 2015: Physiological Reports
K J Coote, D Paisley, S Czarnecki, M Tweed, H Watson, A Young, R Sugar, M Vyas, N J Smith, U Baettig, P J Groot-Kormelink, M Gosling, R Lock, B Ethell, G Williams, A Schumacher, J Harris, W M Abraham, J Sabater, C T Poll, T Faller, S P Collingwood, H Danahay
BACKGROUND AND PURPOSE: Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia...
June 2015: British Journal of Pharmacology
Tamer Y El Mays, Parichita Choudhury, Richard Leigh, Emmanuel Koumoundouros, Joanne Van der Velden, Grishma Shrestha, Cora A Pieron, John H Dennis, Francis Hy Green, Ken J Snibson
BACKGROUND: The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle...
2014: Respiratory Research
Lukas Stulik, Stefan Malafa, Jana Hudcova, Harald Rouha, Bence Z Henics, Donald E Craven, Agnes M Sonnevend, Eszter Nagy
RATIONALE: Colonization of lower airways by Staphylococcus aureus is a risk factor for the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). However, little is known about the virulence factors of methicillin-sensitive and -resistant S. aureus (MSSA and MRSA) that may influence host colonization and progression to VAT and VAP. OBJECTIVES: We evaluated MRSA and MSSA endotracheal aspirates (ETA) for genotype and α-hemolysin activity in relation to the development of VAT and VAP...
November 15, 2014: American Journal of Respiratory and Critical Care Medicine
Songqiao Liu, Yingzi Huang, Maohua Wang, Qiuhua Chen, Ling Liu, Jianfeng Xie, Li Tan, Fengmei Guo, Congshan Yang, Chun Pan, Yi Yang, Haibo Qiu
BACKGROUND: High-frequency oscillatory ventilation (HFOV) allows for small tidal volumes at mean airway pressures (mPaw) above that of conventional mechanical ventilation (CMV), but the effect of HFOV on hemodynamics, oxygen metabolism, and tissue perfusion in acute respiratory distress syndrome (ARDS) remains unclear. We investigated the effects of HFOV and CMV in sheep models with ARDS. METHODS: After inducing ARDS by repeated lavage, twelve adult sheep were randomly divided into a HFOV or CMV group...
2014: Chinese Medical Journal
Verena A Lambermont, Marco Schlepütz, Constanze Dassow, Peter König, Luc J Zimmermann, Stefan Uhlig, Boris W Kramer, Christian Martin
BACKGROUND: Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages. METHODS: Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months...
2014: PloS One
Anushi E Rajapaksa, Jenny J Ho, Aisha Qi, Rob Bischof, Tri-Hung Nguyen, Michelle Tate, David Piedrafita, Michelle P McIntosh, Leslie Y Yeo, Els Meeusen, Ross L Coppel, James R Friend
BACKGROUND: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization...
2014: Respiratory Research
Gianluigi Li Bassi, Montserrat Rigol, Joan-Daniel Marti, Lina Saucedo, Otavio T Ranzani, Ignasi Roca, Maria Cabanas, Laura Muñoz, Valeria Giunta, Nestor Luque, Mariano Rinaudo, Mariano Esperatti, Laia Fernandez-Barat, Miquel Ferrer, Jordi Vila, Jose Ramirez, Antoni Torres
BACKGROUND: Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa...
May 2014: Anesthesiology
Emanuela Zannin, Maria Luisa Ventura, Raffaele L Dellacà, Miria Natile, Paolo Tagliabue, Elizabeth J Perkins, Magdy Sourial, Risha Bhatia, Peter A Dargaville, David G Tingay
BACKGROUND: The aims of the present study were (i) to characterize the relationship between mean airway pressure (PAW) and reactance measured at 5 Hz (reactance of the respiratory system (X RS), forced oscillation technique) and (ii) to compare optimal PAW (P opt) defined by X RS, oxygenation, lung volume (VL), and tidal volume (VT) in preterm lambs receiving high-frequency oscillatory ventilation (HFOV). METHODS: Nine 132-d gestation lambs were commenced on HFOV at PAW of 14 cmH2O (P start)...
April 2014: Pediatric Research
Matthias Lange, Robert A Cox, Daniel L Traber, Atsumori Hamahata, Yoshimitsu Nakano, Lillian D Traber, Perenlei Enkhbaatar
Fire victims often suffer from burn injury and concomitant inhalation trauma, the latter significantly contributing to the morbidity and mortality in these patients. Measurement of blood carboxyhemoglobin levels has been proposed as a diagnostic marker to verify and, perhaps, quantify the degree of lung injury following inhalation trauma. However, this correlation has not yet been sufficiently validated. A total of 77 chronically instrumented sheep received sham injury, smoke inhalation injury, or combined burn and inhalation trauma following an established protocol...
April 2014: Experimental Lung Research
Fabienne Archer, Alain Abi-Rizk, Sophie Desloire, Christine Dolmazon, Barbara Gineys, François Guiguen, Vincent Cottin, Jean-François Mornex, Caroline Leroux
BACKGROUND: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. RESULTS: Lung cells were studied using immunohistochemistry on frozen sections of the lung...
2013: BMC Veterinary Research
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