Current Issue : July - September Volume : 2014 Issue Number : 3 Articles : 6 Articles
Background: Previous work in our laboratory demonstrated that hyperoxia suppressed the expression of vascular\nendothelial growth factor (VEGF) by the embryonic lung, leading to increased epithelial cell apoptosis and failure of\nexplant airway growth and branching that was rescued by the addition of Vegf165. The aims of this study were to\ndetermine protective pathways by which VEGF isoforms attenuate hyperoxic lung growth retardation and to\nidentify the target cell for VEGF action.\nMethods: Timed pregnant CD-1 or fetal liver kinase (FLK1)-eGFP lung explants cultured in 3% or 50% oxygen were\ntreated �± Vegf121, VEGF164/Vegf165 or VEGF188 in the presence or absence of anti-rat neuropilin-1 (NRP1) antibody\nor GO6983 (protein kinase C (PKC) pan-inhibitor) and lung growth and branching quantified. Immunofluorescence\nstudies were performed to determine apoptosis index and location of FLK1 phosphorylation and western blot studies\nof lung explants were performed to define the signaling pathways that mediate the protective effects of VEGF.\nResults: Heparin-binding VEGF isoforms (VEGF164/Vegf165 and VEGF188) but not Vegf121 selectively reduced\nepithelial apoptosis and partially rescued lung bud branching and growth. These protective effects required\nNRP1-dependent FLK1 activation in endothelial cells. Analysis of downstream signaling pathways demonstrated\nthat the VEGF-mediated anti-apoptotic effects were dependent on PKC activation.\nConclusions: Vegf165 activates FLK1-NRP1 signaling in endothelial cells, leading to a PKC-dependent paracrine\nsignal that in turn inhibits epithelial cell apoptosis...
Background: The formation of discrete elastin bands at the tips of secondary alveolar septa is important for normal\nalveolar development, but the mechanisms regulating the lung elastogenic program are incompletely understood.\nJNK suppress elastin synthesis in the aorta and is important in a host of developmental processes. We sought to\ndetermine whether JNK suppresses pulmonary fibroblast elastogenesis during lung development.\nMethods: Alveolar size, elastin content, and mRNA of elastin-associated genes were quantitated in wild type and\nJNK-deficient mouse lungs, and expression profiles were validated in primary lung fibroblasts. Tropoelastin protein\nwas quantitated by Western blot. Changes in lung JNK activity throughout development were quantitated, and\npJNK was localized by confocal imaging and lineage tracing.\nResults: By morphometry, alveolar diameters were increased by 7% and lung elastin content increased 2-fold in\nJNK-deficient mouse lungs compared to wild type. By Western blot, tropoelastin protein was increased 5-fold in\nJNK-deficient lungs. Postnatal day 14 (PND14) lung JNK activity was 11-fold higher and pJNK:JNK ratio 6-fold higher\ncompared to PN 8 week lung. Lung tropoelastin, emilin-1, fibrillin-1, fibulin-5, and lysyl oxidase mRNAs inversely\ncorrelated with lung JNK activity during alveolar development. Phosphorylated JNK localized to pulmonary\nlipofibroblasts. PND14 JNK-deficient mouse lungs contained 7-fold more tropoelastin, 2,000-fold more emilin-1,\n800-fold more fibrillin-1, and 60-fold more fibulin-5 than PND14 wild type lungs. Primarily lung fibroblasts from\nwild type and JNK-deficient mice showed similar differences in elastogenic mRNAs.\nConclusions: JNK suppresses fibroblast elastogenesis during the alveolar stage of lung development...
Background: Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with\ncommunity-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors\nand impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.\nMethods: This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three\nhospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with\nneither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on\nadmission.\nResults: Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C.\nPatients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001),\nCOPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated\nwith age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001)\nand renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001.\nAfter adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence\nof both ARF and SS had an OR of 6.32 (p < 0.001).\nConclusions: The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients\ninto three different clinical phenotypes...
Background: Impaired skeletal muscle regeneration could contribute to the progression of muscle atrophy in\npatients with chronic obstructive pulmonary disease (COPD).\nMethods: Satellite cells and myogenesis-related proteins were compared between healthy subjects and patients\nwith COPD, with or without muscle atrophy. Satellite cells were isolated and cultured to assess their proliferative\nand differentiation aptitudes.\nResults: Although satellite cell numbers in muscle samples were similar between groups, the proportion of muscle\nfibers with central nuclei was increased in COPD. In muscle homogenates, increased expression of MyoD and\ndecreased expression of myogenin and MRF4 were observed in COPD. In cultured satellite cells of patients with\nCOPD, increased protein content was observed for Pax7, Myf5 (proliferation phase) and myogenin (differentiation\nphase) while myosin heavy chain protein content was significantly lower during differentiation.\nConclusion: In COPD, the number of central nuclei was increased in muscle fibers suggesting a greater number of\nattempts to regenerate muscle tissue than in healthy subjects. Myogenesis signaling was also altered in muscle\nhomogenates in patients with COPD and there was a profound reduction in the differentiation potential in this\npopulation as indicated by a reduced ability to incorporate myosin heavy chain into newly formed myotubes.\nCollectively, these results indicate that skeletal muscle regenerative capacity termination is impaired in COPD and\ncould contribute to the progression of muscle atrophy progression in this population...
Background: Clinical studies of the associations of vitamin E with lung function have reported conflicting results.\r\nHowever, these reports primarily examine the a-tocopherol isoform of vitamin E and have not included the isoform\r\n?-tocopherol which we recently demonstrated in vitro opposes the function of a-tocopherol. We previously\r\ndemonstrated, in vitro and in animal studies, that the vitamin E isoform a-tocopherol protects, but the isoform\r\n?-tocopherol promotes lung inflammation and airway hyperresponsiveness.\r\nMethods: To translate these findings to humans, we conducted analysis of 4526 adults in the Coronary Artery\r\nRisk Development in Young Adults (CARDIA) multi-center cohort with available spirometry and tocopherol data in\r\nblacks and whites. Spirometry was obtained at years 0, 5, 10, and 20 and serum tocopherol was from years 0, 7\r\nand 15 of CARDIA.\r\nResults: In cross-sectional regression analysis at year 0, higher ?-tocopherol associated with lower FEV1 (p = 0.03\r\nin blacks and p = 0.01 in all participants) and FVC (p = 0.01 in blacks, p = 0.05 in whites, and p = 0.005 in all\r\nparticipants), whereas higher a-tocopherol associated with higher FVC (p = 0.04 in blacks and whites and p = 0.01\r\nin all participants). In the lowest quartile of a-tocopherol, higher ?-tocopherol associated with a lower FEV1\r\n(p = 0.05 in blacks and p = 0.02 in all participants). In contrast, in the lowest quartile of ?-tocopherol, higher\r\na-tocopherol associated with a higher FEV1 (p = 0.03) in blacks. Serum ?-tocopherol >10 Ã?µM was associated\r\nwith a 175ââ?¬â??545 ml lower FEV1 and FVC at ages 21ââ?¬â??55 years.\r\nConclusion: Increasing serum concentrations of ?-tocopherol were associated with lower FEV1 or FVC, whereas\r\nincreasing serum concentrations of a-tocopherol was associated with higher FEV1 or FVC. Based on the prevalence of\r\nserum ?-tocopherol >10 Ã?µM in adults in CARDIA and the adult U.S. population in the 2011 census, we expect that the\r\nlower FEV1 and FVC at these concentrations of serum ?-tocopherol occur in up to 4.5 million adults in the population....
Tobacco use is the leading cause of preventable illness and death. Tobacco is the risk factor for 6 out of 8 leading causes of death in the world. It has been estimated that there are 1.1 billion smokers worldwide and 182 million (16.6%) of them live in India. It has been predicted by the world health organization (WHO) that more than 500 million people alive today will be killed by tobacco by 2030 and tobacco consumption will become the single leading cause of death. It harms everyone who uses it or is exposed to it and kills 1 in every 2 users. In 17 out of 29 states of India, tobacco use is more than 69%. Smoking harms nearly every organ of the body. Tobacco use is major cause of morbidity and mortality worldwide. Health care professionals are ideally placed to advise people on how to stop smoking and to provide information on the supply of medication. All the health care professionals who have direct contact with the public, patients, relatives and care takers have a role to play in helping people to quit smoking. Health care professionals might be the only health care professionals to come in contact with prospective users of these products before or during their quit attempts....
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