Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1

A Non-invasive Method For Assessing Airway Narrowing Of Isolated Airways In Vitro

In this paper a method for measuring the inner and outer diameter of isolated airways in vitro is introduced. This method relies on images to measure outer diameter and on pressure-flow systemic response to measure inner diameter. The hardware/software environment used is introduced and initial experiments are performed as a proof of concept. The authors believe this method can be used to perform experiments in isolated airways that better mimic in-vivo conditions. © 2011 Springer-Verlag Berlin Heidelberg.37137140Kapsali, T., Permutt, S., Laube, B., Scichilone, N., Togias, A., Potent bronchoprotective effect of deep inspiration and its absence in asthma (2000) J Appl Physiol, 89, pp. 711-720LaPrad, A.S., Szabo, T.L., Suki, B., Lutchen, K.R., Tidal strechtes do not modulate responsiveness of intact airways in-vitro (2010) J Appl Physiol, , April 29, doi:10.1152/japplphysiol.00107.2010Mitchell, H.W., Sparrow, M.P., Video-imaging of lumen narrowingmuscle shortening and flow responsiveness in isolated bronchial segments of the pig (1994) Eur Respir J, 7, pp. 1317-1325Noble, P.B., Turner, D.J., Mitchell, H.W., Relationship of airway narrowing, compliance, and cartilage in isolated bronchial segments (2002) J Appl Physiol, 92, pp. 1119-1124Otsu, N., A threshold selection method from gray-level histograms (1979) IEEE Transactions on Systems, Man and Cybernetics, 9, pp. 62-66Bates, J.H., (2009) Lung Mechanics - An Inverse Modeling Approach, pp. 62-68. , Cambridge University Pres

Cálculo De Elastância Em Curvas Pressão-volume Em Pulmões Lesados Por Paraquat: Modelo De Lesão Pulmonar Aguda

Acute lung injury, whose most severe expression is Respiratory Distress Syndrome, was described 40 years ago. Despite all research in this field, mortality rate still remains around 35%. In this study we used a model of acute lung injury with paraquat, an herbicide that causes alveolar instability through destruction of surfactant, to obtain pressure-volume curves of lungs in open-chest rats. The objectives were to study acute lung injury through measurements of lung elastance during inspiratory and expiratory maneuvers. We observed a rise in elastance during the initial part of the inspiratory maneuver (0-5mL approx.) in animals exposed to paraquat possibly due to increased alveolar collapse. We suppose that alveolar recruitment is responsible for the absence of significant elastance changes in other phases of the inspiratory maneuver. © 2013 Springer.33 IFMBE212215SKAN AG,Materialise NV,Bavarian Minist. Econ., Aff., Infrastruct., Transp. Technol.,Bavarian Bureau for International Business Relations GmbH,AKUD - Med Pharm GmbHMacIntyre, N.R., Is there a best way to set positive expiratory-end pressure for mechanical ventilatory support in acute lung injury? (2008) Clin Chest Med, 29, pp. 233-239Erickson, S.E., Martin, G.S., Davis, J.L., Mathay, M.A., Eisner, M.D., Recent trends in acute lung injury mortality: 1996-2005* (2009) Crit Care Med, 37, pp. 1574-1579. , MDMD, MScMDMDMD, MPHfor the NIH NHLBI ARDS NetworkMatute-Bello, G., Frevert, C.W., Martin, T.R., Animal models of acute lung injury J Physiol Lung Cell Mol Physiol, 295, pp. 379-399. , doi:10.1152/ajplung.00010.2008Silva, M.F.R., Saldiva, P.H.N., Paraquat poisoning: An experimental model of dose-dependent acute lung injury due to surfactant dysfunction (1998) Brazilian Journal of Medical and Biological Research, 31 (3), pp. 445-450Silva, M.F.R., Zin, W.A., Saldiva, P.H.N., Airspace configuration at different transpulmonary pressures in normal and paraquat-induced lung injury in rats (1998) American Journal of Respiratory and Critical Care Medicine, 158 (4), pp. 1230-123

Nucleosynthesis in Supernovae

We present the status and open problems of nucleosynthesis in supernova explosions of both types, responsible for the production of the intermediate mass, Fe-group and heavier elements (with the exception of the main s-process). Constraints from observations can be provided through individual supernovae (SNe) or their remnants (e.g. via spectra and gamma-rays of decaying unstable isotopes) and through surface abundances of stars which witness the composition of the interstellar gas at their formation. With a changing fraction of elements heavier than He in these stars (known as metallicity) the evolution of the nucleosynthesis in galaxies over time can be determined. A complementary way, related to gamma-rays from radioactive decays, is the observation of positrons released in beta(+)-decays, as e.g. from Al-26, Ti-44, Ni-56,Ni-57 and possibly further isotopes of their decay chains (in competition with the production of e(+)e(-) pairs in acceleration shocks from SN remnants, pulsars, magnetars or even of particle physics origin). We discuss (a) the role of the core-collapse supernova explosion mechanism for the composition of intermediate mass, Fe-group (and heavier?) ejecta, (b) the transition from neutron stars to black holes as the final result of the collapse of massive stars, and the relation of the latter to supernovae, faint supernovae, and gamma-ray bursts/hypernovae, (c) Type Ia supernovae and their nucleosynthesis (e.g. addressing the Mn-55 puzzle), plus (d) further constraints from galactic evolution, gamma-ray and positron observations. This is complemented by the role of rare magneto-rotational supernovae (related to magnetars) in comparison with the nucleosynthesis of compact binary mergers, especially with respect to forming the heaviest r-process elements in galactic evolution