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Interstitial lung disease animal model

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https://www.readbyqxmd.com/read/28804709/exploring-animal-models-that-resemble-idiopathic-pulmonary-fibrosis
#1
REVIEW
Jun Tashiro, Gustavo A Rubio, Andrew H Limper, Kurt Williams, Sharon J Elliot, Ioanna Ninou, Vassilis Aidinis, Argyrios Tzouvelekis, Marilyn K Glassberg
Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#2
Jhon Cores, M Taylor Hensley, Kathryn Kinlaw, S Michaela Rikard, Phuong-Uyen Dinh, Dipti Paudel, Junnan Tang, Adam C Vandergriff, Tyler A Allen, Yazhou Li, Jianhua Liu, Bo Niu, Yuepeng Chi, Thomas Caranasos, Leonard J Lobo, Ke Cheng
Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells...
August 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28777013/investigational-drugs-for-idiopathic-pulmonary-fibrosis
#3
Francesco Varone, Giuliano Montemurro, Francesco Macagno, Mariarosaria Calvello, Emanuele Conte, Enrica Intini, Bruno Iovene, Paolo Maria Leone, Pier-Valerio Mari, Luca Richeldi
IPF is a specific form of chronic fibrosing interstitial pneumonia of unknown cause, characterized by progressive worsening in lung function and an unfavorable prognosis. Current concepts on IPF pathogenesis are based on a dysregulated wound healing response, leading to an over production of extracellular matrix. Based on recent research however, several other mechanisms are now proposed as potential targets for novel therapeutic strategies. Areas covered: This review analyzes the current investigational strategies targeting extracellular matrix deposition, tyrosine-kinase antagonism, immune and autoimmune response, and cell-based therapy...
August 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28648837/integrative-characterization-of-chronic-cigarette-smoke-induced-cardiopulmonary-comorbidities-in-a-mouse-model
#4
Ágnes Kemény, Kata Csekő, István Szitter, Zoltán V Varga, Péter Bencsik, Krisztina Kiss, Róbert Halmosi, László Deres, Krisztián Erős, Anikó Perkecz, László Kereskai, Terézia László, Tamás Kiss, Péter Ferdinandy, Zsuzsanna Helyes
Cigarette smoke-triggered inflammatory cascades and consequent tissue damage are the main causes of chronic obstructive pulmonary disease (COPD). There is no effective therapy and the key mediators of COPD are not identified due to the lack of translational animal models with complex characterization. This integrative chronic study investigated cardiopulmonary pathophysiological alterations and mechanisms with functional, morphological and biochemical techniques in a 6-month-long cigarette smoke exposure mouse model...
June 22, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28619133/equine-herpesvirus-type-1-induces-both-neurological-and-respiratory-disease-in-syrian-hamsters
#5
Leonardo Pereira Mesquita, Andressa Ferrari Arévalo, Dennis A Zanatto, Samantha Ive Miyashiro, Elenice Maria Sequetin Cunha, Maria do Carmo Custódio de Souza, Eliana Monteforte Cassaro Villalobos, Cláudia Madalena Cabrera Mori, Paulo César Maiorka, Enio Mori
The equine herpesvirus type 1 (EHV-1) is an important cause of myeloencephalopathy and respiratory disease in horses. Animal models for EHV-1 infection have been specially developed using mice and Syrian hamsters (Mesocricetus auratus). However, few studies have attempted to evaluate the pathogenesis of EHV-1 infection in the central nervous system (CNS) and respiratory system of hamsters. Therefore, the aim of this study was to evaluate the pathogenesis of four Brazilian EHV-1 strains within the CNS and lungs of Syrian hamsters...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28500078/a-time-and-compartment-specific-activation-of-lung-macrophages-in-hypoxic-pulmonary-hypertension
#6
Steven C Pugliese, Sushil Kumar, William J Janssen, Brian B Graham, Maria G Frid, Suzette R Riddle, Karim C El Kasmi, Kurt R Stenmark
Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28499635/adenosine-a2a-receptors-are-up-regulated-and-control-the-activation-of-human-alveolar-macrophages
#7
Tiago M Alfaro, Diana I Rodrigues, Ângelo R Tomé, Rodrigo A Cunha, Carlos Robalo Cordeiro
Chronic inflammatory lung diseases remain a health concern and new anti-inflammatory treatments are needed. Targeting adenosine A2A receptors (A2AR) affords robust anti-inflammatory effects in animal models, but the translation of this promising strategy to humans has been challenging, possibly due to interspecies differences in receptor distribution and effects. Thus, we now assessed the efficiency of a selective A2AR agonist to control the activation of fresh human alveolar inflammatory cells. We collected bronchoalveolar lavage fluid from patients with interstitial lung disease and loaded alveolar cells with the intracellular free calcium probe FURA-2/AM...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28456608/chronic-intermittent-hypoxia-worsens-bleomycin-induced-lung-fibrosis-in-rats
#8
Rudolf K Braun, Oleg Broytman, Felix M Braun, Jacqueline A Brinkman, Andrew Clithero, Dhruvangkumar Modi, David F Pegelow, Marlowe Eldridge, Mihaela Teodorescu
Obstructive sleep apnea (OSA) has been linked to increased mortality in pulmonary fibrosis. Its key feature, chronic intermittent hypoxia (CIH), can lead to oxidative stress and inflammation, known to lead to fibrotic pathology in other organs. We tested the effects of CIH in an animal model of bleomycin-induced lung fibrosis. Sprague Dawley rats were instilled intratracheally with bleomycin (Blm) or saline (Sal), and exposed to CIH or normal air (Norm) for 9 or 30 days. Pulmonary function was tested and lungs were harvested for histological and molecular analyses...
April 27, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28438110/temporal-progression-of-lesions-in-guinea-pigs-infected-with-lassa-virus
#9
T M Bell, C I Shaia, J J Bearss, M E Mattix, K A Koistinen, S P Honnold, X Zeng, C D Blancett, G C Donnelly, J D Shamblin, E R Wilkinson, K A Cashman
Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28298912/heterologous-matrix-metalloproteinase-gene-promoter-activity-allows-in-vivo-real-time-imaging-of-bleomycin-induced-lung-fibrosis-in-transiently-transgenized-mice
#10
Fabio Franco Stellari, Francesca Ruscitti, Daniela Pompilio, Francesca Ravanetti, Giulia Tebaldi, Francesca Macchi, Andrea Elizabeth Verna, Gino Villetti, Gaetano Donofrio
Idiopathic pulmonary fibrosis is a very common interstitial lung disease derived from chronic inflammatory insults, characterized by massive scar tissue deposition that causes the progressive loss of lung function and subsequent death for respiratory failure. Bleomycin is used as the standard agent to induce experimental pulmonary fibrosis in animal models for the study of its pathogenesis. However, to visualize the establishment of lung fibrosis after treatment, the animal sacrifice is necessary. Thus, the aim of this study was to avoid this limitation by using an innovative approach based on a double bleomycin treatment protocol, along with the in vivo images analysis of bleomycin-treated mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202030/upregulation-of-interleukin-33-and-thymic-stromal-lymphopoietin-levels-in-the-lungs-of-idiopathic-pulmonary-fibrosis
#11
Jong-Uk Lee, Hun Soo Chang, Hyeon Ju Lee, Chang An Jung, Da Jeong Bae, Hyun Ji Song, Jong Sook Park, Soo-Taek Uh, Young Hoon Kim, Ki-Hyun Seo, Choon-Sik Park
BACKGROUND: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood. METHODS: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19)...
February 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28066100/oropharyngeal-aspiration-of-bleomycin-an-alternative-experimental-model-of-pulmonary-fibrosis-developed-in-swiss-mice
#12
Swarna Bale, Manoj Sunkoju, Shiva Shankar Reddy, Veerabhadra Swamy, Chandraiah Godugu
OBJECTIVE: Pulmonary fibrosis (PF) is a progressive and predominantly lethal form of several interstitial lung diseases with limited current therapeutics; it is, therefore, essential to develop a simple, homogeneous, and noninvasive disease model to investigate possible anti-fibrotic approaches. The present study is designed to develop oropharyngeal aspiration (OPA) model of bleomycin (BLM)-induced PF as a simple and alternative to intratracheal (IT) administration of BLM in Swiss mice strain...
November 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/27807704/animal-models-of-sarcoidosis
#13
REVIEW
Yijie Hu, Betel Yibrehu, Diana Zabini, Wolfgang M Kuebler
Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies...
March 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/27308969/fibrotic-gene-expression-coexists-with-alveolar-proteinosis-in-early-indium-lung
#14
Shuhei Noguchi, Masamitsu Eitoku, Hidenori Kiyosawa, Narufumi Suganuma
Occupational inhalation of indium compounds can cause the so-called "indium lung disease". Most affected individuals show pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease. In animal experiments, inhalation of indium tin oxide or indium oxide has been shown to cause lung damage. However, the mechanisms by which indium compounds lead to indium lung disease remain unknown. In this study, we constructed a mouse model of indium lung disease and analyzed gene expression in response to indium exposure...
August 2016: Inhalation Toxicology
https://www.readbyqxmd.com/read/27144281/map3k19-is-a-novel-regulator-of-tgf-%C3%AE-signaling-that-impacts-bleomycin-induced-lung-injury-and-pulmonary-fibrosis
#15
Stefen A Boehme, Karin Franz-Bacon, Danielle N DiTirro, Tai Wei Ly, Kevin B Bacon
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating disease for which two medications, pirfenidone and nintedanib, have only recently been approved for treatment. The cytokine TGF-β has been shown to be a central mediator in the disease process. We investigated the role of a novel kinase, MAP3K19, upregulated in IPF tissue, in TGF-β-induced signal transduction and in bleomycin-induced pulmonary fibrosis. MAP3K19 has a very limited tissue expression, restricted primarily to the lungs and trachea...
2016: PloS One
https://www.readbyqxmd.com/read/27105895/a-potential-contribution-of-antimicrobial-peptide-ll-37-to-tissue-fibrosis-and-vasculopathy-in-systemic-sclerosis
#16
T Takahashi, Y Asano, K Nakamura, T Yamashita, R Saigusa, Y Ichimura, T Toyama, T Taniguchi, A Yoshizaki, Z Tamaki, Y Tada, M Sugaya, T Kadono, S Sato
BACKGROUND: LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). OBJECTIVES: To elucidate the potential role of LL-37 in SSc. METHODS: The expression of target molecules was evaluated by immunostaining and quantitative reverse-transcription real-time polymerase chain reaction in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation...
December 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27014274/potential-of-pegylated-toll-like-receptor-7-ligands-for-controlling-inflammation-and-functional-changes-in-mouse-models-of-asthma-and-silicosis
#17
Tatiana Paula Teixeira Ferreira, Lívia Lacerda Mariano, Roberta Ghilosso-Bortolini, Ana Carolina Santos de Arantes, Andrey Junior Fernandes, Michelle Berni, Valentina Cecchinato, Mariagrazia Uguccioni, Roberto Maj, Alcide Barberis, Patricia Machado Rodrigues E Silva, Marco Aurélio Martins
Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/26914452/phosphate-induced-renal-fibrosis-requires-the-prolyl-isomerase-pin1
#18
Zhong-Jian Shen, Jie Hu, Kazuhiro Shiizaki, Makoto Kuro-o, James S Malter
Tubulo-interstitial fibrosis is a common, destructive endpoint for a variety of kidney diseases. Fibrosis is well correlated with the loss of kidney function in both humans and rodents. The identification of modulators of fibrosis could provide novel therapeutic approaches to reducing disease progression or severity. Here, we show that the peptidyl-prolyl isomerase Pin1 is an important molecular contributor that facilitates renal fibrosis in a well-characterized animal model. While wild-type mice fed a high phosphate diet (HPD) for 8-12 weeks developed calcium deposition, macrophage infiltration and extracellular matrix (ECM) accumulation in the kidney interstitium, Pin1 null mice showed significantly less pathology...
2016: PloS One
https://www.readbyqxmd.com/read/26881215/establishment-of-a-rat-adjuvant-arthritis-interstitial-lung-disease-model
#19
Liu-nan Song, Xiao-dan Kong, Hong-jiang Wang, Li-bin Zhan
INTRODUCTION: Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD) and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. METHODS: Adult male Wistar rats were studied in an adjuvant arthritis (AA) model induced by the injection of Freund's complete adjuvant (FCA). Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1) and transforming growth factor-β (TGF-β1) protein expression levels...
2016: BioMed Research International
https://www.readbyqxmd.com/read/26824344/integrated-long-non-coding-rna-analyses-identify-novel-regulators-of-epithelial-mesenchymal-transition-in-the-mouse-model-of-pulmonary-fibrosis
#20
Hao Sun, Junjie Chen, Wenyi Qian, Jiang Kang, Jun Wang, Lei Jiang, Li Qiao, Wei Chen, Jinsong Zhang
Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease characterized by aberrant accumulation of fibroblast population and deposition of extra cellular matrix. Increasing evidence support that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a critical process in the pathogenesis of IPF. Although delivery of bleomycin to induce acute lung injury is the most well-studied animal model of pulmonary fibrosis, there is considerable interest to pursue other models to understand the common and/or specific pathological mechanisms...
July 2016: Journal of Cellular and Molecular Medicine
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