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Julio Jiménez, Jute Richter, Taro Nagatomo, Thomas Salaets, Rozenn Quarck, Allard Wagennar, Hongmei Wang, Jeroen Vanoirbeek, Jan Deprest, Jaan Toelen
Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth...
October 24, 2016: International Journal of Molecular Sciences
Changsheng Zhang, Massimiliano Pirrone, David A E Imber, Jeanne B Ackman, Jacopo Fumagalli, Robert M Kacmarek, Lorenzo Berra
Morbidly obese, critically ill patients are prone to develop hypoxemic respiratory failure and ventilator dependency. The best method for recruiting the lungs of these patients and keeping alveoli open without causing injury remains unclear. We present the case of a 31-year-old patient with severe refractory hypoxemia reversed by lung recruitment maneuvers and subsequent application of positive end-expiratory pressure (PEEP) at a level determined by a decremental PEEP trial. The patient was extubated at a high PEEP level of 22 cm H2O followed by noninvasive ventilatory support after extubation...
October 24, 2016: A & A Case Reports
Felicity M Davis, Bethan Lloyd-Lewis, Olivia B Harris, Sarah Kozar, Douglas J Winton, Leila Muresan, Christine J Watson
The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging...
October 25, 2016: Nature Communications
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
Milena V Oliveira, Soraia C Abreu, Gisele A Padilha, Nazareth N Rocha, Lígia A Maia, Christina M Takiya, Debora G Xisto, Bela Suki, Pedro L Silva, Patricia R M Rocco
Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0...
2016: Frontiers in Physiology
Bárbara Olmeda, Marta Martinez-Calle, Jesus Pérez-Gil
Pulmonary surfactant is a lipid-protein complex that lines and stabilizes the respiratory interface in the alveoli, allowing for gas exchange during the breathing cycle. At the same time, surfactant constitutes the first line of lung defense against pathogens. This review presents an updated view on the processes involved in biogenesis and intracellular processing of newly synthesized and recycled surfactant components, as well as on the extracellular surfactant transformations before and after the formation of the surface active film at the air-water interface...
October 20, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Samriddha Ray, Norika Chiba, Changfu Yao, Xiangrong Guan, Alicia M McConnell, Brian Brockway, Loretta Que, Jonathan L McQualter, Barry R Stripp
Recent studies have implicated keratin 5 (KRT5)(+) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5(+) cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2(+) SCGB1A1(-) KRT5(-) progenitor cells in airways...
October 20, 2016: Stem Cell Reports
Dong Liu, Jie-Lu Zhou, Fashui Hong, Yu-Qing Zhang
Titanium dioxide nanoparticles (TiO2 NPs) are used in many fields, such as paints, medicine additives, food additives, sunscreens and agriculture. The aim of this study was to investgate the mechanism behind the formation of inflammation induced by TiO2 NPs. ICR mice were exposed to TiO2 NPs through intragastric administration at 2.5, 5 and 10 mg/kg body weight every day for 90 consecutive days. The experiment suggested that long-term exposure to TiO2 NPs resulted in an obvious inflammatory response in mice lung tissues, which led to a thickened alveoli septum, lung hyperaemia, and titanium accumulation...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Sebastien F Barre, David Haberthür, Tiziana P Cremona, Marco Stampanoni, Johannes C Schittny
The pulmonary airways are subdivided into conducting and gas-exchanging airways. The small tree of gas-exchanging airways which is fed by the most distal conducting airway represents an acinus. Very little is known about the development of the number of acini. The goal of this study was to estimate their number throughout rat postnatal development. Right middle rat lung lobes were obtained at postnatal day 4-60, stained with heavy metals, paraffin embedded, and scanned by synchrotron radiation based X-ray tomographic microscopy or imaged using micro computed tomography after critical point drying...
October 19, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Elizabeth M Todd, Julie Y Zhou, Taylor P Szasz, Lauren E Deady, June A D'Angelo, Matthew D Cheung, Alfred H J Kim, Sharon Celeste Morley
Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages. Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar macrophages and failed to effectively clear pulmonary pneumococcal infection, showing that immunodeficiency results from reduced alveolar macrophage numbers...
October 6, 2016: Blood
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
Suzanne Miller, Amanda P Henry, Emily Hodge, Alexander K Kheirallah, Charlotte K Billington, Tracy L Rimington, Sangita K Bhaker, Ma'en Obeidat, Erik Melén, Simon K Merid, Caroline Swan, Catherine Gowland, Carl P Nelson, Ceri E Stewart, Charlotte E Bolton, Iain Kilty, Anders Malarstig, Stuart G Parker, Miriam F Moffatt, Andrew J Wardlaw, Ian P Hall, Ian Sayers
INTRODUCTION: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model...
2016: PloS One
A Jézéquel, M Kerjouan, M Lederlin, C Lainé-Caroff, C Camus, P Delaval, S Jouneau
INTRODUCTION: Auto-immune pulmonary alveolar proteinosis is a rare disorder characterized by the accumulation of surfactant proteins in the alveoli. CASE REPORT: We report a case of a 41-year-old smoker, presenting initially with acute respiratory failure. Whole lung lavages were effective initially but only for a few weeks. GM-CSF subcutaneous injections were not effective, and then plasmapheresis were tried. CONCLUSION: This is the fifth report of the use of this treatment in auto-immune pulmonary alveolar proteinosis...
October 13, 2016: Revue des Maladies Respiratoires
Peter B Terry, Richard J Traystman
Oxygen delivery and carbon dioxide removal being critical to cell survival, mammals have developed collateral vascular and ventilation systems to ensure tissue viability. Collateral ventilation, defined as ventilation of alveoli via pathways that bypass normal airways, is present in humans and many other species. The presence of collateral ventilation can be beneficial in certain disease states, while its relative absence can predispose to other diseases. These well defined anatomical pathways contribute little to ventilation in normal humans, but modulate ventilation perfusion imbalance in a variety of diseases including obstructive diseases such as asthma and emphysema...
October 14, 2016: Annals of the American Thoracic Society
F Cau, E Pisu, C Gerosa, G Senes, F Ronchi, C Botta, E Di Felice, F Uda, V Marinelli, G Faa, V Fanos, C Moretti, D Fanni
The surfactant complex, thanks to its multiple actions including decrease of surface- tension and antimicrobial activity, plays a fundamental role in newborn survival, lowering the risk of respiratory distress syndrome. The aim of this work was to determine if the synthesis of two surfactant proteins (SP), SPA and pro-SPB, shows some inter-individual variability during lung development in the intrauterine life. Immunoreactivity for SPA and pro-SPB was investigated in the lungs of  40 subjects, including 15 fetuses, ranging from 14 to 22 weeks of gestation, and 25 neonates, from 24 to 41 weeks...
September 26, 2016: European Journal of Histochemistry: EJH
J E Skjaeraasen, J A Devine, J A Godiksen, M Fonn, H OtterÅ, O S Kjesbu, B Norberg, Ø Langangen, Ø Karlsen
Wild caught North Sea saithe Pollachius virens were monitored for growth, sex steroid profiles and oocyte development pre-spawning and measured for egg size and group fecundity during the spawning season in the laboratory. Vitellogenesis commenced in late October-early November, at a leading cohort size (CL ) of c. 250 µm, after which oocytes grew rapidly in size until spawning started in February. Notably, a distinct cortical alveoli stage was virtually absent with yolk granules observed in developing oocytes at the very beginning of vitellogenesis...
October 13, 2016: Journal of Fish Biology
Anna Bratek-Skicki, Paulina Żeliszewska, Juan M Ruso
Fibrinogen has been known since the mid-nineteenth century. Although initially its interest had been within the field of physiology over time its study has spread to new disciplines such as biochemistry, colloids and interfaces or biotechnology. First, we will describe the bulk properties of the molecule as well as its supramolecular assembly with different ligands by using different techniques and theoretical models. In the next step we will analyze the interfacial properties, an important topic because fibrinogen is considered to be a major inhibitor of lung surfactants' function at the lining layer of alveoli...
October 10, 2016: Soft Matter
B Stubbe, S Schipf, C Schäper, S B Felix, A Steveling, M Nauck, H Völzke, H Wallaschofski, N Friedrich, R Ewert, T Ittermann, S Gläser
Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients...
October 4, 2016: Experimental and Clinical Endocrinology & Diabetes
Ahmad A El-Ebiary, Sabah El-Ghaiesh, Ehab Hantash, Suliman Alomar
Induction of oxidative stress and inflammation are considered the primary mechanism of cadmium (Cd) toxicity. Nigella sativa (NS) seeds and their oil (NSO) have been reported to possess antioxidant and anti-inflammatory potential. This study was conducted to assess the protective effect of NSO on Cd-induced lung damage in rat. Forty adult male Wistar rats were divided equally into 4 groups. Animals in groups I, II, and III received 1 ml of isotonic saline intraperitoneally (IP), 2 mg/kg of cadmium chloride (CdCl2) dissolved in isotonic saline IP, and 1 ml/kg of NSO by gastric gavage, respectively...
October 1, 2016: Environmental Science and Pollution Research International
Akira Yoshikawa, Shuntaro Sato, Tomonori Tanaka, Mikiko Hashisako, Yukio Kashima, Tomoshi Tsuchiya, Naoya Yamasaki, Takeshi Nagayasu, Hiroshi Yamamoto, Junya Fukuoka
PURPOSE: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. PATIENTS AND METHODS: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU)...
2016: International Journal of Chronic Obstructive Pulmonary Disease
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