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Epithelial lining fluid

Kyosuke Kanai, Ah-Mee Park, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
EBI3 functions as the subunit of immune-regulatory cytokines, such as IL-27 and IL-35, by pairing with p28 and p35, respectively. We treated wild-type and EBI3-deficient mice with intratracheal administration of LPS and obtained bronchoalveolar lavage fluid (BALF) 24 h later. Although neutrophils were the predominant cells in BALF from both groups of mice, eosinophils were highly enriched and there was increased production of eosinophil-attracting chemokines CCL11 and CCL24 in BALF of EBI3-deficient mice. The bronchial epithelial cells and alveolar macrophages were the major producers of CCL11 and CCL24...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jianshuang Wang, Yang Gao, Drew W Dorshorst, Fang Cai, Meire Bremer, Dennis Milanowski, Tracy L Staton, Stephanie S Cape, Brian Dean, Xiao Ding
In human respiratory disease studies, liquid samples such as nasal secretion (NS), lung epithelial lining fluid (ELF), or upper airway mucosal lining fluid (MLF) are frequently collected, but their volumes often remain unknown. The lack of volume information makes it hard to estimate the actual concentration of recovered active pharmaceutical ingredient or biomarkers. Urea has been proposed to serve as a sample volume marker because it can freely diffuse through most body compartments and is less affected by disease states...
January 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
Cornelia B Landersdorfer, Tri-Hung Nguyen, Linh Thuy Lieu, Gary Nguyen, Robert J Bischof, Els N Meeusen, Jian Li, Roger L Nation, Michelle P McIntosh
Colistin, administered as its inactive prodrug colistin methanesulfonate (CMS), is often used in multidrug-resistant Gram-negative pulmonary infections. The CMS and colistin pharmacokinetics in plasma and epithelial lining fluid (ELF) following intravenous and pulmonary dosing have not been evaluated in a large animal model with similar pulmonary architecture to humans.Six merino sheep (34-43kg) received an intravenous or pulmonary dose of 4-8 mg/kg CMS (sodium) or 2-3 mg/kg colistin (sulfate) in a 4-way crossover study...
November 7, 2016: Antimicrobial Agents and Chemotherapy
Kazuhiro Oshima, Shigeki Nakamura, Naoki Iwanaga, Koji Takemoto, Taiga Miyazaki, Kastunori Yanagihara, Yoshitsugu Miyazaki, Hiroshi Mukae, Shigeru Kohno, Koichi Izumikawa
High-dose meropenem (MEPM; 6 g/day) has been approved as a treatment for purulent meningitis; however, little is known regarding its in vivo efficacy in refractory lower respiratory tract infection. The purpose of this study was to evaluate the efficacy of 6 g/day MEPM in a murine model of severe pneumonia caused by MEPM-resistant Pseudomonas aeruginosa Experimental pneumonia induced by MEPM-resistant P. aeruginosa was treated with normal-dose MEPM (150 mg/kg, simulating 3 g/day regimen in humans) or high-dose MEPM (500 mg/kg, simulating 6 g/day regimen in humans)...
October 31, 2016: Antimicrobial Agents and Chemotherapy
Kamilia Abdelraouf, David P Nicolau
Given that tedizolid exhibits substantial lung penetration, we hypothesize that it could achieve good efficacy against Streptococcus pneumoniae lung infections. We evaluated the pharmacodynamics of tedizolid for treatment of S. pneumoniae lung infections and compared efficacy of tedizolid human-simulated epithelial lining fluid (ELF) exposures in immunocompetent and neutropenic murine lung infection models. ICR mice were rendered neutropenic via intraperitoneal cyclophosphamide injections, then inoculated intranasally with S...
October 31, 2016: Antimicrobial Agents and Chemotherapy
Fekade Bruck Sime, Adam Johnson, Sarah Whalley, Anahi Santoyo-Castelazo, A Bruce Montgomery, Kathie Ann Walters, Jeffrey Lipman, William W Hope, Jason A Roberts
There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia, caused by multi-drug resistant pathogens. A combination formulation of amikacin/fosfomycin is currently undergoing clinical testing although the exposure response-relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs 16 mg/L; 64 mg/L) and Klebsiella pneumoniae (MICs 2 mg/L; 64 mg/L) using the dynamic hollow-fiber infection model over 7-days...
October 24, 2016: Antimicrobial Agents and Chemotherapy
Kayhan Başak, Pınar Y Başak
Follicular hybrid cysts including two or more components of the epithelial skin adnexa are very rare. The epithelial lining of hybrid cysts varies, and either contains epidermis, and trichilemmal squamous epithelium, or other epithelia of the skin adnexa. Hybrid cysts may also be associated with neoplasia, such as in situ carcinoma, Bowen's disease and squamous cell carcinoma. A 37-year-old female was complaining of a cyst on her scalp. The unilocular cystic lesion was lined with markedly atypical squamous cells with trichilemmal differentiation...
October 28, 2016: Journal of Cutaneous Pathology
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
Abrar K Thabit, Jared L Crandon, David P Nicolau
Increasing antimicrobial resistance in community-acquired pneumonia (CAP) pathogens has contributed to infection-related morbidity and mortality. Delafloxacin is a novel fluoroquinolone with broad-spectrum activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to define the pharmacodynamic profile of delafloxacin against CAP pathogens using a neutropenic murine lung infection model. Five S. pneumoniae, 2 methicillin-susceptible S...
September 29, 2016: International Journal of Antimicrobial Agents
Na-Rae Shin, Hyung-Won Ryu, Je-Won Ko, Ji-Won Park, Ok-Kyoung Kwon, Sei-Ryang Oh, Jong-Choon Kim, In-Sik Shin, Kyung-Seop Ahn
ETHNOPHARMACOLOGICAL RELEVANCE: A standardized bark extract of Pinus pinaster Aiton (Pycnogenol(®); PYC) used as an herbal medicine to treat various diseases in Europe and North America. AIM OF THE STUDY: This study evaluates the ability of PYC to inhibit chronic obstructive pulmonary disease (COPD) in the cigarette smoke extract (CSE)-stimulated human airway epithelial cell line NCI-H292 and in a cigarette smoke (CS) and lipopolysaccharide (LPS)-induced mouse model...
October 7, 2016: Journal of Ethnopharmacology
Adam M Speen, Hye-Young H Kim, Rebecca N Bauer, Megan Meyer, Kymberly M Gowdy, Michael B Fessler, Kelly E Duncan, Wei Liu, Ned A Porter, Ilona Jaspers
When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species...
November 25, 2016: Journal of Biological Chemistry
Yohei Funatsu, Sadatomo Tasaka, Takahiro Asami, Ho Namkoong, Hiroshi Fujiwara, Osamu Iketani, Kazuma Yagi, Yoshifumi Kimizuka, Makoto Ishii, Tomoyasu Nishimura, Haruhiko Ogata, Satoshi Iwata, Tomoko Betsuyaku, Naoki Hasegawa
BACKGROUND: Some subtypes of influenza virus, such as H5N1 and H7N9, cause severe viral pneumonia, for which the intraluminal concentration of the anti-influenza agent in the airway is critical. However, the pharmacokinetics of peramivir, the only available injectable neuraminidase inhibitor formulation, in the airway epithelial lining fluid (ELF) remains unclear. In this study, we aimed to determine the time course of peramivir in the pharyngeal ELF, bronchial ELF and plasma of healthy volunteers using bronchoscopic microsampling technique...
October 3, 2016: Antiviral Therapy
S Giguère, A J Burton, L J Berghaus, A D Haspel
The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week-old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells...
September 29, 2016: Journal of Veterinary Pharmacology and Therapeutics
Evangelia Zilelidou, Christina-Vasiliki Karmiri, Georgia Zoumpopoulou, Eleni Mavrogonatou, Dimitris Kletsas, Effie Tsakalidou, Konstantinos Papadimitriou, Eleftherios Drosinos, Panagiotis Skandamis
: Various Listeria monocytogenes strains may contaminate a single food potentially resulting in simultaneous exposure of consumers to multiple strains. However, L. monocytogenes strains isolated from foods by selective enrichment (SE) might not always represent those that can better survive a patient immune system, due to bias in strain recovery. We investigated the effect of co-cultivation in TSB-Y at 10°C for 8 days on i) the detection of L. monocytogenes strains during SE with the ISO 11290-1:1996/Amd 1:2004 protocol and ii) the in vitro virulence of strains towards the human colon epithelial cancer cell line Caco-2 following exposure to simulated gastric fluid (SGF, pH 2...
September 16, 2016: Applied and Environmental Microbiology
M Evans, T Murofushi, H Tsuda, Y Mikami, N Zhao, K Ochiai, T Kurita-Ochiai, M Yamamoto, K Otsuka, N Suzuki
BACKGROUND AND OBJECTIVE: Bacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival crevicular fluid. Furthermore, some gram-negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms...
September 13, 2016: Journal of Periodontal Research
Pascale S J Lakey, Thomas Berkemeier, Haijie Tong, Andrea M Arangio, Kurt Lucas, Ulrich Pöschl, Manabu Shiraiwa
Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases...
2016: Scientific Reports
Kengyeh K Chu, Diana Mojahed, Courtney M Fernandez, Yao Li, Linbo Liu, Eric J Wilsterman, Bradford Diephuis, Susan E Birket, Hannah Bowers, G Martin Solomon, Benjamin S Schuster, Justin Hanes, Steven M Rowe, Guillermo J Tearney
Clinical manifestations of cystic fibrosis (CF) result from an increase in the viscosity of the mucus secreted by epithelial cells that line the airways. Particle-tracking microrheology (PTM) is a widely accepted means of determining the viscoelastic properties of CF mucus, providing an improved understanding of this disease as well as an avenue to assess the efficacies of pharmacologic therapies aimed at decreasing mucus viscosity. Among its advantages, PTM allows the measurement of small volumes, which was recently utilized for an in situ study of CF mucus formed by airway cell cultures...
September 6, 2016: Biophysical Journal
Megan M Cartwright, Stefanie C Schmuck, Charlie Corredor, Bingbing Wang, David K Scoville, Claire R Chisholm, Hui-Wen Wilkerson, Zahra Afsharinejad, Theodor K Bammler, Jonathan D Posner, Vaithiyalingam Shutthanandan, Donald R Baer, Somenath Mitra, William A Altemeier, Terrance J Kavanagh
Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice...
August 21, 2016: Redox Biology
Maria Lasalvia, Stefano Castellani, Palma D'Antonio, Giuseppe Perna, Annalucia Carbone, Anna Laura Colia, Angela Bruna Maffione, Vito Capozzi, Massimo Conese
The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module...
October 15, 2016: Experimental Cell Research
Joyce F Liu, Sangeetha Palakurthi, Qing Zeng, Shan Zhou, Elena Ivanova, Wei Huang, Ioannis K Zervantonakis, Laura M Selfors, Yiping Shen, Colin C Pritchard, Mei Zheng, Vilmos Adleff, Eniko Papp, Huiying Piao, Marian Novak, Susan Fotheringham, Gerburg Wulf, Jessie English, Paul T Kirschmeier, Victor E Velculescu, Cloud P Paweletz, Gordon B Mills, David M Livingston, Joan S Brugge, Ursula A Matulonis, Ronny Drapkin
PURPOSE: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease. EXPERIMENTAL DESIGN: Clinically-annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures...
August 29, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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