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in vivo imaging pneumonia

Andrés E Marcoleta, Macarena A Varas, Javiera Ortiz-Severín, Leonardo Vásquez, Camilo Berríos-Pastén, Andrea V Sabag, Francisco P Chávez, Miguel L Allende, Carlos A Santiviago, Octavio Monasterio, Rosalba Lagos
Multiresistant and invasive hypervirulent Klebsiella pneumoniae strains have become one of the most urgent bacterial pathogen threats. Recent analyses revealed a high genomic plasticity of this species, harboring a variety of mobile genetic elements associated with virulent strains, encoding proteins of unknown function whose possible role in pathogenesis have not been addressed. K. pneumoniae virulence has been studied mainly in animal models such as mice and pigs, however, practical, financial, ethical and methodological issues limit the use of mammal hosts...
2018: Frontiers in Cellular and Infection Microbiology
Jenny A Herbert, Andrea M Mitchell, Ryan Ritchie, Jiangtao Ma, Kirsty Ross-Hutchinson, Timothy J Mitchell
Bioluminescence has been harnessed for use in bacterial reporter systems and for in vivo imaging of infection in animal models. Strain Xen35, a bioluminescent derivative of Streptococcus pneumoniae serotype 4 strain TIGR4 was previously constructed for use for in vivo imaging of infections in animal models. We have shown that strain Xen35 is less virulent than its parent TIGR4 and that this is associated with the expression of the genes for bioluminescence. The expression of the luxA-E genes in the pneumococcus reduces virulence and down regulates the expression of the pneumococcal pilus...
2018: PloS One
Brandon G Ginley, Tiffany Emmons, Brendon Lutnick, Constantin F Urban, Brahm H Segal, Pinaki Sarder
Neutrophil extracellular traps (NETs) are extracellular defense mechanisms used by neutrophils, where chromatin is expelled together with histones and granular/cytoplasmic proteins. They have become an immunology hotspot, implicated in infections, but also in a diverse array of diseases such as systemic lupus erythematosus, diabetes, and cancer. However, the precise assessment of in vivo relevance in different disease settings has been hampered by limited tools to quantify occurrence of extracellular traps in experimental models and human samples...
December 19, 2017: Scientific Reports
Keith A Rodvold, William W Hope, Sara E Boyd
Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e...
October 2017: Current Opinion in Pharmacology
Jinbao Qin, Zhen Zhao, Ruihua Wang, Kaichuang Ye, Weimin Li, Xiaobing Liu, Guang Liu, Chaoyi Cui, Huihua Shi, Zhiyou Peng, Fukang Yuan, Xinrui Yang, Min Lu, Xintian Huang, Mier Jiang, Xin Wang, Minyi Yin, Xinwu Lu
BACKGROUND: Reconstruction of the aortic major branches during thoracic endovascular aortic repair is complicated because of the complex anatomic configuration and variation of the aortic arch. In situ laser fenestration has shown great potential for the revascularization of aortic branches. This study aims to evaluate the feasibility, effectiveness, and safety of in situ laser fenestration on the three branches of the aortic arch during thoracic endovascular aortic repair. METHODS AND RESULTS: Before clinical application, the polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser system ex vivo, which did not damage the bare metal portion of the endografts and created a clean fenestration while maintaining the integrity of the endografts...
April 21, 2017: Journal of the American Heart Association
Peng Meng, Gan Liang Tan, Su Ying Low, Angela Takano, Yuen Li Ng, Devanand Anantham
BACKGROUND: Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. METHODS: In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope...
December 2016: Journal of Thoracic Disease
Sandra Fuentes, Diego Arenas, Martin M Moore, Hana Golding, Surender Khurana
Respiratory Syncytial virus (RSV) is one of the leading causes of pneumonia among infants with no human vaccine or efficient curative treatments. Efforts are underway to develop new RSV vaccines and therapeutics. There is a dire need for animal models for preclinical evaluation and selection of products against RSV. Herein, we developed a whole body bioluminescence imaging to follow replication of RSV A2 virus strain expressing firefly luciferase (RSVA2-line19-FFL) in live BALB/c mice that can be used as an extremely sensitive readout for studying effects of antiviral and vaccines in living mice...
December 15, 2016: Vaccine
Arthur H Totten, Li Xiao, Donna M Crabb, Amy E Ratliff, Kevin Dybvig, Ken B Waites, T Prescott Atkinson
BACKGROUND: Mycoplasma pneumoniae (Mpn), one of the smallest self-replicating prokaryotes, is known to readily adhere to host cells and to form aggregates in suspension. Having only one cell membrane and no cell wall, mycoplasmas present questions as to optimal aggregate disruption method while minimizing cell death in vitro. We compared conventional vortex mixing with other methods for disruption of bacterial aggregates and for its effect on cell viability. METHODS: Strain UAB PO1, a clinical Mpn isolate, was dispersed using a conventional vortex mixer with or without nonionic detergent (0...
January 2017: Journal of Microbiological Methods
Nis Pedersen Jørgensen, Aage K O Alstrup, Frank V Mortensen, Karoline Knudsen, Steen Jakobsen, Line Bille Madsen, Dirk Bender, Peter Breining, Mikkel Steen Petersen, Mariane Høgsberg Schleimann, Frederik Dagnæs-Hansen, Lars C Gormsen, Per Borghammer
INTRODUCTION: Immune cells utilize acetylcholine as a paracrine-signaling molecule. Many white blood cells express components of the cholinergic signaling pathway, and these are up-regulated when immune cells are activated. However, in vivo molecular imaging of cholinergic signaling in the context of inflammation has not previously been investigated. METHODS: We performed positron emission tomography (PET) using the glucose analogue 18F-FDG, and 11C-donepezil and 18F-FEOBV, markers of acetylcholinesterase and the vesicular acetylcholine transporter, respectively...
March 2017: European Journal of Nuclear Medicine and Molecular Imaging
Hanaa Shafiek, Federico Fiorentino, Borja G Cosio, Ana Kersul, Luc Thiberville, Cristina Gómez, Melchor Riera, Maria L Martín, Rocio Martínez, Maria A Noguera, Alvar Agustí, Jaume Sauleda
BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. OBJECTIVES: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. METHODS: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE...
2016: Respiration; International Review of Thoracic Diseases
Brandon L Hatcher, Joanetha Y Hale, David E Briles
Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood-brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs...
September 2016: Infection and Immunity
Chia-Yu Chang, Hui-Jen Lin, Bor-Ran Li, Yaw-Kuen Li
Streptococcus pneumoniae, a penicillin-sensitive bacterium, is recognized as a major cause of pneumonia and is treated clinically with penicillin-based antibiotics. The rapid increase in resistance to penicillin and other antibiotics affects 450 million people globally and results in 4 million deaths every year. To unveil the mechanism of resistance of S. pneumoniae is thus an important issue to treat streptococcal disease that might consequently save millions of lives around the world. In this work, we isolated a streptococci-conserved L-ascorbate 6-phosphate lactonase, from S...
2016: PloS One
Megan V Jackson, Thomas J Morrison, Declan F Doherty, Daniel F McAuley, Michael A Matthay, Adrien Kissenpfennig, Cecilia M O'Kane, Anna D Krasnodembskaya
Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia...
August 2016: Stem Cells
Mariette Barbier, F Heath Damron
Since their discovery, fluorescent proteins have been widely used to study protein function, localization or interaction, promoter activity and regulation, drug discovery or for non-invasive imaging. They have been extensively modified to improve brightness, stability, and oligomerization state. However, only a few studies have focused on understanding the dynamics of fluorescent proteins expression in bacteria. In this work, we developed a set plasmids encoding 12 fluorescent proteins for bacterial labeling to facilitate the study of pathogen-host interactions...
2016: PloS One
Shahper N Khan, Asad U Khan
Multidrug-resistant (MDR) bacteria have become a severe threat to community wellbeing. Conventional antibiotics are getting progressively more ineffective as a consequence of resistance, making it imperative to realize improved antimicrobial options. In this review we emphasized the microorganisms primarily reported of being resistance, referred as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacteriaceae) accentuating their capacity to "escape" from routine antimicrobial regimes...
2016: Frontiers in Microbiology
Yongan Xu, Lin Ge, Osama Abdel-Razek, Sumeet Jain, Zhiyong Liu, Yucai Hong, Gary Nieman, Francis Johnson, Lorne M Golub, Robert N Cooney, Guirong Wang
Staphylococcus aureus is a common cause of nosocomial pneumonia frequently resulting in acute respiratory distress syndrome (ARDS). Surfactant protein B (SP-B) gene expresses two proteins involved in lowering surface tension and host defense. Genotyping studies demonstrate a significant association between human SP-B genetic variants and ARDS. Curcumins have been shown to attenuate host inflammation in many sepsis models. Our hypothesis is that functional differences of SP-B variants and treatment with curcumin (CMC2...
April 2016: Shock
Julia Désirée Boehme, Sabine Pietkiewicz, Inna Lavrik, Andreas Jeron, Dunja Bruder
PURPOSE: Chronic lung inflammation commonly induces a multitude of structural and functional adaptations within the lung tissue and airspaces. Yet the impact of a persistent inflammatory environment on alveolar macrophages is still incompletely understood. Here, we examined morphology and function of alveolar macrophages in a transgenic mouse model of chronic lung disease. METHODS: Imaging flow cytometry, flow cytometry, and microscopic evaluation of alveolar macrophages isolated from healthy and inflamed lungs were performed...
December 2015: Lung
Gunnar N Schroeder, Philipp Aurass, Clare V Oates, Edward W Tate, Elizabeth L Hartland, Antje Flieger, Gad Frankel
Legionella pneumophila is a bacterial pathogen that thrives in alveolar macrophages, causing a severe pneumonia. The virulence of L. pneumophila depends on its Dot/Icm type IV secretion system (T4SS), which delivers more than 300 effector proteins into the host, where they rewire cellular signaling to establish a replication-permissive niche, the Legionella-containing vacuole (LCV). Biogenesis of the LCV requires substantial redirection of vesicle trafficking and remodeling of intracellular membranes. In order to achieve this, several T4SS effectors target regulators of membrane trafficking, while others resemble lipases...
October 2015: Infection and Immunity
Mick M Welling, Anton Bunschoten, Joeri Kuil, Rob G H H Nelissen, Freek J Beekman, Tessa Buckle, Fijs W B van Leeuwen
In trauma and orthopedic surgery, infection of implants has a major impact on the outcome for patients. Infections may develop either during the initial implantation or during the lifetime of an implant. Both infections, as well as aseptic loosening of the implant, are reasons for revision of the implants. Therefore, discrimination between aseptic-mechanical-loosening and septic-bacterial-loosening of implants is critical during selection of a patient-tailored treatment policy. Specific detection and visualization of infections is a challenge because it is difficult to discriminate infections from inflammation...
May 20, 2015: Bioconjugate Chemistry
Shirui Tan, Changpei Gan, Rongpeng Li, Yan Ye, Shuang Zhang, Xu Wu, Yi Yan Yang, Weimin Fan, Min Wu
Klebsiella pneumoniae (Kp) is one of the most common pathogens in nosocomial infections and is increasingly becoming multiple drug resistant. However, the molecular pathogenesis of Kp in causing tissue injury and dysregulated host defense remains elusive, further dampening the development of novel therapeutic measures. We have previously screened a series of synthetic antimicrobial beta-sheet forming peptides and identified a peptide (IRIKIRIK; ie, IK8L) with a broad range of bactericidal activity and low cytotoxicity in vitro...
2015: International Journal of Nanomedicine
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