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Pulmonary fibrosis

Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Hui Ren, Nigel P Birch, Vinod Suresh
Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2...
2016: PloS One
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent fat embolism syndrome (FES) occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FES is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system (RAS) plays a significant role in the pathophysiology of FE since drugs interfering with the RAS, captopril and losartan, reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
October 25, 2016: Journal of Trauma and Acute Care Surgery
Lisa R Young, Peter M Gulleman, Chelsi W Short, Harikrishna Tanjore, Taylor Sherrill, Aidong Qi, Andrew P McBride, Rinat Zaynagetdinov, John T Benjamin, William E Lawson, Sergey V Novitskiy, Timothy S Blackwell
Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice...
October 20, 2016: JCI Insight
Deniz Koksal, Aydin Seref Koksal, Ahmet Gurakar
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease caused by diffuse inflammation, destruction and fibrosis of the intrahepatic bile ducts, ultimately leading to cirrhosis, portal hypertension and liver failure. The pathogenesis of PBC is incompletely understood, but current data suggest roles for genetic susceptibility and environmental factors. PBC is often thought of as an organ-specific autoimmune disease, which mainly targets the liver; however, lung tissue is also a site for autoimmune involvement of PBC...
September 28, 2016: Journal of Clinical and Translational Hepatology
Irsa Tahir, Muhammad Rashid Khan, Naseer Ali Shah, Maryam Aftab
BACKGROUND: In the present study the antioxidant potential of a methanol extract of Phyllanthus emblica leaves (PELE) was determined by in vitro methods as well as by an in vivo animal model, along with HPLC-DAD screening for phyto-constituents. METHODS: The in vitro antioxidant potential of PELE was assessed by scavenging of DPPH, nitric oxide and anti-lipid peroxidation assays. For in vivo evaluation, a 60-day experimental plan was followed in which Sprague Dawley rats were administered with 1 mL/kg of CCl4 (CCl4 : DMSO + Olive oil; 30 % v/v) alone or with different doses of PELE (200, 400 mg/kg p...
October 24, 2016: BMC Complementary and Alternative Medicine
Jingjin Yang, Ting Wang, Yan Li, Wenxi Yao, Xiaoming Ji, Qiuyun Wu, Lei Han, Ruhui Han, Weiwen Yan, Jiali Yuan, Chunhui Ni
Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Ruijuan Guan, Xia Wang, Xiaomei Zhao, Nana Song, Jimin Zhu, Jijiang Wang, Jin Wang, Chunmei Xia, Yonghua Chen, Danian Zhu, Linlin Shen
Aberrant activation of TGF-β1 is frequently encountered and promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. The present study investigated whether emodin mediates its effect via suppressing TGF-β1-induced EMT and fibroblast activation in bleomycin (BLM)-induced pulmonary fibrosis in rats. Here, we found that emodin induced apoptosis and inhibited cellular proliferation, migration and differentiation in TGF-β1-stimulated human embryonic lung fibroblasts (HELFs)...
October 24, 2016: Scientific Reports
Alexander J Sweidan, Navneet K Singh, Natasha Dang, Vinh Lam, Jyoti Datta
INTRODUCTION: Amiodarone is often used in the suppression of tachyarrhythmias. One of the more serious adverse effects includes amiodarone pulmonary toxicity (APT). Several pulmonary diseases can manifest including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary nodules or masses, and pleural effusion. Incidence of APT varies from 5-15% and is correlated to dosage, age of the patient, and preexisting lung disease...
2016: Clinical Medicine Insights. Case Reports
Helen L Barr, Nigel Halliday, David A Barrett, Paul Williams, Douglas L Forrester, Daniel Peckham, Kate Williams, Alan R Smyth, David Honeybourne, Joanna L Whitehouse, Edward F Nash, Jane Dewar, Andrew Clayton, Alan J Knox, Miguel Cámara, Andrew W Fogarty
BACKGROUND: Pulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are detectable in the sputum, plasma and urine of adults with CF, suggesting that they have potential as biomarkers for P. aeruginosa infection. AIM: To investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P...
October 20, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Yuan Liu, Monica Vela, Tanya Rudakevych, Christopher Wigfield, Edward Garrity, Milda R Saunders
BACKGROUND: Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. METHODS: We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV1] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration...
August 21, 2016: Journal of Heart and Lung Transplantation
YanRui Wang, ShaoJie Yue, ZiQiang Luo, ChuanDing Cao, XiaoHe Yu, ZhengChang Liao, MingJie Wang
BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8)...
October 21, 2016: Respiratory Research
Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
Li Gao, Sheng Xie, Hui Liu, Pingping Liu, Yan Xiong, Jiping Da, Chengli Que, Huaping Dai, Chen Wang
OBJECTIVE: Combined pulmonary fibrosis and emphysema (CPFE) is a newly defined entity that comprises upper lobe emphysema and lower lobe fibrosis. Patients with CPFE are at high risk for lung cancer and have poor prognoses. To investigate the clinical and pathological characteristics of lung cancer with CPFE, lung cancers with CPFE and Non-CPFE interstitial lung disease (ILD) were reevaluated by 2015 WHO classification and compared. METHODS: A total of 60 patients with histologically proven lung cancer were selected from the database of two institutional medical centers...
October 21, 2016: Clinical Respiratory Journal
Margaret L Salisbury, David A Lynch, Edwin J R van Beek, Ella A Kazerooni, Junfeng Guo, Meng Xia, Susan Murray, Kevin J Anstrom, Eric Yow, Fernando J Martinez, Eric A Hoffman, Kevin R Flaherty
RATIONALE: Adaptive Multiple Features Method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. OBJECTIVES: We evaluated AMFM and visual quantification of HRCT patterns and their relationship with disease progression in Idiopathic Pulmonary Fibrosis. METHODS: IPF patients in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal were measured by AMFM and 3 radiologists, documenting baseline disease extent and post-baseline change...
October 21, 2016: American Journal of Respiratory and Critical Care Medicine
Vidya Ramachandraiah, Wilbert Aronow, Dipak Chandy
Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas, the exact etiology of which is yet to be determined. Pulmonary involvement occurs in the majority of patients and its severity ranges from asymptomatic involvement of mediastinal lymph nodes to progressive pulmonary fibrosis and chronic respiratory failure that is insensitive to treatment. Diagnosis of pulmonary sarcoidosis requires a compatible clinical picture supported by radiologic and pathologic data. A recent development in establishing the diagnosis of pulmonary sarcoidosis is endobronchial ultrasound that increases the yield of transbronchial needle aspiration of hilar and/or mediastinal lymph nodes...
October 21, 2016: Postgraduate Medicine
Denis E O'Donnell, J Alberto Neder, Ingrid Harle, Onofre Moran-Mendoza
Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, with a median survival time of two to five years. Most patients with IPF experience chronic breathlessness, which is closely linked to poor perceived quality of life and significant restriction of daily activities; therefore, effective management of this distressing symptom is a major goal of patient care. Areas covered: This report summarizes the physiology of IPF during rest and exercise, outlines current concepts of the mechanisms of breathlessness, and provides a physiological rationale for optimal management of individual patient...
October 21, 2016: Expert Review of Respiratory Medicine
Paul Castellanos, Manjunath Mk, Ihab Atallah
The management of tracheobronchomalacia is a very challenging problem with few treatment options. This study aims to evaluate the outcomes of a novel surgical treatment for membranous tracheobronchomalacia. A consecutive series of patients with tracheobronchomalacia were treated with two to three holmium laser scarring surgeries of the hyperdynamic tracheal and bronchial walls for the purpose of stiffening them through fibrosis. Patients filled out a Dyspnea Index questionnaire before and after treatment. Ten patients were treated for their tracheobronchomalacia with a mean age of 54 years...
October 20, 2016: European Archives of Oto-rhino-laryngology
Shingo Matsushima, Junichi Ishiyama
MicroRNAs play an important role in the development and progression of various diseases, such as idiopathic pulmonary fibrosis (IPF). Although the accumulation of aberrant fibroblasts resistant to apoptosis is a hallmark in IPF lungs, the mechanism regulating apoptosis susceptibility is not fully understood. Here, we investigated the role of miR-29, which is the most downregulated microRNA in IPF lungs and is also known as a regulator of extracellular matrix (ECM), in the mechanism of apoptosis resistance. We found that functional inhibition of miR-29c caused resistance to Fas-mediated apoptosis in lung fibroblasts...
October 7, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Steffen T Simon, Irene J Higginson, Sara Booth, Richard Harding, Vera Weingärtner, Claudia Bausewein
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2010, on 'Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults'. Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non-malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. At the time of the previously published Cochrane review, there was no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in people with advanced cancer and chronic obstructive pulmonary disease (COPD)...
October 20, 2016: Cochrane Database of Systematic Reviews
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