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Sample records for detectable pulmonary inflammation

  1. Inflammation in pulmonary arterial hypertension.

    PubMed

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  2. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation

    PubMed Central

    2014-01-01

    The increasing manufacture and use of products based on nanotechnology raises concerns for both workers and consumers. Various studies report induction of pulmonary inflammation after inhalation exposure to nanoparticles, which can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Each of these aspects can affect their toxicity, although it is largely unknown to what extent. The aim of the current review is to analyse published data on inhalation of nanoparticles to identify and evaluate the contribution of their physicochemical characteristics to the onset and development of pulmonary inflammation. Many physicochemical characteristics of nanoparticles affect their lung deposition, clearance, and pulmonary response that, in combination, ultimately determine whether pulmonary inflammation will occur and to what extent. Lung deposition is mainly determined by the physical properties of the aerosol (size, density, shape, hygroscopicity) in relation to airflow and the anatomy of the respiratory system, whereas clearance and translocation of nanoparticles are mainly determined by their geometry and surface characteristics. Besides size and chemical composition, other physicochemical characteristics influence the induction of pulmonary inflammation after inhalation. As some nanoparticles dissolve, they can release toxic ions that can damage the lung tissue, making dissolution rate an important characteristic that affects lung inflammation. Fibre-shaped materials are more toxic to the lungs compared to spherical shaped nanoparticles of the same chemical composition. In general, cationic nanoparticles are more cytotoxic than neutral or anionic nanoparticles. Finally, surface reactivity correlates well with observed pulmonary inflammation. With all these characteristics affecting different stages of the events leading to pulmonary inflammation, no unifying dose metric could be identified to describe pulmonary

  3. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

    PubMed

    Rabinovitch, Marlene; Guignabert, Christophe; Humbert, Marc; Nicolls, Mark R

    2014-06-20

    This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. PMID:24951765

  4. Semaphorin 7A Aggravates Pulmonary Inflammation during Lung Injury

    PubMed Central

    Schneider, Mariella; Granja, Tiago Folgosa; Rosenberger, Peter

    2016-01-01

    The extent of pulmonary inflammation during lung injury ultimately determines patient outcome. Pulmonary inflammation is initiated by the migration of neutrophils into the alveolar space. Recent work has demonstrated that the guidance protein semaphorin 7A (SEMA7A) influences the migration of neutrophils into hypoxic tissue sites, yet, its role during lung injury is not well understood. Here, we report that the expression of SEMA7A is induced in vitro through pro-inflammatory cytokines. SEMA7A itself induces the production of pro-inflammatory cytokines in endothelial and epithelial cells, enhancing pulmonary inflammation. The induction of SEMA7A facilitates the transendothelial migration of neutrophils. In vivo, animals with deletion of SEMA7A expression showed reduced signs of pulmonary inflammatory changes following lipopolysaccharide challenge. We define here the role of SEMA7A in the development of lung injury and identify a potential pathway to interfere with these detrimental changes. Future anti-inflammatory strategies for the treatment of lung injury might be based on this finding. PMID:26752048

  5. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity.

    PubMed

    Poulsen, Sarah S; Jackson, Petra; Kling, Kirsten; Knudsen, Kristina B; Skaug, Vidar; Kyjovska, Zdenka O; Thomsen, Birthe L; Clausen, Per Axel; Atluri, Rambabu; Berthing, Trine; Bengtson, Stefan; Wolff, Henrik; Jensen, Keld A; Wallin, Håkan; Vogel, Ulla

    2016-11-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects. PMID:27323647

  6. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity.

    PubMed

    Poulsen, Sarah S; Jackson, Petra; Kling, Kirsten; Knudsen, Kristina B; Skaug, Vidar; Kyjovska, Zdenka O; Thomsen, Birthe L; Clausen, Per Axel; Atluri, Rambabu; Berthing, Trine; Bengtson, Stefan; Wolff, Henrik; Jensen, Keld A; Wallin, Håkan; Vogel, Ulla

    2016-11-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.

  7. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

    PubMed Central

    Poulsen, Sarah S.; Jackson, Petra; Kling, Kirsten; Knudsen, Kristina B.; Skaug, Vidar; Kyjovska, Zdenka O.; Thomsen, Birthe L.; Clausen, Per Axel; Atluri, Rambabu; Berthing, Trine; Bengtson, Stefan; Wolff, Henrik; Jensen, Keld A.; Wallin, Håkan; Vogel, Ulla

    2016-01-01

    Abstract Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects. PMID:27323647

  8. Biology of diesel exhaust effects on allergic pulmonary inflammation.

    PubMed

    Inoue, Ken-ichiro; Takano, Hirohisa

    2011-03-01

    Although the adverse health effects of diesel exhaust particles (DEP) have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions (pathological conditions) have not been fully identified. On the other hand, there exist hypersensitive subjects against particulate matters. In this review, we provide insights into the immunotoxicity of DEP as an aggravating factor in hypersusceptible subjects, especially those with allergic pulmonary diseases using our in vivo experimental model. In brief, we examined the effects of DEP on allergic asthma in vivo, and showed that repetitive pulmonary exposure to DEP has promoting effects on allergic airway inflammation, including adjuvanticity on Th2-milieu. Further, we propose a causal machinery regarding the adverse impacts, i.e., via inappropriate activation of antigen-presenting cells such as dendritic cells.

  9. Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

    PubMed Central

    Fuster, Antonia; Sauleda, Jaume; Sala, Ernest; Barceló, Bernardí; Pons, Jaume; Carrera, Miguel; Noguera, Aina; Togores, Bernat; Agustí, Alvar GN

    2008-01-01

    Objective Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients. Patients and methods To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV1] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV1 98 ± 5% ref). Results We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD. Conclusions This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise. PMID:18488438

  10. ICAM-1 Targeted Nanogels Loaded with Dexamethasone Alleviate Pulmonary Inflammation

    PubMed Central

    Coll Ferrer, M. Carme; Shuvaev, Vladimir V.; Zern, Blaine J.; Composto, Russell J.; Muzykantov, Vladimir R.; Eckmann, David M.

    2014-01-01

    Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with “stealth” properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV) injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i) ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG); and, ii) DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation. PMID:25019304

  11. CFTR-regulated MAPK/NF-κB signaling in pulmonary inflammation in thermal inhalation injury

    PubMed Central

    Dong, Zhi Wei; Chen, Jing; Ruan, Ye Chun; Zhou, Tao; Chen, Yu; Chen, YaJie; Tsang, Lai Ling; Chan, Hsiao Chang; Peng, Yi Zhi

    2015-01-01

    The mechanism underlying pulmonary inflammation in thermal inhalation injury remains elusive. Cystic fibrosis, also hallmarked with pulmonary inflammation, is caused by mutations in CFTR, the expression of which is temperature-sensitive. We investigated whether CFTR is involved in heat-induced pulmonary inflammation. We applied heat-treatment in 16HBE14o- cells with CFTR knockdown or overexpression and heat-inhalation in rats in vivo. Heat-treatment caused significant reduction in CFTR and, reciprocally, increase in COX-2 at early stages both in vitro and in vivo. Activation of ERK/JNK, NF-κB and COX-2/PGE2 were detected in heat-treated cells, which were mimicked by knockdown, and reversed by overexpression of CFTR or VX-809, a reported CFTR mutation corrector. JNK/ERK inhibition reversed heat-/CFTR-knockdown-induced NF-κB activation, whereas NF-κB inhibitor showed no effect on JNK/ERK. IL-8 was augmented by heat-treatment or CFTR-knockdown, which was abolished by inhibition of NF-κB, JNK/ERK or COX-2. Moreover, in vitro or in vivo treatment with curcumin, a natural phenolic compound, significantly enhanced CFTR expression and reversed the heat-induced increases in COX-2/PGE2/IL-8, neutrophil infiltration and tissue damage in the airway. These results have revealed a CFTR-regulated MAPK/NF-κB pathway leading to COX-2/PGE2/IL-8 activation in thermal inhalation injury, and demonstrated therapeutic potential of curcumin for alleviating heat-induced pulmonary inflammation. PMID:26515683

  12. Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure

    PubMed Central

    Nurkiewicz, Timothy R.; Porter, Dale W.; Barger, Mark; Millecchia, Lyndell; Rao, K. Murali K.; Marvar, Paul J.; Hubbs, Ann F.; Castranova, Vincent; Boegehold, Matthew A.

    2006-01-01

    The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well known, but the systemic mechanisms that drive this effect remain unclear. We have previously shown that acute pulmonary exposure to PM impairs or abolishes endothelium-dependent arteriolar dilation in the rat spinotrapezius muscle. The purpose of this study was to further characterize the effect of pulmonary PM exposure on systemic microvascular function and to identify local inflammatory events that may contribute to these effects. Rats were intratracheally instilled with residual oil fly ash (ROFA) or titanium dioxide at 0.1 or 0.25 mg/rat 24 hr before measurement of pulmonary and systemic microvascular responses. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar responses to intraluminal infusion of the Ca2+ ionophore A23187 or iontophoretic abluminal application of the adrenergic agonist phenylephrine (PHE). Leukocyte rolling and adhesion were quantified in venules paired with the studied arterioles. Histologic techniques were used to assess pulmonary inflammation, characterize the adherence of leukocytes to systemic venules, verify the presence of myeloperoxidase (MPO) in the systemic microvascular wall, and quantify systemic microvascular oxidative stress. In the lungs of rats exposed to ROFA or TiO2, changes in some bronchoalveolar lavage markers of inflammation were noted, but an indication of cellular damage was not found. In rats exposed to 0.1 mg ROFA, focal alveolitis was evident, particularly at sites of particle deposition. Exposure to either ROFA or TiO2 caused a dose-dependent impairment of endothelium-dependent arteriolar dilation. However, exposure to these particles did not affect microvascular constriction in response to PHE. ROFA and TiO2 exposure significantly increased leukocyte rolling and adhesion in paired venules, and these cells were positively identified as

  13. Systemic microvascular dysfunction and inflammation after pulmonary particulate matter exposure.

    PubMed

    Nurkiewicz, Timothy R; Porter, Dale W; Barger, Mark; Millecchia, Lyndell; Rao, K Murali K; Marvar, Paul J; Hubbs, Ann F; Castranova, Vincent; Boegehold, Matthew A

    2006-03-01

    The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well known, but the systemic mechanisms that drive this effect remain unclear. We have previously shown that acute pulmonary exposure to PM impairs or abolishes endothelium-dependent arteriolar dilation in the rat spinotrapezius muscle. The purpose of this study was to further characterize the effect of pulmonary PM exposure on systemic microvascular function and to identify local inflammatory events that may contribute to these effects. Rats were intratracheally instilled with residual oil fly ash (ROFA) or titanium dioxide at 0.1 or 0.25 mg/rat 24 hr before measurement of pulmonary and systemic microvascular responses. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar responses to intraluminal infusion of the Ca2+ ionophore A23187 or iontophoretic abluminal application of the adrenergic agonist phenylephrine (PHE). Leukocyte rolling and adhesion were quantified in venules paired with the studied arterioles. Histologic techniques were used to assess pulmonary inflammation, characterize the adherence of leukocytes to systemic venules, verify the presence of myeloperoxidase (MPO) in the systemic microvascular wall, and quantify systemic microvascular oxidative stress. In the lungs of rats exposed to ROFA or TiO2, changes in some bronchoalveolar lavage markers of inflammation were noted, but an indication of cellular damage was not found. In rats exposed to 0.1 mg ROFA, focal alveolitis was evident, particularly at sites of particle deposition. Exposure to either ROFA or TiO2 caused a dose-dependent impairment of endothelium-dependent arteriolar dilation. However, exposure to these particles did not affect microvascular constriction in response to PHE. ROFA and TiO2 exposure significantly increased leukocyte rolling and adhesion in paired venules, and these cells were positively identified as

  14. Asiatic acid inhibits pulmonary inflammation induced by cigarette smoke.

    PubMed

    Lee, Jae-Won; Park, Hyun Ah; Kwon, Ok-Kyoung; Jang, Yin-Gi; Kim, Ju Yeong; Choi, Bo Kyung; Lee, Hee Jae; Lee, Sangwoo; Paik, Jin-Hyub; Oh, Sei-Ryang; Ahn, Kyung-Seop; Lee, Hyun-Jun

    2016-10-01

    Asiatic acid (AA) is one of the major components of Titrated extract of Centella asiatica (TECA), which has been reported to possess antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the protective effect of AA on pulmonary inflammation induced by cigarette smoke (CS). AA significantly attenuated the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) of CS exposure mice. AA also decreased ROS production and NE activity, and inhibited the release of proinflammatory cytokines in BALF. AA reduced the recruitment of inflammatory cells and MCP-1 expression in lung tissue of CS exposure mice. AA also attenuated mucus overproduction, and decreased the activation of MAPKs and NF-kB in lung tissue. Furthermore, AA increased HO-1 expression and inhibited the reduced expression of SOD3 in lung tissue. These findings indicate that AA effectively inhibits pulmonary inflammatory response, which is an important process in the development of chronic obstructive pulmonary disease (COPD) via suppression of inflammatory mediators and induction of HO-1. Therefore, we suggest that AA has the potential to treat inflammatory disease such as COPD.

  15. Inhalation of Carbon Black Nanoparticles Aggravates Pulmonary Inflammation in Mice

    PubMed Central

    Saputra, Devina; Yoon, Jin-ha; Park, Hyunju; Heo, Yongju; Yang, Hyoseon; Lee, Eun Ji; Lee, Sangjin; Song, Chang-Woo; Lee, Kyuhong

    2014-01-01

    An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-γ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be 12.5 μg/m3) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions. PMID:25071917

  16. Immune Inflammation and Disease Progression in Idiopathic Pulmonary Fibrosis.

    PubMed

    Balestro, Elisabetta; Calabrese, Fiorella; Turato, Graziella; Lunardi, Francesca; Bazzan, Erica; Marulli, Giuseppe; Biondini, Davide; Rossi, Emanuela; Sanduzzi, Alessandro; Rea, Federico; Rigobello, Chiara; Gregori, Dario; Baraldo, Simonetta; Spagnolo, Paolo; Cosio, Manuel G; Saetta, Marina

    2016-01-01

    The clinical course in idiopathic pulmonary fibrosis (IPF) is highly heterogeneous, with some patients having a slow progression and others an accelerated clinical and functional decline. This study aims to clinically characterize the type of progression in IPF and to investigate the pathological basis that might account for the observed differences in disease behavior. Clinical and functional data were analyzed in 73 IPF patients, followed long-time as candidates for lung transplantation. The forced vital capacity (FVC) change/year (< or ≥10% predicted) was used to define "slow" or "rapid" disease progression. Pathological abnormalities were quantified in the explanted lung of 41 out of 73 patients undergoing lung transplantation. At diagnosis, slow progressors (n = 48) showed longer duration of symptoms and lower FVC than rapid progressors (n = 25). Eleven slow and 3 rapid progressors developed an acute exacerbation (AE) during follow-up. Quantitative lung pathology showed a severe innate and adaptive inflammatory infiltrate in rapid progressors, markedly increased compared to slow progressors and similar to that observed in patients experiencing AE. The extent of inflammation was correlated with the yearly FVC decline (r = 0.52, p = 0.005). In conclusion an innate and adaptive inflammation appears to be a prominent feature in the lung of patients with IPF and could contribute to determining of the rate of disease progression. PMID:27159038

  17. Establishment of a mouse model for pulmonary inflammation and fibrosis by intratracheal instillation of polyhexamethyleneguanidine phosphate

    PubMed Central

    Lee, Sang Jin; Park, Jong-Hwan; Lee, Jun-Young; Jeong, Yu-Jin; Song, Jeong Ah; Lee, Kyuhong; Kim, Dong-Jae

    2016-01-01

    Although several animal models have been developed to study human pulmonary fibrosis, lack of a perfect model has raised the need for various animal models of pulmonary fibrosis. In this study, we evaluated the pulmonary effect of polyhexamethyleneguanidine phosphate instillation into the lungs of mice to determine the potential of these mice as a murine model of pulmonary fibrosis. Intratracheal instillation of polyhexamethyleneguanidine phosphate induced severe lung inflammation manifested by the infiltration of mononuclear cells and neutrophils and increased production of IL-6, TNF-α, CCL2 and CXCL1. The lung inflammation gradually increased until 28 days after polyhexamethyleneguanidine phosphate exposure, and increases of collagen deposition and TGF-β production, which are indicators of pulmonary fibrosis, were seen. Our study showed that intratracheal instillation of polyhexamethyleneguanidine phosphate induces pulmonary inflammation and fibrosis in mice. PMID:27182113

  18. Dihydroartemisinin supresses inflammation and fibrosis in bleomycine-induced pulmonary fibrosis in rats

    PubMed Central

    Yang, Dongxia; Yuan, Wendan; Lv, Changjun; Li, Naie; Liu, Tongshen; Wang, Liang; Sun, Yufei; Qiu, Xueshan; Fu, Qiang

    2015-01-01

    Pulmonary fibrosis is a respiratory disease with a high mortality rate and its pathogenesis involves multiple mechanisms including epithelial cell injury, fibroblast proliferation, inflammation, and collagen coagulation. The treatment regimens still fail to recover this disease. We have previously found that dihydroartemisinin inhibits the development of pulmonary fibrosis in rats. This study aimed to determine the mechanisms of dihydroartemisinin in bleomycin-induced pulmonary fibrosis. The experimental rats were divided into six groups as normal saline control group (NS group), bleomycin group (BLM group), dihydroartemisinin-1, -2, or -3 group (DHA-1, DHA-2 and DHA-3 group) and dexamethasone group (DXM group). In BLM group, rats were treated with intratracheal instillation of bleomycin. NS group received the same volume of saline instead of bleomycin. In DHA-1, DHA-2 and DHA-3 group, in addition to intratracheal instillation of bleomycin, respectively, dihydroartemisinin (25 mg/kg, 50 mg/kg, 100 mg/kg daily) was administrated by intraperitoneal instillation. In DXM group, rats were treated with intraperitoneal instillation of dexamethasone as control. Immunocytochemical assay, reverse transcription PCR and western blot were used for detecting the expression of TGF-β1, TNF-α, α-SMA and NF-κB in lung tissues. What’s more, morphological change and collagen deposition were analyzed by hematoxylin-eosin staining and Masson staining. Collagen synthesis was detected by hydroxyproline chromatometry. Results showed that dihydroartemisinin significantly decreased the amount of inflammatory cytokines and collagen synthesis, and inhibited fibroblast proliferation in bleomycin-induced pulmonary fibrosis (P < 0.001). This study provides experimental evidence that dihydroartemisinin could decrease cytokines, alveolar inflammation and attenuates lung injury and fibrosis. PMID:25973011

  19. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

    SciTech Connect

    Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.; Wewers, M.D.; Adelberg, S.; Crystal, R.G.

    1986-05-22

    We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known.

  20. Pulmonary oxidative stress, inflammation and dysregulated iron homeostatis in rat models of cardiovascular disease

    EPA Science Inventory

    Underlying cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms ofvariation in susceptibility. Pulmonary oxidative stress, inflammation and altere...

  1. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    EPA Science Inventory

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  2. Protective role of interleukin-10 in Ozone-induced pulmonary inflammation**

    EPA Science Inventory

    Background: The mechanisms underlying ozone (03)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: We investigated the molecular mechanisms underlying interleuken-10...

  3. Balance impairment and systemic inflammation in chronic obstructive pulmonary disease

    PubMed Central

    Tudorache, Emanuela; Oancea, Cristian; Avram, Claudiu; Fira-Mladinescu, Ovidiu; Petrescu, Lucian; Timar, Bogdan

    2015-01-01

    Background/purpose Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment. The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation. Methods We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data. We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers. Results The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001). The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001). We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes. In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test. Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire. Conclusion According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity

  4. Immune Modulatory Effects of IL-22 on Allergen-Induced Pulmonary Inflammation

    PubMed Central

    Fang, Ping; Zhou, Li; Zhou, Yuqi; Kolls, Jay K.; Zheng, Tao; Zhu, Zhou

    2014-01-01

    IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA)-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR) were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox) induction, IL-22 protein was readily detected in the large (CC10 promoter) and small (SPC promoter) airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL), and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma. PMID:25254361

  5. Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats.

    PubMed

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

    2016-01-01

    With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs. PMID:27524893

  6. Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

    PubMed Central

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

    2016-01-01

    With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs. PMID:27524893

  7. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    PubMed Central

    Jacobsen, Nicklas Raun; Møller, Peter; Jensen, Keld Alstrup; Vogel, Ulla; Ladefoged, Ole; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles. PMID:19138394

  8. Skeletal muscle response to inflammation--lessons for chronic obstructive pulmonary disease.

    PubMed

    Reid, W Darlene; Rurak, Jennifer; Harris, R Luke

    2009-10-01

    To describe how inflammation affects muscle adaptation and performance in people with chronic obstructive pulmonary disease. In chronic obstructive pulmonary disease, an increasingly sedentary lifestyle is a primary contributor to muscle dysfunction that results in a loss of mobility and independence and, ultimately, mortality. Given the systemic chronic inflammation and profound limb muscle atrophy in chronic obstructive pulmonary disease, it is tempting to speculate that the inflammatory process is deleterious to skeletal muscle. In healthy people, however, the inflammatory process initially is dominated by a destructive phase that is tightly regulated and modulates a reparative, regenerative phase. Although the inflammatory process and associated oxidative stress is more closely connected to muscle wasting in animal models of chronic obstructive pulmonary disease, the causative role of inflammation toward muscle atrophy and weakness in people with chronic obstructive pulmonary disease has not been definitively shown. Anti-inflammatory interventions aimed toward tempering muscle wasting and weakness in chronic obstructive pulmonary disease may not prove to be beneficial because of longer-term disruption of the regeneration of muscle tissue. Temporally and spatially targeted interventions aimed toward ameliorating oxidative stress, such as antioxidants, nutritional supplements, and chronic exercise training, may optimize outcomes toward maintaining muscle mass and performance.

  9. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients

    PubMed Central

    do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients. PMID:25848241

  10. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

    PubMed

    do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.

  11. Inhibitory effects of hydrogen sulphide on pulmonary fibrosis in smoking rats via attenuation of oxidative stress and inflammation.

    PubMed

    Zhou, Xiang; An, Guoyin; Chen, Jianchang

    2014-06-01

    Accumulating evidence has demonstrated that hydrogen sulphide (H2 S) is involved in the pathogenesis of various respiratory diseases. In the present study, we established a rat model of passive smoking and investigated whether or not H2 S has protective effects against pulmonary fibrosis induced by chronic cigarette smoke exposure. Rat lung tissues were stained with haematoxylin-eosin and Masson's trichrome. The expression of type I collagen was detected by immunohistochemistry. Oxidative stress was evaluated by detecting serum levels of malondialdehyde, superoxide dismutase and glutathione peroxidase and measuring reactive oxygen species generation in lung tissue. Inflammation was assessed by measuring serum levels of inflammatory cytokines, including high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin (IL)-1β and IL-6. The protein expression of Nrf2, NF-κB and phosphorylated mitogen-activated protein kinases (MAPKs) in the pulmonary tissue was determined by Western blotting. Our findings indicated that administration of NaHS (a donor of H2 S) could protect against pulmonary fibrosis in the smoking rats. H2 S was found to induce the nuclear accumulation of Nrf2 in lung tissue and consequently up-regulate the expression of antioxidant genes HO-1 and Trx-1 in the smoking rats. Moreover, H2 S could also reduce cigarette smoking-induced inflammation by inhibiting the phosphorylation of ERK 1/2, JNK and p38 MAPKs and negatively regulating NF-κB activation. In conclusion, our study suggests that H2 S has protective effects against pulmonary fibrosis in the smoking rats by attenuating oxidative stress and inflammation.

  12. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  13. The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes

    PubMed Central

    Poth, Jens M.; Fini, Mehdi A.; Olschewski, Andrea; El Kasmi, Karim C.; Stenmark, Kurt R.

    2014-01-01

    Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease. PMID:25416383

  14. Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease

    PubMed Central

    Ghosh, Sumit; Hoselton, Scott A.; Dorsam, Glenn P.; Schuh, Jane M.

    2015-01-01

    Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung. PMID:25582403

  15. Inflammation in pulmonary hypertension: what we know and what we could logically and safely target first.

    PubMed

    Cohen-Kaminsky, Sylvia; Hautefort, Aurélie; Price, Laura; Humbert, Marc; Perros, Frédéric

    2014-08-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in most of the animal models of pulmonary arterial hypertension (PAH), and therapeutic targeting of inflammation in these models blocks PAH development. In humans, pulmonary vascular lesions of PAH are the source of cytokine and chemokine production, related to inflammatory cell recruitment and lymphoid neogenesis. Circulating autoantibodies to endothelial cells and to fibroblasts have been reported in 10-40% of patients with idiopathic PAH, suggesting a possible role for autoimmunity in the pathogenesis of pulmonary vascular lesions. Current specific PAH treatments have immunomodulatory properties, and some studies have demonstrated a correlation between levels of circulating inflammatory mediators and patient survival. New immunopathological approaches to PAH should enable the development of innovative treatments for this severe condition. PMID:24747559

  16. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.

    PubMed

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F; Hoyle, Gary W

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury.

  17. Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae.

    PubMed

    Olivo, Clarice R; Miyaji, Eliane N; Oliveira, Maria Leonor S; Almeida, Francine M; Lourenço, Juliana D; Abreu, Rodrigo M; Arantes, Petra M M; Lopes, Fernanda Dtqs; Martins, Milton A

    2014-11-01

    Aerobic exercise has been recognized as a stimulator of the immune system, but its effect on bacterial infection has not been extensively evaluated. We studied whether moderate aerobic exercise training prior to Streptococcus pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into four groups: Sedentary Untreated (sedentary without infection); Sedentary Infected (sedentary with infection); Trained Untreated (aerobic training without infection); and Trained Infected (aerobic training with infection). Animals underwent aerobic training for 4 wk, and 72 h after last exercise training, animals received a challenge with S. pneumoniae and were evaluated either 12 h or 10 days after instillation. In acute phase, Sedentary Infected group had an increase in respiratory system resistance and elastance; number of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BAL); polymorphonuclear cells in lung parenchyma; and levels of keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β (IL-1β) in lung homogenates. Exercise training significantly attenuated the increase in all of these parameters and induced an increase in expression of antioxidant enzymes (CuZnSOD and MnSOD) in lungs. Trained Infected mice had a significant decrease in the number of colony-forming units of pneumococci in the lungs compared with Sedentary Infected animals. Ten days after infection, Trained Infected group exhibited lower numbers of macrophages in BAL, polymorphonuclear cells in lung parenchyma and IL-6 in lung homogenates compared with Sedentary Infected group. Our results suggest a protective effect of moderate exercise training against respiratory infection with S. pneumoniae. This effect is most likely secondary to an effect of exercise on oxidant-antioxidant balance.

  18. Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

    PubMed

    Loutsios, Chrystalla; Farahi, Neda; Simmonds, Rosalind; Cullum, Ian; Gillett, Daniel; Solanki, Chandra; Solanki, Kishor; Buscombe, John; Condliffe, Alison M; Peters, A Mike; Chilvers, Edwin R

    2015-11-01

    The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.

  19. Combined radiation and burn injury results in exaggerated early pulmonary inflammation

    PubMed Central

    Palmer, Jessica L.; Deburghgraeve, Cory R.; Bird, Melanie D.; Hauer-Jensen, Martin; Chen, Michael M.; Yong, Sherri; Kovacs, Elizabeth J.

    2014-01-01

    Events such as a nuclear meltdown accident or nuclear attack have potential for severe radiation injuries. Radiation injury frequently occurs in combination with other forms of trauma, most often burns. Thus far, combined injury studies have focused mainly on skin wound healing and damage to the gut. Since both radiation exposure and remote burn have pulmonary consequences, we examined the early effects of combined injury on the lung. C57BL/6 male mice were subjected to 5 Gy of total body irradiation followed by a 15% total body surface area scald burn. Lungs from surviving animals were examined for evidence of inflammation and pneumonitis. At 48 hours post-injury, pathology of the lungs from combined injury mice showed greater inflammation compared to all other treatment groups, with marked red blood cell and leukocyte congestion of the pulmonary vasculature. There was excessive leukocyte accumulation, primarily neutrophils, in the vasculature and interstitium, with occasional cells in the alveolar space. At 24 and 48 hours post-injury, myeloperoxidase levels in lungs of mice given combined injury were elevated compared to all other treatment groups (p<0.01), confirming histological evidence of neutrophil accumulation. Pulmonary levels of the neutrophil chemoattractant KC (CXCL1) were 3 times above that of either injury alone (p<0.05). Further, monocyte chemotactic protein-1 (MCP-1, CCL2) was increased 2-fold and 3-fold compared to burn injury or radiation injury, respectively (p<0.05). Together, these data suggest that combined radiation and burn injury augments early pulmonary congestion and inflammation.. Currently, countermeasures for this unique type of injury are extremely limited. Further research is needed to elucidate the mechanisms behind the synergistic effects of combined injury in order to develop appropriate treatments. PMID:23899376

  20. Non-invasive biomarkers of pulmonary damage and inflammation: Application to children exposed to ozone and trichloramine

    SciTech Connect

    Bernard, Alfred . E-mail: bernard@toxi.ucl.ac.be; Carbonnelle, Sylviane; Nickmilder, Marc; Burbure, Claire de

    2005-08-07

    To date, airways injury or inflammation caused by air pollutants has been evaluated mainly by analysis of bronchoalveolar lavage, an invasive technique totally unsuitable to children. The assessment of respiratory risks in this particularly vulnerable population has thus for a long time relied on spirometric tests and self-reported symptoms which are relatively late and inaccurate indicators of lung damage. Research in the field of biomarkers is now opening new perspectives with the development of non-invasive tests allowing to monitor inflammation and damage in the deep lung. Blood tests measuring lung-specific proteins (pneumoproteins) such as Clara cell protein (CC16) and surfactant-associated proteins (A, B or D) are now available to evaluate the permeability and/or the cellular integrity of the pulmonary epithelium. The application of these tests to children has recently led to the discovery of a lung epithelium hyperpermeability caused by trichloramine (nitrogen trichloride), an irritant gas contaminating the air of indoor-chlorinated pools. Serum CC16 can also serve to detect increases of airway permeability during short-term exposures to ambient ozone. Indicators measurable in exhaled air such as nitric oxide (NO) appear more useful to detect airway inflammation. By applying the exhaled NO test to children attending summer camps, we recently found that ambient ozone produces an acute inflammatory response in children from levels slightly lower than current air quality guidelines. In a study exploring the links between atopy, asthma, and exposure to chlorination products in indoor pools, we also found that the exhaled NO test can serve to detect the chronic airway inflammation associated with excessive exposure to trichloramine. Lung-specific proteins measurable in serum and markers in exhaled air represent sensitive tools that can be used to assess non-invasively the effects of air pollutants on the respiratory tract of children.

  1. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    SciTech Connect

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  2. Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection

    PubMed Central

    Akthar, Samia; Patel, Dhiren F.; Beale, Rebecca C.; Peiró, Teresa; Xu, Xin; Gaggar, Amit; Jackson, Patricia L.; Blalock, J. Edwin; Lloyd, Clare M.; Snelgrove, Robert J.

    2015-01-01

    Bioactive matrix fragments (matrikines) have been identified in a myriad of disorders, but their impact on the evolution of airway inflammation has not been demonstrated. We recently described a pathway where the matrikine and neutrophil chemoattractant proline–glycine–proline (PGP) could be degraded by the enzyme leukotriene A4 hydrolase (LTA4H). LTA4H classically functions in the generation of pro-inflammatory leukotriene B4, thus LTA4H exhibits opposing pro- and anti-inflammatory activities. The physiological significance of this secondary anti-inflammatory activity remains unknown. Here we show, using readily resolving pulmonary inflammation models, that loss of this secondary activity leads to more pronounced and sustained inflammation and illness owing to PGP accumulation. PGP elicits an exacerbated neutrophilic inflammation and protease imbalance that further degrades the extracellular matrix, generating fragments that perpetuate inflammation. This highlights a critical role for the secondary anti-inflammatory activity of LTA4H and thus has consequences for the generation of global LTA4H inhibitors currently being developed. PMID:26400771

  3. Effect of naturally occurring ozone air pollution episodes on pulmonary oxidative stress and inflammation.

    PubMed

    Pirozzi, Cheryl; Sturrock, Anne; Weng, Hsin-Yi; Greene, Tom; Scholand, Mary Beth; Kanner, Richard; Paine, Robert

    2015-05-12

    This study aimed to determine if naturally occurring episodes of ozone air pollution in the Salt Lake Valley in Utah, USA, during the summer are associated with increased pulmonary inflammation and oxidative stress, increased respiratory symptoms, and decreased lung function in individuals with chronic obstructive pulmonary disease (COPD) compared to controls. We measured biomarkers (nitrite/nitrate (NOx), 8-isoprostane) in exhaled breath condensate (EBC), spirometry, and respiratory symptoms in 11 former smokers with moderate-to-severe COPD and nine former smokers without airflow obstruction during periods of low and high ozone air pollution. High ozone levels were associated with increased NOx in EBC in both COPD (8.7 (±8.5) vs. 28.6 (±17.6) μmol/L on clean air vs. pollution days, respectively, p < 0.01) and control participants (7.6 (±16.5) vs. 28.5 (±15.6) μmol/L on clean air vs. pollution days, respectively, p = 0.02). There was no difference in pollution effect between COPD and control groups, and no difference in EBC 8-isoprostane, pulmonary function, or respiratory symptoms between clean air and pollution days in either group. Former smokers both with and without airflow obstruction developed airway oxidative stress and inflammation in association with ozone air pollution episodes.

  4. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1.

    PubMed

    Peng, Zhanglong; Pati, Shibani; Potter, Daniel; Brown, Ryan; Holcomb, John B; Grill, Raymond; Wataha, Kathryn; Park, Pyong Woo; Xue, Hasen; Kozar, Rosemary A

    2013-09-01

    We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan 1 and that the early use of fresh frozen plasma (FFP) in these patients is correlated with improved clinical outcomes. As the lungs are frequently injured after trauma, we hypothesized that hemorrhagic shock-induced shedding of syndecan 1 exposes the underlying pulmonary vascular endothelium to injury resulting in inflammation and hyperpermeability and that these effects would be mitigated by FFP. In vitro, pulmonary endothelial permeability, endothelial monolayer flux, transendothelial electrical resistance, and leukocyte-endothelial binding were measured in pulmonary endothelial cells after incubation with equal volumes of FFP or lactated Ringer's (LR). In vivo, using a coagulopathic mouse model of trauma and hemorrhagic shock, pulmonary hyperpermeability, neutrophil infiltration, and syndecan 1 expression and systemic shedding were assessed after 3 h of resuscitation with either 1× FFP or 3× LR and compared with shock alone and shams. In vitro, endothelial permeability and flux were decreased, transendothelial electrical resistance was increased, and leukocyte-endothelial binding was inhibited by FFP compared with LR-treated endothelial cells. In vivo, hemorrhagic shock was associated with systemic shedding of syndecan 1, which correlated with decreased pulmonary syndecan 1 and increased pulmonary vascular hyperpermeability and inflammation. Fresh frozen plasma resuscitation, compared with LR resuscitation, abrogated these injurious effects. After hemorrhagic shock, FFP resuscitation inhibits endothelial cell hyperpermeability and inflammation and restores pulmonary syndecan 1 expression. Modulation of pulmonary syndecan 1 expression may mechanistically contribute to the beneficial effects FFP.

  5. Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.

    PubMed

    Wood, Tyler T; Winden, Duane R; Marlor, Derek R; Wright, Alex J; Jones, Cameron M; Chavarria, Michael; Rogers, Geraldine D; Reynolds, Paul R

    2014-11-15

    The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.

  6. Cell- and isoform-specific increases in arginase expression in acute silica-induced pulmonary inflammation.

    PubMed

    Poljakovic, Mirjana; Porter, Dale W; Millecchia, Lyndell; Kepka-Lenhart, Diane; Beighley, Christopher; Wolfarth, Michael G; Castranova, Vincent; Morris, Sidney M

    2007-01-15

    Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase were elucidated in lungs of Sprague-Dawley rats 24 h following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time polymerase chain reaction (PCR), and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced two- and three-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100 g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no inducible nitric oxide synthase (iNOS) immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica. PMID:17365572

  7. Cell- and Isoform-specific Increases in Arginase Expression in Acute Silica-induced Pulmonary Inflammation

    PubMed Central

    Poljakovic, Mirjana; Porter, Dale W.; Millecchia, Lyndell; Kepka-Lenhart, Diane; Beighley, Christopher; Wolfarth, Michael G.; Castranova, Vincent; Morris, Sidney M.

    2009-01-01

    Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase was elucidated in lungs of Sprague-Dawley rats 24 hr following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time PCR, and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced 2- and 3-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no iNOS immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica. PMID:17365572

  8. Serum amyloid A opposes lipoxin A₄ to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease.

    PubMed

    Bozinovski, Steven; Uddin, Mohib; Vlahos, Ross; Thompson, Michelle; McQualter, Jonathan L; Merritt, Anne-Sophie; Wark, Peter A B; Hutchinson, Anastasia; Irving, Louis B; Levy, Bruce D; Anderson, Gary P

    2012-01-17

    Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A(4) (LXA(4)) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA(2) 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA(4). Human lung macrophages (CD68(+)) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC(50) 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA(4) but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

  9. Silver Nanoparticles: A study of dissolution, kinetics, and factors affecting pulmonary inflammation

    NASA Astrophysics Data System (ADS)

    Saunders, Eric L.

    The growing use of silver (Ag) nanoparticles (NP) in consumer and industrial goods has led to an increase in interest in the health effects associated with exposure, both occupationally and environmentally. The aim of this research is to examine the contribution of size, shape, and dissolution of AgNP, with its corresponding effect on pulmonary inflammation and clearance. In addition this study looks at metallothionein (MT) and the role it plays as an inflammatory modulator. A nose only exposure method was used to expose three strains of mouse (two inbred, one knockout) to two different sizes of AgNP (˜25 nm and ˜100 nm). This research demonstrates that size, chemistry, and dissolution play key roles in NP deposition and inflammatory response, while no conclusions could be drawn about shape. Additionally, this study found that the main factors affecting the deposition of NP in mice both acutely and sub-chronically are particle size and mouse strain. The results of this study also indicate a relationship between MT2 and inflammation. It was found that the mRNA levels of MT2 were greatly up-regulated in the livers and lungs of mice exposed to AgNP, while MT protein levels were not significantly altered to correlate with the altered regulation of mRNA. Finally, this study showed that, for AgNP, the mechanisms of pulmonary clearance and dissolution happened rapidly and that they, combined, likely represent a major pathway of AgNP transport out of the lung. Taken as a whole, the data in this study show that dissolution, coupled with protein interaction, is a significant mediator of pulmonary inflammation and translocation of AgNP.

  10. Acute effect of glucan-spiked office dust on nasal and pulmonary inflammation in guinea pigs.

    PubMed

    Straszek, S P; Adamcakova-Dodd, A; Metwali, N; Pedersen, O F; Sigsgaard, T; Thorne, P S

    2007-11-01

    The acute effects of pure inhaled glucan on respiratory inflammation remain inconclusive and not sufficiently examined with regards to the simultaneous interaction of glucan, endotoxin (lipopolysaccharide, LPS), and house dust in airway inflammation. This study aims at determining effects of simultaneous exposure to office dust and glucan on nasal and pulmonary inflammation. This is relevant for humans with occupational exposure in waste handling and farming and buildings with mold problems. Office dust collected from Danish offices was spiked with 1% (1-3)-beta-glucan (curdlan). Guinea pig nasal cavity volume was measured by acoustic rhinometry (AR) and animals were exposed by inhalation for 4 h to curdlan-spiked dust, unspiked dust, purified air (negative controls), or LPS (positive controls). After exposure (+5 h) or the following day (+18 h), measurements were repeated by AR and followed by bronchoalveolar lavage (BAL). Total and differential cell counts, interleukin (IL)-8 in BAL fluid, and change in nasal volume were compared between groups. A 5-10% increase in nasal volume was seen for all groups including clean air except for a significant 5% decrease for spiked-dust inhalation (+18 h). No marked differences were observed in BAL cells or IL-8 except in LPS-exposed controls. The delayed decrease of nasal cavity volume after exposure to glucan spiked dust suggests a slow effect on the upper airways for curdlan and office dust together, though no pulmonary response or direct signs of inflammation were observed. Glucan-spiked office dust exposures produced a delayed nasal subacute congestion in guinea pigs compared to office dust alone, but extrapolated to nasal congestion in humans, paralleling the nasal congestion seen in human volunteers exposed to the same dust, this may not have clinical importance. PMID:17966063

  11. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    PubMed Central

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  12. Decreased pulmonary inflammation after ethanol exposure and burn injury in intercellular adhesion molecule-1 knockout mice.

    PubMed

    Bird, Melanie D; Morgan, Michelle O; Ramirez, Luis; Yong, Sherri; Kovacs, Elizabeth J

    2010-01-01

    Clinical and laboratory evidence suggests that alcohol consumption dysregulates immune function. Burn patients who consume alcohol before their injuries demonstrate higher rates of morbidity and mortality, including acute respiratory distress syndrome, than patients without alcohol at the time of injury. Our laboratory observed higher levels of proinflammatory cytokines and leukocyte infiltration in the lungs of mice after ethanol exposure and burn injury than with either insult alone. To understand the mechanism of the increased pulmonary inflammatory response in mice treated with ethanol and burn injury, we investigated the role of intercellular adhesion molecule (ICAM)-1. Wild-type and ICAM-1 knockout (KO) mice were treated with vehicle or ethanol and subsequently given a sham or burn injury. Twenty-four hours postinjury, lungs were harvested and analyzed for indices of inflammation. Higher numbers of neutrophils were observed in the lungs of wild-type mice after burn and burn with ethanol treatment. This increase in pulmonary inflammatory cell accumulation was significantly lower in the KO mice. In addition, levels of KC, interleukin-1beta, and interleukin-6 in the lung were decreased in the ICAM-1 KO mice after ethanol exposure and burn injury. Interestingly, no differences were observed in serum or lung tissue content of soluble ICAM-1 24 hours postinjury. These data suggest that upregulation of adhesion molecules such as ICAM-1 on the vascular endothelium may play a critical role in the excessive inflammation seen after ethanol exposure and burn injury.

  13. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways.

    PubMed

    Perros, Frederic; Lambrecht, Bart N; Hammad, Hamida

    2011-01-01

    Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin. Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs. PMID:21943186

  14. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways

    PubMed Central

    2011-01-01

    Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin. Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs. PMID:21943186

  15. Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: a role in tumor promotion.

    PubMed

    Bauer, A K; Dwyer-Nield, L D; Keil, K; Koski, K; Malkinson, A M

    2001-01-01

    Chronic pulmonary inflammatory diseases predispose towards lung cancer by unknown mechanisms. Butylated hydroxytoluene (BHT) administration to mice causes lung injury and a subsequent inflammatory response, and when administered chronically to certain inbred strains following carcinogen treatment, increases lung tumor multiplicity. We hypothesize that inflammation promotes lung tumor growth in this model system and have begun to examine this hypothesis by assessing inflammatory parameters in inbred strains that vary in their susceptibility to promotion. Positive correlations were found between susceptibilities to tumor promotion and BHT induction of alveolar macrophage and lymphocyte infiltration into alveolar airspaces, and increased vascular permeability (P < .03, P < .04, and P < .005, respectively). The amounts of pulmonary cyclooxygenase (COX)-1 and COX-2 did not strongly correlate with promotion. Because persistent elevation of macrophage content is the hallmark of a chronic inflammatory response, the alveolar macrophage population was depleted by adding chlorine to the drinking water prior to carcinogenesis. This treatment reduced lung tumor multiplicity following 2-stage carcinogenesis (P < .05). These correlations between inflammatory and tumorigenic responses to BHT, along with decreased tumorigenesis after macrophage depletion, are consistent with a role of inflammation in promotion. Inflammatory mediators may provide targets for early diagnosis and chemoprevention.

  16. Pulmonary inflammation after ethanol exposure and burn injury is attenuated in the absence of IL-6.

    PubMed

    Chen, Michael M; Bird, Melanie D; Zahs, Anita; Deburghgraeve, Cory; Posnik, Bartlomiej; Davis, Christopher S; Kovacs, Elizabeth J

    2013-05-01

    Alcohol consumption leads to an exaggerated inflammatory response after burn injury. Elevated levels of interleukin-6 (IL-6) in patients are associated with increased morbidity and mortality after injury, and high systemic and pulmonary levels of IL-6 have been observed after the combined insult of ethanol exposure and burn injury. To further investigate the role of IL-6 in the pulmonary inflammatory response, we examined leukocyte infiltration and cytokine and chemokine production in the lungs of wild-type and IL-6 knockout mice given vehicle or ethanol (1.11 g/kg) and subjected to a sham or 15% total body surface area burn injury. Levels of neutrophil infiltration and neutrophil chemoattractants were increased to a similar extent in wild-type and IL-6 knockout mice 24 h after burn injury. When ethanol exposure preceded the burn injury, however, a further increase of these inflammatory markers was seen only in the wild-type mice. Additionally, signal transducer and activator of transcription-3 (STAT3) phosphorylation did not increase in response to ethanol exposure in the IL-6 knockout mice, in contrast to their wild-type counterparts. Visual and imaging analysis of alveolar wall thickness supported these findings and similar results were obtained by blocking IL-6 with antibody. Taken together, our data suggest a causal relationship between IL-6 and the excessive pulmonary inflammation observed after the combined insult of ethanol and burn injury.

  17. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation

    PubMed Central

    Kreisel, Daniel; Nava, Ruben G.; Li, Wenjun; Zinselmeyer, Bernd H.; Wang, Baomei; Lai, Jiaming; Pless, Robert; Gelman, Andrew E.; Krupnick, Alexander S.; Miller, Mark J.

    2010-01-01

    Immune-mediated pulmonary diseases are a significant public health concern. Analysis of leukocyte behavior in the lung is essential for understanding cellular mechanisms that contribute to normal and diseased states. Here, we used two-photon imaging to study neutrophil extravasation from pulmonary vessels and subsequent interstitial migration. We found that the lungs contained a significant pool of tissue-resident neutrophils in the steady state. In response to inflammation produced by bacterial challenge or transplant-mediated, ischemia-reperfusion injury, neutrophils were rapidly recruited from the circulation and patrolled the interstitium and airspaces of the lung. Motile neutrophils often aggregated in dynamic clusters that formed and dispersed over tens of minutes. These clusters were associated with CD115+ F4/80+ Ly6C+ cells that had recently entered the lung. The depletion of blood monocytes with clodronate liposomes reduced neutrophil clustering in the lung, but acted by inhibiting neutrophil transendothelial migration upstream of interstitial migration. Our results suggest that a subset of monocytes serve as key regulators of neutrophil extravasation in the lung and may be an attractive target for the treatment of inflammatory pulmonary diseases. PMID:20923880

  18. Resolvin D1 Dampens Pulmonary Inflammation and Promotes Clearance of Nontypeable Haemophilus influenzae.

    PubMed

    Croasdell, Amanda; Lacy, Shannon H; Thatcher, Thomas H; Sime, Patricia J; Phipps, Richard P

    2016-03-15

    Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative, opportunistic pathogen that frequently causes ear infections, bronchitis, pneumonia, and exacerbations in patients with underlying inflammatory diseases, such as chronic obstructive pulmonary disease. In mice, NTHi is rapidly cleared, but a strong inflammatory response persists, underscoring the concept that NTHi induces dysregulation of normal inflammatory responses and causes a failure to resolve. Lipid-derived specialized proresolving mediators (SPMs) play a critical role in the active resolution of inflammation by both suppressing proinflammatory actions and promoting resolution pathways. Importantly, SPMs lack the immunosuppressive properties of classical anti-inflammatory therapies. On the basis of these characteristics, we hypothesized that aspirin-triggered resolvin D1 (AT-RvD1) would dampen NTHi-induced inflammation while still enhancing bacterial clearance. C57BL/6 mice were treated with AT-RvD1 and infected with live NTHi. AT-RvD1-treated mice had lower total cell counts and neutrophils in bronchoalveolar lavage fluid, and had earlier influx of macrophages. In addition, AT-RvD1-treated mice showed changes in temporal regulation of inflammatory cytokines and enzymes, with decreased KC at 6 h and decreased IL-6, TNF-α, and cyclooxygenase-2 expression at 24 h post infection. Despite reduced inflammation, AT-RvD1-treated mice had reduced NTHi bacterial load, mediated by enhanced clearance by macrophages and a skewing toward an M2 phenotype. Finally, AT-RvD1 protected NTHi-infected mice from weight loss, hypothermia, hypoxemia, and respiratory compromise. This research highlights the beneficial role of SPMs in pulmonary bacterial infections and provides the groundwork for further investigation into SPMs as alternatives to immunosuppressive therapies like steroids.

  19. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

    PubMed Central

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

    2014-01-01

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  20. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    PubMed

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  1. Immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation-coagulation interactions.

    PubMed

    Zelaya, Hortensia; Tsukida, Kohichiro; Chiba, Eriko; Marranzino, Gabriela; Alvarez, Susana; Kitazawa, Haruki; Agüero, Graciela; Villena, Julio

    2014-03-01

    The exacerbated disease due to immune- and coagulative-mediated pulmonary injury during acute respiratory viruses infection results in severe morbidity and mortality. Identifying novel approaches to modulate virus-induced inflammation-coagulation interactions could be important alternatives for treating acute respiratory viruses infections. In this study we investigated the effect of the probiotic strain Lactobacillus rhamnosus CRL1505 on lung TLR3-mediated inflammation, and its ability to modulate inflammation-coagulation interaction during respiratory viral infection. Our findings reveal for the first time that a probiotic bacterium is able to influence lung immune-coagulative reaction triggered by TLR3 activation, by modulating the production of proinflammatory and anti-inflammatory cytokines as well as expression of tissue factor and thrombomodulin in the lung. We also demonstrated that the preventive treatment with the probiotic bacteria beneficially modulates the fine tune balance between clearing respiratory viruses (respiratory syncytial virus and influenza virus) and controlling immune-coagulative responses in the lung, allowing normal lung function to be maintained in the face of a viral attack. Our data also pinpoint a crucial role for IL-10 in the immune protection induced by L. rhamnosus CRL1505 during respiratory viral infections. These observations might be helpful to propose new preventive or therapeutic approaches to better control virus-inflammatory lung damage using probiotic functional foods.

  2. Incidentally detected unilateral pulmonary artery agenesis with pulmonary hypoplasia in a 67 year old woman

    PubMed Central

    Muthusami, Prakash; Ananthakrishnan, Ramesh; Elangovan, S.

    2010-01-01

    Unilateral pulmonary artery agenesis is commonly seen associated with other congenital cardiovascular defects, when it is detected early in life, but isolated absence of the pulmonary artery is a rare entity, usually detected in adulthood. The latter patients are usually asymptomatic or might present with varied non-specific manifestations such as respiratory tract infections and hemoptysis. This report describes the imaging findings of a 67 year old female with absence of the right pulmonary artery. The embryology and clinical manifestations of the condition are reviewed. PMID:22470700

  3. Mean platelet volume as an inflammation marker in active pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background The mean platelet volume (MPV) reflects the size of platelets. It has been shown to be inversely correlated with level of the inflammation in some chronic inflammatory diseases. This prospective study aims to show the usability of MPV as an inflammation marker in patients with active pulmonary tuberculosis (PTB) by comparison with healthy controls. In addition, its relationships with other inflammatory markers such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as well as with the radiological extent of disease were examined. Methods This study included 82 patients with active PTB and 95 healthy subjects (control group). Whole blood counts, CRP level, and ESR were compared between the two groups. In the PTB group, the relationships between the radiological extent of disease and the MPV and other inflammation markers were investigated. Results The MPV was 7.74 ± 1.33/μL in the PTB group and 8.20 ± 1.13/μL in the control group (p = 0.005). The blood platelet count, CRP level, and ESR were significantly higher in the active PTB group than in the control group (p < 0.0001). In the PTB group, CRP levels (r = 0.26, p = 0.003) and ESR (r = 0.39, p = 0.003), but not MPV (p = 0.80), were significantly correlated with the radiologic extent of the disease. Conclusions The MPV was lower in patients with PTB than in healthy controls, however, the difference was limited. The MPV does not reflect the severity of the disease. The use of MPV as an inflammation marker and a negative acute-phase reactant in PTB does not seem to be reliable. PMID:24581084

  4. Pneumocystis murina infection and cigarette smoke exposure interact to cause increased organism burden, development of airspace enlargement, and pulmonary inflammation in mice.

    PubMed

    Christensen, Paul J; Preston, Angela M; Ling, Tony; Du, Ming; Fields, W Bradley; Curtis, Jeffrey L; Beck, James M

    2008-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction and lung destruction with airspace enlargement. In addition to cigarette smoking, respiratory pathogens play a role in pathogenesis, but specific organisms are not always identified. Recent reports demonstrate associations between the detection of Pneumocystis jirovecii DNA in lung specimens or respiratory secretions and the presence of emphysema in COPD patients. Additionally, human immunodeficiency virus-infected individuals who smoke cigarettes develop early emphysema, but a role for P. jirovecii in pathogenesis remains speculative. We developed a new experimental model using immunocompetent mice to test the interaction of cigarette smoke exposure and environmentally acquired Pneumocystis murina infection in vivo. We hypothesized that cigarette smoke and P. murina would interact to cause increases in total lung capacity, airspace enlargement, and pulmonary inflammation. We found that exposure to cigarette smoke significantly increases the lung organism burden of P. murina. Pulmonary infection with P. murina, combined with cigarette smoke exposure, results in changes in pulmonary function and airspace enlargement characteristic of pulmonary emphysema. P. murina and cigarette smoke exposure interact to cause increased lung inflammatory cell accumulation. These findings establish a novel animal model system to explore the role of Pneumocystis species in the pathogenesis of COPD. PMID:18490462

  5. CD14 contributes to pulmonary inflammation and mortality during murine tuberculosis

    PubMed Central

    Wieland, Catharina W; van der Windt, Gerritje J W; Wiersinga, W Joost; Florquin, Sandrine; van der Poll, Tom

    2008-01-01

    Toll-like receptors play an essential role in the innate recognition of micro-organisms by the host. CD14 is one of the extracellular adaptor proteins required for recognition of Gram-negative bacteria and possibly also Mycobacterium tuberculosis. Therefore, we intranasally infected wild-type (WT) and CD14 knock-out (KO) mice with virulent M. tuberculosis H37Rv. We found no differences in bacterial load in the main target organ lung up to 32 weeks after infection. From 20 weeks onward 57% of WT mice succumbed, whereas all CD14 KO mice survived. The improved outcome of CD14 KO mice was accompanied by reduced pulmonary inflammation; lung cell counts and percentage of inflamed lung tissue were reduced in CD14 WT mice. These data suggest that during chronic infection CD14 KO mice are protected from lethality caused by lung tuberculosis because of a reduction of the inflammatory response. PMID:18393969

  6. Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease.

    PubMed

    Sohal, Sukhwinder Singh; Ward, Chris; Danial, Wan; Wood-Baker, Richard; Walters, Eugene Haydn

    2013-06-01

    The authors have reviewed the current literature on airway inflammation and remodeling in smoking-related chronic obstructive pulmonary disease (COPD). Detailed data on airway remodeling in COPD are especially sparse and how these changes lead to decline in lung function is not well understood. Small airway fibrosis and obliteration are likely to be the main contributors to physiological airway dysfunction and occur earlier than any subsequent development of emphysema. One potential mechanism contributing to small airway fibrosis/obliteration and change in extracellular matrix is epithelial-mesenchymal transition. When associated with angiogenesis (so-called epithelial-mesenchymal transition type 3) it may well also be the link with the development of cancer, which is closely associated with COPD, predominantly in large airways. The authors have focused on our recent publications in these areas. Further investigations teasing out these mechanisms will help improve our understanding of key airway disease processes in COPD, which may have major therapeutic implications.

  7. Prior exposure to acrolein accelerates pulmonary inflammation in influenza A-infected mice.

    PubMed

    Ong, Ferrer H C; Henry, Peter J; Burcham, Philip C

    2012-08-01

    The combustion product acrolein contributes to several smoke-related health disorders, but whether this immunomodulatory toxicant alters pulmonary susceptibility to viruses has received little attention. To study the effects of prior acrolein dosing on the severity of influenza A viral infection, male BALB/c mice received acrolein (1mg/kg) or saline (control) via oropharyngeal aspiration either 4- or 7-days prior to intranasal inoculation with either influenza A/PR/8/34 virus or vehicle. At 0, 2, 4 and 7 days post-inoculation, lung samples were assessed for histological changes while pulmonary inflammation was monitored by estimating immune cell numbers and cytokine levels in bronchoalveolar lavage fluid (BALF). After viral challenge, animals that were exposed to acrolein 4 days previously experienced greater weight loss and exhibited an accelerated inflammatory response at 2 days after viral inoculation. Thus compared to saline-pretreated, virus-challenged controls, BALF recovered from these mice contained higher numbers of macrophages and neutrophils in addition to increased levels of several inflammatory cytokines, including IL-1α, IL-1β, IL-6, TNF, IFN-γ, KC, and MCP-1. The acrolein-induced increase in viral susceptibility was suppressed by the carbonyl scavenger bisulphite. These findings suggest acute acrolein intoxication "primes" the lung to mount an accelerated immune response to inhaled viruses.

  8. The Prevalence of Oral Inflammation Among Denture Wearing Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Przybyłowska, D; Rubinsztajn, R; Chazan, R; Swoboda-Kopeć, E; Kostrzewa-Janicka, J; Mierzwińska-Nastalska, E

    2015-01-01

    Oral inflammation is an important contributor to the etiology of chronic obstructive pulmonary disease, which can impact patient's health status. Previous studies indicate that people with poor oral health are at higher risk for nosocomial pneumonia. Denture wearing is one promoting factor in the development of mucosal infections. Colonization of the denture plaque by Gram-negative bacteria, Candida spp., or other respiratory pathogens, occurring locally, may be aspirated to the lungs. The studies showed that chronic obstructive pulmonary disease (COPD) patients treated with combinations of medicines with corticosteroids more frequently suffer from Candida-associated denture stomatitis. Treatment of oral candidiasis in patients with COPD constitutes a therapeutic problem. Therefore, it is essential to pay attention to the condition of oral mucosal membrane and denture hygiene habits. The guidelines for care and maintenance of dentures for COPD patients are presented in this paper. The majority of patients required improvement of their prosthetic and oral hygiene. Standard oral hygiene procedures in relation to dentures, conducted for prophylaxis of stomatitis complicated by mucosal infection among immunocompromised patients, are essential to maintain healthy oral tissues. The elimination of traumatic denture action in dental office, compliance with oral and denture hygiene, proper use and storage of prosthetic appliances in a dry environment outside the oral cavity can reduce susceptibility to infection. Proper attention to hygiene, including brushing and rinsing the mouth, may also help prevent denture stomatitis in these patients.

  9. Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium

    PubMed Central

    Matsuyama, Masashi; Ishii, Yukio; Sakurai, Hirofumi; Ano, Satoshi; Morishima, Yuko; Yoh, Keigyou; Takahashi, Satoru; Ogawa, Kenji; Hizawa, Nobuyuki

    2016-01-01

    Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection. PMID:26784959

  10. Restrictive pulmonary deficit is associated with inflammation in sub-optimally controlled obese diabetics

    PubMed Central

    Seemungal, Terence A. R.; Teelucksingh, Surujpal; Nayak, B. Shivananda

    2013-01-01

    Caribbean data linking inflammation, pulmonary dysfunction and diabetes is unavailable. Spirometry, acanthosis nigricans, hs-CRP were assessed in 109 type 2 diabetics (43% males) mean age=55.6 years, BMI=29.29 kg/m2, waist circumference=103.86 cm. Residual FEV1/FVC increased with age (P=0.005), BMI (P=0.011) and waist circumference (P=0.003). Residual FVC related inversely to hs-CRP (–0.178), P<0.06) systolic (–0.028, P<0.031), diastolic (–0.247, P<0.010) pressure and weight (–0.25, P<0.009). Residual FEV1 related inversely to diastolic pressure (–0.219, P<0.023), hs-CRP (–0.234, P<0.015), acanthosis nigricans (–0.029, P<0.029). HbA1C and residual FEV1 predict high hs-CRP (P=0.011, P=0.046). Low FVC with inflammation presents in poorly controlled obese diabetics. PMID:23825761

  11. Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis.

    PubMed

    Bauer, Alison K; Dixon, Darlene; DeGraff, Laura M; Cho, Hye-Youn; Walker, Christopher R; Malkinson, Alvin M; Kleeberger, Steven R

    2005-12-01

    Because chronic pulmonary diseases predispose to lung neoplasia, the identification of the molecular mechanisms involved could provide novel preventive, diagnostic, and therapeutic strategies. Toll-like receptors (TLRs) transduce exogenous and endogenous signals into the production of inflammatory cytokines to coordinate adaptive immune responses. To determine the role of Tlr4 in chronic lung inflammation, we compared lung permeability, leukocyte infiltration, and nuclear factor kappa B (NFkappaB) and activator protein 1 (AP-1) DNA binding in butylated hydroxytoluene (BHT)-treated (four weekly injections of 125-200 mg/kg each) inbred mouse strains with functional Tlr4 (OuJ and BALB) and mutated Tlr4 (HeJ and BALB(Lps-d)). We also measured primary tumor formation in these mice after single-carcinogen injection (3-methylcholanthrene; 10 microg/kg), followed by BHT treatment (six weekly injections of 125-200 mg/kg each). Mice with functional Tlr4 had reduced lung permeability, leukocyte inflammation, and primary tumor formation (BALB(Lps-d), mean = 22.3 tumors/mouse, versus BALB, mean = 13.9 tumors/mouse, difference = 8.4 tumors/mouse, 95% confidence interval = 4.6 to 12.1 tumors/mouse; P = .025) compared with mice with mutated Tlr4. NFkappaB DNA binding activity was higher in OuJ than in HeJ mice; however, AP-1 activity was elevated in HeJ mice. To our knowledge, this is the first model to demonstrate a modulatory role for Tlr4 in chronic lung inflammation and tumorigenesis.

  12. Edge density based automatic detection of inflammation in colonoscopy videos.

    PubMed

    Ševo, I; Avramović, A; Balasingham, I; Elle, O J; Bergsland, J; Aabakken, L

    2016-05-01

    Colon cancer is one of the deadliest diseases where early detection can prolong life and can increase the survival rates. The early stage disease is typically associated with polyps and mucosa inflammation. The often used diagnostic tools rely on high quality videos obtained from colonoscopy or capsule endoscope. The state-of-the-art image processing techniques of video analysis for automatic detection of anomalies use statistical and neural network methods. In this paper, we investigated a simple alternative model-based approach using texture analysis. The method can easily be implemented in parallel processing mode for real-time applications. A characteristic texture of inflamed tissue is used to distinguish between inflammatory and healthy tissues, where an appropriate filter kernel was proposed and implemented to efficiently detect this specific texture. The basic method is further improved to eliminate the effect of blood vessels present in the lower part of the descending colon. Both approaches of the proposed method were described in detail and tested in two different computer experiments. Our results show that the inflammatory region can be detected in real-time with an accuracy of over 84%. Furthermore, the experimental study showed that it is possible to detect certain segments of video frames containing inflammations with the detection accuracy above 90%. PMID:27043856

  13. Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model

    PubMed Central

    Rusu, Mirabela; Golden, Thea; Wang, Haibo; Gow, Andrew; Madabhushi, Anant

    2015-01-01

    Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic

  14. Montelukast versus Dexamethasone Treatment in a Guinea Pig Model of Chronic Pulmonary Neutrophilic Inflammation.

    PubMed

    Abdel Kawy, Hala S

    2016-08-01

    Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours apart with or without treatment with Montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p < 0.05). Montelukast, at a dose of 30 mg /kg, significantly reduced specific airway resistance after the 9th LPS exposure, attenuated AHR to MCh, decreased LTB4 and increased HDAC activity in comparison to dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids. PMID:26751767

  15. Time course of inflammation resolution in patients with frequent exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Chang, Chun; Yao, Wanzhen

    2014-01-01

    Background When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations. Material/Methods Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10–14), and 8 weeks after discharge. Results We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10–14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators. Conclusions Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life. PMID:24569299

  16. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.

    PubMed

    Huang, Tsung-Teng; Lai, Hsin-Chih; Ko, Yun-Fei; Ojcius, David M; Lan, Ying-Wei; Martel, Jan; Young, John D; Chong, Kowit-Yu

    2015-01-01

    Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1-induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1-treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin-induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis. PMID:26497260

  17. Acrolein induced both pulmonary inflammation and the death of lung epithelial cells.

    PubMed

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-Ichi

    2014-09-01

    Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c(+)F4/80(high) macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages.

  18. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo

    PubMed Central

    Huang, Tsung-Teng; Lai, Hsin-Chih; Ko, Yun-Fei; Ojcius, David M.; Lan, Ying-Wei; Martel, Jan; Young, John D.; Chong, Kowit-Yu

    2015-01-01

    Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis. PMID:26497260

  19. CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension

    PubMed Central

    Shen, Yongchun; Wan, Chun; Tian, Panwen; Wu, Yanqiu; Li, Xiaoou; Yang, Ting; An, Jing; Wang, Tao; Chen, Lei; Wen, Fuqiang

    2014-01-01

    Abstract To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis. A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance. This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84. Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography. PMID:25501096

  20. Chronic allergic inflammation causes vascular remodeling and pulmonary hypertension in BMPR2 hypomorph and wild-type mice.

    PubMed

    Mushaben, Elizabeth M; Hershey, Gurjit Khurana; Pauciulo, Michael W; Nichols, William C; Le Cras, Timothy D

    2012-01-01

    Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene have been identified in patients with heritable pulmonary arterial hypertension (PAH); however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT) Balb/c/Byj mice were exposed to house dust mite (HDM) allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP) was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR) to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations.

  1. Detection of pulmonary amylase activity in exhaled breath condensate.

    PubMed

    Zweifel, M; Rechsteiner, T; Hofer, M; Boehler, A

    2013-12-01

    Amylase activity in exhaled breath condensate (EBC) is usually interpreted as an indication of oropharyngeal contamination despite the fact that amylase can be found in pulmonary excretions. The aim of this study was to recruit and refine an amylase assay in order to detect amylase activity in any EBC sample and to develop a method to identify EBC samples containing amylase of pulmonary origin. EBC was collected from 40 volunteers with an EcoScreen condenser. Amylase assays and methods to discriminate between oropharyngeal and pulmonary proteins were tested and developed using matched EBC and saliva samples. Our refined 2-chloro-4-nitrophenyl-α-D-maltotriosid (CNP-G3) assay was 40-fold more sensitive than the most sensitive commercial assay and allowed detection of amylase activity in 30 µl of EBC. We developed a dot-blot assay which allowed detection of salivary protein in saliva diluted up to 150 000-fold. By plotting amylase activity against staining intensity we identified a few EBC samples with high amylase activity which were aligned with diluted saliva. We believe that EBC samples aligned with diluted saliva contain amylase activity introduced during EBC collection and that all other EBC samples contain amylase activity of pulmonary origin and are basically free of oropharyngeal protein contamination.

  2. Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.

    PubMed

    Abram, Melanie; Wegmann, Michael; Fokuhl, Verena; Sonar, Sanchaita; Luger, Elke Olga; Kerzel, Sebastian; Radbruch, Andreas; Renz, Harald; Zemlin, Michael

    2009-04-15

    Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-kappaB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease.

  3. Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease.

    PubMed

    Nocker, R E; Schoonbrood, D F; van de Graaf, E A; Hack, C E; Lutter, R; Jansen, H M; Out, T A

    1996-02-01

    We have investigated whether IL-8 is present in airway secretions from patients with asthma and chronic obstructive pulmonary disease (COPD) to obtain information on its possible role in airway inflammation in obstructive airways disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable patients with asthma the levels of IL-8 were increased compared to 10 healthy subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p < 0.005). In the patients with asthma the levels of IL-8 correlated with the percentage neutrophils in the BALF (r = 0.81; p < 0.001) and with a parameter of the permeability of the respiratory membrane, the quotient (alpha 2-macroglobulin in BALF)/(alpha 2-macroglobulin in serum) (r = 0.66; p < 0.025). In the sputum sol phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in 9 patients with COPD (asthma: 6.4 ng/ml; COPD: 16.3 ng/ml; p < 0.02) and significantly correlated with those of neutrophilic myeloperoxidase (MPO; r = 0.85; p < 0.005). The increased levels of IL-8 in the airway secretions from both patients with asthma and COPD may be markers of an ongoing inflammatory process, which is more pronounced in patients with COPD. In patients with asthma the strong correlation between the levels of IL-8 and the percentage neutrophils and/or the levels of MPO points to a role of IL-8 in the recruitment and activation of neutrophils in the airway lumen.

  4. Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation

    PubMed Central

    2014-01-01

    Background We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. Methods iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. Results rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. Conclusions These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation. PMID:24684897

  5. Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke–Exposed Mice

    PubMed Central

    Bucher, Hannes; Duechs, Matthias J.; Tilp, Cornelia; Jung, Birgit

    2016-01-01

    Viral infections trigger exacerbations in chronic obstructive pulmonary disease (COPD), and tiotropium, a M3 receptor antagonist, reduces exacerbations in patients by unknown mechanisms. In this report, we investigated whether tiotropium has anti-inflammatory effects in mice exposed to cigarette smoke (CS) and infected with influenza virus A/PR/8/34 (H1N1) or respiratory syncytial virus (RSV) and compared these effects with those of steroid fluticasone and PDE4-inhibitor roflumilast. Mice were exposed to CS; infected with H1N1 or RSV; and treated with tiotropium, fluticasone, or roflumilast. The amount of cells and cytokine levels in the airways, lung function, and viral load was determined. NCI-H292 cells were infected with H1N1 or RSV and treated with the drugs. In CS/H1N1-exposed mice, tiotropium reduced neutrophil and macrophage numbers and levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ) in the airways and improved lung function. In contrast, fluticasone increased the loss of body weight; failed to reduce neutrophil or macrophage numbers; increased IL-6, KC, and tumor necrosis factor-α (TNF-α) in the lungs; and worsened lung function. Treatment with roflumilast reduced macrophage numbers, IL-6, and KC in the lungs but had no effect on neutrophil numbers or lung function. In CS/RSV-exposed mice, treatment with tiotropium, but not fluticasone or roflumilast, reduced neutrophil numbers and IL-6 and TNF-α levels in the lungs. Viral load of H1N1 and RSV was significantly elevated in CS/virus-exposed mice and NCI-H292 cells after fluticasone treatment, whereas tiotropium and roflumilast had no effect. In conclusion, tiotropium has anti-inflammatory effects on CS/virus-induced inflammation in mice that are superior to the effects of roflumilast and fluticasone. This finding might help to explain the observed reduction of exacerbation rates in COPD patients. PMID:27016458

  6. Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models.

    PubMed

    Kodavanti, Urmila P; Ledbetter, Allen D; Thomas, Ronald F; Richards, Judy E; Ward, William O; Schladweiler, Mette C; Costa, Daniel L

    2015-01-01

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure dependent on the type and severity of disease. Healthy male 12-14-week-old Wistar Kyoto (WKY), Wistar (WS) and Sprague Dawley (SD); and CVD-compromised spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), stroke-prone spontaneously hypertensive (SHSP), obese spontaneously hypertensive heart failure (SHHF) and obese JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h; pulmonary injury and inflammation were analyzed immediately following (0-h) or 20-h later. Baseline bronchoalveolar lavage fluid (BALF) protein was higher in CVD strains except for FHH when compared to healthy. Ozone-induced increases in protein and inflammation were concentration-dependent within each strain but the degree of response varied from strain to strain and with time. Among healthy rats, SD were least affected. Among CVD strains, lean rats were more susceptible to protein leakage from ozone than obese rats. Ozone caused least neutrophilic inflammation in SH and SHHF while SHSP and FHH were most affected. BALF neutrophils and protein were poorly correlated when considering the entire dataset (r = 0.55). The baseline and ozone-induced increases in cytokine mRNA varied markedly between strains and did not correlate with inflammation. These data illustrate that the degree of ozone-induced lung injury/inflammation response is likely influenced by both genetic and physiological factors that govern the nature of cardiovascular compromise in CVD models.

  7. Exposure to Deepwater Horizon Crude Oil Burnoff Particulate Matter Induces Pulmonary Inflammation and Alters Adaptive Immune Response.

    PubMed

    Jaligama, Sridhar; Chen, Zaili; Saravia, Jordy; Yadav, Nikki; Lomnicki, Slawomir M; Dugas, Tammy R; Cormier, Stephania A

    2015-07-21

    The ″in situ burning" of trapped crude oil on the surface of Gulf waters during the 2010 Deepwater Horizon (DWH) oil spill released numerous pollutants, including combustion-generated particulate matter (PM). Limited information is available on the respiratory impact of inhaled in situ burned oil sail particulate matter (OSPM). Here we utilized PM collected from in situ burn plumes of the DWH oil spill to study the acute effects of exposure to OSPM on pulmonary health. OSPM caused dose-and time-dependent cytotoxicity and generated reactive oxygen species and superoxide radicals in vitro. Additionally, mice exposed to OSPM exhibited significant decreases in body weight gain, systemic oxidative stress in the form of increased serum 8-isoprostane (8-IP) levels, and airway inflammation in the form of increased macrophages and eosinophils in bronchoalveolar lavage fluid. Further, in a mouse model of allergic asthma, OSPM caused increased T helper 2 cells (Th2), peribronchiolar inflammation, and increased airway mucus production. These findings demonstrate that acute exposure to OSPM results in pulmonary inflammation and alteration of innate/adaptive immune responses in mice and highlight potential respiratory effects associated with cleaning up an oil spill. PMID:26115348

  8. Exposure to Deepwater Horizon Crude Oil Burnoff Particulate Matter Induces Pulmonary Inflammation and Alters Adaptive Immune Response.

    PubMed

    Jaligama, Sridhar; Chen, Zaili; Saravia, Jordy; Yadav, Nikki; Lomnicki, Slawomir M; Dugas, Tammy R; Cormier, Stephania A

    2015-07-21

    The ″in situ burning" of trapped crude oil on the surface of Gulf waters during the 2010 Deepwater Horizon (DWH) oil spill released numerous pollutants, including combustion-generated particulate matter (PM). Limited information is available on the respiratory impact of inhaled in situ burned oil sail particulate matter (OSPM). Here we utilized PM collected from in situ burn plumes of the DWH oil spill to study the acute effects of exposure to OSPM on pulmonary health. OSPM caused dose-and time-dependent cytotoxicity and generated reactive oxygen species and superoxide radicals in vitro. Additionally, mice exposed to OSPM exhibited significant decreases in body weight gain, systemic oxidative stress in the form of increased serum 8-isoprostane (8-IP) levels, and airway inflammation in the form of increased macrophages and eosinophils in bronchoalveolar lavage fluid. Further, in a mouse model of allergic asthma, OSPM caused increased T helper 2 cells (Th2), peribronchiolar inflammation, and increased airway mucus production. These findings demonstrate that acute exposure to OSPM results in pulmonary inflammation and alteration of innate/adaptive immune responses in mice and highlight potential respiratory effects associated with cleaning up an oil spill.

  9. Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease

    PubMed Central

    Wiegman, Coen H.; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J.; Russell, Kirsty E.; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J.; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P.; Kirkham, Paul A.; Chung, Kian Fan; Adcock, Ian M.; Brightling, Christopher E.; Davies, Donna E.; Finch, Donna K.; Fisher, Andrew J.; Gaw, Alasdair; Knox, Alan J.; Mayer, Ruth J.; Polkey, Michael; Salmon, Michael; Singh, David

    2015-01-01

    Background Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology. Objective We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Methods Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Results Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release. Conclusions Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell

  10. Automated detection of pulmonary nodules in CT images with support vector machines

    NASA Astrophysics Data System (ADS)

    Liu, Lu; Liu, Wanyu; Sun, Xiaoming

    2008-10-01

    Many methods have been proposed to avoid radiologists fail to diagnose small pulmonary nodules. Recently, support vector machines (SVMs) had received an increasing attention for pattern recognition. In this paper, we present a computerized system aimed at pulmonary nodules detection; it identifies the lung field, extracts a set of candidate regions with a high sensitivity ratio and then classifies candidates by the use of SVMs. The Computer Aided Diagnosis (CAD) system presented in this paper supports the diagnosis of pulmonary nodules from Computed Tomography (CT) images as inflammation, tuberculoma, granuloma..sclerosing hemangioma, and malignant tumor. Five texture feature sets were extracted for each lesion, while a genetic algorithm based feature selection method was applied to identify the most robust features. The selected feature set was fed into an ensemble of SVMs classifiers. The achieved classification performance was 100%, 92.75% and 90.23% in the training, validation and testing set, respectively. It is concluded that computerized analysis of medical images in combination with artificial intelligence can be used in clinical practice and may contribute to more efficient diagnosis.

  11. Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats

    SciTech Connect

    Desouza, Ivani A. . E-mail: ivanidesouza@fcm.unicamp.br; Franco-Penteado, Carla F.; Camargo, Enilton A.; Lima, Carmen S.P.; Teixeira, Simone A.; Muscara, Marcelo N.; De Nucci, Gilberto; Antunes, Edson

    2006-11-15

    Staphylocococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.4 ml). Airways exposition to SEB (7.5-250 ng/trachea) caused a dose- and time-dependent neutrophil accumulation in BAL fluid, the maximal effects of which were observed at 4 h post-SEB exposure (250 ng/trachea). Eosinophils were virtually absent in BAL fluid, whereas mononuclear cell counts increased only at 24 h post-SEB. Significant elevations of granulocytes in bone marrow (mature and immature forms) and peripheral blood have also been detected. In BAL fluid, marked elevations in the levels of lipid mediators (LTB{sub 4} and PGE{sub 2}) and cytokines (TNF-{alpha}, IL-6 and IL-10) were observed after SEB instillation. The SEB-induced neutrophil accumulation in BAL fluid was reduced by pretreatment with dexamethasone (0.5 mg/kg), the COX-2 inhibitor celecoxib (3 mg/kg), the selective iNOS inhibitor compound 1400 W (5 mg/kg) and the lipoxygenase inhibitor AA-861 (200 {mu}g/kg). In separate experiments carried out with rat isolated peripheral neutrophils, SEB failed to induce neutrophil adhesion to serum-coated plates and chemotaxis. In conclusion, rat airways exposition to SEB causes a neutrophil-dependent lung inflammation at 4 h as result of the release of proinflammatory (NO, PGE{sub 2}, LTB{sub 4}, TNF-{alpha}, IL-6) and anti-inflammatory mediators (IL-10)

  12. Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease.

    PubMed

    Li, Lingling; Wang, Yujie; Gao, Wei; Yuan, Cheng; Zhang, Sini; Zhou, Hong; Huang, Mao; Yao, Xin

    2015-11-13

    Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Klotho, an anti-aging protein, has an anti-inflammatory function. However, the role of Klotho has never been investigated in COPD. The aim of this study is to investigate the possible role of Klotho by alveolar macrophages in airway inflammation in COPD. Klotho levels were assessed in the lung samples and peripheral blood mononuclear cells of non-smokers, smokers, and patients with COPD. The regulation of Klotho expression by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced inflammation. Klotho expression was reduced in alveolar macrophages in the lungs and peripheral blood mononuclear cells of COPD patients. CSE decreased Klotho expression and release from MH-S cells. Knockdown of endogenous Klotho augmented the expression of the inflammatory mediators, such as MMP-9, IL-6, and TNF-α, by MH-S cells. Exogenous Klotho inhibited the expression of CSE-induced inflammatory mediators. Furthermore, we showed that Klotho interacts with IκBα of the NF-κB pathway. Dexamethasone treatment increased the expression and release level of Klotho in MH-S cells. Our findings suggest that Klotho plays a role in sustained inflammation of the lungs, which in turn may have therapeutic implications in COPD.

  13. Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury.

    PubMed

    Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo; Bucht, Anders; Jonasson, Sofia

    2016-10-15

    We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl2) with the aim to understand the pathogenesis of the long-term sequelae of Cl2-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5h up to 90days after a single inhalation of Cl2. A single dose of dexamethasone (10mg/kg) was administered 1h following Cl2-exposure. A 15-min inhalation of 200ppm Cl2 was non-lethal in Sprague-Dawley rats. At 24h post exposure, Cl2-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24h but did not influence the AHR. Inhalation of Cl2 in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl2-induced respiratory dysfunction. PMID:27586366

  14. Lipopolysaccharide and Interleukin 1 Augment the Effects of Hypoxia and Inflammation in Human Pulmonary Arterial Tissue

    NASA Astrophysics Data System (ADS)

    Ziesche, Rolf; Petkov, Venzeslav; Williams, John; Zakeri, Schaker M.; Mosgoller, Wilhelm; Knofler, Martin; Block, Lutz H.

    1996-10-01

    The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor α on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1β , or tumor necrosis factor α augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.

  15. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    SciTech Connect

    Husain, Mainul; Saber, Anne T.; Guo, Charles; Jacobsen, Nicklas R.; Jensen, Keld A.; Yauk, Carole L.; Williams, Andrew; Vogel, Ulla; Wallin, Hakan; Halappanavar, Sabina

    2013-06-15

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO{sub 2}). Female C57BL/6 mice were exposed to rutile nano-TiO{sub 2} via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO{sub 2} in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO{sub 2} in the lungs up to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p < 0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO{sub 2} in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO{sub 2} were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose

  16. Pentoxifylline inhibits pulmonary inflammation induced by infrarenal aorticcross-clamping dependent of adenosine receptor A2A

    PubMed Central

    Li, Hali; Tan, Gang; Tong, Liquan; Han, Peng; Zhang, Feng; Liu, Bing; Sun, Xueying

    2016-01-01

    Infrarenal aortic cross-clamping (IAC) is commonly used during infrarenal vascular operations. Prolonged IAC causes ischemia-reperfusion injury to local tissues, resulting in the release of inflammatory cytokines and acute lung injury (ALI). Pentoxifylline (PTX) is a clinically used drug for chronic occlusive arterial diseases and exerts protective effects against ALI induced by various factors in experimental models. In this study, we evaluated the protective effects of PTX in a rat model of IAC. Wistar rats underwent IAC for 2 h, followed by 4 h reperfusion. PTX alone, or in combination with ZM-241385 (an adenosine receptor A2A antagonist) or CGS-21680 (an A2A agonist), was pre-administered to rats 1 h prior to IAC, and the severity of lung injury and inflammation were examined. Administration of PTX significantly attenuated ALI induced by IAC, evidenced by reduced histological scores and wet lung contents, improved blood gas parameters, decreased cell counts and protein amounts in bronchoalveolar lavage fluids, and inhibition of MPO activity and ICAM-1 expression in lung tissues, and lower plasma levels of TNF-α, IL-6, IL-1β and soluble ICAM-1. ZM-241385 significantly abrogated, while CGS-21680 slightly enhanced, the effects of PTX in ameliorating ALI and inhibiting pulmonary inflammation. In exploration of the mechanisms, we found that PTX stimulated IL-10 production through the phosphorylation of STAT3, and A2A receptor participated in this regulation. The study indicates PTX plays a protective role in IAC-induced ALI in rats by inhibiting pulmonary inflammation through A2A signaling pathways. PMID:27347328

  17. Early pulmonary inflammation and lung damage in children with cystic fibrosis.

    PubMed

    Schultz, André; Stick, Stephen

    2015-05-01

    Individuals with cystic fibrosis (CF) suffer progressive airway inflammation, infection and lung damage. Airway inflammation and infection are present from early in life, often before children are symptomatic. CF gene mutations cause changes in the CF transmembrane regulator protein that result in an aberrant airway microenvironment including airway surface liquid (ASL) dehydration, reduced ASL acidity, altered airway mucin and a dysregulated inflammatory response. This review discusses how an altered microenvironment drives CF lung disease before overt airway infection, the response of the CF airway to early infection, and methods to prevent inflammation and early lung disease.

  18. The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease

    PubMed Central

    Han, Bing; Poppinga, Wilfred J.; Zuo, Haoxiao; Zuidhof, Annet B.; Bos, I. Sophie T.; Smit, Marieke; Vogelaar, Pieter; Krenning, Guido; Henning, Robert H.; Maarsingh, Harm; Halayko, Andrew J.; van Vliet, Bernard; Stienstra, Stef; Graaf, Adrianus Cornelis van der; Meurs, Herman; Schmidt, Martina

    2016-01-01

    COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress. PMID:27229886

  19. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

    PubMed

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-02-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system.

  20. Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation.

    PubMed

    Bhattacharya, Kunal; Andón, Fernando Torres; El-Sayed, Ramy; Fadeel, Bengt

    2013-12-01

    Carbon nanotubes have gained tremendous interest in a wide range of applications due to their unique physical, chemical, and electronic properties. Needless to say, close attention to the potential toxicity of carbon nanotubes is of paramount importance. Numerous studies have linked exposure of carbon nanotubes to the induction of inflammation, a complex protective response to harmful stimuli including pathogens, damaged or dying cells, and other irritants. However, inflammation is a double-edged sword as chronic inflammation can lead to destruction of tissues thus compromising the homeostasis of the organism. Here, we provide an overview of the process of inflammation, the key cells and the soluble mediators involved, and discuss research on carbon nanotubes and inflammation, including recent studies on the activation of the so-called inflammasome complex in macrophages resulting in secretion of pro-inflammatory cytokines. Moreover, recent work has shown that inflammatory cells i.e. neutrophils and eosinophils are capable of enzymatic degradation of carbon nanotubes, with mitigation of the pro-inflammatory and pro-fibrotic effects of nanotubes thus underscoring that inflammation is both good and bad.

  1. Variability in Ozone-Induced Pulmonary Injury and Inflammation in Healthy and Cardiovascular Compromised Rat Models

    EPA Science Inventory

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure depe...

  2. Cartwheel projections of segmented pulmonary vasculature for the detection of pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Pulmonary embolism (PE) detection via contrast-enhanced computed tomography (CT) images is an increasingly important topic of research. Accurate identification of PE is of critical importance in determining the need for further treatment. However, current multi-slice CT scanners provide datasets typically containing 600 or more images per patient, making it desirable to have a visualization method to help radiologists focus directly on potential candidates that might otherwise have been overlooked. This is especially important when assessing the ability of CT to identify smaller, sub-segmental emboli. We propose a cartwheel projection approach to PE visualization that computes slab projections of the original data aided by vessel segmentation. Previous research on slab visualization for PE has utilized the entire volumetric dataset, requiring thin slabs and necessitating the use of maximum intensity projection (MIP). Our use of segmentation within the projection computation allows the use of thicker slabs than previous methods, as well as the ability to employ visualization variations that are only possible with segmentation. Following automatic segmentation of the pulmonary vessels, slabs may be rotated around the X-, Y- or Z-axis. These slabs are rendered by preferentially using voxels within the lung vessels. This effectively eliminates distracting information not relevant to diagnosis, lessening both the chance of overlooking a subtle embolus and minimizing time on spent evaluating false positives. The ability to employ thicker slabs means fewer images need to be evaluated, yielding a more efficient workflow.

  3. Reduction in pulmonary function after CABG surgery is related to postoperative inflammation and hypercortisolemia

    PubMed Central

    Roncada, Gert; Dendale, Paul; Linsen, Loes; Hendrikx, Marc; Hansen, Dominique

    2015-01-01

    Pulmonary function is significantly reduced in the acute phase after coronary artery bypass graft (CABG) surgery. Because pulmonary function partly depends on respiratory muscle strength, we studied whether reductions in pulmonary function are related to postoperative alterations in circulatory factors that affect muscle protein synthesis. Methods: Slow vital capacity (SVC) was assessed in 22 subjects before and 9 ± 3 days after CABG surgery. Blood testosterone, cortisol, insulin-like growth factor-1 (IGF-1), growth hormone, sex-hormone binding globulin (SHBG), glucose, insulin, c-peptide, c-reactive protein (CRP) content, and free androgen index, cortisol/testosterone ratio, HOMA-IR index were assessed before surgery and during the first three days after surgery. Intubation, surgery time and cumulative chest tube drainage were measured. Correlations between changes in SVC and blood parameters after surgery or subject characteristics were studied. This was a prospective observational study. Results: After CABG surgery SVC decreased by 37 ± 18% (P < 0.01). Free androgen index, blood SHBG, testosterone and IGF-1 content decreased, while HOMA-IR index, cortisol/testosterone ratio, blood growth hormone, insulin and CRP content increased (P < 0.0025) in the first three days after surgery. Decrease in SVC was independently (P < 0.05) related to higher preoperative SVC (SC β = 0.66), and greater increase in blood cortisol (SC β = 0.54) and CRP (SC β = 0.37) content after surgery. Conclusions: Larger reductions in pulmonary function after CABG surgery are present in patients experiencing greater postoperative increases in blood CRP and cortisol levels. Decrements in pulmonary function after CABG surgery are, at least in part, thus related to alterations in circulatory factors that affect muscle protein synthesis. PMID:26379888

  4. Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

    PubMed Central

    Wang, Hao; Yang, Ting; Li, Diandian; Wu, Yanqiu; Zhang, Xue; Pang, Caishuang; Zhang, Junlong; Ying, Binwu; Wang, Tao; Wen, Fuqiang

    2016-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. Methods Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. Results First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007). Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25–75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively). Besides, multivariable

  5. Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (D...

  6. Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation.

    PubMed

    Zeidler, Patti C; Millecchia, Lyndell M; Castranova, Vincent

    2004-02-15

    Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-gamma were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time. PMID:14962504

  7. Depletion of Neutrophils Promotes the Resolution of Pulmonary Inflammation and Fibrosis in Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Arango, Julián Camilo

    2016-01-01

    Chronic stages of paracoccidioidomycosis (PCM) are characterized by granulomatous lesions which promote the development of pulmonary fibrosis leading to the loss of respiratory function in 50% of patients; in addition, it has been observed that neutrophils predominate during these chronic stages of P. brasiliensis infection. The goal of this study was to evaluate the role of the neutrophil during the chronic stages of experimental pulmonary PCM and during the fibrosis development and tissue repair using a monoclonal specific to this phagocytic cell. Male BALB/c mice were inoculated intranasally with 1.5x106 P. brasiliensis yeast cells. A monoclonal antibody specific to neutrophils was administered at 4 weeks post-inoculation followed by doses every 48h during two weeks. Mice were sacrificed at 8 and 12 weeks post-inoculation to assess cellularity, fungal load, cytokine/chemokine levels, histopathological analysis, collagen and expression of genes related to fibrosis development. Depletion of neutrophils was associated with a significant decrease in the number of eosinophils, dendritic cells, B cells, CD4-T cells, MDSCs and Treg cells, fungal load and levels of most of the pro-inflammatory cytokines/chemokines evaluated, including IL-17, TNF-α and TGF-β1. Recovery of lung architecture was also associated with reduced levels of collagen, high expression of TGF-β3, matrix metalloproteinase (MMP)-12 and -14, and decreased expression of tissue inhibitor metalloproteinase (TIMP)-2, and MMP-8. Depletion of neutrophils might attenuate lung fibrosis and inflammation through down-regulating TGF-β1, TNF-α, IL-17, MMP-8 and TIMP-2. These results suggest that neutrophil could be considered as a therapeutic target in pulmonary fibrosis induced by P. brasiliensis. PMID:27690127

  8. Acute pulmonary toxicity and inflammation induced by combined exposure to didecyldimethylammonium chloride and ethylene glycol in rats.

    PubMed

    Kwon, Do Young; Kim, Hyun-Mi; Kim, Eunji; Lim, Yeon-Mi; Kim, Pilje; Choi, Kyunghee; Kwon, Jung-Taek

    2016-02-01

    Didecyldimethylammonium chloride (DDAC), an antimicrobial agent, has been reported to induce pulmonary toxicity in animal studies. DDAC is frequently used in spray-form household products in combination with ethylene glycol (EG). The purpose of this study was to evaluate the toxic interaction between DDAC and EG in the lung. DDAC at a sub-toxic dose (100 μg/kg body weight) was mixed with a non-toxic dose of EG (100 or 200 μg/kg body weight), and was administrated to rats via intratracheal instillation. Lactate dehydrogenase activity and total protein content in the bronchoalveolar lavage fluid (BALF) were not changed by singly treated DDAC or EG, but significantly enhanced at 1 d after treatment with the mixture, with the effect dependent on the dose of EG. Total cell count in BALF was largely increased and polymorphonuclear leukocytes were predominantly recruited to the lung in rats administrated with the mixture. Inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 also appeared to be increased by the mixture of DDAC and EG (200 μg/kg body weight) at 1 d post-exposure, which might be associated with the increase in inflammatory cells in lung. BALF protein content and inflammatory cell recruitment in the lung still remained elevated at 7 d after the administration of DDAC with the higher dose of EG. These results suggest that the combination of DDAC and EG can synergistically induce pulmonary cytotoxicity and inflammation, and EG appears to amplify the harmful effects of DDAC on the lung. Therefore pulmonary exposure to these two chemicals commonly found in commercial products can be a potential hazard to human health. PMID:26763389

  9. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    SciTech Connect

    Yanamala, Naveena; Birch, M. Eileen; Kisin, Elena; Bugarski, Aleksandar D.

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.

  10. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

    PubMed

    Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C; Sellati, Timothy J; Harton, Jonathan A

    2016-03-01

    Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

  11. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

    PubMed

    Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C; Sellati, Timothy J; Harton, Jonathan A

    2016-03-01

    Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection.

  12. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

    PubMed Central

    Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

    2016-01-01

    Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

  13. Use of Metal Oxide Nanoparticle Band Gap to Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation

    PubMed Central

    Zhang, Haiyuan; Ji, Zhaoxia; Xia, Tian; Meng, Huan; Low-Kam, Cecile; Liu, Rong; Pokhrel, Suman; Lin, Sijie; Wang, Xiang; Liao, Yu-Pei; Wang, Meiying; Li, Linjiang; Rallo, Robert; Damoiseaux, Robert; Telesca, Donatello; Mädler, Lutz; Cohen, Yoram; Zink, Jeffrey I.; Nel, Andre E.

    2014-01-01

    We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (Ec) levels with the cellular redox potential (−4.12 to −4.84 eV) was strongly correlated to the ability of Co3O4, Cr2O3, Ni2O3, Mn2O3 and CoO nanoparticles to induce oxygen radicals, oxidative stress and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of CB57 Bl/6 mice. Co3O4, Ni2O3, Mn2O3 and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by Ec levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. Taken together, these results demonstrate, for the first time, that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials. PMID:22502734

  14. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation

    PubMed Central

    Tufvesson, Ellen; Bjermer, Leif; Ekberg, Marie

    2015-01-01

    Background Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations. Methods Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months. The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction. Results Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase. These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients. In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results. Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients. The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations. Conclusion Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway

  15. Quantitative trait locus mapping of susceptibilities to butylated hydroxytoluene-induced lung tumor promotion and pulmonary inflammation in CXB mice.

    PubMed

    Malkinson, Alvin M; Radcliffe, Richard A; Bauer, Alison K

    2002-03-01

    We have reported previously [Bauer,A.K. et al. (2001) Exp. Lung Res., 27, 197-216] that the 13 CXB recombinant inbred mouse strains derived from BALB/cByJ and C57BL/6J progenitors vary in their responsiveness to both lung tumor promotion and pulmonary inflammation induced by chronic administration of butylated hydroxytoluene (BHT). Herein we have applied these data, along with markers known to be polymorphic among these strains, to conduct linkage analysis of these susceptibilities. This enabled us to assign provisional quantitative trait loci (QTL) that govern these strain variations in susceptibility as a genetic approach to assessing the influence of inflammation on tumorigenesis. A Chr 15 (39.1-55.6 cM) QTL regulated susceptibility to two-stage carcinogenesis, a protocol in which chronic BHT exposure followed a single urethane injection; a similar QTL on Chr 15 (46.7-61.7 cM) influenced BHT induction of cyclooxygenase-2 (COX-2) expression. A Chr 18 (37-41 cM) QTL modulated both the number of lung tumors induced by 3-methylcholanthrene (MCA) injection with subsequent treatment with BHT as well as BHT-induced ingress of macrophages into airways. Other chromosomal sites that affected either the degree of BHT-elicited macrophage infiltration, Chr 9 (48-61 cM), or COX-2 induction, Chr 10 (59-65 cM), were reported to influence susceptibility to lung tumorigenesis in other strains. The fact that common chromosomal locations regulate both inflammation and carcinogenesis suggests a pathogenic role of inflammatory mediators in tumor development that may be exploited for chemoprevention of lung cancer.

  16. Particulate nature of inhaled zinc oxide nanoparticles determines systemic effects and mechanisms of pulmonary inflammation in mice.

    PubMed

    Chen, Jen-Kun; Ho, Chia-Chi; Chang, Han; Lin, Jing-Fang; Yang, Chung Shi; Tsai, Ming-Hsien; Tsai, Hui-Ti; Lin, Pinpin

    2015-02-01

    Inhalation of zinc oxide nanoparticles (ZnONP) has potential health impact. Because zinc ion may involve in the toxicity of ZnONP, we compared adverse effects of inhaled aerosolized ZnONP and zinc nitrate in mice. Aerosolized ZnONP and zinc nitrate were well-dispersed in the inhalation chamber. Inhalation of 0.86 mg/m(3) ZnONP or 1.98 mg/m(3) zinc nitrate for 5 h caused acute inflammation mainly at bronchioloalveolar junctions of lungs at 24-h post-exposure. Inhalation of ZnONP or zinc nitrate increased metallothionein expression in the epithelial cells of brochioloalveolar junction. While the effects on cytokines secretion in bronchoalveolar lavage were similar between ZnONP and zinc nitrate, only ZnONP increased lactate dehydrogenase activity. However, repeated exposure to 0.86 mg/m(3) ZnONP 5 h/day for 5 days failed to cause a similar adverse effect. Either single or repeated exposure to 0.86 mg/m(3) ZnONP increased activities of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and creatine phosphokinase in blood. In contrast, exposure to zinc nitrate had no similar systemic effects. In human bronchial epithelial cells, ZnONP-induced interleukin-8 secretion was partially prevented by co-treatment with the Toll-like receptor 4 (TLR4) inhibitor. Furthermore, ZnONP-induced pulmonary inflammation was greater in wild-type mice than in TLR4-deficent mice. It appears that ZnONP-induced acute pulmonary inflammation partially depended on TLR4. In summary, we demonstrated the dose-responsive effects for inhalation of ZnONP and zinc nitrate in mice. The threshold of cytokines induction for inhalation of ZnONP for 5 h was 0.43 mg/m(3). The particulate characters of ZnONP might contribute to the systemic adverse effects and shall be evaluated for assessing its health impact in humans.

  17. Characteristics of Allergic Pulmonary Inflammation in CXCR3Knockout Mice Sensitized and Challenged with House Dust Mite Protein

    PubMed Central

    Chen, Xiaolan; Gao, Jinming; Guo, Zijian

    2016-01-01

    Chemokine C-X-C motif receptor 3 (CXCR3) is a chemokine receptor that is mainly expressed by activated T lymphocytes. T cells play important roles in allergic pulmonary inflammation, which is a hallmark of asthma and elicits the localized accumulation of activated T cells in the lung. In China, a marked increase in the incidence rate of chronic allergic pulmonary inflammation has made it a major public health threat. In the present study, we investigated the role of CXCR3 and its ligands in airway inflammation induced by house dust mite protein (HDMP) in a CXCR3 knockout (CXCR3KO) asthma mouse model. Pathological manifestations in the lung, cell counts and bronchoalveolar lavage fluid (BALF) classifications were studied using hematoxylin and eosin (H&E) staining. The levels of IL-4 and IFN-γ in the BALF and splenocyte supernatants were measured using ELISA. CD4+ and CD8+ T cells in the lung and spleen were analyzed by flow cytometry. RT-PCR was applied to measure the mRNA transcript levels of monokines induced by IFN-γ(CXCL9) and IFN-γ inducible protein 10(CXCL10). The total cell counts, eosinophil counts, and IL-4 levels in the BALF and cultured splenocyte supernatants were significantly increased, while the levels of IFN-γ were reduced in the HDMP groups(P<0.01). Changes in the total cell counts, eosinophil counts, and lymphocyte counts, as well as the total protein levels in the BALF, the levels of IL-4 in splenocyte supernatants, and the pathological manifestations in the lung, were all greater in CXCR3KO mice than in C57BL/6 wild-type mice. Furthermore, the expression levels of CXCL9 and CXCL10 mRNA transcripts in the lungs of CXCR3KO mice were lower than those in C57BL/6 wild-type mice (P<0.05). CXCR3 and its ligands (i.e., CXCL9 and CXCL10) may play anti-inflammatory roles in this animal model. Promoting the expression of CXCR3 and its ligands may represent a novel therapeutic approach for preventing and curing asthma. PMID:27727269

  18. Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

    PubMed

    Fernandez-Bustamante, A; Easley, R B; Fuld, M; Mulreany, D; Chon, D; Lewis, J F; Simon, B A

    2012-08-15

    The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1β), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1β were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

  19. Radiotracers Used for the Scintigraphic Detection of Infection and Inflammation

    PubMed Central

    Tsopelas, Chris

    2015-01-01

    Over the last forty years, a small group of commercial radiopharmaceuticals have found their way into routine medical use, for the diagnostic imaging of patients with infection or inflammation. These molecular radiotracers usually participate in the immune response to an antigen, by tagging leukocytes or other molecules/cells that are endogenous to the process. Currently there is an advancing effort by researchers in the preclinical domain to design and develop new agents for this application. This review discusses radiopharmaceuticals used in the nuclear medicine clinic today, as well as those potential radiotracers that exploit an organism's defence mechanisms to an infectious or inflammatory event. PMID:25741532

  20. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus–induced inflammation and infection

    PubMed Central

    Numata, Mari; Chu, Hong Wei; Dakhama, Azzeddine; Voelker, Dennis R.

    2009-01-01

    Respiratory syncytial virus (RSV) is the most common cause of hospitalization for respiratory tract infection in young children. It is also a significant cause of morbidity and mortality in elderly individuals and in persons with asthma and chronic obstructive pulmonary disease. Currently, no reliable vaccine or simple RSV antiviral therapy is available. Recently, we determined that the minor pulmonary surfactant phospholipid, palmitoyl-oleoyl-phosphatidylglycerol (POPG), could markedly attenuate inflammatory responses induced by lipopolysaccharide through direct interactions with the Toll-like receptor 4 (TLR4) interacting proteins CD14 and MD-2. CD14 and TLR4 have been implicated in the host response to RSV. Treatment of bronchial epithelial cells with POPG significantly inhibited interleukin-6 and -8 production, as well as the cytopathic effects induced by RSV. The phospholipid bound RSV with high affinity and inhibited viral attachment to HEp2 cells. POPG blocked viral plaque formation in vitro by 4 log units, and markedly suppressed the expansion of plaques from cells preinfected with the virus. Administration of POPG to mice, concomitant with viral infection, almost completely eliminated the recovery of virus from the lungs at 3 and 5 days after infection, and abrogated IFN-γ (IFN-γ) production and the enhanced expression of surfactant protein D (SP-D). These findings demonstrate an important approach to prevention and treatment of RSV infections using exogenous administration of a specific surfactant phospholipid. PMID:20080799

  1. Pulmonary Inflammation Impacts on CYP1A1-Mediated Respiratory Tract DNA Damage Induced by the Carcinogenic Air Pollutant Benzo[a]pyrene

    PubMed Central

    Arlt, Volker M.; Krais, Annette M.; Godschalk, Roger W.; Riffo-Vasquez, Yanira; Mrizova, Iveta; Roufosse, Candice A.; Corbin, Charmaine; Shi, Quan; Frei, Eva; Stiborova, Marie; van Schooten, Frederik-Jan; Phillips, David H.; Spina, Domenico

    2015-01-01

    Pulmonary inflammation can contribute to the development of lung cancer in humans. We investigated whether pulmonary inflammation alters the genotoxicity of polycyclic aromatic hydrocarbons (PAHs) in the lungs of mice and what mechanisms are involved. To model nonallergic acute inflammation, mice were exposed intranasally to lipopolysaccharide (LPS; 20 µg/mouse) and then instilled intratracheally with benzo[a]pyrene (BaP; 0.5 mg/mouse). BaP-DNA adduct levels, measured by 32P-postlabeling analysis, were approximately 3-fold higher in the lungs of LPS/BaP-treated mice than in mice treated with BaP alone. Pulmonary Cyp1a1 enzyme activity was decreased in LPS/BaP-treated mice relative to BaP-treated mice suggesting that pulmonary inflammation impacted on BaP-induced Cyp1a1 activity in the lung. Our results showed that Cyp1a1 appears to be important for BaP detoxification in vivo and that the decrease of pulmonary Cyp1a1 activity in LPS/BaP-treated mice results in a decrease of pulmonary BaP detoxification, thereby enhancing BaP genotoxicity (ie, DNA adduct formation) in the lung. Because less BaP was detoxified by Cyp1a1 in the lungs of LPS/BaP-treated mice, more BaP circulated via the blood to extrapulmonary tissues relative to mice treated with BaP only. Indeed, we observed higher BaP-DNA adduct levels in livers of LPS/BaP-treated mice compared with BaP-treated mice. Our results indicate that pulmonary inflammation could be a critical determinant in the induction of genotoxicity in the lung by PAHs like BaP. Cyp1a1 appears to be involved in both BaP bioactivation and detoxification although the contribution of other enzymes to BaP-DNA adduct formation in lung and liver under inflammatory conditions remains to be explored. PMID:25911668

  2. Improving performance of computer-aided detection of pulmonary embolisms by incorporating a new pulmonary vascular-tree segmentation algorithm

    NASA Astrophysics Data System (ADS)

    Wang, Xingwei; Song, XiaoFei; Chapman, Brian E.; Zheng, Bin

    2012-03-01

    We developed a new pulmonary vascular tree segmentation/extraction algorithm. The purpose of this study was to assess whether adding this new algorithm to our previously developed computer-aided detection (CAD) scheme of pulmonary embolism (PE) could improve the CAD performance (in particular reducing false positive detection rates). A dataset containing 12 CT examinations with 384 verified pulmonary embolism regions associated with 24 threedimensional (3-D) PE lesions was selected in this study. Our new CAD scheme includes the following image processing and feature classification steps. (1) A 3-D based region growing process followed by a rolling-ball algorithm was utilized to segment lung areas. (2) The complete pulmonary vascular trees were extracted by combining two approaches of using an intensity-based region growing to extract the larger vessels and a vessel enhancement filtering to extract the smaller vessel structures. (3) A toboggan algorithm was implemented to identify suspicious PE candidates in segmented lung or vessel area. (4) A three layer artificial neural network (ANN) with the topology 27-10-1 was developed to reduce false positive detections. (5) A k-nearest neighbor (KNN) classifier optimized by a genetic algorithm was used to compute detection scores for the PE candidates. (6) A grouping scoring method was designed to detect the final PE lesions in three dimensions. The study showed that integrating the pulmonary vascular tree extraction algorithm into the CAD scheme reduced false positive rates by 16.2%. For the case based 3D PE lesion detecting results, the integrated CAD scheme achieved 62.5% detection sensitivity with 17.1 false-positive lesions per examination.

  3. PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation.

    PubMed

    Sun, Qingzhu; Liu, Li; Roth, Michael; Tian, Jia; He, Qirui; Zhong, Bo; Bao, Ruanjuan; Lan, Xi; Jiang, Congshan; Sun, Jian; Yang, Xudong; Lu, Shemin

    2015-07-01

    Protein arginine methyltransferase (PRMT)1, methylating both histones and key cellular proteins, has emerged as a key regulator of various cellular processes. This study aimed to identify the mechanism that regulates PRMT1 in chronic Ag-induced pulmonary inflammation (AIPI) in the E3 rat asthma model. E3 rats were challenged with OVA for 1 or 8 wk to induce acute or chronic AIPI. Expression of mRNAs was detected by real-time quantitative PCR. PRMT1, TGF-β, COX2, and vascular endothelial growth factor protein expression in lung tissues was determined by immunohistochemistry staining and Western blotting. In the in vitro study, IL-4-stimulated lung epithelial cell (A549) medium (ISEM) with or without anti-TGF-β Ab was applied to human fibroblasts from lung (HFL1). The proliferation of HFL1 was determined by MTT. AMI-1 (pan-PRMT inhibitor) was administered intranasally to chronic AIPI rats to determine PRMT effects on asthmatic parameters. In lung tissue sections, PRMT1 expression was significantly upregulated, mainly in epithelial cells, in acute AIPI lungs, whereas it was significantly upregulated mainly in fibroblasts in chronic AIPI lungs. The in vitro study revealed that ISEM elevates PRMT1, COX2, and vascular endothelial growth factor expressions, and it promoted fibroblast proliferation. The application of anti-TGF-β Ab suppressed COX2 upregulation by ISEM. AMI-1 inhibited the expression of COX2 in TGF-β-stimulated cells. In the in vivo experiment, AMI-1 administered to AIPI rats reduced COX2 production and humoral immune response, and it abrogated mucus secretion and collagen generation. These findings suggested that TGF-β-induced PRMT1 expression participates in fibroblast proliferation and chronic airway inflammation in AIPI. PMID:26026059

  4. Equivalent Dipole Vector Analysis for Detecting Pulmonary Hypertension

    NASA Technical Reports Server (NTRS)

    Harlander, Matevz; Salobir, Barbara; Toplisek, Janez; Schlegel, Todd T.; Starc, Vito

    2010-01-01

    Various 12-lead ECG criteria have been established to detect right ventricular hypertrophy as a marker of pulmonary hypertension (PH). While some criteria offer good specificity they lack sensitivity because of a low prevalence of positive findings in the PH population. We hypothesized that three-dimensional equivalent dipole (ED) model could serve as a better detection tool of PH. We enrolled: 1) 17 patients (12 female, 5 male, mean age 57 years, range 19-79 years) with echocardiographically detected PH (systolic pulmonary arterial pressure greater than 35 mmHg) and no significant left ventricular disease; and 2) 19 healthy controls (7 female, 12 male, mean age 44, range 31-53 years) with no known heart disease. In each subject we recorded a 5-minute high-resolution 12-lead conventional ECG and constructed principal signals using singular value decomposition. Assuming a standard thorax dimension of an adult person with homogenous and isotropic distribution of thorax conductance, we determined moving equivalent dipoles (ED), characterized by the 3D location in the thorax, dipolar strength and the spatial orientation, in time intervals of 5 ms. We used the sum of all ED vectors in the second half of the QRS complex to derive the amplitude of the right-sided ED vector (RV), if the orientation of ED was to the right side of the thorax, and in the first half the QRS to derive the amplitude of the left-sided vector (LV), if the orientation was leftward. Finally, the parameter RV/LV ratio was determined over an average of 256 complexes. The groups differed in age and gender to some extent. There was a non-significant trend toward higher RV in patients with PH (438 units 284) than in controls (280 plus or minus 140) (p = 0.066) but the overlap was such that RV alone was not a good predictor of PH. On the other hand, the RV/LV ratio was a better predictor of PH, with 11/17 (64.7%) of PH patients but only in 1/19 (5.3%) control subjects having RV/LV ratio greater than or

  5. Endobronchial ultrasound for the detection of chronic pulmonary artery thrombus.

    PubMed

    Dhillon, Samjot Singh; Harris, Kassem

    2016-01-01

    Endobronchial ultrasound (EBUS) has been shown to be able to successfully identify acute/subacute pulmonary thromboembolism (PE). Most reported cases have required confirmation by computerized tomography (CT) angiography. This report demonstrates a case where CT angiography was not conclusive and the EBUS was useful in clarifying the chronic process inside the pulmonary artery compatible with clinical diagnosis of chronic pulmonary artery thrombosis. PMID:27503162

  6. Elevated expression of IL-23/IL-17 pathway-related mediators correlates with exacerbation of pulmonary inflammation during polymicrobial sepsis.

    PubMed

    Cauvi, David M; Williams, Michael R; Bermudez, Jose A; Armijo, Gabrielle; De Maio, Antonio

    2014-09-01

    Sepsis is a leading cause of death in the United States, claiming more than 215,000 lives every year. A primary condition observed in septic patients is the incidence of acute respiratory distress syndrome, which is characterized by the infiltration of neutrophils into the lung. Prior studies have shown differences in pulmonary neutrophil accumulation in C57BL/6J (B6) and A/J mice after endotoxic and septic shock. However, the mechanism by which neutrophils accumulate in the lung after polymicrobial sepsis induced by cecal ligation and puncture still remains to be fully elucidated. We show in this study that lung inflammation, characterized by neutrophil infiltration and expression of inflammatory cytokines, was aggravated in B6 as compared with A/J mice and correlated with a high expression of p19, the interleukin 23 (IL-23)-specific subunit. Furthermore, lipopolysaccharide stimulation of B6- and A/J-derived macrophages, one of the main producers of IL-23 and IL-12, revealed that B6 mice favored the production of IL-23, whereas A/J-derived macrophages expressed higher levels of IL-12. In addition, expression of IL-17, known to be upregulated by IL-23, was also more elevated in the lung of B6 mice when compared with that in the lung of A/J mice. In contrast, pulmonary expression of interferon-γ was much more pronounced in A/J than that in B6 mice, which was most likely a result of a higher production of IL-12. The expression of the IL-17-dependent neutrophil recruitment factors chemokine (CXC motif) ligand 2 and granulocyte colony-stimulating factor was also higher in B6 mice. Altogether, these results suggest that increased activation of the IL-23/IL-17 pathway has detrimental effects on sepsis-induced lung inflammation, whereas activation of the IL-12/interferon-γ pathway may lead, in contrast, to less pronounced inflammatory events. These two pathways may become possible therapeutic targets for the treatment of sepsis-induced acute respiratory distress

  7. Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS) on pulmonary inflammation induced by bleomycin

    PubMed Central

    Santos, Laisa A.; Silva, Carlos A.; Polacow, Maria L. O.

    2013-01-01

    Background Bleomycin (B) is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. Objective The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS). Method Wistar rats were divided into 4 groups (n=5): a control group (C); a stimulated group (TEDS); a group treated with a single dose of B (intratracheally, 2.5 mg/kg) (B); and a group treated with B and electric stimulation (B + TEDS). After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE) and 8-isoprostane-PGF2α (8-iso-PGF2α). The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2α. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p≤0.05). Results The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. Conclusion B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage. PMID:24346295

  8. What Causes Pulmonary Hypertension?

    MedlinePlus

    ... from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... different types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the ...

  9. Pulmonary inflammation induced by repeated inhalations of beta(1,3)-D-glucan and endotoxin.

    PubMed Central

    Fogelmark, B.; Sjöstrand, M.; Rylander, R.

    1994-01-01

    In an animal model of hypersensitivity pneumonitis (HP) guinea-pigs were exposed for 5 weeks to an aerosol of bacterial endotoxin, beta(1,3)-D-glucan (curdlan) or a combination. Exposure to endotoxin or curdlan showed only small changes in inflammatory cells in airways or the lung wall, histologically or in terms of enzyme secretion from alveolar macrophages. When the two agents were given together, a histology resembling HP was seen with alveolar infiltrates and early granulomas. Inflammatory cells in airways were increased and enzyme production of macrophages was changed, suggesting an effect of curdlan on the inflammatory regulating capacity of airway macrophages. The results suggest that interference with macrophage function and inflammation are important components in the development of HP. PMID:8199009

  10. Dietary Long-Chain Omega-3 Fatty Acids Do Not Diminish Eosinophilic Pulmonary Inflammation in Mice

    PubMed Central

    Bratt, Jennifer M.; Jiang, Xiaowen; Pedersen, Theresa L.; Grapov, Dmitry; Adkins, Yuriko; Kelley, Darshan S.; Newman, John W.; Kenyon, Nicholas J.; Stephensen, Charles B.

    2014-01-01

    Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid–derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma. PMID:24134486

  11. Electrophilic Fatty Acid Species Inhibit 5-Lipoxygenase and Attenuate Sepsis-Induced Pulmonary Inflammation

    PubMed Central

    Awwad, Khader; Steinbrink, Svenja D.; Frömel, Timo; Lill, Nicole; Isaak, Johann; Häfner, Ann-Kathrin; Roos, Jessica; Hofmann, Bettina; Heide, Heinrich; Geisslinger, Gerd; Steinhilber, Dieter; Freeman, Bruce A.; Maier, Thorsten J.; Fleming, Ingrid

    2014-01-01

    Abstract Aims: The reaction of nitric oxide and nitrite-derived species with polyunsaturated fatty acids yields electrophilic fatty acid nitroalkene derivatives (NO2-FA), which display anti-inflammatory properties. Given that the 5-lipoxygenase (5-LO, ALOX5) possesses critical nucleophilic amino acids, which are potentially sensitive to electrophilic modifications, we determined the consequences of NO2-FA on 5-LO activity in vitro and on 5-LO-mediated inflammation in vivo. Results: Stimulation of human polymorphonuclear leukocytes (PMNL) with nitro-oleic (NO2-OA) or nitro-linoleic acid (NO2-LA) (but not the parent lipids) resulted in the concentration-dependent and irreversible inhibition of 5-LO activity. Similar effects were observed in cell lysates and using the recombinant human protein, indicating a direct reaction with 5-LO. NO2-FAs did not affect the activity of the platelet-type 12-LO (ALOX12) or 15-LO-1 (ALOX15) in intact cells or the recombinant protein. The NO2-FA-induced inhibition of 5-LO was attributed to the alkylation of Cys418, and the exchange of Cys418 to serine rendered 5-LO insensitive to NO2-FA. In vivo, the systemic administration of NO2-OA to mice decreased neutrophil and monocyte mobilization in response to lipopolysaccharide (LPS), attenuated the formation of the 5-LO product 5-hydroxyeicosatetraenoic acid (5-HETE), and inhibited lung injury. The administration of NO2-OA to 5-LO knockout mice had no effect on LPS-induced neutrophil or monocyte mobilization as well as on lung injury. Innovation: Prophylactic administration of NO2-OA to septic mice inhibits inflammation and promotes its resolution by interfering in 5-LO-mediated inflammatory processes. Conclusion: NO2-FAs directly and irreversibly inhibit 5-LO and attenuate downstream acute inflammatory responses. Antioxid. Redox Signal. 20, 2667–2680. PMID:24206143

  12. In Vivo Detection of Vascular Adhesion Protein-1 in Experimental Inflammation

    PubMed Central

    Jaakkola, Kimmo; Nikula, Tuomo; Holopainen, Riikka; Vähäsilta, Tommi; Matikainen, Marja-Terttu; Laukkanen, Marja-Leena; Huupponen, Risto; Halkola, Lauri; Nieminen, Lauri; Hiltunen, Jukka; Parviainen, Sakari; Clark, Michael R.; Knuuti, Juhani; Savunen, Timo; Kääpä, Pekka; Voipio-Pulkki, Liisa Maria; Jalkanen, Sirpa

    2000-01-01

    Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation. PMID:10934150

  13. Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function

    PubMed Central

    Giannattasio, Giorgio; Fujioka, Daisuke; Xing, Wei; Katz, Howard R.; Boyce, Joshua A.; Balestrieri, Barbara

    2010-01-01

    We have previously shown that group V secretory phospholipase A2 (sPLA2) regulates phagocytosis of zymosan and Candida albicans by a mechanism that depends on fusion of phagosomes with late endosomes in macrophages. Here we report that group V sPLA2 (Pla2g5)-null mice exposed to an extract of house dust mite Dermatophagoides farinae (Df) had markedly reduced pulmonary inflammation and goblet cell metaplasia compared to wild-type (WT) mice. Pla2g5-null mice had also impaired Th2-type adaptive immune responses to Df compared to WT mice. Pla2g5-null bone marrow-derived dendritic cells (BMDCs) activated by Df had delayed intracellular processing of allergen and impaired allergen-dependent maturation, a pattern recapitulated by the native lung DCs of Df-challenged mice. Adoptively transferred Df-loaded Pla2g5-null BMDCs were less able than Df-loaded WT BMDCs to induce pulmonary inflammation and Th2 polarization in WT mice. However, Pla2g5-null recipients transferred with WT or Pla2g5-null Df-loaded BMDCs exhibited significantly reduced local inflammatory responses to Df, even though the transfer of WT BMDCs still induced an intact Th2 cytokine response in regional lymph nodes. Thus, the expression of group V sPLA2 in APC regulates Ag processing and maturation of dendritic cells, and contributes to pulmonary inflammation and immune response against Df. Furthermore, an additional yet to be identified resident cell type is essential for the development of pulmonary inflammation, likely a cell in which group V sPLA2 is upregulated by Df and whose function is also regulated by group V sPLA2. PMID:20817863

  14. Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice

    PubMed Central

    Dahm, Paul H.; Richards, Jeremy B.; Karmouty-Quintana, Harry; Cromar, Kevin R.; Sur, Sanjiv; Price, Roger E.; Malik, Farhan; Spencer, Chantal Y.; Barreno, Ramon X.; Hashmi, Syed S.; Blackburn, Michael R.; Haque, Ikram U.

    2014-01-01

    Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpefat mice). Accordingly, Cpefat and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpefat compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model. PMID:25009214

  15. Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.

    PubMed

    Dahm, Paul H; Richards, Jeremy B; Karmouty-Quintana, Harry; Cromar, Kevin R; Sur, Sanjiv; Price, Roger E; Malik, Farhan; Spencer, Chantal Y; Barreno, Ramon X; Hashmi, Syed S; Blackburn, Michael R; Haque, Ikram U; Johnston, Richard A

    2014-09-15

    Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). Accordingly, Cpe(fat) and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.

  16. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

    SciTech Connect

    Yao Hongwei; Rahman, Irfan

    2011-07-15

    Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-{kappa}B), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-{kappa}B pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.

  17. Anergy-like immunosuppression in mice bearing pulmonary foreign-body granulomatous inflammation.

    PubMed Central

    Allred, D. C.; Kobayashi, K.; Yoshida, T.

    1985-01-01

    Pulmonary granulomas were induced in BALB/c mice by the intratracheal injection of insoluble polymerized dextran and latex microparticles. Very large granulomas developed around dextran beads, which reached peak intensity within 2-3 days and rapidly declined in size thereafter. Latex beads generated small stable lesions. The involvement of cell-mediated immunity could not be demonstrated in the inflammatory responses induced by either type of bead. Antigen-induced delayed type hypersensitivity (DTH) and mitogen-induced DTH-like footpad reactions were markedly suppressed in immunized mice bearing early dextran granulomas. Mitogen-induced DTH-like footpad reactions were suppressed in unimmunized animals bearing early dextran foreign-body granulomas. Antigen- and mitogen-induced footpad swelling recovered to normal levels as dextran granulomas diminished in size. No suppression of these footpad reactions was observed in mice bearing small latex foreign-body granulomas. The intraperitoneal injection of aqueous extracts prepared from the lungs of unimmunized donor animals bearing early dextran foreign-body granulomas could partially transfer suppression of mitogen DTH-like footpad responses to normal mice. These results suggest that cells within large, nonimmunologic lung granulomas produce a soluble factor which participates in the expression of anergy-like immunosuppression. Images Figure 2 PMID:3907366

  18. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging

    PubMed Central

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E.; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  19. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging.

    PubMed

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von Zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  20. FUMEPOC: Early detection of chronic obstructive pulmonary disease in smokers

    PubMed Central

    2011-01-01

    Background Currently is not feasible using conventional spirometry as a screening method in Primary Care especially among smoking population to detect chronic obstructive pulmonary disease in early stages. Therefore, the FUMEPOC study protocol intends to analyze the validity and reliability of Vitalograph COPD-6 spirometer as simpler tool to aid screening and diagnosis of this disease in early stages in primary care surgery. Methods / Design Study design: An observational, descriptive study of diagnostic tests, undertaken in Primary Care and Pneumology Outpatient Care Centre at San Juan Hospital and Elda Hospital. All smokers attending the primary care surgery and consent to participate in the study will undergo a test with Vitalograph COPD-6 spirometer. Subsequently, a conventional spirometry will be performed in the hospital and the results will be compared with those of the Vitalograph COPD-6 test. Discussion It is difficult to use the spirometry as screening for early diagnose test in real conditions of primary care clinical practice. The use of a simpler tool, Vitalograph COPD-6 spirometer, can help in the early diagnose and therefore, it could improve the clinical management of the disease. PMID:21627787

  1. Update on the Mechanisms of Pulmonary Inflammation and Oxidative Imbalance Induced by Exercise.

    PubMed

    Araneda, O F; Carbonell, T; Tuesta, M

    2016-01-01

    The mechanisms involved in the generation of oxidative damage and lung inflammation induced by physical exercise are described. Changes in lung function induced by exercise involve cooling of the airways, fluid evaporation of the epithelial surface, increased contact with polluting substances, and activation of the local and systemic inflammatory response. The present work includes evidence obtained from the different types of exercise in terms of duration and intensity, the effect of both acute performance and chronic performance, and the influence of special conditions such as cold weather, high altitude, and polluted environments. Levels of prooxidants, antioxidants, oxidative damage to biomolecules, and cellularity, as well as levels of soluble mediators of the inflammatory response and its effects on tissues, are described in samples of lung origin. These samples include tissue homogenates, induced sputum, bronchoalveolar lavage fluid, biopsies, and exhaled breath condensate obtained in experimental protocols conducted on animal and human models. Finally, the need to simultaneously explore the oxidative/inflammatory parameters to establish the interrelation between them is highlighted. PMID:26881028

  2. In Vivo Transcriptional Profiling of Yersinia pestis Reveals a Novel Bacterial Mediator of Pulmonary Inflammation

    PubMed Central

    Pechous, Roger D.; Broberg, Christopher A.; Stasulli, Nikolas M.; Miller, Virginia L.

    2015-01-01

    ABSTRACT Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. Very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. In this work, we analyzed the in vivo transcription kinetics of 288 bacterial open reading frames previously shown by microarray analysis to be dynamically regulated in the lung. Using this approach combined with bacterial genetics, we were able to identify five Y. pestis genes that contribute to the development of pneumonic plague. Deletion of one of these genes, ybtX, did not alter bacterial survival but attenuated host inflammatory responses during late-stage disease. Deletion of ybtX in another lethal respiratory pathogen, Klebsiella pneumoniae, also resulted in diminished host inflammation during infection. Thus, our in vivo transcriptional screen has identified an important inflammatory mediator that is common to two Gram-negative bacterial pathogens that cause severe pneumonia. PMID:25691593

  3. β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.

    PubMed

    Kutty, Geetha; Davis, A Sally; Ferreyra, Gabriela A; Qiu, Ju; Huang, Da Wei; Sassi, Monica; Bishop, Lisa; Handley, Grace; Sherman, Brad; Lempicki, Richard; Kovacs, Joseph A

    2016-09-01

    β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses. PMID:27324243

  4. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS

    PubMed Central

    Yang, Jie; Zhao, Yanfeng; Zhang, Peng; Li, Yuehua; Yang, Yong; Yang, Yang; Zhu, Junjie; Song, Xiao; Jiang, Gening; Fan, Jie

    2016-01-01

    Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI. PMID:27607578

  5. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS.

    PubMed

    Yang, Jie; Zhao, Yanfeng; Zhang, Peng; Li, Yuehua; Yang, Yong; Yang, Yang; Zhu, Junjie; Song, Xiao; Jiang, Gening; Fan, Jie

    2016-01-01

    Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI. PMID:27607578

  6. A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

    PubMed Central

    Small, Donna M; Zani, Marie-Louise; Quinn, Derek J; Dallet-Choisy, Sandrine; Glasgow, Arlene MA; O'Kane, Cecilia; McAuley, Danny F; McNally, Paul; Weldon, Sinéad; Moreau, Thierry; Taggart, Clifford C

    2015-01-01

    Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden. PMID:25189740

  7. Update on the Mechanisms of Pulmonary Inflammation and Oxidative Imbalance Induced by Exercise

    PubMed Central

    Araneda, O. F.; Carbonell, T.; Tuesta, M.

    2016-01-01

    The mechanisms involved in the generation of oxidative damage and lung inflammation induced by physical exercise are described. Changes in lung function induced by exercise involve cooling of the airways, fluid evaporation of the epithelial surface, increased contact with polluting substances, and activation of the local and systemic inflammatory response. The present work includes evidence obtained from the different types of exercise in terms of duration and intensity, the effect of both acute performance and chronic performance, and the influence of special conditions such as cold weather, high altitude, and polluted environments. Levels of prooxidants, antioxidants, oxidative damage to biomolecules, and cellularity, as well as levels of soluble mediators of the inflammatory response and its effects on tissues, are described in samples of lung origin. These samples include tissue homogenates, induced sputum, bronchoalveolar lavage fluid, biopsies, and exhaled breath condensate obtained in experimental protocols conducted on animal and human models. Finally, the need to simultaneously explore the oxidative/inflammatory parameters to establish the interrelation between them is highlighted. PMID:26881028

  8. Update on the Mechanisms of Pulmonary Inflammation and Oxidative Imbalance Induced by Exercise.

    PubMed

    Araneda, O F; Carbonell, T; Tuesta, M

    2016-01-01

    The mechanisms involved in the generation of oxidative damage and lung inflammation induced by physical exercise are described. Changes in lung function induced by exercise involve cooling of the airways, fluid evaporation of the epithelial surface, increased contact with polluting substances, and activation of the local and systemic inflammatory response. The present work includes evidence obtained from the different types of exercise in terms of duration and intensity, the effect of both acute performance and chronic performance, and the influence of special conditions such as cold weather, high altitude, and polluted environments. Levels of prooxidants, antioxidants, oxidative damage to biomolecules, and cellularity, as well as levels of soluble mediators of the inflammatory response and its effects on tissues, are described in samples of lung origin. These samples include tissue homogenates, induced sputum, bronchoalveolar lavage fluid, biopsies, and exhaled breath condensate obtained in experimental protocols conducted on animal and human models. Finally, the need to simultaneously explore the oxidative/inflammatory parameters to establish the interrelation between them is highlighted.

  9. Cold ischemia with selective anterograde in situ pulmonary perfusion preserves gas exchange and mitochondrial homeostasis and curbs inflammation in an experimental model of donation after cardiac death.

    PubMed

    Pottecher, Julien; Santelmo, Nicola; Noll, Eric; Charles, Anne-Laure; Benahmed, Malika; Canuet, Matthieu; Frossard, Nelly; Namer, Izzie J; Geny, Bernard; Massard, Gilbert; Diemunsch, Pierre

    2013-10-01

    The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance (PVR), the PaO2 /FiO2 ratio, the transpulmonary oxygen output (tpVO2 ), and the transpulmonary CO2 clearance (tpCO2 ). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity (Vmax ) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics (mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2 /FiO2 : P = 0.56; tpVO2 : P = 0.46), CO2 diffusion (tpCO2 : P = 0.24), mitochondrial homeostasis (Vmax : P = 0.42; ACR: P = 0.8), and RAGE concentrations (P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion.

  10. Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth restriction and enhances pulmonary function in a newborn mouse model of perinatal inflammation.

    PubMed

    Velten, Markus; Britt, Rodney D; Heyob, Kathryn M; Tipple, Trent E; Rogers, Lynette K

    2014-03-01

    The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothesis that DHA supplementation to the dam would reduce hyperoxic lung injury and growth deficits in a more severe model of systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg diet) or control diets and injected with saline or LPS. Diets were maintained through weaning. At birth, pups were placed in room air or hyperoxia for 14 d. Improvements in birth weight (P < 0.01), alveolarization (P ≤ 0.01), and pulmonary function (P ≤ 0.03) at 2 and 8 wk of age were observed in pups exposed to perinatal inflammation and born to DHA-supplemented dams compared with control diet-exposed pups. These improvements were associated with decreases in tissue macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P ≤ 0.05), and decreases in soluble receptor for advanced glycation end products concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation attenuated pulmonary fibrosis, which was associated with the reduction of matrix metalloproteinases 2, 3, and 8 (P ≤ 0.03) and collagen mRNA (P ≤ 0.05), and decreased collagen (P < 0.01) and vimentin (P ≤ 0.03) protein concentrations. In a model of severe inflammation, maternal DHA supplementation lessened inflammation and improved lung growth in the offspring. Maternal supplementation with DHA may be a therapeutic strategy to reduce neonatal inflammation.

  11. Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo.

    PubMed

    Kontos, C D; Wei, E P; Williams, J I; Kontos, H A; Povlishock, J T

    1992-10-01

    We used a cytochemical technique for the detection of superoxide in cerebral inflammation and ischemia-reperfusion in anesthetized cats. The technique is based on the oxidation of Mn2+ to Mn3+ by superoxide; Mn3+, in turn, oxidizes diaminobenzidine. The oxidized diaminobenzidine forms an osmiophilic electron-dense product that is detected by electron microscopy. The reagents, manganese chloride (2 mM) and diaminobenzidine (2 mg/ml), were placed topically on the brain surface of anesthetized cats equipped with cranial windows. Inflammation was induced by topical carrageenan with or without phorbol 12-myristate 13-acetate to activate leukocytes. In inflammation, superoxide was detected in the plasma membrane and in the phagocytic vacuoles of leukocytes. In ischemia-reperfusion, superoxide was identified in the meninges in association with blood vessels. It was located primarily in the extracellular space and occasionally in endothelial and vascular smooth muscle cells. In both inflammation and ischemia, the reaction product was eliminated by superoxide dismutase or by the omission of either manganese or diaminobenzidine. It was unaffected by sodium azide, which inhibits peroxidases. No superoxide was detected in the brain parenchyma. The findings confirm the generation of superoxide is cerebral ischemia-reperfusion and show that it is produced in cerebral vessels.

  12. Computer-aided detection of pulmonary embolism in computed tomographic pulmonary angiography (CTPA): performance evaluation with independent data sets.

    PubMed

    Zhou, Chuan; Chan, Heang-Ping; Sahiner, Berkman; Hadjiiski, Lubomir M; Chughtai, Aamer; Patel, Smita; Wei, Jun; Cascade, Philip N; Kazerooni, Ella A

    2009-08-01

    The authors are developing a computer-aided detection system for pulmonary emboli (PE) in computed tomographic pulmonary angiography (CTPA) scans. The pulmonary vessel tree is extracted using a 3D expectation-maximization segmentation method based on the analysis of eigen-values of Hessian matrices at multiple scales. A parallel multiprescreening method is applied to the segmented vessels to identify volume of interests (VOIs) that contained suspicious PE. A linear discriminant analysis (LDA) classifier with feature selection is designed to reduce false positives (FPs). Features that characterize the contrast, gray level, and size of PE are extracted as input predictor variables to the LDA classifier. With the IRB approval, 59 CTPA PE cases were collected retrospectively from the patient files (UM cases). With access permission, 69 CTPA PE cases were randomly selected from the data set of the prospective investigation of pulmonary embolism diagnosis (PIOPED) II clinical trial. Extensive lung parenchymal or pleural diseases were present in 22/59 UM and 26/69 PIOPED cases. Experienced thoracic radiologists manually marked 595 and 800 PE as the reference standards in the UM and PIOPED data sets, respectively. PE occlusion of arteries ranged from 5% to 100%, with PE located from the main pulmonary artery to the subsegmental artery levels. Of the 595 PE identified in the UM cases, 245 and 350 PE were located in the subsegmental arteries and the more proximal arteries, respectively. The detection performance was assessed by free response ROC (FROC) analysis. The FROC analysis indicated that the PE detection system could achieve an overall sensitivity of 80% at 18.9 FPs/case for the PIOPED cases when the LDA classifier was trained with the UM cases. The test sensitivity with the UM cases was 80% at 22.6 FPs/cases when the LDA classifier was trained with the PIOPED cases. The detection performance depended on the arterial level where the PE was located and on the

  13. Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism

    PubMed Central

    Qi, Di; Tang, Xumao; He, Jing; Wang, Daoxin; Zhao, Yan; Deng, Wang; Deng, Xinyu; Zhou, Guoqi; Xia, Jing; Zhong, Xi; Pu, Shenglan

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS. PMID:27607575

  14. Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism.

    PubMed

    Qi, Di; Tang, Xumao; He, Jing; Wang, Daoxin; Zhao, Yan; Deng, Wang; Deng, Xinyu; Zhou, Guoqi; Xia, Jing; Zhong, Xi; Pu, Shenglan

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS. PMID:27607575

  15. Disruption of Sirtuin 1-Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease.

    PubMed

    Yao, Hongwei; Sundar, Isaac K; Huang, Yadi; Gerloff, Janice; Sellix, Michael T; Sime, Patricia J; Rahman, Irfan

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERBα, REV-ERBβ, and RORα), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-α released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERBα was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERBα in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-α) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD.

  16. Detection of acute inflammation with /sup 111/In-labeled nonspecific polyclonal IgG

    SciTech Connect

    Fischman, A.J.; Rubin, R.H.; Khaw, B.A.; Callahan, R.J.; Wilkinson, R.; Keech, F.; Nedelman, M.; Dragotakes, S.; Kramer, P.B.; LaMuraglia, G.M.

    1988-10-01

    The detection of focal sites of inflammation is an integral part of the clinical evaluation of the febrile patient. When anatomically distinct abscesses are present, lesion detection can be accomplished by standard radiographic techniques, particularly in patients with normal anatomy. At the phlegmon stage, however, and in patients who have undergone surgery, these techniques are considerably less effective. While radionuclide methods, such as Gallium-67 (67Ga)-citrate and Indium-111 (111In)-labeled WBCs have been relatively successful for the detection of early inflammation, neither approach is ideal. In the course of studies addressing the use of specific organism-directed antibodies for imaging experimental infections in animals, we observed that nonspecific polyclonal immunoglobulin G (IgG) localized as well as specific antibodies. Preliminary experiments suggested that the Fc portion of IgG is necessary for effective inflammation localization. Since polyclonal IgG in gram quantities has been safely used for therapy in patients with immune deficiency states, we decided to test whether milligram quantities of radiolabeled IgG could image focal sites of inflammation in humans. Thus far, we have studied a series of 84 patients with suspected lesions in the abdomen, pelvis, vascular grafts, lungs, or bones/joints. In 48 of 52 patients with focal lesions detected by surgery, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US), the IgG scan correctly localized the site, while 31 patients without focal inflammation had no abnormal focal localization of the radiopharmaceutical. Four patients had false negative scans and one patient had a false positive scan. For this small series, the overall sensitivity and specificity were 92% and 95%, respectively. In this report, we review our experience with this exciting new agent.

  17. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats.

    PubMed

    Lu, Xiaofan; Li, Ya; Li, Jiansheng; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14-18 days. All biomarkers were improved in treated groups with shorter recovery times of 4-10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  18. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    PubMed Central

    Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  19. A Single 9-Colour Flow Cytometric Method to Characterise Major Leukocyte Populations in the Rat: Validation in a Model of LPS-Induced Pulmonary Inflammation.

    PubMed

    Barnett-Vanes, Ashton; Sharrock, Anna; Birrell, Mark A; Rankin, Sara

    2016-01-01

    The rat is a commonly used model for immunological investigation. Yet basic research and characterisation of leukocyte populations and sub-sets lags far behind murine research, with inconsistency on reported leukocyte markers and their overlap. These shortcomings limit the opportunity for more complex and advanced rat immunology research. In this study, we developed a robust 9-colour flow-cytometric protocol to elucidate the major blood and tissue rat leukocyte populations, and validated it in a model of LPS-induced pulmonary inflammation. Blood and tissues (lung, BALF, spleen, liver, bone marrow) from naïve Sprague-Dawley rats were collected and analysed by flow cytometry (FCM). Rats were exposed to aerosolised saline or LPS (1 mg/mL), at 3 and 24 hrs thereafter blood, lung and BALF were collected and analysed using FCM and ELISA. Neutrophils, two monocyte subsets, NK Cells, B Cells, CD4+, CD8+ T Cells and alveolar macrophages can be identified simultaneously across different tissues using a 9-colour panel. Neutrophils and monocytes can be distinguished based upon differential expression of CD43 and His48. Neutrophils and CD43Lo/His48Hi monocyte-macrophages are elevated in the lung at 3 and 24 hrs during LPS-induced pulmonary inflammation. This validated method for leukocyte enumeration will offer a platform for greater consistency in future rat immunology and inflammation research.

  20. EKG-gated digital subtraction angiography in the detection of pulmonary emboli. [Dogs

    SciTech Connect

    Hirji, M.; Gamsu, G.; Webb, W.R.; Brito, A.C.; Kuriyama, K.; Stern, R.G.; Cox, L.

    1984-07-01

    Detection of pulmonary emboli was investigated using electrocardiographically gated (EKG-gated) intravenous digital subtraction angiography (DSA) in 6 anesthetized and paralyzed dogs. Six autologous blood clots were introducted into the internal jugular vein of each dog and both conventional pulmonary angiography and EKG- gated DSA performed in frontal and oblique projections. The authors conclude that DSA can demonstrate individual emboli with good sensitivity and excellent precision. If several emboli are present, KEG-gated DSA should prove highly accurate; however, care must be taken because overinterpretation is more likely with DSA than with conventional pulmonary angiography.

  1. Detection of experimentally produced acute pulmonary arterial occlusion by methyl iodide-131 inhalation imaging

    SciTech Connect

    Grossman, Z.D.; McAfee, J.G.; Subramanian, G.

    1981-08-01

    Methyl iodide-131 (CH/sub 3/I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH/sub 3/I-131 is inhaled, radioactivity passes instantaneously from the alveoli to the lung capillary bed. Where pulmonary blood flow exists, activity is washed out into the systemic circulation, but in areas of blood stasis, a transient pulmonary hot spot remains. CH/sub 3/I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory.

  2. Heme oxygenase-1 and inflammation in experimental right ventricular failure on prolonged overcirculation-induced pulmonary hypertension.

    PubMed

    Belhaj, Asmae; Dewachter, Laurence; Kerbaul, François; Brimioulle, Serge; Dewachter, Céline; Naeije, Robert; Rondelet, Benoît

    2013-01-01

    Heme oxygenase (HO)-1 is a stress response enzyme which presents with cardiovascular protective and anti-inflammatory properties. Six-month chronic overcirculation-induced pulmonary arterial hypertension (PAH) in piglets has been previously reported as a model of right ventricular (RV) failure related to the RV activation of apoptotic and inflammatory processes. We hypothesized that altered HO-1 signalling could be involved in both pulmonary vascular and RV changes. Fifteen growing piglets were assigned to a sham operation (n = 8) or to an anastomosis of the left innominate artery to the pulmonary arterial trunk (n = 7). Six months later, hemodynamics was evaluated after closure of the shunt. After euthanasia of the animals, pulmonary and myocardial tissue was sampled for pathobiological evaluation. Prolonged shunting was associated with a tendency to decreased pulmonary gene and protein expressions of HO-1, while pulmonary gene expressions of interleukin (IL)-33, IL-19, intercellular adhesion molecule (ICAM)-1 and -2 were increased. Pulmonary expressions of constitutive HO-2 and pro-inflammatory tumor necrosis factor (TNF)-α remained unchanged. Pulmonary vascular resistance (evaluated by pressure/flow plots) was inversely correlated to pulmonary HO-1 protein and IL-19 gene expressions, and correlated to pulmonary ICAM-1 gene expression. Pulmonary arteriolar medial thickness and PVR were inversely correlated to pulmonary IL-19 expression. RV expression of HO-1 was decreased, while RV gene expressions TNF-α and ICAM-2 were increased. There was a correlation between RV ratio of end-systolic to pulmonary arterial elastances and RV HO-1 expression. These results suggest that downregulation of HO-1 is associated to PAH and RV failure.

  3. Detection of pulmonary aspiration in children with gastroesophageal reflux

    SciTech Connect

    Orellana, P.; Olea, E.; Pino, C.; Rossel, M.; Ceresa, S.; Gonzalez, P.; Otarola, S.; Astudillo, S.

    1985-05-01

    The presence of pulmonary aspiration (PA) should be suspected in two groups of patients; those with symptoms of gastroesophageal reflux (GER) and pulmonary disease and patient's with pulmonary symptoms without signs of GER in whom other etiologies of pulmonary disease have been excluded. To determine if PA could be diagnosed in children using radionuclides 114 patients aged 3-12 months drank 500 ..mu..Ci of Tc-99m sulfur colloid mixed with infant formula and an additional 1.5 mCi was administered in the evening. All medicine was suspended 24 hours before. Images of the chest in supine position (ant, post views) were acquired on computer in 32 x 32 (byte mode) during 5 min each view at 2 and 18 hours. No outside pressure was applied. None of the patients with digestive symptomatology alone had positive exam. Of 88 patients with bronchopulmonary symptomatology 35 had abnormal examination 35% with moderate symptom were (Abn) and 55% with severe disease were abnormal. The radionuclide method appears to be the ideal study in patients where PA is suspected. The positivity of the method depends on the group of patients selected. The sensitivity is highest in patients with marked symptomatology.

  4. Usefulness of chest ultrasonography in detecting pulmonary embolism in patient with chronic obstructive pulmonary disease and chronic renal failure: a case report.

    PubMed

    Zanobetti, Maurizio; Bigiarini, Sofia; Coppa, Alessandro; Conti, Alberto; Innocenti, Francesca; Pini, Riccardo

    2012-10-01

    We describe the case of a 75-year-old man affected by a chronic obstructive pulmonary disease and chronic renal failure admitted to our emergency department for dyspnea and interscapular stabbing pain. Chest radiography showed diffuse parenchymal consolidation in the lower right lung with bronchiectasis, but the treatment for infection disease did not improve the clinical conditions of the patient. According to Wells score indicating an intermediate risk for pulmonary embolism, we performed a chest ultrasonography that showed ultrasonographic patterns of thromboembolism. Because the presence of chronic renal failure limited the execution of a helical computed tomographic pulmonary angiography, a pulmonary scintigraphy was performed confirming the diagnosis of pulmonary embolism. Our case suggested that chest ultrasonography can be a valuable tool for early detection of pulmonary embolism and to establish immediately an appropriate therapy.

  5. SOPROCARE - 450 nm wavelength detection tool for microbial plaque and gingival inflammation: a clinical study

    NASA Astrophysics Data System (ADS)

    Rechmann, P.; Liou, Shasan W.; Rechmann, Beate M.; Featherstone, John D.

    2014-02-01

    Gingivitis due to microbial plaque and calculus can lead over time if left untreated to advanced periodontal disease with non-physiological pocket formation. Removal of microbial plaque in the gingivitis stage typically achieves gingival health. The SOPROCARE camera system emits blue light at 450 nm wavelength using three blue diodes. The 450 nm wavelength is located in the non-ionizing, visible spectral wavelength region and thus is not dangerous. It is assumed that using the SOPROCARE camera in perio-mode inflamed gingiva can easily be observed and inflammation can be scored due to fluorescence from porphyrins in blood. The assumption is also that illumination of microbial plaque with blue light induces fluorescence due to the bacteria and porphyrin content of the plaque and thus can help to make microbial plaque and calculus visible. Aim of the study with 55 subjects was to evaluate the ability of the SOPROCARE fluorescence camera system to detect, visualize and allow scoring of microbial plaque in comparison to the Turesky modification of the Quigley and Hein plaque index. A second goal was to detect and score gingival inflammation and correlated the findings to the Silness and Löe gingival inflammation index. The study showed that scoring of microbial plaque as well as gingival inflammation levels similar to the established Turesky modified Quigley Hein index and the Silness and Löe gingival inflammation index can easily be done using the SOPROCARE fluorescence system in periomode. Linear regression fits between the different clinical indices and SOPROCARE scores in fluorescence perio-mode revealed the system's capacity for effective discrimination between scores.

  6. Role of Chitinase 3-Like-1 in Interleukin-18-Induced Pulmonary Type 1, Type 2, and Type 17 Inflammation; Alveolar Destruction; and Airway Fibrosis in the Murine Lung.

    PubMed

    Kang, Min-Jong; Yoon, Chang Min; Nam, Milang; Kim, Do-Hyun; Choi, Je-Min; Lee, Chun Geun; Elias, Jack A

    2015-12-01

    Chitinase 3-like 1 (Chi3l1), which is also called YKL-40 in humans and BRP-39 in mice, is the prototypic chitinase-like protein. Recent studies have highlighted its impressive ability to regulate the nature of tissue inflammation and the magnitude of tissue injury and fibroproliferative repair. This can be appreciated in studies that highlight its induction after cigarette smoke exposure, during which it inhibits alveolar destruction and the genesis of pulmonary emphysema. IL-18 is also known to be induced and activated by cigarette smoke, and, in murine models, the IL-18 pathway has been shown to be necessary and sufficient to generate chronic obstructive pulmonary disease-like inflammation, fibrosis, and tissue destruction. However, the relationship between Chi3l1 and IL-18 has not been defined. To address this issue we characterized the expression of Chi3l1/BRP-39 in control and lung-targeted IL-18 transgenic mice. We also characterized the effects of transgenic IL-18 in mice with wild-type and null Chi3l1 loci. The former studies demonstrated that IL-18 is a potent stimulator of Chi3l1/BRP-39 and that this stimulation is mediated via IFN-γ-, IL-13-, and IL-17A-dependent mechanisms. The latter studies demonstrated that, in the absence of Chi3l1/BRP-39, IL-18 induced type 2 and type 17 inflammation and fibrotic airway remodeling were significantly ameliorated, whereas type 1 inflammation, emphysematous alveolar destruction, and the expression of cytotoxic T lymphocyte perforin, granzyme, and retinoic acid early transcript 1 expression were enhanced. These studies demonstrate that IL-18 is a potent stimulator of Chi3l1 and that Chi3l1 is an important mediator of IL-18-induced inflammatory, fibrotic, alveolar remodeling, and cytotoxic responses.

  7. sTREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis, effect of smoking and inflammation.

    PubMed

    Suchankova, M; Bucova, M; E, Tibenska; Demian, J; Majer, I; Novosadova, H; Tedlova, E; Durmanova, V; Paulovicova, E

    2013-01-01

    Soluble TREM-1 (sTREM-1; Triggering receptor expressed on myelocytes) is a new inflammatory marker indicating the intensity of myeloid cells activation and the presence of infection caused by extracellular bacteria and mould.The aim of our work was to detect and compare the levels of sTREM-1 in bronchoalveolar lavage fluid (BALF) in patients with pulmonary sarcoidosis (PS) and other ILD of non-infectious origin. The sTREM-1 levels were assessed by ELISA in 46 patients suffering from ILD, out of them 22 with PS. The levels of BALF sTREM-1 in PS patients were higher than in control group of ILD patients of non-infectious origin, however, the difference was not statistically significant. Since all PS patients except one were non-smokers we compared non-smokers PS with non-smokers ILD patients and found four times higher levels of BALF sTREM-1 in PS patients (P = 0.001). We also recorded the effect of smoking, ILD smokers had higher sTREM-1 levels than non-smokers (P = 0.0019). Higher concentrations of sTREM-1 were detected in BALF of patients with lymphadenopathy and with elevated inflammatory markers in BALF. Our results show that BALF sTREM-1 could be a good inflammatory marker and could help in diagnosis and PS monitoring. Detection of sTREM-1 in BALF indirectly points to myeloid cells activation in the lungs and helps to complete the information about the number of myeloid cells commonly determined in BALF with additional information concerning the intensity of their activation. This is the first study that analyses BALF sTREM-1 levels in patients with PS (Tab. 8, Ref. 28). Text in PDF www.elis.sk.

  8. sTREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis, effect of smoking and inflammation.

    PubMed

    Suchankova, M; Bucova, M; E, Tibenska; Demian, J; Majer, I; Novosadova, H; Tedlova, E; Durmanova, V; Paulovicova, E

    2013-01-01

    Soluble TREM-1 (sTREM-1; Triggering receptor expressed on myelocytes) is a new inflammatory marker indicating the intensity of myeloid cells activation and the presence of infection caused by extracellular bacteria and mould.The aim of our work was to detect and compare the levels of sTREM-1 in bronchoalveolar lavage fluid (BALF) in patients with pulmonary sarcoidosis (PS) and other ILD of non-infectious origin. The sTREM-1 levels were assessed by ELISA in 46 patients suffering from ILD, out of them 22 with PS. The levels of BALF sTREM-1 in PS patients were higher than in control group of ILD patients of non-infectious origin, however, the difference was not statistically significant. Since all PS patients except one were non-smokers we compared non-smokers PS with non-smokers ILD patients and found four times higher levels of BALF sTREM-1 in PS patients (P = 0.001). We also recorded the effect of smoking, ILD smokers had higher sTREM-1 levels than non-smokers (P = 0.0019). Higher concentrations of sTREM-1 were detected in BALF of patients with lymphadenopathy and with elevated inflammatory markers in BALF. Our results show that BALF sTREM-1 could be a good inflammatory marker and could help in diagnosis and PS monitoring. Detection of sTREM-1 in BALF indirectly points to myeloid cells activation in the lungs and helps to complete the information about the number of myeloid cells commonly determined in BALF with additional information concerning the intensity of their activation. This is the first study that analyses BALF sTREM-1 levels in patients with PS (Tab. 8, Ref. 28). Text in PDF www.elis.sk. PMID:24329508

  9. [Diagnostic work-up of pulmonary nodules : Management of pulmonary nodules detected with low‑dose CT screening].

    PubMed

    Wormanns, D

    2016-09-01

    Pulmonary nodules are the most frequent pathological finding in low-dose computed tomography (CT) scanning for early detection of lung cancer. Early stages of lung cancer are often manifested as pulmonary nodules; however, the very commonly occurring small nodules are predominantly benign. These benign nodules are responsible for the high percentage of false positive test results in screening studies. Appropriate diagnostic algorithms are necessary to reduce false positive screening results and to improve the specificity of lung cancer screening. Such algorithms are based on some of the basic principles comprehensively described in this article. Firstly, the diameter of nodules allows a differentiation between large (>8 mm) probably malignant and small (<8 mm) probably benign nodules. Secondly, some morphological features of pulmonary nodules in CT can prove their benign nature. Thirdly, growth of small nodules is the best non-invasive predictor of malignancy and is utilized as a trigger for further diagnostic work-up. Non-invasive testing using positron emission tomography (PET) and contrast enhancement as well as invasive diagnostic tests (e.g. various procedures for cytological and histological diagnostics) are briefly described in this article. Different nodule morphology using CT (e.g. solid and semisolid nodules) is associated with different biological behavior and different algorithms for follow-up are required. Currently, no obligatory algorithm is available in German-speaking countries for the management of pulmonary nodules, which reflects the current state of knowledge. The main features of some international and American recommendations are briefly presented in this article from which conclusions for the daily clinical use are derived. PMID:27495787

  10. Comparison of bronchial brushing and sputum in detection of pediatric pulmonary tuberculosis.

    PubMed

    Chen, Qiao-Pei; Ren, Shi-Feng; Wang, Xin-Feng; Wang, Mao-Shui

    2016-01-27

    The retrospective study aimed to evaluate the diagnostic value of bronchial brushing and sputum using acid fast bacilli smear, mycobacterial culture and real-time PCR in detection of pediatric pulmonary tuberculosis, sensitivity and specificity of bronchial brushing and sputum examined by the three methods were calculated and compared to each other. Data showed there were no significant difference in sensitivity between bronchial brushing and matched sputum using each method. But the specificity of real-time PCR on bronchial brushing was lower than on sputum. Compared with bronchial brushing, sputum was better specimen in detection of pediatric pulmonary tuberculosis.

  11. Improved Diagnosis of Acute Pulmonary Histoplasmosis by Combining Antigen and Antibody Detection

    PubMed Central

    Richer, Sarah M.; Smedema, Melinda L.; Durkin, Michelle M.; Herman, Katie M.; Hage, Chadi A.; Fuller, Deanna; Wheat, L. Joseph

    2016-01-01

    Background. Acute pulmonary histoplasmosis can be severe, especially following heavy inoculum exposure. Rapid diagnosis is critical and often possible by detection of antigen, but this test may be falsely negative in 17% of such cases. Antibody detection by enzyme immunoassay (EIA) may increase sensitivity and permit the measurement of immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of antibodies separately. Methods. Microplates coated with Histoplasma antigen were used for testing of serum from patients with acute pulmonary histoplasmosis and controls in the MVista Histoplasma antibody EIA. Results for IgG and IgM were reported independently. Results. IgG antibodies were detected in 87.5%, IgM antibodies in 67.5%, and IgG and/or IgM antibodies in 88.8% of patients with acute pulmonary histoplasmosis in this assay, while immunodiffusion, complement fixation, and antigen testing showed sensitivities of 55.0%, 73.1%, and 67.5%, respectively (n = 80). Combining antigen and antibody detection increased the sensitivity to 96.3%. Conclusions. The MVista Histoplasma antibody EIA offers increased sensitivity over current antibody tests while also allowing separate detection of IgG and IgM antibodies and complementing antigen detection. Combining antigen and EIA antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis. PMID:26797210

  12. Inflammable gas mixture detection with a single catalytic sensor based on the electric field effect.

    PubMed

    Tong, Ziyuan; Tong, Min-Ming; Meng, Wen; Li, Meng

    2014-01-01

    This paper introduces a new way to analyze mixtures of inflammable gases with a single catalytic sensor. The analysis technology was based on a new finding that an electric field on the catalytic sensor can change the output sensitivity of the sensor. The analysis of mixed inflammable gases results from processing the output signals obtained by adjusting the electric field parameter of the catalytic sensor. For the signal process, we designed a group of equations based on the heat balance of catalytic sensor expressing the relationship between the output signals and the concentration of gases. With these equations and the outputs of different electric fields, the gas concentration in a mixture could be calculated. In experiments, a mixture of methane, butane and ethane was analyzed by this new method, and the results showed that the concentration of each gas in the mixture could be detected with a single catalytic sensor, and the maximum relative error was less than 5%. PMID:24717635

  13. Detecting Renal Allograft Inflammation Using Quantitative Urine Metabolomics and CXCL10

    PubMed Central

    Ho, Julie; Sharma, Atul; Mandal, Rupasri; Wishart, David S.; Wiebe, Chris; Storsley, Leroy; Karpinski, Martin; Gibson, Ian W.; Nickerson, Peter W.; Rush, David N.

    2016-01-01

    Background The goal of this study was to characterize urinary metabolomics for the noninvasive detection of cellular inflammation and to determine if adding urinary chemokine ligand 10 (CXCL10) improves the overall diagnostic discrimination. Methods Urines (n = 137) were obtained before biopsy in 113 patients with no (n = 66), mild (borderline or subclinical; n = 58), or severe (clinical; n = 13) rejection from a prospective cohort of adult renal transplant patients (n = 113). Targeted, quantitative metabolomics was performed with direct flow injection tandem mass spectrometry using multiple reaction monitoring (ABI 4000 Q-Trap). Urine CXCL10 was measured by enzyme-linked immunosorbent assay. A projection on latent structures discriminant analysis was performed and validated using leave-one-out cross-validation, and an optimal 2-component model developed. Chemokine ligand 10 area under the curve (AUC) was determined and net reclassification index and integrated discrimination index analyses were performed. Results PLS2 demonstrated that urinary metabolites moderately discriminated the 3 groups (Cohen κ, 0.601; 95% confidence interval [95% CI], 0.46-0.74; P < 0.001). Using binary classifiers, urinary metabolites and CXCL10 demonstrated an AUC of 0.81 (95% CI, 0.74-0.88) and 0.76 (95% CI, 0.68-0.84), respectively, and a combined AUC of 0.84 (95% CI, 0.78-0.91) for detecting alloimmune inflammation that was improved by net reclassification index and integrated discrimination index analyses. Urinary CXCL10 was the best univariate discriminator, followed by acylcarnitines and hexose. Conclusions Urinary metabolomics can noninvasively discriminate noninflamed renal allografts from those with subclinical and clinical inflammation, and the addition of urine CXCL10 had a modest but significant effect on overall diagnostic performance. These data suggest that urinary metabolomics and CXCL10 may be useful for noninvasive monitoring of alloimmune inflammation in renal

  14. Benefits of texture analysis of dual energy CT for Computer-Aided pulmonary embolism detection.

    PubMed

    Foncubierta-Rodríguez, Antonio; Jiménez del Toro, Óscar Alfonso; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning; Depeursinge, Adrien

    2013-01-01

    Pulmonary embolism is an avoidable cause of death if treated immediately but delays in diagnosis and treatment lead to an increased risk. Computer-assisted image analysis of both unenhanced and contrast-enhanced computed tomography (CT) have proven useful for diagnosis of pulmonary embolism. Dual energy CT provides additional information over the standard single energy scan by generating four-dimensional (4D) data, in our case with 11 energy levels in 3D. In this paper a 4D texture analysis method capable of detecting pulmonary embolism in dual energy CT is presented. The method uses wavelet-based visual words together with an automatic geodesic-based region of interest detection algorithm to characterize the texture properties of each lung lobe. Results show an increase in performance with respect to the single energy CT analysis, as well as an accuracy gain compared to preliminary work on a small dataset.

  15. Benefits of texture analysis of dual energy CT for Computer-Aided pulmonary embolism detection.

    PubMed

    Foncubierta-Rodríguez, Antonio; Jiménez del Toro, Óscar Alfonso; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning; Depeursinge, Adrien

    2013-01-01

    Pulmonary embolism is an avoidable cause of death if treated immediately but delays in diagnosis and treatment lead to an increased risk. Computer-assisted image analysis of both unenhanced and contrast-enhanced computed tomography (CT) have proven useful for diagnosis of pulmonary embolism. Dual energy CT provides additional information over the standard single energy scan by generating four-dimensional (4D) data, in our case with 11 energy levels in 3D. In this paper a 4D texture analysis method capable of detecting pulmonary embolism in dual energy CT is presented. The method uses wavelet-based visual words together with an automatic geodesic-based region of interest detection algorithm to characterize the texture properties of each lung lobe. Results show an increase in performance with respect to the single energy CT analysis, as well as an accuracy gain compared to preliminary work on a small dataset. PMID:24110602

  16. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

    PubMed

    Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

    2015-05-01

    Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. PMID:25656991

  17. Hemoglobin induced lung vascular oxidation, inflammation, and remodeling contributes to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeat dose haptoglobin administration

    PubMed Central

    Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva

    2015-01-01

    Objective Haptoglobin (Hp) is an approved treatment in Japan with indications for trauma, burns and massive transfusion related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia mediated PH. Approach and results Rats were simultaneously exposed to chronic Hb-infusion (35 mg per day) and hypobaric hypoxia for five weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated non-heme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right ventricular hypertrophy, which suggest a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. Conclusions By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia; and (2) suggest a novel therapy for chronic hemolysis associated PH. PMID:25656991

  18. CD28/B7 Deficiency Attenuates Systolic Overload-Induced Congestive Heart Failure, Myocardial and Pulmonary Inflammation, and Activated T Cell Accumulation in the Heart and Lungs.

    PubMed

    Wang, Huan; Kwak, Dongmin; Fassett, John; Hou, Lei; Xu, Xin; Burbach, Brandon J; Thenappan, Thenappan; Xu, Yawei; Ge, Jun-Bo; Shimizu, Yoji; Bache, Robert J; Chen, Yingjie

    2016-09-01

    The inflammatory response regulates congestive heart failure (CHF) development. T cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T cell activation and attenuates CHF development by reducing systemic, cardiac, and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T cells (CD3(+)CD44(high) cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction. CD28 or B7 knockout significantly attenuated transverse aortic constriction-induced CHF development, as indicated by less increase of heart and lung weight and less reduction of left ventricle contractility. CD28 or B7 knockout also significantly reduced transverse aortic constriction-induced CD45(+) leukocyte, T cell, and macrophage infiltration in hearts and lungs, lowered proinflammatory cytokine expression (such as tumor necrosis factor-α and interleukin-1β) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250 μg/mouse every 3 days) attenuated transverse aortic constriction-induced T cell activation, left ventricle hypertrophy, and left ventricle dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T cell activation may be useful in treating CHF. PMID:27432861

  19. CD28/B7 Deficiency Attenuates Systolic Overload-Induced Congestive Heart Failure, Myocardial and Pulmonary Inflammation, and Activated T Cell Accumulation in the Heart and Lungs.

    PubMed

    Wang, Huan; Kwak, Dongmin; Fassett, John; Hou, Lei; Xu, Xin; Burbach, Brandon J; Thenappan, Thenappan; Xu, Yawei; Ge, Jun-Bo; Shimizu, Yoji; Bache, Robert J; Chen, Yingjie

    2016-09-01

    The inflammatory response regulates congestive heart failure (CHF) development. T cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T cell activation and attenuates CHF development by reducing systemic, cardiac, and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T cells (CD3(+)CD44(high) cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction. CD28 or B7 knockout significantly attenuated transverse aortic constriction-induced CHF development, as indicated by less increase of heart and lung weight and less reduction of left ventricle contractility. CD28 or B7 knockout also significantly reduced transverse aortic constriction-induced CD45(+) leukocyte, T cell, and macrophage infiltration in hearts and lungs, lowered proinflammatory cytokine expression (such as tumor necrosis factor-α and interleukin-1β) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250 μg/mouse every 3 days) attenuated transverse aortic constriction-induced T cell activation, left ventricle hypertrophy, and left ventricle dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T cell activation may be useful in treating CHF.

  20. Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens* ,**

    PubMed Central

    Furini, Adriana Antônia da Cruz; Pedro, Heloisa da Silveira Paro; Rodrigues, Jean Francisco; Montenegro, Lilian Maria Lapa; Machado, Ricardo Luiz Dantas; Franco, Célia; Schindler, Haiana Charifker; Batista, Ida Maria Foschiani Dias; Rossit, Andrea Regina Baptista

    2013-01-01

    OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis. PMID:24473765

  1. The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). Methods Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast. Results PM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice. Conclusions These data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment. PMID:24010767

  2. Effects of Schisandra chinensis extracts on cough and pulmonary inflammation in a cough hypersensitivity guinea pig model induced by cigarette smoke exposure.

    PubMed

    Zhong, Shan; Nie, Yi-chu; Gan, Zhen-yong; Liu, Xiao-dong; Fang, Zhang-fu; Zhong, Bo-nian; Tian, Jin; Huang, Chu-qin; Lai, Ke-fang; Zhong, Nan-shan

    2015-05-13

    Schisandra chinensis (S. chinensis) is a traditional Chinese medicine commonly used in prescription medications for the treatment of chronic cough. However, the material basis of S. chinensis in relieving cough has not been completely elucidated yet. This study established a guinea pig model of cough hypersensitivity induced by 14 days of cigarette smoke (CS) exposure, to evaluate the antitussive, antioxidant, and anti-inflammatory effects of three S. chinensis extracts. And then the function of four lignans in reducing expression of TRPV1 and TRPA1 was examined using A549 cells induced by cigarette smoke extract (CSE). The results demonstrated that both ethanol extract (EE) and ethanol-water extract (EWE) of S. chinensis, but not water extract (WE), significantly reduced the cough frequency enhanced by 0.4M citric acid solution in these cough hypersensitivity guinea pigs. Meanwhile, pretreatment with EE and EWE both significantly attenuated the CS-induced increase in infiltration of pulmonary neutrophils and total inflammatory cells, as well as pulmonary MDA, TNF-α, and IL-8, while remarkably increased activities of pulmonary SOD and GSH. According to H&E and immunofluorescence staining assays, airway epithelium hyperplasia, smooth muscle thickening, inflammatory cells infiltration, as well as expression of TRPV1 and TRPA1, were significantly attenuated in animals pretreatment with 1g/kg EE. Moreover, four lignans of EE, including schizandrin, schisantherin A, deoxyschizandrin and γ-schisandrin, significantly inhibited CSE-induced expression of TRPV1, TRPA1 and NOS3, as well as NO release in A549 cells. In conclusion, S. chinensis reduces cough frequency and pulmonary inflammation in the CS-induced cough hypersensitivity guinea pigs. Lignans may be the active components.

  3. Novel ways to noninvasively detect inflammation of the myocardium: contrast-enhanced MRI and myocardial contrast echocardiography

    PubMed Central

    van den Brink, M.R.; Geluk, C.A.; Lindner, J.R.; Velthuis, B.K.; Vonken, E.J.; Cramer, M.J.M.

    2003-01-01

    Both contrast-enhanced magnetic resonance imaging (CE-MRI) and myocardial contrast echocardiography (MCE) are promising tools to detect cardiac inflammation. CE-MRI can be used to characterise the location and extent of myocardial inflammation, since areas of abnormal signal enhancement associated with regional wall motion abnormalities reliably indicate areas of active myocarditis. In MCE, chemically composed microbubbles can be visualised by ultrasound and used to determine the status of the cardiac microvasculature. If there is any inflammation the microbubbles will be phagocytosed by neutrophils and monocytes, thus enabling the degree of inflammation to be assessed. These noninvasive techniques may allow early diagnosis and accurate evaluation of myocardial inflammation. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:25696203

  4. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    EPA Science Inventory

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  5. DIFFERENTIAL PULMONARY INFLAMMATION AND IN VITRO CYTOTOXICITY BY SIZE-FRACTIONATED FLY ASH PARTICLES FROM PULVERIZED COAL COMBUSTION

    EPA Science Inventory

    The paper presents results of research on the adverse health effects associated with exposure to airborne particulate matter. Pulmonary inflammatory responses were examined in CDI mice after intratracheal instillation of 25 or 100 micrograms of ultrafine (<0.2 micrometers), fine ...

  6. Sensitivity and specificity of Ga-67 pulmonary scans for the detection of p. carinii pneumonitis in patients with the acquired immunodefficiency syndrome and pulmonary symptoms

    SciTech Connect

    Hattner, R.S.; Sollitto, R.A.; Golden, J.A.; Coleman, D.L.; Okerlund, M.D.

    1984-01-01

    Acquired immunodeficiency syndrome (AIDS) is a severe disorder of cellular immunity of obscure etiology. Since its original recognition in 1981 the incidence of AIDS has doubled in each of the succeeding six months. The most common causes of death in AIDS are Kaposi's sarcoma and p. carinii pneumonia (PCP). The latter is treatable if diagnosed early, and AIDS patients (pts) may suffer recurrent episodes of PCP. Since the invasive technique of fiberoptic bronchoscopy with transbronchial biopsy, brushing, and bronchialveolar lavage are necessary for diagnosis and follow-up a noninvasive method of categorizing which AIDS pts require this procedure would be most welcome. Twenty-one pts with the syndrome of AIDS and pulmonary symptoms underwent Ga-67 scans of the thoracic region, and fibroptic bronchoscopy with washings, and brush and transbronchial biopsy. Pulmonary activity was graded in a blinded fashion by three experienced observers as follows: 1, less than, or equal to adjacent soft tissues; 2, greater than adjacent soft tissues, but less than liver; 3, equal to liver; 4, greater than liver. Eleven pts had documented PCP, and the remaining ten had non-specific pulmonary inflammation, or other, in some cases, putative, infections. The sensitivity and specificity of Ga-67 scans greater than or equal to grade 3 was 100% and 90% respectively. These results suggests a useful role for graded Ga-67 scans in AIDS pts with pulmonary symptoms, permitting selection of pts with a high risk of PCP for further mandatory invasive investigation of this otherwise usually fatal disease.

  7. Inducible nitric oxide synthase inhibition attenuates lung tissue responsiveness and remodeling in a model of chronic pulmonary inflammation in guinea pigs.

    PubMed

    Starling, Claudia M; Prado, Carla M; Leick-Maldonado, Edna A; Lanças, Tatiana; Reis, Fabiana G; Aristóteles, Luciana R C B R; Dolhnikoff, Marisa; Martins, Mílton A; Tibério, Iolanda F L C

    2009-02-28

    We evaluated the influence of iNOS-derived NO on the mechanics, inflammatory, and remodeling process in peripheral lung parenchyma of guinea pigs with chronic pulmonary allergic inflammation. Animals treated or not with 1400 W were submitted to seven exposures of ovalbumin in increasing doses. Seventy-two hours after the 7th inhalation, lung strips were suspended in a Krebs organ bath, and tissue resistance and elastance measured at baseline and after ovalbumin challenge. The strips were submitted to histopathological measurements. The ovalbumin-exposed animals showed increased maximal responses of resistance and elastance (p<0.05), eosinophils counting (p<0.001), iNOS-positive cells (p<0.001), collagen and elastic fiber deposition (p<0.05), actin density (p<0.05) and 8-iso-PGF2alpha expression (p<0.001) in alveolar septa compared to saline-exposed ones. Ovalbumin-exposed animals treated with 1400 W had a significant reduction in lung functional and histopathological findings (p<0.05). We showed that iNOS-specific inhibition attenuates lung parenchyma constriction, inflammation, and remodeling, suggesting NO-participation in the modulation of the oxidative stress pathway.

  8. False-positive elimination for computer-aided detection of pulmonary micronodules

    NASA Astrophysics Data System (ADS)

    Chang, Sukmoon; Zhou, Jinghao; Metaxas, Dimitris N.; Axel, Leon

    2006-03-01

    Computed Tomography (CT) is generally accepted as the most sensitive way for lung cancer screening. Its high contrast resolution allows the detection of small nodules and, thus, lung cancer at a very early stage. Due to the amount of data it produces, however, automating the nodule detection process is viable. The challenging problem for any nodule detection system is to keep low false-positive detection rate while maintaining high sensitivity. In this paper, we first describe a 3D filter-based method for pulmonary micronodule detection from high-resolution 3D chest CT images. Then, we propose a false-positive elimination method based on a deformable model. Finally, we present promising results of applying our method to various clinical chest CT datasets with over 90% detection rate. The proposed method focuses on the automatic detection of both calcified (high-contrast) and noncalcified (low-contrast) granulomatous nodules less than 5mm in diameter.

  9. p53- and PAI-1-mediated induction of C-X-C chemokines and CXCR2: importance in pulmonary inflammation due to cigarette smoke exposure.

    PubMed

    Tiwari, Nivedita; Marudamuthu, Amarnath S; Tsukasaki, Yoshikazu; Ikebe, Mitsuo; Fu, Jian; Shetty, Sreerama

    2016-03-15

    We previously demonstrated that tumor suppressor protein p53 augments plasminogen activator inhibitor-1 (PAI-1) expression in alveolar epithelial cells (AECs) during chronic cigarette smoke (CS) exposure-induced lung injury. Chronic lung inflammation with elevated p53 and PAI-1 expression in AECs and increased susceptibility to and exacerbation of respiratory infections are all associated with chronic obstructive pulmonary disease (COPD). We recently demonstrated that preventing p53 from binding to the endogenous PAI-1 mRNA in AECs by either suppressing p53 expression or blockading p53 interactions with the PAI-1 mRNA mitigates apoptosis and lung injury. Within this context, we now show increased expression of the C-X-C chemokines (CXCL1 and CXCL2) and their receptor CXCR2, and the intercellular cellular adhesion molecule-1 (ICAM-1), in the lung tissues of patients with COPD. We also found a similar increase in lung tissues and AECs from wild-type (WT) mice exposed to passive CS for 20 wk and in primary AECs treated with CS extract in vitro. Interestingly, passive CS exposure of mice lacking either p53 or PAI-1 expression resisted an increase in CXCL1, CXCL2, CXCR2, and ICAM-1. Furthermore, inhibition of p53-mediated induction of PAI-1 expression by treatment of WT mice exposed to passive CS with caveolin-1 scaffolding domain peptide reduced CXCL1, CXCL2, and CXCR2 levels and lung inflammation. Our study reveals that p53-mediated induction of PAI-1 expression due to chronic CS exposure exacerbates lung inflammation through elaboration of CXCL1, CXCL2, and CXCR2. We further provide evidence that targeting this pathway mitigates lung injury associated with chronic CS exposure.

  10. Comparison of histochemical methods for murine eosinophil detection in a RSV vaccine-enhanced inflammation model

    PubMed Central

    Meyerholz, David K.; Griffin, Michelle A.; Castilow, Elaine M.; Varga, Steven M.

    2009-01-01

    A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was evaluated in tissue sections of neutrophilic soft tissue lesions and bone marrow from respective animals. Eosinophils had granular red to orange-red cytoplasmic staining, depending on the method, whereas neutrophils had, when stained, a more homogenous cytoplasmic pattern. Nonspecific background staining of similar coloration was variably seen in arterial walls and erythrocytes. Astra Blue/Vital New Red, Congo Red, Luna, Modified Hematoxylin & Eosin, and Sirius Red techniques were all effective in detecting increased eosinophil recruitment compared to controls; however, differences in eosinophil quantification significantly varied between techniques. Astra Blue/Vital New Red had the best specificity for differentiating eosinophils and neutrophils, but had a reduced ability to enumerate eosinophils and was the most time intensive. The Luna stain had excessive non specific staining of tissues and a reduced enumeration of infiltrating eosinophils making it suboptimal. For multiple parameters such as eosinophil detection, specificity, and contrast with background tissues, the Sirius Red followed by Congo Red and Modified Hematoxylin & Eosin methods were useful, each with their own staining qualities. PMID:19181630

  11. Hepatic and Pulmonary Toxicogenomic Profiles in Mice Intratracheally Instilled With Carbon Black Nanoparticles Reveal Pulmonary Inflammation, Acute Phase Response, and Alterations in Lipid Homeostasis

    PubMed Central

    Bourdon, Julie A.; Halappanavar, Sabina; Saber, Anne T.; Jacobsen, Nicklas R.; Williams, Andrew; Wallin, Håkan; Vogel, Ulla; Yauk, Carole L.

    2012-01-01

    Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90–exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects. PMID:22461453

  12. Pulmonary hyalinizing granuloma detected in a family member after confirmation of tuberculosis in his father.

    PubMed

    Matsuoka, Katsunari; Imanishi, Naoko; Matsuoka, Takahisa; Nagai, Shinjiro; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is an uncommon lung disease that usually presents as bilateral multiple nodules, and more rarely as a solitary nodule. An exaggerated immune response to antigenic stimuli resulting from infection or an autoimmune process has been suggested as the cause of PHG. Here, we describe a rare case of solitary PHG that was detected in a family member after tuberculosis had been confirmed in his father, without any background of infectious disease or autoimmune abnormality. PMID:23903707

  13. Developing Pulmonary Vasculopathy in Systemic Sclerosis, Detected with Non-Invasive Cardiopulmonary Exercise Testing

    PubMed Central

    Dumitrescu, Daniel; Oudiz, Ronald J.; Karpouzas, George; Hovanesyan, Arsen; Jayasinghe, Amali; Hansen, James E.; Rosenkranz, Stephan; Wasserman, Karlman

    2010-01-01

    Background Patients with systemic sclerosis (SSc) may develop exercise intolerance due to musculoskeletal involvement, restrictive lung disease, left ventricular dysfunction, or pulmonary vasculopathy (PV). The latter is particularly important since it may lead to lethal pulmonary arterial hypertension (PAH). We hypothesized that abnormalities during cardiopulmonary exercise testing (CPET) in patients with SSc can identify PV leading to overt PAH. Methods Thirty SSc patients from the Harbor-UCLA Rheumatology clinic, not clinically suspected of having significant pulmonary vascular disease, were referred for this prospective study. Resting pulmonary function and exercise gas exchange were assessed, including peakVO2, anaerobic threshold (AT), heart rate- VO2 relationship (O2-pulse), exercise breathing reserve and parameters of ventilation-perfusion mismatching, as evidenced by elevated ventilatory equivalent for CO2 (VE/VCO2) and reduced end-tidal pCO2 (PETCO2) at the AT. Results Gas exchange patterns were abnormal in 16 pts with specific cardiopulmonary disease physiology: Eleven patients had findings consistent with PV, while five had findings consistent with left-ventricular dysfunction (LVD). Although both groups had low peak VO2 and AT, a higher VE/VCO2 at AT and decreasing PETCO2 during early exercise distinguished PV from LVD. Conclusions Previously undiagnosed exercise impairments due to LVD or PV were common in our SSc patients. Cardiopulmonary exercise testing may help to differentiate and detect these disorders early in patients with SSc. PMID:21179195

  14. Pulmonary nodule detection using a cascaded SVM classifier

    NASA Astrophysics Data System (ADS)

    Bergtholdt, Martin; Wiemker, Rafael; Klinder, Tobias

    2016-03-01

    Automatic detection of lung nodules from chest CT has been researched intensively over the last decades resulting also in several commercial products. However, solutions are adopted only slowly into daily clinical routine as many current CAD systems still potentially miss true nodules while at the same time generating too many false positives (FP). While many earlier approaches had to rely on rather few cases for development, larger databases become now available and can be used for algorithmic development. In this paper, we address the problem of lung nodule detection via a cascaded SVM classifier. The idea is to sequentially perform two classification tasks in order to select from an extremely large pool of potential candidates the few most likely ones. As the initial pool is allowed to contain thousands of candidates, very loose criteria could be applied during this pre-selection. In this way, the chances that a true nodule is falsely rejected as a candidate are reduced significantly. The final algorithm is trained and tested on the full LIDC/IDRI database. Comparison is done against two previously published CAD systems. Overall, the algorithm achieved sensitivity of 0.859 at 2.5 FP/volume where the other two achieved sensitivity values of 0.321 and 0.625, respectively. On low dose data sets, only slight increase in the number of FP/volume was observed, while the sensitivity was not affected.

  15. Identification of the appropriate dose metric for pulmonary inflammation of silver nanoparticles in an inhalation toxicity study.

    PubMed

    Braakhuis, Hedwig M; Cassee, Flemming R; Fokkens, Paul H B; de la Fonteyne, Liset J J; Oomen, Agnes G; Krystek, Petra; de Jong, Wim H; van Loveren, Henk; Park, Margriet V D Z

    2016-01-01

    A number of studies have shown that induction of pulmonary toxicity by nanoparticles of the same chemical composition depends on particle size, which is likely in part due to differences in lung deposition. Particle size mostly determines whether nanoparticles reach the alveoli, and where they might induce toxicity. For the risk assessment of nanomaterials, there is need for a suitable dose metric that accounts for differences in effects between different sized nanoparticles of the same chemical composition. The aim of the present study is to determine the most suitable dose metric to describe the effects of silver nanoparticles after short-term inhalation. Rats were exposed to different concentrations (ranging from 41 to 1105 µg silver/m(3) air) of 18, 34, 60 and 160 nm silver particles for four consecutive days and sacrificed at 24 h and 7 days after exposure. We observed a concentration-dependent increase in pulmonary toxicity parameters like cell counts and pro-inflammatory cytokines in the bronchoalveolar lavage fluid. All results were analysed using the measured exposure concentrations in air, the measured internal dose in the lung and the estimated alveolar dose. In addition, we analysed the results based on mass, particle number and particle surface area. Our study indicates that using the particle surface area as a dose metric in the alveoli, the dose-response effects of the different silver particle sizes overlap for most pulmonary toxicity parameters. We conclude that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation.

  16. C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

    2015-12-01

    The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium.

  17. Detection of Talaromyces marneffei from Fresh Tissue of an Inhalational Murine Pulmonary Model Using Nested PCR

    PubMed Central

    Liu, Yinghui; Huang, Xiaowen; Yi, Xiuwen; He, Ya; Mylonakis, Eleftherios; Xi, Liyan

    2016-01-01

    Penicilliosis marneffei, often consecutive to the aspiration of Talaromyces marneffei (Penicillium marneffei), continues to be one of the significant causes of morbidity and mortality in immunocompromised patients in endemic regions such as Southeast Asia. Improving the accuracy of diagnosing this disease would aid in reducing the mortality of associated infections. In this study, we developed a stable and reproducible murine pulmonary model that mimics human penicilliosis marneffei using a nebulizer to deliver Talaromyces marneffei (SUMS0152) conidia to the lungs of BALB/c nude mice housed in exposure chamber. Using this model, we further revealed that nested PCR was sensitive and specific for detecting Talaromyces marneffei in bronchoalveolar lavage fluid and fresh tissues. This inhalation model may provide a more representative analysis tool for studying the development of penicilliosis marneffei, in addition to revealing that nested PCR has a predictive value in reflecting pulmonary infection. PMID:26886887

  18. Direct Detection and Quantification of Bacterial Genes Associated with Inflammation in DNA Isolated from Stool

    PubMed Central

    Gómez-Moreno, Ramón; Robledo, Iraida E.; Baerga-Ortiz, Abel

    2014-01-01

    Although predominantly associated with health benefits, the gut microbiota has also been shown to harbor genes that promote inflammation. In this work, we report a method for the direct detection and quantification of these pro-inflammatory bacterial genes by PCR and qPCR in DNA extracted from human stool samples. PCR reactions were performed to detect (i) the pks island genes, (ii) tcpC, which is present in some strains of Escherichia coli and (iii) gelE presented in some strains of Enterococcus faecalis. Additionally, we screened for the presence of the following genes encoding cyclomodulins that disrupted mammalian cell division: (iv) cdt (which encodes the cytolethal distending toxin) and (v) cnf-1 (which encodes the cytotoxic necrotizing factor-1). Our results show that 20% of the samples (N = 41) tested positive for detectable amounts of pks island genes, whereas 10% of individuals were positive for tcpC or gelE and only one individual was found to harbor the cnf-1 gene. Of the 13 individuals that were positive for at least one of the pro-inflammatory genes, 5 were found to harbor more than one. A quantitative version of the assay, which used real-time PCR, revealed the pro-inflammatory genes to be in high copy numbers: up to 1.3 million copies per mg of feces for the pks island genes. Direct detection of specific genes in stool could prove useful toward screening for the presence of pro-inflammatory bacterial genes in individuals with inflammatory bowel diseases or colorectal cancer. PMID:25635239

  19. Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia, and pulmonary inflammation in heart failure-prone rats

    PubMed Central

    Carll, Alex P.; Haykal-Coates, Najwa; Winsett, Darrell W.; Hazari, Mehdi S.; Ledbetter, Allen D.; Richards, Judy H.; Cascio, Wayne E.; Costa, Daniel L.; Farraj, Aimen K.

    2016-01-01

    Acute exposure to ambient fine particulate matter (PM2.5) is tied to cardiovascular morbidity and mortality, especially among those with prior cardiac injury. The mechanisms and pathophysiologic events precipitating these outcomes remain poorly understood but may involve inflammation, oxidative stress, arrhythmia, and autonomic nervous system imbalance. Cardiomyopathy results from cardiac injury, is the leading cause of heart failure, and can be induced in heart failure-prone rats through sub-chronic infusion of isoproterenol (ISO). To test whether cardiomyopathy confers susceptibility to inhaled PM2.5 and can elucidate potential mechanisms, we investigated the cardiophysiologic, ventilatory, inflammatory, and oxidative effects of a single nose-only inhalation of a metal-rich PM2.5 (580 μg/m3, 4h) in ISO-pretreated (35 days * 1.0 mg/kg/day sc) rats. During the 5 days post-treatment, ISO-treated rats had decreased HR and BP and increased pre-ejection period (PEP, an inverse correlate of contractility) relative to saline-treated rats. Before inhalation exposure, ISO-pretreated rats had increased PR and ventricular repolarization time (QT) and heterogeneity (Tp-Te). Relative to clean air, PM2.5 further prolonged PR-interval and decreased systolic BP during inhalation exposure; increased tidal volume, expiratory time, heart rate variability (HRV) parameters of parasympathetic tone, and atrioventricular block arrhythmias over the hours post-exposure; increased pulmonary neutrophils, macrophages, and total antioxidant status one day post-exposure; and decreased pulmonary glutathione peroxidase 8 weeks after exposure, with all effects occurring exclusively in ISO-pretreated rats but not saline-pretreated rats. Ultimately, our findings indicate that cardiomyopathy confers susceptibility to the oxidative, inflammatory, ventilatory, autonomic, and arrhythmogenic effects of acute PM2.5 inhalation. PMID:25600220

  20. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

    NASA Astrophysics Data System (ADS)

    Mäkelä, M. J.; Kanehiro, A.; Borish, L.; Dakhama, A.; Loader, J.; Joetham, A.; Xing, Z.; Jordana, M.; Larsen, G. L.; Gelfand, E. W.

    2000-05-01

    Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10/) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

  1. γδ T Cells Are Required for M2 Macrophage Polarization and Resolution of Ozone-Induced Pulmonary Inflammation in Mice.

    PubMed

    Mathews, Joel A; Kasahara, David I; Ribeiro, Luiza; Wurmbrand, Allison P; Ninin, Fernanda M C; Shore, Stephanie A

    2015-01-01

    We examined the role of γδ T cells in the induction of alternatively activated M2 macrophages and the resolution of inflammation after ozone exposure. Wildtype (WT) mice and mice deficient in γδ T cells (TCRδ-/- mice) were exposed to air or to ozone (0.3 ppm for up to 72h) and euthanized immediately or 1, 3, or 5 days after cessation of exposure. In WT mice, M2 macrophages accumulated in the lungs over the course of ozone exposure. Pulmonary mRNA abundance of the M2 genes, Arg1, Retnla, and Clec10a, also increased after ozone. In contrast, no evidence of M2 polarization was observed in TCRδ-/- mice. WT but not TCRδ-/- mice expressed the M2c polarizing cytokine, IL-17A, after ozone exposure and WT mice treated with an IL-17A neutralizing antibody exhibited attenuated ozone-induced M2 gene expression. In WT mice, ozone-induced increases in bronchoalveolar lavage neutrophils and macrophages resolved quickly after cessation of ozone exposure returning to air exposed levels within 3 days. However, lack of M2 macrophages in TCRδ-/- mice was associated with delayed clearance of inflammatory cells after cessation of ozone and increased accumulation of apoptotic macrophages in the lungs. Delayed restoration of normal lung architecture was also observed in TCRδ-/- mice. In summary, our data indicate that γδ T cells are required for the resolution of ozone-induced inflammation, likely because γδ T cells, through their secretion of IL-17A, contribute to changes in macrophage polarization that promote clearance of apoptotic cells.

  2. The use of liquid chromatography tandem mass spectrometry to detect proteins in saliva from horses with and without systemic inflammation.

    PubMed

    Jacobsen, Stine; Top Adler, Ditte Marie; Bundgaard, Louise; Sørensen, Mette Aamand; Andersen, Pia Haubro; Bendixen, Emøke

    2014-12-01

    The objective of the study was to assess global expression of proteins in equine saliva using liquid chromatography tandem mass spectrometry (LC-MS/MS). Saliva was obtained from seven horses with and six horses without evidence of systemic inflammatory disease. Tryptic peptides from saliva were analysed by LC-MS/MS. Of 195 unique proteins identified, 57 were detected only in saliva samples from horses with systemic inflammation (in two to six of the seven horses). Among the differentially expressed proteins were several acute phase proteins (APPs) such as serum amyloid A, fibrinogen, haptoglobin, and alpha1-acid glycoprotein. The study is the first to describe detection of inflammatory proteins in horse saliva. The proteins detected were similar to those described in saliva from cattle, small ruminants and pigs. Detection of APPs in horses with systemic inflammation suggests that saliva may be used for non-invasive disease monitoring in horses as in humans, pigs and dogs. PMID:25296850

  3. Effects of Mikania glomerata Spreng. and Mikania laevigata Schultz Bip. ex Baker (Asteraceae) extracts on pulmonary inflammation and oxidative stress caused by acute coal dust exposure

    SciTech Connect

    Freitas, T.P.; Silveira, P.C.; Rocha, L.G.; Rezin, G.T.; Rocha, J.; Citadini-Zanette, V.; Romao, P.T.; Dal-Pizzol, F.; Pinho, R.A.; Andrade, V.M.; Streck, E.L.

    2008-12-15

    Several studies have reported biological effects of Mikania glomerata and Mikania laevigata, used in Brazilian folk medicine for respiratory diseases. Pneumoconiosis is characterized by pulmonary inflammation caused by coal dust exposure. In this work, we evaluated the effect of pretreatment with M. glomerata and M. laevigata extracts (MGE and MLE, respectively) (100 mg/kg, s.c.) on inflammatory and oxidative stress parameters in lung of rats subjected to a single coal dust intratracheal instillation. Rats were pretreated for 2 weeks with saline solution, MGE, or MLE. On day 15, the animals were anesthetized, and gross mineral coal dust or saline solutions were administered directly in the lung by intratracheal instillation. Fifteen days after coal dust instillation, the animals were killed. Bronchoalveolar lavage (BAL) was obtained; total cell count and lactate dehydrogenase (LDH) activity were determined. In the lung, myeloperoxidase activity, thiobarbituric acid-reactive substances (TBARS) level, and protein carbonyl and sulfhydryl contents were evaluated. In BAL of treated animals, we verified an increased total cell count and LDH activity. MGE and MLE prevented the increase in cell count, but only MLE prevented the increase in LDH. Myeloperoxidase and TBARS levels were not affected, protein carbonylation was increased, and the protein thiol levels were decreased by acute coal dust intratracheal administration. The findings also suggest that both extracts present an important protective effect on the oxidation of thiol groups. Moreover, pretreatment with MGE and MLE also diminished lung inflammatory infiltration induced by coal dust, as assessed by histopathologic analyses.

  4. Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

    2011-03-01

    Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

  5. Predictive model for the detection of pulmonary hypertension in dogs with myxomatous mitral valve disease.

    PubMed

    Mikawa, Shoma; Miyagawa, Yuichi; Toda, Noriko; Tominaga, Yoshinori; Takemura, Naoyuki

    2015-01-01

    Pulmonary hypertension (PH) often occurs due to a left heart disease, such as myxomatous mitral valve disease (MMVD), in dogs and is diagnosed using Doppler echocardiography and estimated pulmonary arterial pressure. Diagnosis of PH in dogs requires expertise in echocardiography: however, the examination for PH is difficult to perform in a clinical setting. Thus, simple and reliable methods are required for the diagnosis of PH in dogs. The purpose of this study was to develop models using multiple logistic regression analysis to detect PH due to left heart disease in dogs with MMVD without echocardiography. The medical records of dogs with MMVD were retrospectively reviewed, and 81 dogs were included in this study and classified into PH and non-PH groups. Bivariate analysis was performed to compare all parameters between the groups, and variables with P values of <0.25 in bivariate analysis were included in multiple logistic regression analysis to develop models for the detection of PH. In multiple logistic regression analysis, the model included a vertebral heart scale short axis of >5.2 v, and a length of sternal contact of >3.3 v was considered suitable for the detection of PH. The predictive accuracy of this model (85.9%) was judged statistically adequate, and therefore, this model may be useful to screen for PH due to left heart disease in dogs with MMVD without echocardiography.

  6. Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing.

    PubMed

    Youssef, Amir A; Machaly, Shereen A; El-Dosoky, Mohammed E; El-Maghraby, Nermeen M

    2012-07-01

    Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5 years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.

  7. Pulmonary Nodule Detection Model Based on SVM and CT Image Feature-Level Fusion with Rough Sets

    PubMed Central

    Lu, Huiling; Zhang, Junjie; Shi, Hongbin

    2016-01-01

    In order to improve the detection accuracy of pulmonary nodules in CT image, considering two problems of pulmonary nodules detection model, including unreasonable feature structure and nontightness of feature representation, a pulmonary nodules detection algorithm is proposed based on SVM and CT image feature-level fusion with rough sets. Firstly, CT images of pulmonary nodule are analyzed, and 42-dimensional feature components are extracted, including six new 3-dimensional features proposed by this paper and others 2-dimensional and 3-dimensional features. Secondly, these features are reduced for five times with rough set based on feature-level fusion. Thirdly, a grid optimization model is used to optimize the kernel function of support vector machine (SVM), which is used as a classifier to identify pulmonary nodules. Finally, lung CT images of 70 patients with pulmonary nodules are collected as the original samples, which are used to verify the effectiveness and stability of the proposed model by four groups' comparative experiments. The experimental results show that the effectiveness and stability of the proposed model based on rough set feature-level fusion are improved in some degrees. PMID:27722173

  8. False positive reduction for pulmonary nodule detection using two-dimensional principal component analysis

    NASA Astrophysics Data System (ADS)

    Choi, Wook-Jin; Choi, Tae-Sun

    2009-08-01

    Pulmonary nodule detection is a binary classification problem. The main objective is to classify nodule from the lung computed tomography (CT) images. The intra class variability is mainly due to the grey-level variance, texture differences and shape. The purpose of this study is to develop a novel nodule detection method which is based on Two-dimensional Principal Component Analysis (2DPCA). We extract the futures using 2DPCA from nodule candidate images. Nodule candidates are classified using threshold. The proposed method reduces False Positive (FP) rate. We tested the proposed algorithm by using Lung Imaging Database Consortium (LIDC) database of National Cancer Institute (NCI). The experimental results demonstrate the effectiveness and efficiency of the proposed method. The proposed method achieved 85.11% detection rate with 1.13 FPs per scan.

  9. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    PubMed Central

    Yanamala, Naveena; Hatfield, Meghan K.; Farcas, Mariana T.; Schwegler-Berry, Diane; Hummer, Jon A.; Shurin, Michael R.; Birch, M. Eileen; Gutkin, Dmitriy W.; Kisin, Elena; Kagan, Valerian E.; Bugarski, Aleksandar D.; Shvedova, Anna A.

    2015-01-01

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. PMID:23886933

  10. Detecting inflammation and fibrosis in bowel wall with photoacoustic imaging in a Crohn's disease animal model

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Johnson, Laura A.; Hu, Jack; Dillman, Jonathan R.; Higgins, Peter D. R.; Wang, Xueding

    2015-03-01

    Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. This condition may cause obstructing intestinal narrowings (strictures) due to inflammation, fibrosis (deposition of collagen), or a combination of both. Utilizing the unique strong optical absorption of hemoglobin at 532 nm and collagen at 1370 nm, this study investigated the feasibility of non-invasively characterizing intestinal strictures using photoacoustic imaging (PAI). Three normal controls, ten pure inflammation and 9 inflammation plus fibrosis rat bowel wall samples were imaged. Statistical analysis of the PA measurements has shown the capability of discriminating the purely inflammatory from mixed inflammatory and fibrotic strictures.

  11. Automatic detection of large pulmonary solid nodules in thoracic CT images

    SciTech Connect

    Setio, Arnaud A. A. Jacobs, Colin; Gelderblom, Jaap; Ginneken, Bram van

    2015-10-15

    Purpose: Current computer-aided detection (CAD) systems for pulmonary nodules in computed tomography (CT) scans have a good performance for relatively small nodules, but often fail to detect the much rarer larger nodules, which are more likely to be cancerous. We present a novel CAD system specifically designed to detect solid nodules larger than 10 mm. Methods: The proposed detection pipeline is initiated by a three-dimensional lung segmentation algorithm optimized to include large nodules attached to the pleural wall via morphological processing. An additional preprocessing is used to mask out structures outside the pleural space to ensure that pleural and parenchymal nodules have a similar appearance. Next, nodule candidates are obtained via a multistage process of thresholding and morphological operations, to detect both larger and smaller candidates. After segmenting each candidate, a set of 24 features based on intensity, shape, blobness, and spatial context are computed. A radial basis support vector machine (SVM) classifier was used to classify nodule candidates, and performance was evaluated using ten-fold cross-validation on the full publicly available lung image database consortium database. Results: The proposed CAD system reaches a sensitivity of 98.3% (234/238) and 94.1% (224/238) large nodules at an average of 4.0 and 1.0 false positives/scan, respectively. Conclusions: The authors conclude that the proposed dedicated CAD system for large pulmonary nodules can identify the vast majority of highly suspicious lesions in thoracic CT scans with a small number of false positives.

  12. Relevance of Partitioning DLCO to Detect Pulmonary Hypertension in Systemic Sclerosis

    PubMed Central

    Wémeau-Stervinou, Lidwine; De Groote, Pascal; Remy-Jardin, Martine; Denis, Guillaume; Lambert, Marc; Lamblin, Nicolas; Morell-Dubois, Sandrine; Fertin, Marie; Lefevre, Guillaume; Sobanski, Vincent; Le Rouzic, Olivier; Hatron, Pierre-Yves; Wallaert, Benoit; Hachulla, Eric; Perez, Thierry

    2013-01-01

    We investigated whether partitioning DLCO into membrane conductance for CO (DmCO) and pulmonary capillary blood volume (Vcap) was helpful in suspecting precapillary pulmonary (arterial) hypertension (P(A)H) in systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD). We included 63 SSc patients with isolated PAH (n=6), isolated ILD (n=19), association of both (n=12) or without PAH and ILD (n=26). Partitioning of DLCO was performed by the combined DLNO/DLCO method. DLCO, DmCO and Vcap were equally reduced in patients with isolated PAH and patients with isolated ILD but Vcap/alveolar volume (VA) ratio was significantly lower in the isolated PAH group. In patients without ILD, DLCO, DmCO, Vcap and Vcap/VA ratio were reduced in patients with isolated PAH when compared to patients without PAH and both Vcap/VA and DLCO had the highest AUC to detect PAH. In patients with ILD, Vcap had the highest AUC and performed better than DLCO to detect PH in this subgroup. In conclusion, Vcap/VA was lower in PAH than in ILD in SSC whereas DLCO was not different. Vcap/VA ratio and DLCO had similar high performance to detect PAH in patients without ILD. Vcap had better AUC than DLCO, DmCO and FVC/DLCO ratio to detect PH in SSC patients with ILD. These results suggest that partitioning of DLCO might be of interest to detect P(A)H in SSC patients with or without ILD. PMID:24205063

  13. Feasibility of Using Wideband Microwave System for Non-Invasive Detection and Monitoring of Pulmonary Oedema

    PubMed Central

    Rezaeieh, S. Ahdi; Zamani, A.; Bialkowski, K. S.; Mahmoud, A.; Abbosh, A. M.

    2015-01-01

    Pulmonary oedema is a common manifestation of various fatal diseases that can be caused by cardiac or non-cardiac syndromes. The accumulated fluid has a considerably higher dielectric constant compared to lungs’ tissues, and can thus be detected using microwave techniques. Therefore, a non-invasive microwave system for the early detection of pulmonary oedema is presented. It employs a platform in the form of foam-based bed that contains two linear arrays of wideband antennas covering the band 0.7–1 GHz. The platform is designed such that during the tests, the subject lays on the bed with the back of the torso facing the antenna arrays. The antennas are controlled using a switching network that is connected to a compact network analyzer. A novel frequency-based imaging algorithm is used to process the recorded signals and generate an image of the torso showing any accumulated fluids in the lungs. The system is verified on an artificial torso phantom, and animal organs. As a feasibility study, preclinical tests are conducted on healthy subjects to determinate the type of obtained images, the statistics and threshold levels of their intensity to differentiate between healthy and unhealthy subjects. PMID:26365299

  14. Feasibility of Using Wideband Microwave System for Non-Invasive Detection and Monitoring of Pulmonary Oedema

    NASA Astrophysics Data System (ADS)

    Rezaeieh, S. Ahdi; Zamani, A.; Bialkowski, K. S.; Mahmoud, A.; Abbosh, A. M.

    2015-09-01

    Pulmonary oedema is a common manifestation of various fatal diseases that can be caused by cardiac or non-cardiac syndromes. The accumulated fluid has a considerably higher dielectric constant compared to lungs’ tissues, and can thus be detected using microwave techniques. Therefore, a non-invasive microwave system for the early detection of pulmonary oedema is presented. It employs a platform in the form of foam-based bed that contains two linear arrays of wideband antennas covering the band 0.7-1 GHz. The platform is designed such that during the tests, the subject lays on the bed with the back of the torso facing the antenna arrays. The antennas are controlled using a switching network that is connected to a compact network analyzer. A novel frequency-based imaging algorithm is used to process the recorded signals and generate an image of the torso showing any accumulated fluids in the lungs. The system is verified on an artificial torso phantom, and animal organs. As a feasibility study, preclinical tests are conducted on healthy subjects to determinate the type of obtained images, the statistics and threshold levels of their intensity to differentiate between healthy and unhealthy subjects.

  15. Immunohistochemical detection of the expression of pro-inflammatory cytokines by ovine pulmonary macrophages.

    PubMed

    Carrasco, L; Núñez, A; Sánchez-Cordón, P J; Pedrera, M; Fernández de Marco, M; Salguero, F J; Gómez-Villamandos, J C

    2004-11-01

    The aim of this study was to determine the expression of three proinflammatory cytokines by pulmonary macrophages of sheep in paraffin wax-embedded tissue. Samples of lung from seven healthy sheep were fixed by immersion in either 10% neutral buffered formalin, acetic formalin, paraformaldehyde-lysine-periodate or Bouin's solution and processed for structural and immunohistochemical studies. The expression of interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)-alpha by pulmonary intravascular macrophages (PIMs) and alveolar macrophages (AMs) was detected by the avidin-biotin-peroxidase (ABC) technique. Bouin's solution proved to be the most suitable fixative and Tween 20 the most effective pretreatment for increasing permeability. Constitutive expression of IL-1alpha, IL-6 and TNF-alpha by both macrophage populations was detected. The number of PIMs expressing IL-1alpha (the predominant cytokine in ovine lung) was higher than that of AMs, while the expression of IL-6 was greater in AMs. No differences between PIMS and AMs were found in respect of TNF-alpha expression. The evaluation of cytokine expression represents a valuable tool for studying the pathogenesis of disease in the ovine lung.

  16. Detection of Heart Sounds in Children with and without Pulmonary Arterial Hypertension―Daubechies Wavelets Approach

    PubMed Central

    Elgendi, Mohamed; Kumar, Shine; Guo, Long; Rutledge, Jennifer; Coe, James Y.; Zemp, Roger; Schuurmans, Dale; Adatia, Ian

    2015-01-01

    Background Automatic detection of the 1st (S1) and 2nd (S2) heart sounds is difficult, and existing algorithms are imprecise. We sought to develop a wavelet-based algorithm for the detection of S1 and S2 in children with and without pulmonary arterial hypertension (PAH). Method Heart sounds were recorded at the second left intercostal space and the cardiac apex with a digital stethoscope simultaneously with pulmonary arterial pressure (PAP). We developed a Daubechies wavelet algorithm for the automatic detection of S1 and S2 using the wavelet coefficient ‘D6’ based on power spectral analysis. We compared our algorithm with four other Daubechies wavelet-based algorithms published by Liang, Kumar, Wang, and Zhong. We annotated S1 and S2 from an audiovisual examination of the phonocardiographic tracing by two trained cardiologists and the observation that in all subjects systole was shorter than diastole. Results We studied 22 subjects (9 males and 13 females, median age 6 years, range 0.25–19). Eleven subjects had a mean PAP < 25 mmHg. Eleven subjects had PAH with a mean PAP ≥ 25 mmHg. All subjects had a pulmonary artery wedge pressure ≤ 15 mmHg. The sensitivity (SE) and positive predictivity (+P) of our algorithm were 70% and 68%, respectively. In comparison, the SE and +P of Liang were 59% and 42%, Kumar 19% and 12%, Wang 50% and 45%, and Zhong 43% and 53%, respectively. Our algorithm demonstrated robustness and outperformed the other methods up to a signal-to-noise ratio (SNR) of 10 dB. For all algorithms, detection errors arose from low-amplitude peaks, fast heart rates, low signal-to-noise ratio, and fixed thresholds. Conclusion Our algorithm for the detection of S1 and S2 improves the performance of existing Daubechies-based algorithms and justifies the use of the wavelet coefficient ‘D6’ through power spectral analysis. Also, the robustness despite ambient noise may improve real world clinical performance. PMID:26629704

  17. Sensitivity of scintigraphy for detection of pulmonary capillary albumin leak in canine oleic acid ARDS

    SciTech Connect

    Sugerman, H.J.; Strash, A.M.; Hirsch, J.I.; Glauser, F.L.; Shirazi, K.K.; Sharp, D.E.; Greenfield, L.J.

    1981-07-01

    Computerized gamma scintigraphy was shown in this study to be a sensitive technique for the detection and kinetic analysis of a pulmonary capillary protein leak. A rising lung:heart radioactivity of slope of injury was found at each dose of intravenous oleic acid in dogs from 0.01 to 0.20 ml/kg (p less than 0.01). This slope of injury was proportional to the dose of oleic acid (r . +0.97; p less than 0.004) and was more sensitive than changes in arterial oxygen tension, standard chest radiography, bloodless wet:dry lung weight, or alveolar epithelial membrane permeability. Only standard light microscopy and right lymphatic duct flow were able to document the leakage of protein detected by gamma scintigraphy at 0.01 ml/kg oleic acid.

  18. Rapid detection of circulating fibrocytes by flowcytometry in idiopathic pulmonary fibrosis

    PubMed Central

    Alhamad, Esam H.; Shakoor, Zahid; Al-Kassimi, Feisal A.; Almogren, Adel; Gad ElRab, Mohamed O.; Maharaj, Shyam; Kolb, Martin

    2015-01-01

    BACKGROUND: Current protocols for detection of circulating fibrocytes (CFs) in peripheral blood described in various pulmonary and nonpulmonary disorders involve complex and time consuming, non standardized techniques. OBJECTIVE: Testing a method to rapidly detect and quantify CFs using whole blood lysis flow cytometry-based assay in patients with idiopathic pulmonary fibrosis (IPF) and healthy controls. METHODS: One milliliter of venous blood sample in ethylenediaminetetraacetic acid (EDTA) from 33 IPF patients and 35 healthy control subjects was collected. Using whole blood lysis method peripheral blood leukocytes were labeled with monoclonal antibodies for cell surface (CD34 and CD45) and intracellular markers (collagen-1) for flow cytometric analysis. CFs were defined as CD45+ cells coexpressing collagen-I and CD34 molecules. RESULTS: In 29 (87.8%) IPF patients and 10 (28.5%) control subjects, a well-defined highly granular CD45+ cell population was detected in dot plots generated by side scatter properties of CD45+ cells. These CD45+ cells were identified as CFs on the basis of coexpression of collagen-I and CD34; none of the other cell types in the peripheral blood were labeled with these monoclonal antibodies. In IPF patients the percentage of CFs was significantly higher compared to healthy controls (median (range): 1.37% (0.52-5.65) and 1.04% (0.1-1.84), respectively; P = 0.03). CONCLUSIONS: Whole blood lysis method combined with fluorescence-activated cell sorting (FACS) allows detecting a well-defined homogeneous population of CFs. This method is simple, reproducible, and provides an accurate and rapid estimation of CFs. PMID:26664567

  19. Automatic 3D pulmonary nodule detection in CT images: A survey.

    PubMed

    Valente, Igor Rafael S; Cortez, Paulo César; Neto, Edson Cavalcanti; Soares, José Marques; de Albuquerque, Victor Hugo C; Tavares, João Manuel R S

    2016-02-01

    This work presents a systematic review of techniques for the 3D automatic detection of pulmonary nodules in computerized-tomography (CT) images. Its main goals are to analyze the latest technology being used for the development of computational diagnostic tools to assist in the acquisition, storage and, mainly, processing and analysis of the biomedical data. Also, this work identifies the progress made, so far, evaluates the challenges to be overcome and provides an analysis of future prospects. As far as the authors know, this is the first time that a review is devoted exclusively to automated 3D techniques for the detection of pulmonary nodules from lung CT images, which makes this work of noteworthy value. The research covered the published works in the Web of Science, PubMed, Science Direct and IEEEXplore up to December 2014. Each work found that referred to automated 3D segmentation of the lungs was individually analyzed to identify its objective, methodology and results. Based on the analysis of the selected works, several studies were seen to be useful for the construction of medical diagnostic aid tools. However, there are certain aspects that still require attention such as increasing algorithm sensitivity, reducing the number of false positives, improving and optimizing the algorithm detection of different kinds of nodules with different sizes and shapes and, finally, the ability to integrate with the Electronic Medical Record Systems and Picture Archiving and Communication Systems. Based on this analysis, we can say that further research is needed to develop current techniques and that new algorithms are needed to overcome the identified drawbacks. PMID:26652979

  20. Detecting Splicing Variants in Idiopathic Pulmonary Fibrosis from Non-Differentially Expressed Genes

    PubMed Central

    Deng, Nan; Sanchez, Cecilia G.; Lasky, Joseph A.; Zhu, Dongxiao

    2013-01-01

    Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown cause that lacks a proven therapy for altering its high mortality rate. Microarrays have been employed to investigate the pathogenesis of IPF, but are presented mostly at the gene-expression level due to technologic limitations. In as much as, alternative RNA splicing isoforms are increasingly identified as potential regulators of human diseases, including IPF, we propose a new approach with the capacity to detect splicing variants using RNA-seq data. We conducted a joint analysis of differential expression and differential splicing on annotated human genes and isoforms, and identified 122 non-differentially expressed genes with a high degree of “switch” between major and minor isoforms. Three cases with variant mechanisms for alternative splicing were validated using qRT-PCR, among the group of genes in which expression was not significantly changed at the gene level. We also identified 35 novel transcripts that were unique to the fibrotic lungs using exon-exon junction evidence, and selected a representative for qRT-PCR validation. The results of our study are likely to provide new insight into the pathogenesis of pulmonary fibrosis and may eventuate in new treatment targets. PMID:23844188

  1. Pulmonary embolism detection using localized vessel-based features in dual energy CT

    NASA Astrophysics Data System (ADS)

    Dicente Cid, Yashin; Depeursinge, Adrien; Foncubierta Rodríguez, Antonio; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning

    2015-03-01

    Pulmonary embolism (PE) affects up to 600,000 patients and contributes to at least 100,000 deaths every year in the United States alone. Diagnosis of PE can be difficult as most symptoms are unspecific and early diagnosis is essential for successful treatment. Computed Tomography (CT) images can show morphological anomalies that suggest the existence of PE. Various image-based procedures have been proposed for improving computer-aided diagnosis of PE. We propose a novel method for detecting PE based on localized vessel-based features computed in Dual Energy CT (DECT) images. DECT provides 4D data indexed by the three spatial coordinates and the energy level. The proposed features encode the variation of the Hounsfield Units across the different levels and the CT attenuation related to the amount of iodine contrast in each vessel. A local classification of the vessels is obtained through the classification of these features. Moreover, the localization of the vessel in the lung provides better comparison between patients. Results show that the simple features designed are able to classify pulmonary embolism patients with an AUC (area under the receiver operating curve) of 0.71 on a lobe basis. Prior segmentation of the lung lobes is not necessary because an automatic atlas-based segmentation obtains similar AUC levels (0.65) for the same dataset. The automatic atlas reaches 0.80 AUC in a larger dataset with more control cases.

  2. The value of telehealth in the early detection of chronic obstructive pulmonary disease exacerbations: A prospective observational study.

    PubMed

    Hamad, Ghassan A; Crooks, Michael; Morice, Alyn H

    2016-06-01

    We aim to establish the value of telemonitoring in the early detection of chronic obstructive pulmonary disease exacerbations. We followed up patients undergoing chronic obstructive pulmonary disease telemonitoring for 4 months. We studied changes in the telemonitored data in the week prior to admission or to community chronic obstructive pulmonary disease exacerbation. A total of 183 patients were studied. In all, 30 chronic obstructive pulmonary disease-related hospital admissions and 68 chronic obstructive pulmonary disease community exacerbations were recorded. Changes in telehealth parameters occurred in 80 per cent (24/30) of admissions and 82 per cent (56/68) of community exacerbations. Although changes in telehealth data occurred in the majority of exacerbations, most individual symptoms was present in less than half the exacerbations and almost 20 per cent of exacerbations were not preceded by any change in telemonitoring data. Cough created significantly more alerts by those treated in the community (p = 0.008), whereas a drop in oxygen saturation created significantly more alerts pre-hospitalisation (p = 0.049). We conclude that further work is required to develop methods of identifying impending chronic obstructive pulmonary disease exacerbations with greater sensitivity and specificity.

  3. Improvement of method for computer-assisted detection of pulmonary nodules in CT of the chest

    NASA Astrophysics Data System (ADS)

    Fiebich, Martin; Wormanns, Dag; Heindel, Walter

    2001-07-01

    Computed tomography of the chest can be used as a screening method for lung cancer in a high-risk population. However, the detection of lung nodules is a difficult and time-consuming task for radiologists. The developed technique should improve the sensitivity of the detection of lung nodules without showing too many false positive nodules. In the first step the CAD technique for nodule detection in CT examinations of the lung eliminates all air outside the patient, then soft tissue and bony structures are removed. In the remaining lung fields a three-dimensional region detection is performed and rule-based analysis is used to detect possible lung nodules. In a study, which should evaluate the feasibility of screening lung cancer, about 2000 thoracic examinations were performed. The CAD system was used for reporting in a consecutive subset (n=100) of those studies. Computation time is about 5 min on an Silicon Graphics O2 workstation. Of the total number of found nodules >= 5 mm (n=68) 26 were found by the CAD scheme, 59 were detected by the radiologist. The CAD workstation helped the radiologist to identify 9 additional nodules. The false positive rate was less than 0.1 per image. The nodules missed by the CAD scheme were analyzed and the reasons for failure categorized into the density of the nodule is too low, nodules is connected to chest wall, segmentation error, and misclassification. Possible solutions for those problems are presented. We have developed a technique, which increased the detection rate of the radiologist in the detection of pulmonary nodules in CT exams of the chest. Correction of the CAD scheme using the analysis of the missed nodules will further enhance the performance of this method.

  4. Analysis of repeated 24-core saturation prostate biopsy: Inverse association between asymptomatic histological inflammation and prostate cancer detection

    PubMed Central

    Kato, Tomonori; Komiya, Akira; Morii, Akihiro; Iida, Hiroaki; Ito, Takatoshi; Fuse, Hideki

    2016-01-01

    Saturation prostate biopsy protocols have been developed to improve the prostate cancer (PCa) detection rate, particularly in the setting of repeat biopsies. The present study attempted to clarify the association between PCa detection and various risk factors in repeat saturation biopsies. A retrospective analysis was conducted on 78 Japanese patients for whom findings had caused suspicion of PCa despite previous negative prostate biopsies, and who consecutively underwent a 24-core transperineal repeat biopsy at Toyama University Hospital (Toyama, Japan). PCa was confirmed histologically in 16 of the 78 patients (20.5%). A univariate analysis revealed that the prostate-specific antigen (PSA) level at repeat biopsy was higher (P<0.01), the fPSA/tPSA ratio was lower (P=0.04), the total prostate volume was smaller (P=0.01) and the PSA density was higher (P<0.01) in PCa patients than in patients with benign prostatic disease (BPD). Histological inflammation was more frequently observed in BPD patients than in PCa patients (P<0.01). A multivariate analysis revealed that histological inflammation was the only independent predictor of the presence of a malignant lesion on repeat biopsy (odds ratio, 0.027; P=0.01). It must be considered that inflammation may cause a PSA increase in some patients with a negative initial biopsy, leading to unnecessary repeat biopsy. PMID:27446407

  5. CAD System for Pulmonary Nodule Detection Using Gabor Filtering and Template Matching

    NASA Astrophysics Data System (ADS)

    Bastawrous, Hany Ayad; Nitta, Norihisa; Tsudagawa, Masaru

    This paper aims at developing a Computer Aided Diagnosis (CAD) system used for the detection of pulmonary nodules in chest Computed Tomography (CT) images. These lung nodules include both solid nodules and Ground Glass Opacity (GGO) nodules. In our scheme, we apply Gabor filter on the CT image in order to enhance the detection process. After this we perform some morphological operations including threshold process and labeling to extract all the objects inside the lung area. Then, some feature analysis is used to examine these objects to decide which of them are likely to be potential cancer candidates. Following the feature examination, a template matching between the potential cancer candidates and some Gaussian reference models is performed to determine the similarity between them. The algorithm was applied on 715 slices containing 25 GGO nodules and 82 solid nodules and achieved detection sensitivity of 92% for GGO nodules and 95% for solid nodules with False Positive (FP) rate of 0.75 FP/slice for GGO nodules and 2.32 FP/slice for solid nodules. Finally, we used an Artificial Neural Network (ANN) to reduce the number of FP findings. After using ANN, we were able to reduce the FP rate to 0.25 FP/slice for GGO nodules and 1.62 FP/slice for solid nodules but at the expense of detection sensitivity, which became 84 % for GGO nodules and 91% for solid nodules.

  6. [Case of multiple pulmonary arteriovenous fistulas detected during treatment for severe pneumonia].

    PubMed

    Kyoraku, Yuka; Ashitani, Jun-Ichi; Imazu, Yoshifumi; Fukuyama, Chikara; Miyoshi, Kahori; Kodama, Tsuyoshi; Yanagi, Shigehisa; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2008-09-01

    A 55-year-old woman who developed severe hypoxemia associated with severe pneumonia was admitted to our hospital for mechanical ventilation. She was treated with antibiotics under a diagnosis of mycoplasma pneumonia. Although most clinical findings improved, hypoxemia remained. As a chest CT film showed multiple nodules and an enhanced CT film revealed arterial filling in the nodules, multiple pulmonary arteriovenous fistulas (PAVFs) were considered to be an underlying cause of hypoxemia. Transcatheter coil embolization for 5 PAVFs, significantly ameliorated hypoxemia in the patient. PAVF is a congenital desease, and in many cases, is asymptomatic. Therefore, it was rare for PAVFs to be detected in a middle-aged patient with prolonged hypoxemia associated with pneumonia. PMID:18939419

  7. Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

    PubMed

    Seppala, N; Cala, A; Klebe, S

    2009-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

  8. Multiple pulmonary sclerosing hemangiomas (pneumocytoma) mimicking lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2014-01-01

    Pulmonary sclerosing hemangioma (PSH), or the alternative name of “sclerosing pneumocytoma,” is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary or multiple pulmonary nodules on radiologic imaging studies. Few articles have been reported to describe the fluorodeoxyglucose positron emission tomography (FDG PET) findings about PSH. The authors describe an interesting but uncommonly encountered cause of false positive FDG PET scan in the thorax in a 25-year-old woman, a known case of arteriovenous malformation of oral cavity who underwent embolization and presented with incidental detection of bilateral lung nodules. She is asymptomatic and is on follow-up. PMID:25210285

  9. Multiple pulmonary sclerosing hemangiomas (pneumocytoma) mimicking lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2014-07-01

    Pulmonary sclerosing hemangioma (PSH), or the alternative name of "sclerosing pneumocytoma," is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary or multiple pulmonary nodules on radiologic imaging studies. Few articles have been reported to describe the fluorodeoxyglucose positron emission tomography (FDG PET) findings about PSH. The authors describe an interesting but uncommonly encountered cause of false positive FDG PET scan in the thorax in a 25-year-old woman, a known case of arteriovenous malformation of oral cavity who underwent embolization and presented with incidental detection of bilateral lung nodules. She is asymptomatic and is on follow-up.

  10. The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution.

    PubMed

    Park, Sung-Hyun; Chen, Wen-Chi; Durmus, Nedim; Bleck, Bertram; Reibman, Joan; Riemekasten, Gabriela; Grunig, Gabriele

    2015-01-01

    Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wild type and B cell-deficient mice were primed with antigen and then challenged with antigen and urban particulate matter and injected with antibodies as appropriate. Our data surprisingly showed that B cells were necessary for the development of increased right ventricular pressures and molecular changes in the right heart in response to sensitization and intranasal challenge with antigen and PM2.5. Further, our studies showed that both, the increase in right ventricular systolic pressure and right ventricular molecular changes were restored by reconstituting the B cell KO mice with antigen specific IgG1. In addition, our studies identified a critical, non-redundant role of B cells for the IL-17A-directed inflammation in response to exposure with antigen and PM2.5, which was not corrected with antigen-specific IgG1. In contrast, IL-13-directed inflammatory markers, as well as severe pulmonary arterial remodeling induced by challenge with antigen and PM2.5 were similar in B cell

  11. The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution.

    PubMed

    Park, Sung-Hyun; Chen, Wen-Chi; Durmus, Nedim; Bleck, Bertram; Reibman, Joan; Riemekasten, Gabriela; Grunig, Gabriele

    2015-01-01

    Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wild type and B cell-deficient mice were primed with antigen and then challenged with antigen and urban particulate matter and injected with antibodies as appropriate. Our data surprisingly showed that B cells were necessary for the development of increased right ventricular pressures and molecular changes in the right heart in response to sensitization and intranasal challenge with antigen and PM2.5. Further, our studies showed that both, the increase in right ventricular systolic pressure and right ventricular molecular changes were restored by reconstituting the B cell KO mice with antigen specific IgG1. In addition, our studies identified a critical, non-redundant role of B cells for the IL-17A-directed inflammation in response to exposure with antigen and PM2.5, which was not corrected with antigen-specific IgG1. In contrast, IL-13-directed inflammatory markers, as well as severe pulmonary arterial remodeling induced by challenge with antigen and PM2.5 were similar in B cell

  12. The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution

    PubMed Central

    Park, Sung-Hyun; Chen, Wen-Chi; Durmus, Nedim; Bleck, Bertram; Reibman, Joan; Riemekasten, Gabriela; Grunig, Gabriele

    2015-01-01

    Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wild type and B cell-deficient mice were primed with antigen and then challenged with antigen and urban particulate matter and injected with antibodies as appropriate. Our data surprisingly showed that B cells were necessary for the development of increased right ventricular pressures and molecular changes in the right heart in response to sensitization and intranasal challenge with antigen and PM2.5. Further, our studies showed that both, the increase in right ventricular systolic pressure and right ventricular molecular changes were restored by reconstituting the B cell KO mice with antigen specific IgG1. In addition, our studies identified a critical, non-redundant role of B cells for the IL-17A-directed inflammation in response to exposure with antigen and PM2.5, which was not corrected with antigen-specific IgG1. In contrast, IL-13-directed inflammatory markers, as well as severe pulmonary arterial remodeling induced by challenge with antigen and PM2.5 were similar in B cell

  13. Right Pulmonary Artery Distensibility Index (RPAD Index). A field study of an echocardiographic method to detect early development of pulmonary hypertension and its severity even in the absence of regurgitant jets for Doppler evaluation in heartworm-infected dogs.

    PubMed

    Venco, Luigi; Mihaylova, Liliya; Boon, June A

    2014-11-15

    invasively and noninvasively if possible. Results of these evaluations indicated that RPAD Index is a valuable method for early detection of the presence and severity of pulmonary hypertension in heartworm-infected dogs even in the absence of regurgitant jets for Doppler evaluation and that there is a strong correlation between the RPAD Index and the level of pulmonary hypertension.

  14. Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus)

    PubMed Central

    Bouch, Sheena; Harding, Richard; O’Reilly, Megan; Wood, Lisa G.; Sozo, Foula

    2016-01-01

    Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of

  15. Relationship between Household Air Pollution from Biomass Smoke Exposure, and Pulmonary Dysfunction, Oxidant-Antioxidant Imbalance and Systemic Inflammation in Rural Women and Children in Nigeria

    PubMed Central

    Oluwole, Oluwafemi; Arinola, Ganiyu O.; Ana, Godson R.; Wiskel, Tess; Huo, Dezheng; Olopade, Olufunmilayo I.; Olopade, Christopher O.

    2013-01-01

    Background: Exposure to particulate matter from burning biomass fuels is believed to affect oxidant-antioxidant balance and to induce oxidative stress. Methods: Fifty-nine mother-child pairs from 59 households that used firewood exclusively for cooking in three rural communities in southwest Nigeria underwent blood test for albumin, pre-albumin, retinol-binding protein (RBP), superoxide dismutase (SOD), vitamins C, vitamin E, malondialdehyde (MDA) and C-reactive protein (CRP). Spirometry was performed and indoor levels of PM2.5 were determined. Results: Mean age (± SD; years) of mothers and children was 43.0±11.7 and 13.6±3.2, respectively. The median indoor PM2.5 level was 1575.1 µg/m3 (IQR 943.6–2847.0, p<0.001), which is substantially higher than the World Health Organization (WHO) standard of 25 µg/m3. The mean levels of pre-albumin (0.21±0.14 g/dL) and RBP (0.03±0.03 g/dL) in women were significantly lower than their respective normal ranges (1-3 g/dL and 0.2-0.6 g/dL, respectively, p<0.05). Similarly, the mean levels of pre-albumin (0.19±0.13 g/dL) and RBP (0.01±0.01 g/dL) in children were significantly lower than the respective normal ranges (1-3 g/dL and 0.2-0.6 g/dL, respectively, p<0.05). Mean serum concentrations of MDA in children (5.44±1.88 µmol/L) was positively correlated to serum concentrations of CRP (r=0.3, p=0.04) and negatively correlated to lung function (FEV1/FVC) in both mothers and children (both r=-0.3, p<0.05). Also, regression analysis indicates that CRP and SOD are associated with lung function impairment in mothers (-2.55±1.08, p<0.05) and children (-5.96±3.05, p=0.05) respectively. Conclusion: Exposure to HAP from biomass fuel is associated with pulmonary dysfunction, reduced antioxidant defense and inflammation of the airways. Further studies are needed to better define causal relationships and the mechanisms involved. PMID:23777718

  16. Anti-inflammatory actions of Chemoattractant Receptor-homologous molecule expressed on Th2 by the antagonist MK-7246 in a novel rat model of Alternaria alternata elicited pulmonary inflammation.

    PubMed

    Gil, Malgorzata A; Caniga, Michael; Woodhouse, Janice D; Eckman, Joseph; Lee, Hyun-Hee; Salmon, Michael; Naber, John; Hamilton, Valerie T; Sevilla, Raquel S; Bettano, Kimberly; Klappenbach, Joel; Moy, Lily; Correll, Craig C; Gervais, Francois G; Siliphaivanh, Phieng; Zhang, Weisheng; Zhang-Hoover, Jie; McLeod, Robbie L; Cicmil, Milenko

    2014-11-15

    Alternaria alternata is a fungal allergen linked to the development of severe asthma in humans. In view of the clinical relationship between A. alternata and asthma, we sought to investigate the allergic activity of this antigen after direct application to the lungs of Brown Norway rats. Here we demonstrate that a single intratracheal instillation of A. alternata induces dose and time dependent eosinophil influx, edema and Type 2 helper cell cytokine production in the lungs of BN rats. We established the temporal profile of eosinophilic infiltration and cytokine production, such as Interleukin-5 and Interleukin-13, following A. alternata challenge. These responses were comparable to Ovalbumin induced models of asthma and resulted in peak inflammatory responses 48h following a single challenge, eliminating the need for multiple sensitizations and challenges. The initial perivascular and peribronchiolar inflammation preceded alveolar inflammation, progressing to a more sub-acute inflammatory response with notable epithelial cell hypertrophy. To limit the effects of an A. alternata inflammatory response, MK-7246 was utilized as it is an antagonist for Chemoattractant Receptor-homologous molecule expressed in Th2 cells. In a dose-dependent manner, MK-7246 decreased eosinophil influx and Th2 cytokine production following the A. alternata challenge. Furthermore, therapeutic administration of corticosteroids resulted in a dose-dependent decrease in eosinophil influx and Th2 cytokine production. Reproducible asthma-related outcomes and amenability to pharmacological intervention by mechanisms relevant to asthma demonstrate that an A. alternata induced pulmonary inflammation in BN rats is a valuable preclinical pharmacodynamic in vivo model for evaluating the pharmacological inhibitors of allergic pulmonary inflammation.

  17. Pulmonary chondroid hamartoma with nontuberculous mycobacterial infection: two case reports.

    PubMed

    Lee, Yong Chul; Moon, Jin Chang; Gang, Su Jin; Park, Seung Yong; Kim, So Ri

    2015-04-01

    Solitary pulmonary nodules (SPNs) can be manifested in a variety of disorders including neoplasms, infection, inflammation, and vascular or congenital abnormalities. In addition, they are often accompanied with other pulmonary pathologic lesions such as consolidations and several pulmonary disorders present as similar pulmonary nodular lesions simultaneously. Diagnostic workup is important for these SPNs; however, many physicians often miss the second diagnosis for multiple pulmonary lesions with SPNs due to lack of clinical suspicion that each pulmonary nodule or pathologic lesion can have each other's diagnosis. Herein, we report 2 cases of coexistence of pulmonary chondroid hamartoma with nontuberculous mycobacterial (NTM) infection presenting as pulmonary nodules and multiple consolidative lesions. A 60-year-old man was admitted for the evaluation of multifocal pulmonary lesions including SPN with chronic exertional dyspnea. Multiple lung tissues were obtained from each lesion through percutaneous transthoracic needle biopsy (PTNB). At the same time, bacteriologic examination was performed using respiratory samples obtained by bronchoscopy. Based on pathologic and microbiologic results, the patient diagnosed as pulmonary chondroid hamartoma with pulmonary NTM infectious disease. In addition, a 56-year-old woman visited for the evaluation of a small SPN. The SPN was resected surgically for the pathologic examination and turned out to be pulmonary chondroid hamartoma. Interestingly, the diagnostic workup revealed that the patient had Lady Windermere syndrome which is one of features for Mycobacterium avium complex (MAC) pulmonary disease. Both patients were treated with the standard antibiotics against MAC as recommended by the ATS/IDSA guideline. This is the first report of 2 patients, as far as we know, that chondroid hamartoma and NTM disease develop simultaneously in the lung. This report emphasizes that physicians should endeavor to confirm the individual

  18. Validation of an Automated Cough Detection Algorithm for Tracking Recovery of Pulmonary Tuberculosis Patients

    PubMed Central

    Larson, Sandra; Comina, Germán; Gilman, Robert H.; Tracey, Brian H.; Bravard, Marjory; López, José W.

    2012-01-01

    Background A laboratory-free test for assessing recovery from pulmonary tuberculosis (TB) would be extremely beneficial in regions of the world where laboratory facilities are lacking. Our hypothesis is that analysis of cough sound recordings may provide such a test. In the current paper, we present validation of a cough analysis tool. Methodology/Principal Findings Cough data was collected from a cohort of TB patients in Lima, Peru and 25.5 hours of recordings were manually annotated by clinical staff. Analysis software was developed and validated by comparison to manual scoring. Because many patients cough in bursts, coughing was characterized in terms of cough epochs. Our software correctly detects 75.5% of cough episodes with a specificity of 99.6% (comparable to past results using the same definition) and a median false positive rate of 4 false positives/hour, due to the noisy, real-world nature of our dataset. We then manually review detected coughs to eliminate false positives, in effect using the algorithm as a pre-screening tool that reduces reviewing time to roughly 5% of the recording length. This cough analysis approach provides a foundation to support larger-scale studies of coughing rates over time for TB patients undergoing treatment. PMID:23071550

  19. Pulmonary nodule detection in CT images based on shape constraint CV model

    SciTech Connect

    Wang, Bing; Tian, Xuedong; Wang, Qian; Yang, Ying; Xie, Hongzhi E-mail: xiehongzhi@medmail.com.cn; Zhang, Shuyang; Gu, Lixu E-mail: xiehongzhi@medmail.com.cn

    2015-03-15

    Purpose: Accurate detection of pulmonary nodules remains a technical challenge in computer-aided diagnosis systems because some nodules may adhere to the blood vessels or the lung wall, which have low contrast compared to the surrounding tissues. In this paper, the analysis of typical shape features of candidate nodules based on a shape constraint Chan–Vese (CV) model combined with calculation of the number of blood branches adhered to nodule candidates is proposed to reduce false positive (FP) nodules from candidate nodules. Methods: The proposed scheme consists of three major stages: (1) Segmentation of lung parenchyma from computed tomography images. (2) Extraction of candidate nodules. (3) Reduction of FP nodules. A gray level enhancement combined with a spherical shape enhancement filter is introduced to extract the candidate nodules and their sphere-like contour regions. FPs are removed by analysis of the typical shape features of nodule candidates based on the CV model using spherical constraint and by investigating the number of blood branches adhered to the candidate nodules. The constrained shapes of CV model are automatically achieved from the extracted candidate nodules. Results: The detection performance was evaluated on 127 nodules of 103 cases including three types of challenging nodules, which are juxta-pleural nodules, juxta-vascular nodules, and ground glass opacity nodules. The free-receiver operating characteristic (FROC) curve shows that the proposed method is able to detect 88% of all the nodules in the data set with 4 FPs per case. Conclusions: Evaluation shows that the authors’ method is feasible and effective for detection of three types of nodules in this study.

  20. Automated detection of pulmonary embolism (PE) in computed tomographic pulmonary angiographic (CTPA) images: multiscale hierachical expectation-maximization segmentation of vessels and PEs

    NASA Astrophysics Data System (ADS)

    Zhou, Chuan; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Chughtai, Aamer; Patel, Smita; Cascade, Philip N.; Sahiner, Berkman; Wei, Jun; Ge, Jun; Kazerooni, Ella A.

    2007-03-01

    CT pulmonary angiography (CTPA) has been reported to be an effective means for clinical diagnosis of pulmonary embolism (PE). We are developing a computer-aided detection (CAD) system to assist radiologist in PE detection in CTPA images. 3D multiscale filters in combination with a newly designed response function derived from the eigenvalues of Hessian matrices is used to enhance vascular structures including the vessel bifurcations and suppress non-vessel structures such as the lymphoid tissues surrounding the vessels. A hierarchical EM estimation is then used to segment the vessels by extracting the high response voxels at each scale. The segmented vessels are pre-screened for suspicious PE areas using a second adaptive multiscale EM estimation. A rule-based false positive (FP) reduction method was designed to identify the true PEs based on the features of PE and vessels. 43 CTPA scans were used as an independent test set to evaluate the performance of PE detection. Experienced chest radiologists identified the PE locations which were used as "gold standard". 435 PEs were identified in the artery branches, of which 172 and 263 were subsegmental and proximal to the subsegmental, respectively. The computer-detected volume was considered true positive (TP) when it overlapped with 10% or more of the gold standard PE volume. Our preliminary test results show that, at an average of 33 and 24 FPs/case, the sensitivities of our PE detection method were 81% and 78%, respectively, for proximal PEs, and 79% and 73%, respectively, for subsegmental PEs. The study demonstrates the feasibility that the automated method can identify PE accurately on CTPA images. Further study is underway to improve the sensitivity and reduce the FPs.

  1. Long-Circulating and pH-Sensitive Liposome Preparation Trapping a Radiotracer for Inflammation Site Detection.

    PubMed

    Mota, Luciene Das Graças; de Barros, André Luís Branco; Fuscaldi, Leonardo Lima; de Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

    2015-06-01

    Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity. Radiotracer encapsulation percentage in liposomes was 10.65%, of which 4.88% was adsorbed on the surface of the vesicles. Furthermore, liposomes presented positive zeta potential. Freeze-dried liposomes, stored for 180 days at 4 degrees C, did not show significant changes in the mean diameter, indicating good stability. Free radiotracer and radiolabeled liposomes were injected into inflammation focus-bearing rats, and ex-vivo biodistribution studies and scintigraphic images were performed. Results showed that radiopharmaceutical, free and encapsulated into liposomes, were able to identify the inflamed site. Target/non-target ratios, obtained by scintigraphic images, were greater than 1.5 at all investigated times. Data did not show significant differences between the free radiotracer and radiolabeled liposomes. Results suggest that this liposomal preparation could be employed as an alternative procedure for inflamed site detection by means of scintigraphic images. However, as the radiotracer is adsorbed onto the liposome surface by electrostatic forces, it is suggested that a neutral radiopharmaceutical be used to confirm the potential of this formulation as a scintigraphic probe for inflammation/infection detection. PMID:26369024

  2. Quantitative In Vivo Detection of Chlamydia muridarum Associated Inflammation in a Mouse Model Using Optical Imaging

    PubMed Central

    Patel, Manishkumar; Boddicker, Melissa A.; DeMaula, Christopher; Connolly, Brett; Bednar, Bohumil; Heinrichs, Jon H.; Smith, Jeffrey G.

    2015-01-01

    Chlamydia trachomatis is a bacterial sexually transmitted disease with over 1.3 million cases reported to the CDC in 2010. While Chlamydia infection is easily treated with antibiotics, up to 70% of infections are asymptomatic and go untreated. The current mouse model relies on invasive upper genital tract gross pathology readouts at ~60–80 days postinfection. High throughput optical imaging through the use of biomarkers has been successfully used to quickly evaluate several disease processes. Here we evaluate Neutrophil Elastase 680 (Elastase680) for its ability to measure Chlamydia muridarum associated inflammation in live mice using fluorescence molecular tomography (FMT) and In Vivo Imaging System (IVIS). Optical imaging was able to distinguish with statistical significance between vaccinated and nonvaccinated mice as well as mock-challenged and challenged mice 2 weeks after challenge which was 9 weeks sooner than typical gross pathological assessment. Immunohistochemistry confirmed the presence of neutrophils and correlated well with both in vivo and ex vivo imaging. In this report we demonstrate that Elastase680 can be used as a molecular imaging biomarker for inflammation associated with chlamydial infection in a mouse model and that these biomarkers can significantly decrease the time for pathology evaluation and thus increase the rate of therapeutics discovery. PMID:26663988

  3. Lipids Derived from Virulent Francisella tularensis Broadly Inhibit Pulmonary Inflammation via Toll-Like Receptor 2 and Peroxisome Proliferator-Activated Receptor α

    PubMed Central

    Crane, Deborah D.; Ireland, Robin; Alinger, Joshua B.; Small, Pamela

    2013-01-01

    Francisella tularensis is a Gram-negative facultative intracellular pathogen that causes an acute lethal respiratory disease in humans. The heightened virulence of the pathogen is linked to its unique ability to inhibit Toll-like receptor (TLR)-mediated inflammatory responses. The bacterial component and mechanism of this inhibition are unknown. Here we show that lipids isolated from virulent but not attenuated strains of F. tularensis are not detected by host cells, inhibit production of proinflammatory cytokines by primary macrophages in response to known TLR ligands, and suppress neutrophil recruitment in vivo. We further show that lipid-mediated inhibition of inflammation is dependent on TLR2, MyD88, and the nuclear hormone and fatty acid receptor peroxisome proliferator-activated receptor α (PPARα). Pathogen lipid-mediated interference with inflammatory responses through the engagement of TLR2 and PPARα represents a novel manipulation of host signaling pathways consistent with the ability of highly virulent F. tularensis to efficiently evade host immune responses. PMID:23925884

  4. Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis

    PubMed Central

    Chen, Gui-Lan; Jiang, Hongni; Zou, Fangdong

    2016-01-01

    Background Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. Material/Methods Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. Results LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. Conclusions LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels. PMID:27471122

  5. Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease.

    PubMed

    Abd El-Fatah, Marwa F; Ghazy, Mohamed A; Mostafa, Mohamed S; El-Attar, May M; Osman, Ahmed

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is a complex immunological disease with multiple pathological features that is primarily induced by smoking together with additional genetic risk factors. COPD is frequently underdiagnosed; forced expiratory volume in the first second (FEV1) is considered to be the main diagnostic measure for COPD, yet it is insufficiently sensitive to monitor disease progression. Biomarkers capable of monitoring COPD progression and severity are needed. In this report, we evaluated matrix metalloproteinase-9 (MMP-9) as an early marker for the detection and staging of COPD, by assessing the mRNA levels of MMP-9 in peripheral blood samples collected from 22 COPD patients, 6 asymptomatic smokers, and 5 healthy controls. Our results demonstrate that the mRNA levels of MMP-9 increased more than two-fold in severe COPD relative to non-COPD smokers or moderate COPD groups. Moreover, in the very severe COPD group, MMP-9 mRNA levels showed a 4-fold increase relative to the non-COPD smokers or the moderate COPD groups, while there was a mild increase (∼40%) when compared to the severe COPD group. Taken together, our results suggest that MMP-9 serves as a biomarker for the grade and severity of COPD.

  6. Pulmonary intravascular lymphoma detected by FDG PET-CT: a case report.

    PubMed

    Kohan, A A; Paganini, L; Biedak, P; Arma, J I; Dalurzo, M C L; Garcia-Monaco, R D

    2013-01-01

    Intravascular lymphoma is a rare subtype of extranodal Non-Hodgkin's lymphoma. Its prognosis is poor in a high percentage of cases due to its insidious appearance and low clinical suspicion. Its diagnosis is usually only reached after an autopsy. It may affect different organs as a whole or only one organ. It is extremely rare that the lung is the only damaged organ. Its diagnosis depends of the clinician's suspicion and proper evaluation with imaging studies as well as correct selection of the organ to be biopsied. When detected on time, the treatment of choice is a combination of a series of chemotherapy associated to a monoclonal antibody (anti-CD20). We present the case of a male patient who underwent a positron emission tomography-computed tomography with 2-[F-18]-fluoro-2 deoxy-D-glucose (FDG) due to symptoms suggestive of a lymphoproliferative disease with no clear structural abnormalities. The images led to a diagnosis of pulmonary intravascular large B cell lymphoma.

  7. Multislice CT perfusion imaging of the lung in detection of pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Hong, Helen; Lee, Jeongjin

    2006-03-01

    We propose a new subtraction technique for accurately imaging lung perfusion and efficiently detecting pulmonary embolism in chest MDCT angiography. Our method is composed of five stages. First, optimal segmentation technique is performed for extracting same volume of the lungs, major airway and vascular structures from pre- and post-contrast images with different lung density. Second, initial registration based on apex, hilar point and center of inertia (COI) of each unilateral lung is proposed to correct the gross translational mismatch. Third, initial alignment is refined by iterative surface registration. For fast and robust convergence of the distance measure to the optimal value, a 3D distance map is generated by the narrow-band distance propagation. Fourth, 3D nonlinear filter is applied to the lung parenchyma to compensate for residual spiral artifacts and artifacts caused by heart motion. Fifth, enhanced vessels are visualized by subtracting registered pre-contrast images from post-contrast images. To facilitate visualization of parenchyma enhancement, color-coded mapping and image fusion is used. Our method has been successfully applied to ten patients of pre- and post-contrast images in chest MDCT angiography. Experimental results show that the performance of our method is very promising compared with conventional methods with the aspects of its visual inspection, accuracy and processing time.

  8. A novel computer-aided detection system for pulmonary nodule identification in CT images

    NASA Astrophysics Data System (ADS)

    Han, Hao; Li, Lihong; Wang, Huafeng; Zhang, Hao; Moore, William; Liang, Zhengrong

    2014-03-01

    Computer-aided detection (CADe) of pulmonary nodules from computer tomography (CT) scans is critical for assisting radiologists to identify lung lesions at an early stage. In this paper, we propose a novel approach for CADe of lung nodules using a two-stage vector quantization (VQ) scheme. The first-stage VQ aims to extract lung from the chest volume, while the second-stage VQ is designed to extract initial nodule candidates (INCs) within the lung volume. Then rule-based expert filtering is employed to prune obvious FPs from INCs, and the commonly-used support vector machine (SVM) classifier is adopted to further reduce the FPs. The proposed system was validated on 100 CT scans randomly selected from the 262 scans that have at least one juxta-pleural nodule annotation in the publicly available database - Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI). The two-stage VQ only missed 2 out of the 207 nodules at agreement level 1, and the INCs detection for each scan took about 30 seconds in average. Expert filtering reduced FPs more than 18 times, while maintaining a sensitivity of 93.24%. As it is trivial to distinguish INCs attached to pleural wall versus not on wall, we investigated the feasibility of training different SVM classifiers to further reduce FPs from these two kinds of INCs. Experiment results indicated that SVM classification over the entire set of INCs was in favor of, where the optimal operating of our CADe system achieved a sensitivity of 89.4% at a specificity of 86.8%.

  9. Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia, pulmonary inflammation in heart failure-prone rats

    EPA Science Inventory

    Acute exposure to ambient fine particulate matter (PM2.5) is tied to cardiovascular morbidity and mortality, especially among those with prior cardiac injury. The mechanisms and pathophysiologic events precipitating these outcomes remain poorly understood but may involve inflamm...

  10. A symptom-related monitoring program following pulmonary embolism for the early detection of CTEPH: a prospective observational registry study

    PubMed Central

    2014-01-01

    Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following an acute pulmonary embolism (PE). It is frequently diagnosed at advanced stages which is concerning as delayed treatment has important implications for favourable clinical outcome. Performing a follow-up examination of patients diagnosed with acute PE regardless of persisting symptoms and using all available technical procedures would be both cost-intensive and possibly ineffective. Focusing diagnostic procedures therefore on only symptomatic patients may be a practical approach for detecting relevant CTEPH. This study aimed to evaluate if a follow-up program for patients with acute PE based on telephone monitoring of symptoms and further examination of only symptomatic patients could detect CTEPH. In addition, we investigated the role of cardiopulmonary exercise testing (CPET) as a diagnostic tool. Methods In a prospective cohort study all consecutive patients with newly diagnosed PE (n=170, 76 males, 94 females within 26 months) were recruited according to the inclusion and exclusion criteria. Patients were contacted via telephone and asked to answer standardized questions relating to symptoms. At the time of the final analysis 130 patients had been contacted. Symptomatic patients underwent a structured evaluation with echocardiography, CPET and complete work-up for CTEPH. Results 37.7%, 25.5% and 29.3% of the patients reported symptoms after three, six, and twelve months respectively. Subsequent clinical evaluation of these symptomatic patients saw 20.4%, 11.5% and 18.8% of patients at the respective three, six and twelve months time points having an echocardiography suggesting pulmonary hypertension (PH). CTEPH with pathological imaging and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg at rest was confirmed in eight subjects. Three subjects with mismatch perfusion defects showed an exercise induced increase of PAP without increasing pulmonary artery

  11. Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology

    PubMed Central

    Thornton, Christopher; Johnson, Gemma; Agrawal, Samir

    2012-01-01

    Invasive pulmonary aspergillosis (IPA) is a leading cause of morbidity and mortality in haematological malignancy patients and hematopoietic stem cell transplant recipients1. Detection of IPA represents a formidable diagnostic challenge and, in the absence of a 'gold standard', relies on a combination of clinical data and microbiology and histopathology where feasible. Diagnosis of IPA must conform to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycology Study Group (EORTC/MSG) consensus defining "proven", "probable", and "possible" invasive fungal diseases2. Currently, no nucleic acid-based tests have been externally validated for IPA detection and so polymerase chain reaction (PCR) is not included in current EORTC/MSG diagnostic criteria. Identification of Aspergillus in histological sections is problematic because of similarities in hyphal morphologies with other invasive fungal pathogens3, and proven identification requires isolation of the etiologic agent in pure culture. Culture-based approaches rely on the availability of biopsy samples, but these are not always accessible in sick patients, and do not always yield viable propagules for culture when obtained. An important feature in the pathogenesis of Aspergillus is angio-invasion, a trait that provides opportunities to track the fungus immunologically using tests that detect characteristic antigenic signatures molecules in serum and bronchoalveolar lavage (BAL) fluids. This has led to the development of the Platelia enzyme immunoassay (GM-EIA) that detects Aspergillus galactomannan and a 'pan-fungal' assay (Fungitell test) that detects the conserved fungal cell wall component (1 →3)-β-D-glucan, but not in the mucorales that lack this component in their cell walls1,4. Issues surrounding the accuracy of these tests1,4-6 has led to the recent development of next-generation monoclonal antibody (MAb)-based assays that detect

  12. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker

    PubMed Central

    Li, Yong; Liu, Jun; Liu, Zong-zhi; Duan, Da-peng

    2016-01-01

    Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression. PMID:27380953

  13. The usefulness of telemedicine for the detection of infection/inflammation at the point of care.

    PubMed

    Rotstein, R; Berliner, S; Fusman, R; Shapira, I; Avitzour, D; Arber, N; Zeltser, D

    2001-01-01

    The objective of this study is to examine the possibility of using Telemedicine to diagnose the presence of the inflammatory response and to assess its intensity at the point of care. One drop of citrated peripheral venous blood from 15 patients with infection/inflammation and 15 controls were used to prepare the slides. Unstained pictures were analyzed using a microscope, video camera and image analyzer (INFLAMETTM, Biovision, Tel Aviv, Israel). The jpg-compressed images were transferred via telephone to a physician in a remote location. A significant correlation was noted between the white blood cell count and the number of leukocytes per square mm by image analysis (r = 0.67 p < 0.0001 n = 30), between the degree of leukocyte adhesiveness/aggregation and the concentration of C-reactive protein (r = 0.42 p = 0.02 n = 29) and between the degree of erythrocyte aggregation and either fibrinogen concentrations (r = 0.73 p < 0.0001) or erythrocyte sedimentation (r = 0.83, p < 0.0001). No problems occurred during file transmission and there were no transfer errors. Physicians can successfully estimate the presence of an inflammatory response and its intensity using a simple slide test, image analysis, and Telemedicine technology.

  14. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker.

    PubMed

    Li, Yong; Liu, Jun; Liu, Zong-Zhi; Duan, Da-Peng

    2016-08-01

    Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression. PMID:27380953

  15. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker.

    PubMed

    Li, Yong; Liu, Jun; Liu, Zong-Zhi; Duan, Da-Peng

    2016-08-01

    Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression.

  16. Effect of monitor luminance on the detection of a solitary pulmonary nodule: ROC analysis

    NASA Astrophysics Data System (ADS)

    Song, Koun-Sik; Lee, Jin S.; Kim, Hae Y.; Lim, Tae H.

    1999-05-01

    We compared the detectability of solitary pulmonary nodule (SPN) in chest radiographs displayed on different gray-scale monitor luminance. From the long-term archive of Asan Medical Center PACS 40 normal chest PA images and 40 chest PA images with SPN were fetched into the short-term storage. All Chest PA images were acquired using Fuji FCR 9501 or 9500 HQ and down-sampled from 4k to 2k pixel resolutions, and archived to ODJ with 10:1 compression ratio. Mean diameter of the nodules were 12 mm ranging in size from 8 to 20 mm. Nodules were located within the free lung fields (10 cases), overlapped with rib (13 cases), and overlapped with hilum, heart, or subphrenic areas (17 cases). Gray-scale monitors compared in our study were Image Systems M21P2KHBMAX monitor with 100 fL brightness and M21PMAX monitor with 65 fL brightness. After randomization, eight board-certified radiologists determined the presence or absence of nodules independently using worksheet. All radiologists interpreted the images displayed on low-brightness monitors, then after 10 days interpreted the images displayed on high-brightness monitors. Data were gathered using five rating categories, and ROC analysis was performed. Area under the ROC curve was compared for low and high brightness monitors. Mean area under the ROC curve for low-brightness monitor was 0.8597 and high-brightness monitor was 0.8734. Although high-brightness monitor is slightly superior to low-brightness monitor, there was no statistically significant differences between low-brightness and high- brightness monitors (p equals 0.3). Further studies are required for various other subtle lung diseases, long-term physiological effect.

  17. The Effect Of Pixel Size On The Detection Rate Of Early Pulmonary Sarcoidosis In Digital Chest Radiographic Systems

    NASA Astrophysics Data System (ADS)

    MacMahon, Heber; Vyborny, Carl; Powell, Gregory; Doi, Kunio; Metz, Charles E.

    1984-08-01

    In digital radiography the pixel size used determines the potential spatial resolution of the system. The need for spatial resolution varies depending on the subject matter imaged. In many areas, including the chest, the minimum spatial resolution requirements have not been determined. Sarcoidosis is a disease which frequently causes subtle interstitial infiltrates in the lungs. As the initial step in an investigation designed to determine the minimum pixel size required in digital chest radiographic systems, we have studied 1 mm pixel digitized images on patients with early pulmonary sarcoidosis. The results of this preliminary study suggest that neither mild interstitial pulmonary infiltrates nor other abnormalities such as pneumothoraces may be detected reliably with 1 mm pixel digital images.

  18. Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection

    PubMed Central

    Zang, Na; Zhuang, Jianguo; Deng, Yu; Yang, Zhimei; Ye, Zhixu; Xie, Xiaohong; Ren, Luo; Fu, Zhou; Luo, Zhengxiu; Xu, Fadi

    2015-01-01

    ABSTRACT Children with acute respiratory syncytial virus (RSV) infection often develop sequelae of persistent airway inflammation and wheezing. Pulmonary C fibers (PCFs) are involved in the generation of airway inflammation and resistance; however, their role in persistent airway diseases after RSV is unexplored. Here, we elucidated the pathogenesis of PCF activation in RSV-induced persistent airway disorders. PCF-degenerated and intact mice were used in the current study. Airway inflammation and airway resistance were evaluated. MMP408 and FSLLRY-NH2 were the selective antagonists for MMP-12 and PAR2, respectively, to investigate the roles of MMP-12 and PAR2 in PCFs mediating airway diseases. As a result, PCF degeneration significantly reduced the following responses to RSV infection: augmenting of inflammatory cells, especially macrophages, and infiltrating of inflammatory cells in lung tissues; specific airway resistance (sRaw) response to methacholine; and upregulation of MMP-12 and PAR2 expression. Moreover, the inhibition of MMP-12 reduced the total number of cells and macrophages in bronchiolar lavage fluid (BALF), as well infiltrating inflammatory cells, and decreased the sRaw response to methacholine. In addition, PAR2 was upregulated especially at the later stage of RSV infection. Downregulation of PAR2 ameliorated airway inflammation and resistance following RSV infection and suppressed the level of MMP-12. In all, the results suggest that PCF involvement in long-term airway inflammation and airway hyperresponsiveness occurred at least partially via modulating MMP-12, and the activation of PAR2 might be related to PCF-modulated MMP-12 production. Our initial findings indicated that the inhibition of PCF activity would be targeted therapeutically for virus infection-induced long-term airway disorders. IMPORTANCE The current study is critical to understanding that PCFs are involved in long-term airway inflammation and airway resistance after RSV infection

  19. Inhaled extended-release microparticles of heparin elicit improved pulmonary pharmacodynamics against antigen-mediated airway hyper-reactivity and inflammation.

    PubMed

    Yildiz, Ayca; John, Elinor; Özsoy, Yildiz; Araman, Ahmet; Birchall, James C; Broadley, Kenneth J; Gumbleton, Mark

    2012-09-10

    Inhaled heparin appears to provide benefit in the management of airway hyper-reactivity and inflammation. The pharmacodynamics of inhaled heparin are however transient. Providing sustained heparin concentrations in the respiratory tract should provide for an extended duration of action. We examined the in-vivo efficacy of a nebulised controlled-release microparticle formulation of heparin in modifying antigen-induced airway hyper-reactivity (AHR) and lung inflammation. Heparin-loaded biodegradable poly (D,L-lactide-co-glycolide) microparticles were prepared by spray-drying. Aerosol properties for both nebulised heparin solution and heparin microparticles displayed characteristics consistent with heparin delivery to the respiratory tract. In vitro release assays showed heparin to be released from the microparticles over 8-12 h and for the heparin to remain functional. Temporal pharmacodynamic responses were studied in an ovalbumin-sensitised in vivo model exhibiting AHR and airway inflammation. Despite a reduced total dose of heparin deposited in the airways following nebulisation with heparin microparticles, this treatment led to a more sustained inhibitory effect upon AHR and airway inflammation than equivalent doses of nebulised heparin solution. The work supports extended-release heparin as an inhalation dosing strategy in experimental therapeutic applications aimed at improving the pharmacodynamics of heparin in the treatment of AHR and lung inflammation.

  20. RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rhodes, Christopher J.; Im, Hogune; Cao, Aiqin; Hennigs, Jan K.; Wang, Lingli; Sa, Silin; Chen, Pin-I; Nickel, Nils P.; Miyagawa, Kazuya; Hopper, Rachel K.; Tojais, Nancy F.; Li, Caiyun G.; Gu, Mingxia; Spiekerkoetter, Edda; Xian, Zhaoying; Chen, Rui; Zhao, Mingming; Kaschwich, Mark; del Rosario, Patricia A.; Bernstein, Daniel; Zamanian, Roham T.; Wu, Joseph C.; Snyder, Michael P.

    2015-01-01

    Rationale: Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. Objectives: RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts. Methods: The endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. Measurements and Main Results: Fold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased β-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries. Conclusions: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension. PMID:26030479

  1. Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation.

    PubMed

    Primiano, Michael J; Lefker, Bruce A; Bowman, Michael R; Bree, Andrea G; Hubeau, Cedric; Bonin, Paul D; Mangan, Matthew; Dower, Ken; Monks, Brian G; Cushing, Leah; Wang, Stephen; Guzova, Julia; Jiao, Aiping; Lin, Lih-Ling; Latz, Eicke; Hepworth, David; Hall, J Perry

    2016-09-15

    A critical component of innate immune response to infection and tissue damage is the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome, and this pathway and its activation products have been implicated in the pathophysiology of a variety of diseases. NLRP3 inflammasome activation leads to the cleavage of pro-IL-1β and pro-IL-18, as well as the subsequent release of biologically active IL-1β, IL-18, and other soluble mediators of inflammation. In this study, we further define the pharmacology of the previously reported NLRP3 inflammasome-selective, IL-1β processing inhibitor CP-456,773 (also known as MCC950), and we demonstrate its efficacy in two in vivo models of inflammation. Specifically, we show that in human and mouse innate immune cells CP-456,773 is an inhibitor of the cellular release of IL-1β, IL-1α, and IL-18, that CP-456,773 prevents inflammasome activation induced by disease-relevant soluble and crystalline NLRP3 stimuli, and that CP-456,773 inhibits R848- and imiquimod-induced IL-1β release. In mice, CP-456,773 demonstrates potent inhibition of the release of proinflammatory cytokines following acute i.p. challenge with LPS plus ATP in a manner that is proportional to the free/unbound concentrations of the drug, thereby establishing an in vivo pharmacokinetic/pharmacodynamic model for CP-456,773. Furthermore, CP-456,773 reduces ear swelling in an imiquimod cream-induced mouse model of skin inflammation, and it reduces airway inflammation in mice following acute challenge with house dust mite extract. These data implicate the NLRP3 inflammasome in the pathogenesis of dermal and airway inflammation, and they highlight the utility of CP-456,773 for interrogating the contribution of the NLRP3 inflammasome and its outputs in preclinical models of inflammation and disease. PMID:27521339

  2. Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation.

    PubMed

    Primiano, Michael J; Lefker, Bruce A; Bowman, Michael R; Bree, Andrea G; Hubeau, Cedric; Bonin, Paul D; Mangan, Matthew; Dower, Ken; Monks, Brian G; Cushing, Leah; Wang, Stephen; Guzova, Julia; Jiao, Aiping; Lin, Lih-Ling; Latz, Eicke; Hepworth, David; Hall, J Perry

    2016-09-15

    A critical component of innate immune response to infection and tissue damage is the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome, and this pathway and its activation products have been implicated in the pathophysiology of a variety of diseases. NLRP3 inflammasome activation leads to the cleavage of pro-IL-1β and pro-IL-18, as well as the subsequent release of biologically active IL-1β, IL-18, and other soluble mediators of inflammation. In this study, we further define the pharmacology of the previously reported NLRP3 inflammasome-selective, IL-1β processing inhibitor CP-456,773 (also known as MCC950), and we demonstrate its efficacy in two in vivo models of inflammation. Specifically, we show that in human and mouse innate immune cells CP-456,773 is an inhibitor of the cellular release of IL-1β, IL-1α, and IL-18, that CP-456,773 prevents inflammasome activation induced by disease-relevant soluble and crystalline NLRP3 stimuli, and that CP-456,773 inhibits R848- and imiquimod-induced IL-1β release. In mice, CP-456,773 demonstrates potent inhibition of the release of proinflammatory cytokines following acute i.p. challenge with LPS plus ATP in a manner that is proportional to the free/unbound concentrations of the drug, thereby establishing an in vivo pharmacokinetic/pharmacodynamic model for CP-456,773. Furthermore, CP-456,773 reduces ear swelling in an imiquimod cream-induced mouse model of skin inflammation, and it reduces airway inflammation in mice following acute challenge with house dust mite extract. These data implicate the NLRP3 inflammasome in the pathogenesis of dermal and airway inflammation, and they highlight the utility of CP-456,773 for interrogating the contribution of the NLRP3 inflammasome and its outputs in preclinical models of inflammation and disease.

  3. Exposure for ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats*

    EPA Science Inventory

    Rationale: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the related molecular mechanisms are poorly understood. Previously we studied cardiovascular responses in healthy WKY rats following inhalation exposure to ultrafine carbon particles (UfCPs...

  4. [New perspectives in the measurement of cardiovascular risk: explorations to detect subclinical atherosclerosis and inflammation markers].

    PubMed

    Fernández-Miranda, Consuelo

    2007-03-10

    Among the new technologies for the detection of subclinical atherosclerosis, ankle-brachial index, carotid ultrasonography, computed tomography detection of coronary calcifications and high-resolution nuclear magnetic resonance are those of greatest clinical usefulness. These explorations are especially useful for patients with an intermediate cardiovascular risk, or a 10-20% risk according to the National Cholesterol Education Program-Adult Treatment Panel III or 3-4% according to the SCORE project. This is because they allow the identification of high-risk patients who need a more intense treatment. In addition, high-sensitivity C-reactive protein concentrations may be considered as a new marker for the evaluation of cardiovascular risk. In this article, the current state of knowledge about these explorations and the guidelines of the main scientific societies are reviewed, and the practical conclusions of the working group are provided.

  5. Follow-up Recommendation Detection on Radiology Reports with Incidental Pulmonary Nodules.

    PubMed

    Oliveira, Lucas; Tellis, Ranjith; Qian, Yuechen; Trovato, Karen; Mankovich, Gabe

    2015-01-01

    The management of follow-up recommendations is fundamental for the appropriate care of patients with incidental pulmonary findings. The lack of communication of these important findings can result in important actionable information being lost in healthcare provider electronic documents. This study aims to analyze follow-up recommendations in radiology reports containing pulmonary incidental findings by using Natural Language Processing and Regular Expressions. Our evaluation highlights the different follow-up recommendation rates for oncology and non-oncology patient cohorts. The results reveal the need for a context-sensitive approach to tracking different patient cohorts in an enterprise-wide assessment. PMID:26262328

  6. Detection of the Inflammation Biomarker C-Reactive Protein in Serum Samples: Towards an Optimal Biosensor Formula

    PubMed Central

    Fakanya, Wellington M.; Tothill, Ibtisam E.

    2014-01-01

    The development of an electrochemical immunosensor for the biomarker, C-reactive protein (CRP), is reported in this work. CRP has been used to assess inflammation and is also used in a multi-biomarker system as a predictive biomarker for cardiovascular disease risk. A gold-based working electrode sensor was developed, and the types of electrode printing inks and ink curing techniques were then optimized. The electrodes with the best performance parameters were then employed for the construction of an immunosensor for CRP by immobilizing anti-human CRP antibody on the working electrode surface. A sandwich enzyme-linked immunosorbent assay (ELISA) was then constructed after sample addition by using anti-human CRP antibody labelled with horseradish peroxidase (HRP). The signal was generated by the addition of a mediator/substrate system comprised of 3,3,5',5'-Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H2O2). Measurements were conducted using chronoamperometry at −200 mV against an integrated Ag/AgCl reference electrode. A CRP limit of detection (LOD) of 2.2 ng·mL−1 was achieved in spiked serum samples, and performance agreement was obtained with reference to a commercial ELISA kit. The developed CRP immunosensor was able to detect a diagnostically relevant range of the biomarker in serum without the need for signal amplification using nanoparticles, paving the way for future development on a cardiac panel electrochemical point-of-care diagnostic device. PMID:25587427

  7. Role of Computer Aided Diagnosis (CAD) in the detection of pulmonary nodules on 64 row multi detector computed tomography

    PubMed Central

    Prakashini, K; Babu, Satish; Rajgopal, KV; Kokila, K Raja

    2016-01-01

    Aims and Objectives: To determine the overall performance of an existing CAD algorithm with thin-section computed tomography (CT) in the detection of pulmonary nodules and to evaluate detection sensitivity at a varying range of nodule density, size, and location. Materials and Methods: A cross-sectional prospective study was conducted on 20 patients with 322 suspected nodules who underwent diagnostic chest imaging using 64-row multi-detector CT. The examinations were evaluated on reconstructed images of 1.4 mm thickness and 0.7 mm interval. Detection of pulmonary nodules, initially by a radiologist of 2 years experience (RAD) and later by CAD lung nodule software was assessed. Then, CAD nodule candidates were accepted or rejected accordingly. Detected nodules were classified based on their size, density, and location. The performance of the RAD and CAD system was compared with the gold standard that is true nodules confirmed by consensus of senior RAD and CAD together. The overall sensitivity and false-positive (FP) rate of CAD software was calculated. Observations and Results: Of the 322 suspected nodules, 221 were classified as true nodules on the consensus of senior RAD and CAD together. Of the true nodules, the RAD detected 206 (93.2%) and 202 (91.4%) by the CAD. CAD and RAD together picked up more number of nodules than either CAD or RAD alone. Overall sensitivity for nodule detection with the CAD program was 91.4%, and FP detection per patient was 5.5%. The CAD showed comparatively higher sensitivity for nodules of size 4–10 mm (93.4%) and nodules in hilar (100%) and central (96.5%) location when compared to RAD's performance. Conclusion: CAD performance was high in detecting pulmonary nodules including the small size and low-density nodules. CAD even with relatively high FP rate, assists and improves RAD's performance as a second reader, especially for nodules located in the central and hilar region and for small nodules by saving RADs time. PMID:27578931

  8. Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation

    PubMed Central

    Crowell, Trevor A; Fletcher, James LK; Sereti, Irini; Pinyakorn, Suteeraporn; Dewar, Robin; Krebs, Shelly J; Chomchey, Nitiya; Rerknimitr, Rungsun; Schuetz, Alexandra; Michael, Nelson L; Phanuphak, Nittaya; Chomont, Nicolas; Ananworanich, Jintanat

    2016-01-01

    Introduction Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART). Methods From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable (≥50 copies/mg) or undetectable in homogenized colon biopsy specimens. Biomarkers and HIV burden in blood, colon and cerebrospinal fluid were compared between groups and after 24 weeks of ART. Results Colonic HIV RNA was detectable in 31 participants (76%) and was associated with longer duration since HIV exposure (median 16 vs. 11 days, p=0.02), higher median plasma levels of cytokines and inflammatory markers (CXCL10 476 vs. 148 pg/mL, p=0.02; TNF-RII 1036 vs. 649 pg/mL, p<0.01; neopterin 2405 vs. 1368 pg/mL, p=0.01) and higher levels of CD8+ T cell activation in the blood (human leukocyte antigen - antigen D related (HLA-DR)/CD38 expression 14.4% vs. 7.6%, p <0.01) and colon (8.9% vs. 4.5%, p=0.01). After 24 weeks of ART, participants with baseline detectable colonic HIV RNA demonstrated persistent elevations in total HIV DNA in colonic mucosal mononuclear cells (CMMCs) (median 61 vs. 0 copies/106 CMMCs, p=0.03) and a trend towards higher total HIV DNA in peripheral blood mononuclear cells (PBMC) (41 vs. 1.5 copies/106 PBMCs, p=0.06). There were no persistent differences in immune activation and inflammation. Conclusions The presence of detectable colonic HIV RNA at the time of ART initiation during AHI is associated with higher levels of proviral DNA after 24 weeks of treatment. Seeding of HIV in the gut may have long-lasting effects on the size of persistent viral reservoirs and may represent an important therapeutic target in eradication strategies. PMID:27637172

  9. A novel spherical shell filter for reducing false positives in automatic detection of pulmonary nodules in thoracic CT scans

    NASA Astrophysics Data System (ADS)

    van de Leemput, Sil; Dorssers, Frank; Ehteshami Bejnordi, Babak

    2015-03-01

    Early detection of pulmonary nodules is crucial for improving prognosis of patients with lung cancer. Computer-aided detection of lung nodules in thoracic computed tomography (CT) scans has a great potential to enhance the performance of the radiologist in detecting nodules. In this paper we present a computer-aided lung nodule detection system for computed tomography (CT) scans that works in three steps. The system first segments the lung using thresholding and hole filling. From this segmentation the system extracts candidate nodules using Laplacian of Gaussian. To reject false positives among the detected candidate nodules, multiple established features are calculated. We propose a novel feature based on a spherical shell filter, which is specifically designed to distinguish between vascular structures and nodular structures. The performance of the proposed CAD system was evaluated by partaking in the ANODE09 challenge, which presents a platform for comparing automatic nodule detection programs. The results from the challenge show that our CAD system ranks third among the submitted works, demonstrating the efficacy of our proposed CAD system. The results also show that our proposed spherical shell filter in combination with conventional features can significantly reduce the number of false positives from the detected candidate nodules.

  10. A method for generating pulmonary neutrophilia using aerosolized lipopolysaccharide.

    PubMed

    Roos, Abraham B; Berg, Tove; Ahlgren, Kerstin M; Grunewald, Johan; Nord, Magnus

    2014-01-01

    Acute lung injury (ALI) is a severe disease characterized by alveolar neutrophilia, with limited treatment options and high mortality. Experimental models of ALI are key in enhancing our understanding of disease pathogenesis. Lipopolysaccharide (LPS) derived from gram positive bacteria induces neutrophilic inflammation in the airways and lung parenchyma of mice. Efficient pulmonary delivery of compounds such as LPS is, however, difficult to achieve. In the approach described here, pulmonary delivery in mice is achieved by challenge to aerosolized Pseudomonas aeruginosa LPS. Dissolved LPS was aerosolized by a nebulizer connected to compressed air. Mice were exposed to a continuous flow of LPS aerosol in a Plexiglas box for 10 min, followed by 2 min conditioning after the aerosol was discontinued. Tracheal intubation and subsequent bronchoalveolar lavage, followed by formalin perfusion was next performed, which allows for characterization of the sterile pulmonary inflammation. Aerosolized LPS generates a pulmonary inflammation characterized by alveolar neutrophilia, detected in bronchoalveolar lavage and by histological assessment. This technique can be set up at a small cost with few appliances, and requires minimal training and expertise. The exposure system can thus be routinely performed at any laboratory, with the potential to enhance our understanding of lung pathology. PMID:25548888

  11. The Most Common Detected Risk and Etiologic Factors of Pulmonary Thromboembolism

    PubMed Central

    Cukic, Vesna; Baljic, Rusmir

    2012-01-01

    Introduction: Pulmonary thromboembolism (PTE) is the most serious manifestation of thromboembolic disease. Objective: To determine the most common risk and etiologic factors of pulmonary tromboembolism in patients treated in Intensive care unit of Clinic for Pulmonary Diseases and TB “Podhrastovi” in three-year- period from 2008. to 2010. Material and methods: We retrospectively analysed patients with PTE treated in Intensive care unit of Clinic for Pulmonary Diseases and TB “Podhrastovi” in three-year period from 2008. to 2010. PTE was diagnosed by high resolute computed tomography, in most of them ventilatory /perfusion scintigraphy (V/P SPECT) was made, with proper laboratory analyses (D-dimmer, platelets , fibrinogen, and if it was needed protein C, S and AT III factor were examined). In all of them echosonography of abdomen and pelvis was done, also the examination by angiologist, and in patients with indications echosonography of the heart and Color Doppler of leg veins was made. We analysed risk and etiologic factors for PTE in each patient. Results: In 222 treated patients with PTE risk factors were found in 124 or 55.86% patients, etiologic factors were found in 31 or 13.96%, and both risk and etiologic factors in one patient were found in 18 or 8.11% patients. Conclusion: PTE is very serious disease that very often has fatal prognosis, and can develop with previously entirely healthy people, and as soon as we become suspicious of its presence we have to made appropriate diagnostic procedures and include appropriate therapy. We can after look for risk and etiologic factors and try to influence them. PMID:23922531

  12. Sandstorm Appearance of Pulmonary Alveolar Microlithiasis Incidentally Detected in a Young, Asymptomatic Male

    PubMed Central

    Bux, Shaik Ismail; Liam, Chong Kin; Rahman, Nazarina Abdul; Ho, Choon Yan

    2013-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM. PMID:24043987

  13. Sandstorm appearance of pulmonary alveolar microlithiasis incidentally detected in a young, asymptomatic male.

    PubMed

    Ch'ng, Li Shyan; Bux, Shaik Ismail; Liam, Chong Kin; Rahman, Nazarina Abdul; Ho, Choon Yan

    2013-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM. PMID:24043987

  14. Single-exposure dual-energy subtraction chest radiography: detection of pulmonary nodules and masses in clinical practice.

    PubMed

    Szucs-Farkas, Zsolt; Patak, Michael A; Yuksel-Hatz, Seyran; Ruder, Thomas; Vock, Peter

    2008-01-01

    The purpose of this retrospective study was to evaluate the impact of energy subtraction (ES) chest radiography on the detection of pulmonary nodules and masses in daily routine. Seventy-seven patients and 25 healthy subjects were examined with a single exposure digital radiography system. Five blinded readers evaluated first the non-subtracted PA and lateral chest radiographs alone and then together with the subtracted PA soft tissue images. The size, location and number of lung nodules or masses were registered with the confidence level. CT was used as standard of reference. For the 200 total lesions, a sensitivity of 33.5-52.5% was found at non-subtracted and a sensitivity of 43.5-58.5% at energy-subtracted radiography, corresponding to a significant improvement in four of five readers (p < 0.05). However, in three of five readers the rate of false positives was higher with ES. With ES, sensitivity, but not the area under the alternative free-response receiver operating characteristics (AFROC) curve, showed a good correlation with reader experience (R = 0.90, p = 0.026). In four of five readers, the diagnostic confidence improved with ES (p = 0.0036). We conclude that single-exposure digital ES chest radiography improves detection of most pulmonary nodules and masses, but identification of nodules <1 cm and false-positive findings remain a problem.

  15. Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

    PubMed Central

    Carron, Philippe; Lambert, Bieke; Van Praet, Liesbet; De Vos, Filip; Varkas, Gaëlle; Jans, Lennart; Elewaut, Dirk; Van den Bosch, Filip

    2016-01-01

    Background Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more ‘evidence-based biological therapy’. Objectives Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. Methods CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. Results In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). Conclusions Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response. Trial registration number NCT01590966; Results. PMID:27403334

  16. Atypical presentation of intra-abdominal extralobar pulmonary sequestration detected in prenatal care: a case report

    PubMed Central

    Costa, Márcio Rodrigues; Costa, Théo Rodrigues; Leite, Mauricio Sérgio Brasil; de Souza, Fernandes Rodrigues; Reis, Alexandre Magno Bahia; Pereira, Bruno Paiva; de Oliveira, Arthur Magalhães

    2016-01-01

    Abstract Objective: To describe an unusual clinical presentation of intra-abdominal extralobar pulmonary sequestration in a 2-year, 9 month-old patient and assess diagnostic and treatment aspects of this pathology. Case description: An undefined intra-abdominal mass was identified in the right adrenal region in a male fetus. Postnatal evaluation with ultrasound images, computed tomography, magnetic resonance imaging and laboratory testing was insufficient to determine the nature of the lesion. After two years, laparoscopic resection of the mass and histopathological examination of the surgical specimen allowed to establish the diagnosis of intra-abdominal extralobar pulmonary sequestration. Comments: This malformation can be monitored clinically; however, surgical excision is often performed, probably due to the impossibility of attaining diagnosis with non-invasive methods, such as in the present case, in which the lesion appeared in an unusual position for intra-abdominal extralobar pulmonary sequestration. Therefore, the surgical approach seems to be the key to attain the diagnosis and establish the conduct for this type of congenital malformation. PMID:26611889

  17. Pulmonary edema

    MedlinePlus

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  18. Efficacy of Simple Short-Term in Vitro Assays for Predicting the Potential of Metal Oxide Nanoparticles to Cause Pulmonary Inflammation

    PubMed Central

    Lu, Senlin; Duffin, Rodger; Poland, Craig; Daly, Paul; Murphy, Fiona; Drost, Ellen; MacNee, William; Stone, Vicki; Donaldson, Ken

    2009-01-01

    Background There has been concern regarding risks from inhalation exposure to nanoparticles (NPs). The large number of particles requiring testing means that alternative approaches to animal testing are needed. Objectives We set out to determine whether short-term in vitro assays that assess intrinsic oxidative stress potential and membrane-damaging potency of a panel of metal oxide NPs can be used to predict their inflammogenic potency. Methods For a panel of metal oxide NPs, we investigated intrinsic free radical generation, oxidative activity in an extracellular environment, cytotoxicity to lung epithelial cells, hemolysis, and inflammation potency in rat lungs. All exposures were carried out at equal surface area doses. Results Only nickel oxide (NiO) and alumina 2 caused significant lung inflammation when instilled into rat lungs at equal surface area, suggesting that these two had extra surface reactivity. We observed significant free radical generation with 4 of 13 metal oxides, only one of which was inflammogenic. Only 3 of 13 were significantly hemolytic, two of which were inflammogenic. Conclusions Potency in generating free radicals in vitro did not predict inflammation, whereas alumina 2 had no free radical activity but was inflammogenic. The hemolysis assay was correct in predicting the proinflammatory potential of 12 of 13 of the particles examined. Using a battery of simple in vitro tests, it is possible to predict the inflammogenicity of metal oxide NPs, although some false-positive results are likely. More research using a larger panel is needed to confirm the efficacy and generality of this approach for metal oxide NPs. PMID:19270794

  19. Cannabinoids for the treatment of inflammation.

    PubMed

    Ashton, John C

    2007-05-01

    Cannabinoids are effective at suppressing immune and inflammation functions in leukocytes in vitro, and in animal models of acute inflammation, such as the mouse hind paw, ear and air pouch models, as well as gastrointestinal, pulmonary, myocardial, vascular, periodontal, neural, hepatic, pancreatic and arthritic inflammation models. The non-psychoactive cannabinoid receptor CB2 is emerging as a critical target for cannabinoid regulation of inflammation, and thus CB2-selective agonists are undergoing intense investigation and research. This review discusses the evidence for cannabinoid regulation of inflammation across a range of models and highlights the most promising drug candidates.

  20. Exercise stress echocardiography for detection of pulmonary arterial hypertension in a patient with systemic sclerosis.

    PubMed

    Cotrim, Carlos; Cordeiro, Ana; Loureiro, Maria José; Santos, Maria José; Simões, Otília; Cordeiro, Pedro; da Silva, J Canas; Carrageta, Manuel

    2006-02-01

    The authors report the case of a 57-year-old patient, diagnosed with systemic sclerosis 16 years ago. She had been followed in the rheumatology outpatient clinic since 2003 and complained of marked fatigue and dyspnea on exertion. In addition to full medical evaluation, she also underwent standard Doppler echocardiography at rest, which was unremarkable, and exercise stress echocardiography. In the latter examination, she was diagnosed with pulmonary arterial hypertension, later confirmed during right heart catheterization. The authors discuss the potential value of this methodology for the study of patients with systemic sclerosis.

  1. Novel biomarkers for pulmonary arterial hypertension.

    PubMed

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  2. Multiscale intensity homogeneity transformation method and its application to computer-aided detection of pulmonary embolism in computed tomographic pulmonary angiography (CTPA)

    NASA Astrophysics Data System (ADS)

    Guo, Yanhui; Zhou, Chuan; Chan, Heang-Ping; Wei, Jun; Chughtai, Aamer; Sundaram, Baskaran; Hadjiiski, Lubomir M.; Patel, Smita; Kazerooni, Ella A.

    2013-04-01

    A 3D multiscale intensity homogeneity transformation (MIHT) method was developed to reduce false positives (FPs) in our previously developed CAD system for pulmonary embolism (PE) detection. In MIHT, the voxel intensity of a PE candidate region was transformed to an intensity homogeneity value (IHV) with respect to the local median intensity. The IHVs were calculated in multiscales (MIHVs) to measure the intensity homogeneity, taking into account vessels of different sizes and different degrees of occlusion. Seven new features including the entropy, gradient, and moments that characterized the intensity distributions of the candidate regions were derived from the MIHVs and combined with the previously designed features that described the shape and intensity of PE candidates for the training of a linear classifier to reduce the FPs. 59 CTPA PE cases were collected from our patient files (UM set) with IRB approval and 69 cases from the PIOPED II data set with access permission. 595 and 800 PEs were identified as reference standard by experienced thoracic radiologists in the UM and PIOPED set, respectively. FROC analysis was used for performance evaluation. Compared with our previous CAD system, at a test sensitivity of 80%, the new method reduced the FP rate from 18.9 to 14.1/scan for the PIOPED set when the classifier was trained with the UM set and from 22.6 to 16.0/scan vice versa. The improvement was statistically significant (p<0.05) by JAFROC analysis. This study demonstrated that the MIHT method is effective in reducing FPs and improving the performance of the CAD system.

  3. Electrical impedance tomography for assessing ventilation/perfusion mismatch for pulmonary embolism detection without interruptions in respiration.

    PubMed

    Nguyen, Doan Trang; Thiagalingam, Aravinda; Bhaskaran, Abhishek; Barry, Michael A; Pouliopoulos, Jim; Jin, Craig; McEwan, Alistair L

    2014-01-01

    Recent studies have shown high correlation between pulmonary perfusion mapping with impedance contrast enhanced Electrical Impedance Tomography (EIT) and standard perfusion imaging methods such as Computed Tomography (CT) and Single Photon Emission Computerized Tomography (SPECT). EIT has many advantages over standard imaging methods as it is highly portable and non-invasive. Contrast enhanced EIT uses hypertonic saline bolus instead of nephrotoxic contrast medium that are utilized by CT and nuclear Ventilation/Perfusion (V/Q) scans. However, current implementation of contrast enhanced EIT requires induction of an apnea period for perfusion measurement, rendering it disadvantageous compared with current gold standard imaging modalities. In the present paper, we propose the use of a wavelet denoising algorithm to separate perfusion signal from ventilation signal such that no interruption in patient's ventilation would be required. Furthermore, right lung to left lung perfusion ratio and ventilation ratio are proposed to assess the mismatch between ventilation and perfusion for detection of Pulmonary Embolism (PE). The proposed methodology was validated on an ovine model (n=3, 83.7±7.7 kg) with artificially induced PE in the right lung. The results showed a difference in right lung to left lung perfusion ratio between baseline and diseased states in all cases with all paired t-tests between baseline and PE yielding p <; 0.01, while the right lung to left lung ventilation ratio remained unchanged in two out of three experiments. Statistics were pooled from multiple repetitions of measurements per experiment.

  4. Evaluation of methods for detection and identification of Mycobacterium species in patients suspected of having pulmonary tuberculosis.

    PubMed

    Marchi, A M; Juttel, I D; Kawacubo, E M; Dalmarco, E M; Blatt, S L; Cordova, C M M

    2008-10-01

    Tuberculosis control is a priority for the Ministry of Health policies in Brazil. In the present work, the detection of Mycobacterium tuberculosis by the Polymerase Chain Reaction (PCR) was standardized, and the laboratory diagnosis of pulmonary tuberculosis was evaluated comparing baciloscopy, culture and PCR tests. The study was carried out with 117 sputum samples from different patients suspected of having pulmonary tuberculosis, for whom physicians had ordered a baciloscopy test. Baciloscopy was performed using the Ziehl-Neelsen method, and culture was performed by incubation of treated samples in Lowenstein-Jensen's medium at 37°C for eight weeks. For PCR, DNA was amplified with a specific pair of primers to the M. tuberculosis complex, with a resulting product of 123 bp from the insertion element IS6110. Three (2.56%) samples presented a positive baciloscopy result and a positive PCR result (100% agreement), and nine (7.69%) presented Mycobacterium sp. growth in culture (P= 0.1384). Among six samples with positive results in culture, one was identified by PCR-RFLP as belonging to the M. tuberculosis complex and one was identified as a non-tuberculosis mycobacteria. Sensitivity and specificity of PCR compared to culture were 33.3% and 100%, respectively. PMID:24031276

  5. Indium 111 platelet imaging for the detection of deep venous thrombosis and pulmonary embolism in patients without symptoms after surgery

    SciTech Connect

    Clarke-Pearson, D.L.; Coleman, R.E.; Siegel, R.; Synan, I.S.; Petry, N.

    1985-07-01

    Indium 111 platelet imaging for the detection of deep vein thrombosis and pulmonary emboli was performed in 171 patients after abdominal and pelvic surgery. Fifteen patients were found to have inadequate circulating blood pools of indium 111 platelets, making the study nondiagnostic. Of 156 patients with technically satisfactory images, 46 (29.5%) had images consistent with deep venous thrombosis and/or pulmonary emboli. The incidence, time of occurrence, and location of thromboemboli was similar to those of other reports of postoperative patients groups studied by iodine 125 fibrinogen uptake testing. Eighty patients had normal indium 111 platelets and 30 patients had diffusely distributed indium 111 platelets found in the operative field, suggesting accumulation in a postoperative hematoma. None of these results was confused with a diagnosis of deep venous thrombosis. When compared with another accurate diagnostic test in 23 patients, indium 111 platelet imaging was found to have a sensitivity of 100% and specificity of 90%. The technique of indium 111 platelet imaging is performed easily in patients after surgery with some limitations as to the use of donor platelets and the occasionally altered imaging of the operative site. This diagnostic technique enjoys the distinct advantage in that it allows surveillance of the legs, pelvis, abdomen, and chest by a single method, making it a near-ideal method of postoperative thromboembolism surveillance.

  6. Detection of pulmonary nodule growth with dose reduced chest tomosynthesis: a human observer study using simulated nodules

    NASA Astrophysics Data System (ADS)

    Söderman, Christina; Johnsson, Ã. se; Vikgren, Jenny; Rossi Norrlund, Rauni; Molnar, David; Mirzai, Maral; Svalkvist, Angelica; Mânsson, Lars Gunnar; Bâth, Magnus

    2016-03-01

    Chest tomosynthesis may be a suitable alternative to computed tomography for the clinical task of follow up of pulmonary nodules. The aim of the present study was to investigate the detection of pulmonary nodule growth suggestive of malignancy using chest tomosynthesis. Previous studies have indicated remained levels of detection of pulmonary nodules at dose levels corresponding to that of a conventional lateral radiograph, approximately 0.04 mSv, which motivated to perform the present study this dose level. Pairs of chest tomosynthesis image sets, where the image sets in each pair were acquired of the same patient at two separate occasions, were included in the study. Simulated nodules with original diameters of approximately 8 mm were inserted in the pairs of image sets, simulating situations where the nodule had remained stable in size or increased isotropically in size between the two different imaging occasions. Four different categories of nodule growth were included, corresponding to a volume increase of approximately 21 %, 68 %, 108 % and 250 %. All nodules were centered in the depth direction in the tomosynthesis images. All images were subjected to a simulated dose reduction, resulting in images corresponding to an effective dose of 0.04 mSv. Four observers were given the task of rating their confidence that the nodule was stable in size or not on a five-level rating scale. This was done both before any size measurements were made of the nodule as well as after measurements were performed. Using Receiver operating characteristic analysis, the rating data for the nodules that were stable in size was compared to the rating data for the nodules simulated to have increased in size. Statistically significant differences between the rating distributions for the stable nodules and all of the four nodule growth categories were found. For the three largest nodule growths, nearly perfect detection of nodule growth was seen. In conclusion, the present study

  7. Rapid detection of Candida species in bronchoalveolar lavage fluid from patients with pulmonary symptoms

    PubMed Central

    Zarrinfar, Hossein; Kaboli, Saeed; Dolatabadi, Somayeh; Mohammadi, Rasoul

    2016-01-01

    Candida species, especially C. albicans, are commensals on human mucosal surfaces, but are increasingly becoming one of the important invasive pathogens as seen by a rise in its prevalence in immunocompromised patients and in antibiotic consumption. Thus, an accurate identification of Candida species in patients with pulmonary symptoms can provide important information for effective treatment. A total of 75 clinical isolates of Candida species were obtained from the bronchoalveolar lavage fluid of both immunocompromised and immunocompetent patients with pulmonary symptoms. Candida cultures were identified based on nuclear ribosomal Internal Transcribed Spacer (ITS1-ITS2 rDNA) sequence analysis by polymerase chain reaction–restriction fragment length polymorphisms (PCR-RFLP). Molecular identification indicated that the isolates belonged predominantly to C. albicans (52%), followed by C. tropicalis (24%), C. glabrata (14.7%), C. krusei (5.3%), C. parapsilosis (1.3%), C. kefyr (1.3%) and C. guilliermondii (1.3%). Given the increasing complexity of disease profiles and their management regimens in diverse patients, rapid and accurate identification of Candida species can lead to timely and appropriate antifungal therapy. PMID:26887241

  8. 17(R)-resolvin D1 ameliorates bleomycin-induced pulmonary fibrosis in mice.

    PubMed

    Yatomi, Masakiyo; Hisada, Takeshi; Ishizuka, Tamotsu; Koga, Yasuhiko; Ono, Akihiro; Kamide, Yosuke; Seki, Kaori; Aoki-Saito, Haruka; Tsurumaki, Hiroaki; Sunaga, Noriaki; Kaira, Kyoichi; Dobashi, Kunio; Yamada, Masanobu; Okajima, Fumikazu

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. Inflammation plays an integral role in the development of pulmonary fibrosis. Unresolved inflammatory responses can lead to substantial tissue injury, chronic inflammation, and fibrosis. The resolvins are a family of endogenous ω-3 fatty acid derived-lipid mediators of inflammation resolution. Resolvin D1 (RvD1) displays potent anti-inflammatory, pro-resolving activity, without causing immunosuppression. Its epimer, 17(R)-resolvin D1 (17(R)-RvD1), exhibits equivalent functionality to RvD1. In addition, 17(R)-RvD1 is resistant to rapid inactivation by eicosanoid oxidoreductases. In the present study, we tested the hypothesis that 17(R)-RvD1 can provide a therapeutic benefit in IPF by reducing inflammation and pulmonary fibrosis, while leaving the normal immune response intact. Mice were exposed to bleomycin (BLM) via micro-osmotic pump to induce pulmonary fibrosis, and were then treated with 17(R)-RvD1 or vehicle by intraperitoneal injection. Administration of 17(R)-RvD1 from the start of BLM treatment attenuated neutrophil alveolar infiltration, lung collagen content, and Interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and type I collagen mRNA expression, along with subsequent reduction in histologically detectable fibrosis. The 17(R)-RvD1-induced infiltration of inflammatory cells was inhibited by an antagonist of lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). The administration of 17(R)-RvD1 at the later fibrotic stage also improved the lung failure. These results suggest that 17(R)-RvD1 attenuates pulmonary fibrosis by promoting the resolution of neutrophilic inflammation and also provides pulmonary restoration. These data highlight the therapeutic potential of 17(R)-RvD1 in the management of this intractable disease. PMID:26660549

  9. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    SciTech Connect

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki

    2012-05-15

    The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50 mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis. -- Highlights: ► BE treatment protects from inflammatory cells and mast-cells accumulation in lungs. ► BE altered the expressions of TNF

  10. LED fluorescence microscopy increases the detection of smear-positive pulmonary tuberculosis in medical colleges of India.

    PubMed

    Reza, L W; Satyanarayana, S; Pandey, A; Kumar, S; Devendrappa, N M; Anand, L; Singh, G; Kumar, A M V; Chadha, S S; Wilson, N; Sachdeva, K S; Nair, S A

    2013-09-21

    In July 2012, light-emitting diode fluorescence microscopy (LED-FM) replaced conventional light microscopy using Ziehl-Neelsen stain in the detection of sputum-positive pulmonary tuberculosis in 190 microscopy centres of medical colleges operating under India's Revised National Tuberculosis Control Programme. We compared the performance of LED-FM (July-December 2012) to that of conventional microscopy (July-December 2011) across 190 sites. Of 222 658 patients examined using conventional microscopy, 28 042 (12.6%) were smear-positive, while of 224 714 examined using LED-FM, 33 552 (14.9%) were smear-positive, an additional yield of 5251 cases after adjusting for the increase in patients examined. We recommend replacing conventional microscopy with LED-FM in high workload microscopy centres in India.

  11. Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling.

    PubMed

    Zhang, Wen-zhou; Jiang, Zheng-kui; He, Bao-xia; Liu, Xian-ben

    2015-08-01

    Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling.

  12. Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling.

    PubMed

    Zhang, Wen-zhou; Jiang, Zheng-kui; He, Bao-xia; Liu, Xian-ben

    2015-08-01

    Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling. PMID:25616905

  13. The Src family tyrosine kinases src and yes have differential effects on inflammation-induced apoptosis in human pulmonary microvascular endothelial cells.

    PubMed

    Nelin, Leif D; White, Hilary A; Jin, Yi; Trittmann, Jennifer K; Chen, Bernadette; Liu, Yusen

    2016-05-01

    Endothelial cells are essential for normal lung function: they sense and respond to circulating factors and hemodynamic alterations. In inflammatory lung diseases such as acute respiratory distress syndrome, endothelial cell apoptosis is an inciting event in pathogenesis and a prominent pathological feature. Endothelial cell apoptosis is mediated by circulating inflammatory factors, which bind to receptors on the cell surface, activating signal transduction pathways, leading to caspase-3-mediated apoptosis. We hypothesized that yes and src have differential effects on caspase-3 activation in human pulmonary microvascular endothelial cells (hPMVEC) due to differential downstream signaling effects. To test this hypothesis, hPMVEC were treated with siRNA against src (siRNAsrc), siRNA against yes (siRNAyes), or their respective scramble controls. After recovery, the hPMVEC were treated with cytomix (LPS, IL-1β, TNF-α, and IFN-γ). Treatment with cytomix induced activation of the extracellular signal-regulated kinase (ERK) pathway and caspase-3-mediated apoptosis. Treatment with siRNAsrc blunted cytomix-induced ERK activation and enhanced cleaved caspase-3 levels, while treatment with siRNAyes enhanced cytomix-induced ERK activation and attenuated levels of cleaved caspase-3. Inhibition of the ERK pathway using U0126 enhanced cytomix-induced caspase-3 activity. Treatment of hPMVEC with cytomix induced Akt activation, which was inhibited by siRNAsrc. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway using LY294002 prevented cytomix-induced ERK activation and augmented cytomix-induced caspase-3 cleavage. Together, our data demonstrate that, in hPMVEC, yes activation blunts the ERK cascade in response to cytomix, resulting in greater apoptosis, while cytomix-induced src activation induces the phosphatidylinositol 3-kinase pathway, which leads to activation of Akt and ERK and attenuation of apoptosis.

  14. Detection of Mycobacterium tuberculosis (MTB) in Fecal Specimens From Adults Diagnosed With Pulmonary Tuberculosis Using the Xpert MTB/Rifampicin Test

    PubMed Central

    Kokuto, Hiroyuki; Sasaki, Yuka; Yoshimatsu, Shoji; Mizuno, Kazue; Yi, Lina; Mitarai, Satoshi

    2015-01-01

    Background. The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) is a fully automated diagnostic test that allows for the detection of MTB including its RIF resistance. Although the test is used for the diagnosis of tuberculosis (TB) in sputum samples worldwide, studies using fecal specimens are scarce. We therefore evaluated the efficacy of the Xpert MTB/RIF test for detection of MTB in fecal specimens obtained from adult pulmonary TB patients, confirmed by culture and/or molecular diagnostic methods. Methods. We conducted a retrospective case-control study to provide proof-of-concept regarding the efficacy of the Xpert MTB/RIF test using fecal samples for diagnosing pulmonary TB via detection of MTB in adult patients (≥20 years) at the Fukujuji Hospital in Tokyo, Japan. Results. Fecal specimens were obtained from 56 active pulmonary TB patients (including 48 sputum smear-positive and 8 sputum smear-negative patients), 10 non-TB patients (including 4 Myocobacterium avium complex infections), and 27 healthy individuals who were exposed to active pulmonary TB patients. The sensitivity of the fecal Xpert MTB/RIF was 100% (81.7%–100%) for detection of MTB in specimens from sputum smear-positive (1+ to 3+) patients, 81.0% (58.1%–94.6%) in specimens from sputum smear scanty positive patients, and 50.0% (15.7%–84.3%) in specimens from sputum smear-negative patients. Meanwhile, each of the fecal specimens from the non-TB group was negative for MTB (specificity 100%; 95% confidence interval, 86.2–100). Conclusions. The fecal Xpert MTB/RIF test could detect MTB in a large proportion of smear-positive pulmonary TB patients, without frequent false-positive results at a TB referral hospital in Japan. PMID:26125035

  15. Clinical application of a novel computer-aided detection system based on three-dimensional CT images on pulmonary nodule

    PubMed Central

    Zeng, Jian-Ye; Ye, Hai-Hong; Yang, Shi-Xiong; Jin, Ren-Chao; Huang, Qi-Liang; Wei, Yong-Chu; Huang, Si-Guang; Wang, Bin-Qiang; Ye, Jia-Zhou; Qin, Jian-Ying

    2015-01-01

    The aim of this study was to investigate the clinical application effects of a novel computer-aided detection (CAD) system based on three-dimensional computed tomography (CT) images on pulmonary nodule. 98 cases with pulmonary nodule (PN) in our hospital from Jun, 2009 to Jun, 2013 were analysed in this study. All cases underwent PN detection both by the simple spiral CT scan and by the computer-aided system based on 3D CT images, respectively. Postoperative pathological results were considered as the “gold standard”, for both two checking methods, the diagnostic accuracies for determining benign and malignant PN were calculated. Under simple spiral CT scan method, 63 cases is malignant, including 50 true positive cases and 13 false positive cases from the “gold standard”; 35 cases is benign, 16 true negative case and 19 false negative cases, the Sensitivity 1 (Se1)=0.725, Specificity1 (Sp1)=0.448, Agreement rate1 (Kappa 1)=0.673, J1 (Youden’s index 1)=0.173, LR(+)1=1.616, LR(-)1=0.499. Kappa 1=0.673 between the 0.4 and 0.75, has a moderate consistency. Underwent computer-aided detection (CAD) based on 3D CT method, 67cases is malignant, including 62 true positive cases and 7 false positive cases; 31 cases is benign, 24 true negative case and 7 false negative cases, Sensitivity 2 (Se2)=0.899, Specificity2 (Sp2)=0.828, Agreement rate (Kappa 2)=0.877, J2 (Youden’s index 2)=0.727, LR(+)2=5.212, LR(-)2=0.123. Kappa 2=0.877 >0.75, has a good consistency. Computer-aided PN detecting system based on 3D CT images has better clinical application value, and can help doctor carry out early diagnosis of lung disease (such as cancer, etc.) through CT images. PMID:26629115

  16. Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2015-01-01

    Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs. PMID:26640533

  17. Contribution of exhaled nitric oxide measurement in airway inflammation assessment in asthma. A position paper from the French Speaking Respiratory Society.

    PubMed

    Dinh-Xuan, A T; Annesi-Maesano, I; Berger, P; Chambellan, A; Chanez, P; Chinet, T; Degano, B; Delclaux, C; Demange, V; Didier, A; Garcia, G; Magnan, A; Mahut, B; Roche, N

    2015-02-01

    Nitric oxide (NO) is both a gas and a ubiquitous inter- and intracellular messenger with numerous physiological functions. As its synthesis is markedly increased during inflammatory processes, NO can be used as a surrogate marker of acute and/or chronic inflammation. It is possible to quantify fractional concentration of NO in exhaled breath (FENO) to detect airway inflammation, and thus improve the diagnosis of asthma by better characterizing asthmatic patients with eosinophilic bronchial inflammation, and eventually improve the management of targeted asthmatic patients. FENO measurement can therefore be viewed as a new, reproducible and easy to perform pulmonary function test. Measuring FENO is the only non-invasive pulmonary function test allowing (1) detecting, (2) quantifying and (3) monitoring changes in inflammatory processes during the course of various respiratory disorders, including corticosensitive asthma.

  18. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low. PMID:27695680

  19. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low.

  20. Clinical experience with a computer-aided diagnosis system for automatic detection of pulmonary nodules at spiral CT of the chest

    NASA Astrophysics Data System (ADS)

    Wormanns, Dag; Fiebich, Martin; Saidi, Mustafa; Diederich, Stefan; Heindel, Walter

    2001-05-01

    The purpose of the study was to evaluate a computer aided diagnosis (CAD) workstation with automatic detection of pulmonary nodules at low-dose spiral CT in a clinical setting for early detection of lung cancer. Two radiologists in consensus reported 88 consecutive spiral CT examinations. All examinations were reviewed using a UNIX-based CAD workstation with a self-developed algorithm for automatic detection of pulmonary nodules. The algorithm was designed to detect nodules with at least 5 mm diameter. The results of automatic nodule detection were compared to the consensus reporting of two radiologists as gold standard. Additional CAD findings were regarded as nodules initially missed by the radiologists or as false positive results. A total of 153 nodules were detected with all modalities (diameter: 85 nodules <5mm, 63 nodules 5-9 mm, 5 nodules >= 10 mm). Reasons for failure of automatic nodule detection were assessed. Sensitivity of radiologists for nodules >=5 mm was 85%, sensitivity of CAD was 38%. For nodules >=5 mm without pleural contact sensitivity was 84% for radiologists at 45% for CAD. CAD detected 15 (10%) nodules not mentioned in the radiologist's report but representing real nodules, among them 10 (15%) nodules with a diameter $GREW5 mm. Reasons for nodules missed by CAD include: exclusion because of morphological features during region analysis (33%), nodule density below the detection threshold (26%), pleural contact (33%), segmentation errors (5%) and other reasons (2%). CAD improves detection of pulmonary nodules at spiral CT significantly and is a valuable second opinion in a clinical setting for lung cancer screening. Optimization of region analysis and an appropriate density threshold have a potential for further improvement of automatic nodule detection.

  1. Air pollution source apportionment before, during, and after the 2008 Beijing Olympics and association of sources to aldehydes and biomarkers of blood coagulation, pulmonary and systemic inflammation, and oxidative stress in healthy young adults

    NASA Astrophysics Data System (ADS)

    Altemose, Brent A.

    Based on principal component analysis (PCA) of air pollution data collected during the Summer Olympic Games held in Beijing, China during 2008, the five source types of air pollution identified -- natural soil/road dust, vehicle and industrial combustion, vegetative burning, oil combustion, and secondary formation, were all distinctly lower during the Olympics. This was particularly true for vehicle and industrial combustion and oil combustion, and during the main games period between the opening and closing ceremonies. The reduction in secondary formation was reflective of a reduction in nitrogen oxides, but this also contributed to increased ozone concentrations during the Olympic period. Among three toxic aldehydes measured in Beijing during the same time period, only acetaldehyde had a reduction in mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Accordingly, acetaldehyde was significantly correlated with primary emission sources including vegetative burning and oil combustion, and with several pollutants emitted mainly from primary sources. In contrast, formaldehyde and acrolein increased during the Olympic air pollution control period; accordingly both were significantly correlated with ozone and with the secondary formation source type. These findings indicate primary sources may dominate for acetaldehyde while secondary sources may dominate for formaldehyde and acrolein. Biomarkers for pulmonary inflammation (exhaled breath condensate (EBC) pH, exhaled nitric oxide, and EBC nitrite) and hemostasis and blood coagulation (vWF and sCD62p) were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The systemic inflammation biomarker 8-OHdG was most consistently associated with vehicle and industrial combustion. In contrast, the associations between the biomarkers and the aldehydes were generally not significant or in the hypothesized direction, although

  2. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-03-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with /sup 125/I or /sup 111/In was compared to that of (/sup 67/Ga)citrate and (/sup 99m/Tc)albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, (/sup 111/In)IgG showed greater accumulation at the lesion than (/sup 99m/Tc)HSA (p less than 0.01). Both (/sup 125/I)IgG and (/sup 111/In)IgG showed greater accumulation than (/sup 67/Ga)citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of (/sup 67/Ga)citrate or (/sup 99m/Tc)HSA (p less than 0.01). At all imaging times, (/sup 67/Ga)citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, (/sup 111/In)IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.

  3. iPads and LCDs show similar performance in the detection of pulmonary nodules

    NASA Astrophysics Data System (ADS)

    McEntee, Mark F.; Lowe, Joanna; Butler, Marie Louise; Pietrzyk, Mariusz; Evanoff, Michael G.; Ryan, John; Brennan, Patrick C.; Rainford, Louise A.

    2012-02-01

    In February 2011 the University of Chicago Medical School distributed iPads to its trainee doctors for use when reviewing clinical information and images on the ward or clinics. The use of tablet computing devices is becoming widespread in medicine with Apple™ heralding them as "revolutionary" in medicine. The question arises, just because it is technical achievable to use iPads for clinical evaluation of images, should we do so? The current work assesses the diagnostic efficacy of iPads when compared with LCD secondary display monitors for identifying lung nodules on chest x-rays. Eight examining radiologists of the American Board of Radiology were involved in the assessment, reading chest images on both the iPad and the an off-the-shelf LCD monitor. Thirty chest images were shown to each observer, of which 15 had one or more lung nodules. Radiologists were asked to locate the nodules and score how confident they were with their decision on a scale of 1-5. An ROC and JAFROC analysis was performed and modalities were compared using DBM MRMC. The results demonstrate no significant differences in performance between the iPad and the LCD for the ROC AUC (p<0.075) or JAFROC FOM (p<0.059) for random readers and random cases. Sample size estimation showed that this result is significant at a power of 0.8 and an effect size of 0.05 for ROC and 0.07 for JAFROC. This work demonstrates that for the task of identifying pulmonary nodules, the use of the iPad does not significantly change performance compared to an off-the-shelf LCD.

  4. Pulmonary atresia

    MedlinePlus

    ... disease - pulmonary atresia; Cyanotic heart disease - pulmonary atresia; Valve - disorder pulmonary atresia ... septum may also have a poorly developed tricuspid valve. They may also have an underdeveloped right ventricle ...

  5. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  6. Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis – limitations for the underlying COPD detection

    PubMed Central

    Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan

    2016-01-01

    Background During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. Purpose The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Patients and methods Prospective, nest case–control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. Results From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%–20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%–20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%–0.700% for 95% CI; P=0.047), leukocyte count (0.020%–1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%–0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01–1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02–1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. Conclusion AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel

  7. Mycobacterium genotypes in pulmonary tuberculosis infections and their detection by trained African giant pouched rats.

    PubMed

    Mgode, Georgies F; Cohen-Bacrie, Stéphan; Bedotto, Marielle; Weetjens, Bart J; Cox, Christophe; Jubitana, Maureen; Kuipers, Dian; Machang'u, Robert S; Kazwala, Rudovick; Mfinanga, Sayoki G; Kaufmann, Stefan H E; Drancourt, Michel

    2015-02-01

    Tuberculosis (TB) diagnosis in low-income countries is mainly done by microscopy. Hence, little is known about the diversity of Mycobacterium spp. in TB infections. Different genotypes or lineages of Mycobacterium tuberculosis vary in virulence and induce different inflammatory and immune responses. Trained Cricetomys rats show a potential for rapid diagnosis of TB. They detect over 28 % of smear-negative, culture-positive TB. However, it is unknown whether these rats can equally detect sputa from patients infected with different genotypes of M. tuberculosis. A 4-month prospective study on diversity of Mycobacterium spp. was conducted in Dar es Salaam, Tanzania. 252 sputa from 161 subjects were cultured on Lowenstein-Jensen medium and thereafter tested by rats. Mycobacterial isolates were subjected to molecular identification and multispacer sequence typing (MST) to determine species and genotypes. A total of 34 Mycobacterium spp. isolates consisting of 32 M. tuberculosis, 1 M. avium subsp. hominissuis and 1 M. intracellulare were obtained. MST analyses of 26 M. tuberculosis isolates yielded 10 distinct MST genotypes, including 3 new genotypes with two clusters of related patterns not grouped by geographic areas. Genotype MST-67, shared by one-third of M. tuberculosis isolates, was associated with the Mwananyamala clinic. This study shows that diverse M. tuberculosis genotypes (n = 10) occur in Dar es Salaam and trained rats detect 80 % of the genotypes. Sputa with two M. tuberculosis genotypes (20 %), M. avium hominissuis and M. intracellulare were not detected. Therefore, rats detect sputa with different M. tuberculosis genotypes and can be used to detect TB in resource-poor countries.

  8. Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

    PubMed Central

    Ju, Hyunsu; Wheat, L. Joseph; Baden, Lindsey; Stafford, Susan; Wu, Zheng; Issa, Nicolas; Caliendo, Angela M.; Denning, David W.; Soman, Kizhake; Clancy, Cornelius J.; Nguyen, M. Hong; Sugrue, Michele W.; Alexander, Barbara D.; Wingard, John R.

    2015-01-01

    Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment

  9. Evaluation of Giant African Pouched Rats for Detection of Pulmonary Tuberculosis in Patients from a High-Endemic Setting

    PubMed Central

    Reither, Klaus; Jugheli, Levan; Glass, Tracy R.; Sasamalo, Mohamed; Mhimbira, Francis A.; Weetjens, Bart J.; Cox, Christophe; Edwards, Timothy L.; Mulder, Christiaan; Beyene, Negussie W.; Mahoney, Amanda

    2015-01-01

    Background This study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting. Methods The TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania. Results Of 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66–0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0–66.3), specificity of 80.5% (95% CI 72.5–86.9), positive and negative predictive value of 71.3% (95% CI 60.6–80.5) and 68.7% (95% CI 60.6–76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status. Conclusion Giant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health

  10. [COPD: bronchial and systemic inflammation].

    PubMed

    Macario, Ciro Casanova; de Torres Tajes, Juan Pablo; Córdoba Lanus, Elizabeth

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is considered to be an inflammatory disease of the airways, in which there can be low-grade systemic inflammation. The etiology of this disease is multifactorial but is mainly due to an anomalous and amplified inflammatory response to tobacco smoke. This inflammatory response involves innate and acquired immunity. The latter is characterized by a Th1-type (CD8) response and its presence seems to be associated with progression to advanced stages of the disease. Currently, it is unknown whether bronchial and systemic inflammation are related or whether they act as independent compartments. Most of the available data on COPD are drawn from cross-sectional studies and consequently a causal relation between the possible inflammatory mediators and the genetic factors involved in pulmonary and extrapulmonary involvement in this disease cannot be established. Further studies are required that would allow the inflammatory response to be correlated with the distinct COPD phenotypes.

  11. A New Method of Detecting Pulmonary Nodules with PET/CT Based on an Improved Watershed Algorithm

    PubMed Central

    Zhao, Juanjuan; Ji, Guohua; Qiang, Yan; Han, Xiaohong; Pei, Bo; Shi, Zhenghao

    2015-01-01

    Background Integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is widely performed for staging solitary pulmonary nodules (SPNs). However, the diagnostic efficacy of SPNs based on PET/CT is not optimal. Here, we propose a method of detection based on PET/CT that can differentiate malignant and benign SPNs with few false-positives. Method Our proposed method combines the features of positron-emission tomography (PET) and computed tomography (CT). A dynamic threshold segmentation method was used to identify lung parenchyma in CT images and suspicious areas in PET images. Then, an improved watershed method was used to mark suspicious areas on the CT image. Next, the support vector machine (SVM) method was used to classify SPNs based on textural features of CT images and metabolic features of PET images to validate the proposed method. Results Our proposed method was more efficient than traditional methods and methods based on the CT or PET features alone (sensitivity 95.6%; average of 2.9 false positives per scan). PMID:25853496

  12. A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

    PubMed

    Weber, Benjamin; Hochhaus, Guenther

    2015-07-01

    The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

  13. Pulmonary-impedance power spectral analysis: A facile means of detecting radiation-induced gastrointestinal distress and performance decrement in man

    NASA Technical Reports Server (NTRS)

    Rick, R. C.; Lushbaugh, C. C.; Mcdow, E.; Frome, E.

    1972-01-01

    Changes in respiratory variance revealed by power spectral analysis of the pulmonary impedance pneumogram can be used to detect and measure stresses directly or indirectly affecting human respiratory function. When gastrointestinal distress occurred during a series of 5 total-body exposures of 30 R at a rate of 1.5 R/min, it was accompanied by typical shifts in pulmonary impedance power spectra. These changes did not occur after protracted exposure of 250 R (30 R daily) at 1.5 R/hr that failed to cause radiation sickness. This system for quantitating respiratory effort can also be used to detect alterations in one's ability to perform under controlled exercise conditions.

  14. Magnetic bead fluorescent immunoassay for the rapid detection of the novel inflammation marker YKL40 at the point-of-care.

    PubMed

    Schmalenberg, Michael; Beaudoin, Christopher; Bulst, Ludwig; Steubl, Dominik; Luppa, Peter B

    2015-12-01

    Pneumonia is one of the leading causes of death worldwide.We present a magnetic bead fluorescent sandwich immunoassay that allows rapid serum measurement of the novel inflammation marker YKL40 (CHI3L1) at the point of care (POC) that could aid pneumonia diagnosis. The magnetic beads serve as the solid phase for separation of YKL40 from serum. The readout is performed using a small and robust fluorescence reader,which detects the turnover of a fluorescent substrate. The assay procedure, from sample addition to data retrieval, consists of three steps and is performed in less than 20 min. The presented assay has a linear range from 3 to 111 ng/mL, with a limit of detection of 2.9 ng/mL. The average recoveries were found between 101 and 111%. The developed method was applied in sera from healthy subjects (n= 14; c(YKL40)= 50 ± 49 ng/mL) and from pneumonia patients (n = 14; c(YKL40) = 333.6 ± 225 ng/mL). The elevated YKL40 concentrations in pneumonia-diseased patients are in good agreement with previously published data. The POC-ready device provides a simple immunoassay that could help to optimize pneumonia inflammation diagnostics in low-resource settings. PMID:26434383

  15. Comparison of sensitivity and reading time for the use of computer-aided detection (CAD) of pulmonary nodules at MDCT as concurrent or second reader.

    PubMed

    Beyer, F; Zierott, L; Fallenberg, E M; Juergens, K U; Stoeckel, J; Heindel, W; Wormanns, D

    2007-11-01

    The purpose of this study was to compare sensitivity for detection of pulmonary nodules in MDCT scans and reading time of radiologists when using CAD as the second reader (SR) respectively concurrent reader (CR). Four radiologists analyzed 50 chest MDCT scans chosen from clinical routine two times and marked all detected pulmonary nodules: first with CAD as CR (display of CAD results immediately in the reading session) and later (median 14 weeks) with CAD as SR (display of CAD markers after completion of first reading without CAD). A Siemens LungCAD prototype was used. Sensitivities for detection of nodules and reading times were recorded. Sensitivity of reading with CAD as SR was significantly higher than reading without CAD (p < 0.001) and CAD as CR (p < 0.001). For nodule size of 1.75 mm or above no significant sensitivity difference between CAD as CR and reading without CAD was observed; e.g., for nodules above 4 mm sensitivity was 68% without CAD, 68% with CAD as CR (p = 0.45) and 75% with CAD as SR (p < 0.001). Reading time was significantly shorter for CR (274 s) compared to reading without CAD (294 s; p = 0.04) and SR (337 s; p < 0.001). In our study CAD could either speed up reading of chest CT cases for pulmonary nodules without relevant loss of sensitivity when used as CR, or it increased sensitivity at the cost of longer reading times when used as SR.

  16. Robustness evaluation of a computer-aided detection system for pulmonary embolism (PE) in CTPA using independent test set from multiple institutions

    NASA Astrophysics Data System (ADS)

    Zhou, Chuan; Chan, Heang-Ping; Chughtai, Aamer; Kuriakose, Jean W.; Kazerooni, Ella A.; Hadjiiski, Lubomir M.; Wei, Jun; Patel, Smita

    2015-03-01

    We have developed a computer-aided detection (CAD) system for assisting radiologists in detection of pulmonary embolism (PE) in computed tomographic pulmonary angiographic (CTPA) images. The CAD system includes stages of pulmonary vessel segmentation, prescreening of PE candidates and false positive (FP) reduction to identify suspicious PEs. The system was trained with 59 CTPA PE cases collected retrospectively from our patient files (UM set) with IRB approval. Five feature groups containing 139 features that characterized the intensity texture, gradient, intensity homogeneity, shape, and topology of PE candidates were initially extracted. Stepwise feature selection guided by simplex optimization was used to select effective features for FP reduction. A linear discriminant analysis (LDA) classifier was formulated to differentiate true PEs from FPs. The purpose of this study is to evaluate the performance of our CAD system using an independent test set of CTPA cases. The test set consists of 50 PE cases from the PIOPED II data set collected by multiple institutions with access permission. A total of 537 PEs were manually marked by experienced thoracic radiologists as reference standard for the test set. The detection performance was evaluated by freeresponse receiver operating characteristic (FROC) analysis. The FP classifier obtained a test Az value of 0.847 and the FROC analysis indicated that the CAD system achieved an overall sensitivity of 80% at 8.6 FPs/case for the PIOPED test set.

  17. Studies on experimental pulmonary granulomas. I. Detection of lymphokines in granulomatous lesions.

    PubMed Central

    Masih, N.; Majeska, J.; Yoshida, T.

    1979-01-01

    Granulomatous reactions were immunologically induced in guinea pigs by several procedures, including intravenous injections of Bacille Calmette Gúerin (BCG) into animals immunized with complete Freund's Adjuvant and an intravenous injection of agarose beads linked to a specific antigen (dinitrophenylated bovine serum albumin) into immune animals. The tissue extracts obtained from lungs at various stages of granuloma formation were examined for macrophage migration inhibition (MIF) activity. The activity was found in a high incidence during the early stages of the granulomatous response. In contrast, MIF activity could be detected only rarely in granulomatous spleens and not in granulomatous livers. Chemotactic factor activity and mitogenic factor activity were only sporadically detectable. The MIF activity was associated with fractions showing chemical heterogeneity. One fraction was physicochemically indistinguishable from conventional lymphocyte-derived MIF; the other was a substance of large molecular weight. These results demonstrate the presence of biologically active mediators in immune granulomas, which may be related to early events involved in the induction or enhancement of such reactions. Images Figure 2 Figure 3 Figure 1 Figure 4 PMID:377991

  18. Pulmonary Hypertension Secondary to COPD.

    PubMed

    Shujaat, Adil; Bajwa, Abubakr A; Cury, James D

    2012-01-01

    The development of pulmonary hypertension in COPD adversely affects survival and exercise capacity and is associated with an increased risk of severe acute exacerbations. Unfortunately not all patients with COPD who meet criteria for long term oxygen therapy benefit from it. Even in those who benefit from long term oxygen therapy, such therapy may reverse the elevated pulmonary artery pressure but cannot normalize it. Moreover, the recent discovery of the key roles of endothelial dysfunction and inflammation in the pathogenesis of PH provides the rationale for considering specific pulmonary vasodilators that also possess antiproliferative properties and statins.

  19. [First detection of psittacid herpesvirus 2 in Congo African grey parrots (Psittacus erithacus erithacus) associated with pharyngeal papillomas and cloacal inflammation in Germany].

    PubMed

    Legler, Marko; Kothe, Ruth; Wohlsein, Peter; Hewicker-Trautwein, Marion; Kummerfeld, Norbert; Rautenschlein, Silke

    2014-01-01

    Congo African Grey Parrots (GP; Psittacus erithacus erithacus) from four different avicultures, presented in the Clinic for Exotic Pets, Reptiles and Birds, University of Veterinary Medicine Hannover, Foundation, showed choanal papillomas or hyperemia of the cloacal mucosa. Histologically, the mucosal choanal proliferations were diagnosed as exophytic papillomas and a mild hyperplasia of the cloacal mucosa with lympho-histiocytic inflammation with no visible inclusion bodies was found. Herpesvirus genome was detected by nested PCR in pooled choanal and cloacal swabs from clinically diseased parrots and healthy contact animals. Sequencing of parts of the herpesvirus DNA-polymerase gene indicated 98-100% homology of the detected herpesviruses with the Psittacid Herpesvirus 2 (PsHV-2). In one aviculture with cloacal inflammation papillomavirus-DNA was concurrently found to a PsHV-2 infection. In addition to the four avicultures with clinical symptoms 25 more flocks of grey parrots, in total 57 Congo-GP and 13 Timneh-GP, were examined for a herpesvirus infection. A total of six out of 29 studied parrot avicultures were tested positive for PsHV-2. The detection of this virus also in flocks of GP, which were bred in Europe, shows the establishment of this infection in the GP population in captivity. As indicated in the literature as well as in our study PsHV-2 could be only detected in Congo-GP, independently if they were kept either alone or in mixed avicultures with amazon and macaw species. These findings suggest that PsHV-2 is adapted to this Psittacus species.

  20. Automatic pulmonary fissure detection and lobe segmentation in CT chest images

    PubMed Central

    2014-01-01

    Background Multi-detector Computed Tomography has become an invaluable tool for the diagnosis of chronic respiratory diseases. Based on CT images, the automatic algorithm to detect the fissures and divide the lung into five lobes will help regionally quantify, amongst others, the lung density, texture, airway and, blood vessel structures, ventilation and perfusion. Methods Sagittal adaptive fissure scanning based on the sparseness of the vessels and bronchi is employed to localize the potential fissure region. Following a Hessian matrix based line enhancement filter in the coronal slice, the shortest path is determined by means of Uniform Cost Search. Implicit surface fitting based on Radial Basis Functions is used to extract the fissure surface for lobe segmentation. By three implicit fissure surface functions, the lung is divided into five lobes. The proposed algorithm is tested by 14 datasets. The accuracy is evaluated by the mean (±S.D.), root mean square, and the maximum of the shortest Euclidian distance from the manually-defined fissure surface to that extracted by the algorithm. Results Averaged over all datasets, the mean (±S.D.), root mean square, and the maximum of the shortest Euclidian distance are 2.05 ± 1.80, 2.46 and 7.34 mm for the right oblique fissure. The measures are 2.77 ± 2.12, 3.13 and 7.75 mm for the right horizontal fissure, 2.31 ± 1.76, 3.25 and 6.83 mm for the left oblique fissure. The fissure detection works for the data with a small lung nodule nearby the fissure and a small lung subpleural nodule. The volume and emphysema index of each lobe can be calculated. The algorithm is very fast, e.g., to finish the fissure detection and fissure extension for the dataset with 320 slices only takes around 50 seconds. Conclusions The sagittal adaptive fissure scanning can localize the potential fissure regions quickly. After the potential region is enhanced by a Hessian based line enhancement filter, Uniform Cost Search can

  1. Genotyping of Endocervical Chlamydia trachomatis Strains and Detection of Serological Markers of Acute and Chronic Inflammation in Their Host

    PubMed Central

    Taheri Beni, Behrouz; Jenab, Anahita; Roghanian, Rasoul; Motamedi, Hossein; Golbang, Naser; Golbang, Pouran; Yazdi, Javad Zaeimi

    2012-01-01

    Background Chlamydia trachomatis (C. trachomatis) is the most prevalent cause of bacterial sexually transmitted infections (STI) recognized throughout the world. The aim of this study is to determine different genotypes of genital C. trachomatis and the association between the serological markers of inflammation and genotypes of C. trachomatis in sexually active women (n=80) attending Shahid Beheshti Hospital in Isfahan, Iran. Materials and Methods In this descriptive study, endocervical swabs were collected from 80 women. There were 17 endocervical samples that showed positivity for C. trachomatis by plasmid polymerase chain reaction (PCR) using KL1 and KL2 primers. The omp1 gene was directly amplified in 17 plasmid PCR positive samples and was used to differentiate the clinical genotypes by omp1 gene PCR-restriction fragment length polymorphism (PCR-RFLP). The levels of IgG and IgA specific to C. trachmatis and C-reactive protein (CRP) were evaluated. Results Based on restriction-digestion patterns, four genotypes were identified. Genotypes E (35.3%) and F (35.3%) were the most prevalent, followed by D/Da (23.5%) and K (5.9%). There was no significant association between genotypes and the presence of IgG and CRP. Patients infected with genotype E showed a serological marker of chronic inflammation, i.e. IgA seropositivity, significantly more than patients infected with other genotypes (p=0.042). Conclusion Nested PCR could increase the sensitivity of omp1 amplification. Based on the presence of IgA, chronic C. trachomatis infections were observed more frequently among genotype E-infected patients in our population. PMID:25493166

  2. Can calcified pulmonary metastases detected by (18)F-FDG PET/CT suggest the primary tumor?

    PubMed

    Hong, Chae Moon; Ahn, Byeong Cheol

    2016-01-01

    Many calcified nodules are encountered on the (18)F-FDG PET/CT scan and even though most of them are benign, the possibility of calcified pulmonary metastases (CPM) should be considered. The CT portion can often differentiate benign diseases due to their morphology. Measuring SUVmax is very important. Understanding the mechanism of calcification in malignant metastatic pulmonary lesions may be useful to suggest their origin. PMID:27035906

  3. 99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation

    PubMed Central

    Liu, Guobing; Hu, Yan; Xiao, Jie; Li, Xiao; Li, Yanli; Tan, Hui; Zhao, Yanzhao; Cheng, Dengfeng; Shi, Hongcheng

    2016-01-01

    It remains challenging to predict the risk of rupture for a specific atherosclerotic plaque timely, a thrombotic trigger tightly linked to inflammation. CD11b, is a biomarker abundant on inflammatory cells, not restricted to monocytes/macrophages. In this study, we fabricated a probe named as 99mTc-MAG3-anti-CD11b for detecting inflamed atherosclerotic plaques with single photon emission computed tomography/computed tomography (SPECT/CT). The ApoE-knockout (ApoE−/−) mice were selected to establish animal models, with C57BL/6J mice used for control. A higher CD11b+-cell recruitment with higher CD11b expression and more serious whole-body inflammatory status were identified in ApoE−/− mice. The probe showed high in vitro affinity and specificity to the Raw-264.7 macrophages, as well as inflammatory cells infiltrated in atherosclerotic plaques, either in ex vivo fluorescent imaging or in in vivo micro-SPECT/CT imaging, which were confirmed by ex vivo planar gamma imaging, Oil-Red-O staining and CD11b-immunohistochemistry staining. A significant positive relationship was identified between the radioactivity intensity on SPECT/CT images and the CD11b expression in plaques. In summary, this study demonstrates the feasibility of anti-CD11b antibody mediated noninvasive SPECT/CT imaging of inflammatory leukocytes in murine atherosclerotic plaques. This imaging strategy can identify inflammation-rich plaques at risk for rupture and evaluate the effectiveness of inflammation-targeted therapies in atheroma. PMID:26877097

  4. Implementation of combined SVM-algorithm and computer-aided perception feedback for pulmonary nodule detection

    NASA Astrophysics Data System (ADS)

    Pietrzyk, Mariusz W.; Rannou, Didier; Brennan, Patrick C.

    2012-02-01

    This pilot study examines the effect of a novel decision support system in medical image interpretation. This system is based on combining image spatial frequency properties and eye-tracking data in order to recognize over and under calling errors. Thus, before it can be implemented as a detection aided schema, training is required during which SVMbased algorithm learns to recognize FP from all reported outcomes, and, FN from all unreported prolonged dwelled regions. Eight radiologists inspected 50 PA chest radiographs with the specific task of identifying lung nodules. Twentyfive cases contained CT proven subtle malignant lesions (5-20mm), but prevalence was not known by the subjects, who took part in two sequential reading sessions, the second, without and with support system feedback. MCMR ROC DBM and JAFROC analyses were conducted and demonstrated significantly higher scores following feedback with p values of 0.04, and 0.03 respectively, highlighting significant improvements in radiology performance once feedback was used. This positive effect on radiologists' performance might have important implications for future CAD-system development.

  5. Alpha4-integrin (CD49d) expression on bovine peripheral blood neutrophils is related to inflammation of the respiratory system.

    PubMed

    Soethout, Ernst C; Rutten, Victor P M G; Houwers, Dirk J; de Groot, Hugo S J; Antonis, Adriaan F G; Niewold, Theo A; Müller, Kerstin E

    2003-05-30

    Neutrophil emigration from the pulmonary vasculature, is mediated by cellular adhesion molecules (CAM) expressed on the outer membranes of endothelial cells and neutrophils. Although beta(2)-integrin-dependent migration is a major mechanism of neutrophil migration, which was demonstrated by extensive invasion of neutrophils in pulmonary tissue of calves suffering from a genetic deficit in expression of beta(2)-integrins, termed bovine leukocyte adhesion deficiency (LAD), the role of alternative CAM is still unclear. We investigated whether an alternate CAM for beta(2)-integrin function, i.e. the alpha(4)-integrin, was expressed on peripheral blood neutrophils of calves. As we detected basal but significant expression, the effect of naturally acquired pulmonary infection on the expression of either integrin was determined, as an indication for its function in the migration process. In our experiments, basal expression of alpha(4)-integrins on peripheral blood neutrophils from clinically healthy calves was detected. On neutrophils of calves, experiencing field outbreaks of enzootic bronchopneumonia, higher expression of the alpha(4)-integrin was detected, which returned to normal after successful treatment of the disease. In addition, its level of expression was linearly related to plasma acute phase protein (haptoglobin) concentrations, which is a sensitive parameter for severity of respiratory inflammation. Increased expression of the alpha(4)-integrin on peripheral blood neutrophils during pulmonary inflammation indicates a role for this CAM in neutrophil migration in the lung. PMID:12753772

  6. Detection of Mycobacterium tuberculosis Complex in Formalin-Fixed, Paraffin-Embedded Tissue Specimens with Necrotizing Granulomatous Inflammation by Strand Displacement Amplification

    PubMed Central

    Johansen, Isik Somuncu; Thomsen, Vibeke Østergaard; Forsgren, Arne; Hansen, Birgit Fischer; Lundgren, Bettina

    2004-01-01

    Rapid, reliable diagnosis of tuberculosis is essential to initiate correct treatment, avoid severe complications, and prevent transmission. Conventional microbiological methods may not be an option if samples are formalin-fixed and paraffin-embedded (FFPE) for histopathological examination. With the demonstration of necrotizing granulomatous inflammation, tuberculosis becomes an important differential diagnosis, although it was not initially suspected. Following paraffin extraction, BDProbeTec ET strand displacement amplification for detection of Mycobacterium tuberculosis complex (MTC) was applied to 47 prospectively and 19 retrospectively collected FFPE samples from various sources with granulomatous inflammation and results were compared to tuberculosis notification. Of the prospective samples, 20 were from patients who were notified as having tuberculosis and the assay was positive in 18 (90%). Specificity was 100%. For 27 of the patients with prospectively collected FFPE specimens, culture was performed on a specimen collected at a later date from the same location. Culture revealed MTC in 14 and nontuberculous mycobacteria in four. BDProbeTec ET was positive in 13 (92.8%) of the patients with positive MTC culture and negative in the remaining. The sensitivity and specificity in 19 archival samples was 40% and 100%, respectively, compared to notification data. The assay provided rapid, correct diagnosis on different sources of FFPE samples collected prospectively and therefore offers an important supplementary method for patients where tuberculosis was not initially suspected. PMID:15269300

  7. Is diagnostic accuracy for detecting pulmonary nodules in chest CT reduced after a long day of reading?

    NASA Astrophysics Data System (ADS)

    Krupinski, Elizabeth A.; Berbaum, Kevin S.; Caldwell, Robert; Schartz, Kevin M.

    2012-02-01

    Radiologists are reading more cases with more images, especially in CT and MRI and thus working longer hours than ever before. There have been concerns raised regarding fatigue and whether it impacts diagnostic accuracy. This study measured the impact of reader visual fatigue by assessing symptoms, visual strain via dark focus of accommodation, and diagnostic accuracy. Twenty radiologists and 20 radiology residents were given two diagnostic performance tests searching CT chest sequences for a solitary pulmonary nodule before (rested) and after (tired) a day of clinical reading. 10 cases used free search and navigation, and the other 100 cases used preset scrolling speed and duration. Subjects filled out the Swedish Occupational Fatigue Inventory (SOFI) and the oculomotor strain subscale of the Simulator Sickness Questionnaire (SSQ) before each session. Accuracy was measured using ROC techniques. Using Swensson's technique yields an ROC area = 0.86 rested vs. 0.83 tired, p (one-tailed) = 0.09. Using Swensson's LROC technique yields an area = 0.73 rested vs. 0.66 tired, p (one-tailed) = 0.09. Using Swensson's Loc Accuracy technique yields an area = 0.77 rested vs. 0.72 tired, p (one-tailed) = 0.13). Subjective measures of fatigue increased significantly from early to late reading. To date, the results support our findings with static images and detection of bone fractures. Radiologists at the end of a long work day experience greater levels of measurable visual fatigue or strain, contributing to a decrease in diagnostic accuracy. The decrease in accuracy was not as great however as with static images.

  8. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker

    PubMed Central

    Li, Yong; Liu, Jun; Liu, Zong-zhi; Duan, Da-peng

    2016-01-01

    Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression. PMID:27380953

  9. CT-Guided Biopsy in Suspected Spondylodiscitis – The Association of Paravertebral Inflammation with Microbial Pathogen Detection

    PubMed Central

    Spira, Daniel; Germann, Thomas; Lehner, Burkhard; Hemmer, Stefan; Akbar, Michael; Jesser, Jessica; Weber, Marc-André; Rehnitz, Christoph

    2016-01-01

    Objectives To search for imaging characteristics distinguishing patients with successful from those with futile microbiological pathogen detection by CT-guided biopsy in suspected spondylodiscitis. Methods 34 consecutive patients with suspected spondylodiscitis underwent CT-guided biopsy for pathogen detection. MR-images were assessed for inflammatory infiltration of disks, adjacent vertebrae, epidural and paravertebral space. CT-images were reviewed for arrosion of adjacent end plates and reduced disk height. Biopsy samples were sent for microbiological examination in 34/34 patients, and for additional histological analysis in 28/34 patients. Results Paravertebral infiltration was present in all 10/10 patients with positive microbiology and occurred in only 12/24 patients with negative microbiology, resulting in a sensitivity of 100% and a specificity of 50% for pathogen detection. Despite its limited sensitivities, epidural infiltration and paravertebral abscesses showed considerably higher specificities of 83.3% and 90.9%, respectively. Paravertebral infiltration was more extensive in patients with positive as compared to negative microbiology (p = 0.002). Even though sensitivities for pathogen detection were also high in case of vertebral and disk infiltration, or end plate arrosion, specificities remained below 10%. Conclusions Inflammatory infiltration of the paravertebral space indicated successful pathogen detection by CT-guided biopsy. Specificity was increased by the additional occurrence of epidural infiltration or paravertebral abscesses. PMID:26727377

  10. Detection of Acute Pulmonary Embolism by Bedside Ultrasound in a Patient Presenting in PEA Arrest: A Case Report

    PubMed Central

    Chung-Esaki, Hangyul; Knight, Roneesha; Noble, Jeanne; Wang, Ralph; Coralic, Zlatan

    2012-01-01

    Optimal management of the critically ill patient in shock requires rapid identification of its etiology. We describe a successful application of an emergency physician performed bedside ultrasound in a patient presenting with shock and subsequent cardiac arrest. Pulmonary embolus was diagnosed using bedside echocardiogram and confirmed with CTA of the thorax. Further validation and real-time implementation of this low-cost modality could facilitate the decision to implement thrombolytics for unstable patients with massive pulmonary embolism who cannot undergo formal radiographic evaluation. PMID:23326723

  11. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  12. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  13. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  14. Curved planar reformation and optimal path tracing (CROP) method for false positive reduction in computer-aided detection of pulmonary embolism in CTPA

    NASA Astrophysics Data System (ADS)

    Zhou, Chuan; Chan, Heang-Ping; Guo, Yanhui; Wei, Jun; Chughtai, Aamer; Hadjiiski, Lubomir M.; Sundaram, Baskaran; Patel, Smita; Kuriakose, Jean W.; Kazerooni, Ella A.

    2013-03-01

    The curved planar reformation (CPR) method re-samples the vascular structures along the vessel centerline to generate longitudinal cross-section views. The CPR technique has been commonly used in coronary CTA workstation to facilitate radiologists' visual assessment of coronary diseases, but has not yet been used for pulmonary vessel analysis in CTPA due to the complicated tree structures and the vast network of pulmonary vasculature. In this study, a new curved planar reformation and optimal path tracing (CROP) method was developed to facilitate feature extraction and false positive (FP) reduction and improve our PE detection system. PE candidates are first identified in the segmented pulmonary vessels at prescreening. Based on Dijkstra's algorithm, the optimal path (OP) is traced from the pulmonary trunk bifurcation point to each PE candidate. The traced vessel is then straightened and a reformatted volume is generated using CPR. Eleven new features that characterize the intensity, gradient, and topology are extracted from the PE candidate in the CPR volume and combined with the previously developed 9 features to form a new feature space for FP classification. With IRB approval, CTPA of 59 PE cases were retrospectively collected from our patient files (UM set) and 69 PE cases from the PIOPED II data set with access permission. 595 and 800 PEs were manually marked by experienced radiologists as reference standard for the UM and PIOPED set, respectively. At a test sensitivity of 80%, the average FP rate was improved from 18.9 to 11.9 FPs/case with the new method for the PIOPED set when the UM set was used for training. The FP rate was improved from 22.6 to 14.2 FPs/case for the UM set when the PIOPED set was used for training. The improvement in the free response receiver operating characteristic (FROC) curves was statistically significant (p<0.05) by JAFROC analysis, indicating that the new features extracted from the CROP method are useful for FP reduction.

  15. States of low pulmonary blood flow can be detected non-invasively at the bedside measuring alveolar dead space.

    PubMed

    Tusman, Gerardo; Suarez-Sipmann, Fernando; Paez, Gabriel; Alvarez, Jorge; Bohm, Stephan H

    2012-06-01

    We tested whether the ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) can detect states of low pulmonary blood flow (PBF) in a non-invasive way. Fifteen patients undergoing cardiovascular surgeries with cardiopulmonary bypass (CPB) were studied. CPB is a technique that excludes the lungs from the general circulation. The weaning of CPB is a model that manipulates PBF in vivo because each time blood flow through the CPB decreases, expected PBF (ePBF) increases. Patients were liberated from CPB in steps of 20 % every 2' starting from 100 % CPB (very low ePBF) to 0 % CPB (100 % ePBF). During constant ventilation, volumetric capnograms were recorded and Bohr's dead space ratio (VD(Bohr)/VT), VD(alv)/VT(alv) and the ratio of airway dead space to tidal volume (VD(aw)/VT) were calculated. Before CPB, VD(Bohr)/VT was 0.36 ± 0.05, VD(aw)/VT 0.21 ± 0.04 and VD(alv)/VT(alv) 0.18 ± 0.06 (mean ± SD). During weaning from CPB, VD(aw)/VT remained unchanged while VD(Bohr)/VT and VD(alv)/VT(alv) decreased with increasing ePBF. At CPB of 80, 60, 40 and 20 % VD(Bohr)/VT was 0.64 ± 0.06, 0.55 ± 0.06, 0.47 ± 0.05 and 0.40 ± 0.04, respectively; p < 0.001 and VD(alv)/VT(alv) 0.53 ± 0.07, 0.40 ± 0.07, 0.29 ± 0.06 and 0.25 ± 0.04, respectively; p < 0.001). After CPB, VD(Bohr)/VT and VD(alv)/VT(alv) reached values similar to baseline (0.37 ± 0.04 and 0.19 ± 0.06, respectively). At constant ventilation the alveolar component of VD(Bohr)/VT increased in proportion to the deficit in lung perfusion.

  16. Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Nalabotu, Siva Krishna

    The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

  17. Cardiovascular function in pulmonary emphysema.

    PubMed

    Visca, Dina; Aiello, Marina; Chetta, Alfredo

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

  18. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  19. Molecular insights into the progression of crystalline silica-induced pulmonary toxicity in rats

    PubMed Central

    Sellamuthu, Rajendran; Umbright, Christina; Roberts, Jenny R.; Cumpston, Amy; McKinney, Walter; Chen, Bean T.; Frazer, David; Li, Shengqiao; Kashon, Michael; Joseph, Pius

    2015-01-01

    Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m−3, 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5-fold change and <0.01 false discovery rate P-value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA. PMID:22431001

  20. Detection of fusobacterium nucleatum and fadA adhesin gene in patients with orthodontic gingivitis and non-orthodontic periodontal inflammation.

    PubMed

    Liu, Ping; Liu, Yi; Wang, Jianning; Guo, Yang; Zhang, Yujie; Xiao, Shuiqing

    2014-01-01

    Fusobacterium nucleatum is one of the most abundant gram-negative bacilli colonizing the subgingival plaque and closely associated with periodontal disease. However it is unclear whether F. nucleatum is involved in gingival inflammation under orthodontic appliance. A novel adhesin, FadA, which is unique to oral Fusobacteria, is required for F. nucleatum binding and invasion to epithelial cells and thus may play an important role in colonization of Fusobacterium in the host. In this study, we evaluated the prevalence of F. nucleatum and its virulence factor FadA adhesion gene (fadA) in 169 subgingival biofilm samples from 55 cases of gingivitis patients with orthodontic appliances, 49 cases of gingivitis patients without orthodontic treatment, 35 cases of periodontitis patients and 30 cases of periodontally healthy people via PCR. The correlations between the F. nucleatum/fadA and gingivitis index(GI)was also analyzed. The detection rate of F. nucleatum/fadA in periodontitis group and non-orthodontic gingivitis group was higher than the other two groups (p<0.01) while it was higher in orthodontic gingivitis group than in health people (p<0.05). An obviously positive correlation was observed between the prevalence of F. nucleatum/fadA and GI. F. nucleatum carrying fadA may be more closely related to the development of gingivitis and periodontal disease compared with orthodontic gingivitis.

  1. Detection of fusobacterium nucleatum and fadA adhesin gene in patients with orthodontic gingivitis and non-orthodontic periodontal inflammation.

    PubMed

    Liu, Ping; Liu, Yi; Wang, Jianning; Guo, Yang; Zhang, Yujie; Xiao, Shuiqing

    2014-01-01

    Fusobacterium nucleatum is one of the most abundant gram-negative bacilli colonizing the subgingival plaque and closely associated with periodontal disease. However it is unclear whether F. nucleatum is involved in gingival inflammation under orthodontic appliance. A novel adhesin, FadA, which is unique to oral Fusobacteria, is required for F. nucleatum binding and invasion to epithelial cells and thus may play an important role in colonization of Fusobacterium in the host. In this study, we evaluated the prevalence of F. nucleatum and its virulence factor FadA adhesion gene (fadA) in 169 subgingival biofilm samples from 55 cases of gingivitis patients with orthodontic appliances, 49 cases of gingivitis patients without orthodontic treatment, 35 cases of periodontitis patients and 30 cases of periodontally healthy people via PCR. The correlations between the F. nucleatum/fadA and gingivitis index(GI)was also analyzed. The detection rate of F. nucleatum/fadA in periodontitis group and non-orthodontic gingivitis group was higher than the other two groups (p<0.01) while it was higher in orthodontic gingivitis group than in health people (p<0.05). An obviously positive correlation was observed between the prevalence of F. nucleatum/fadA and GI. F. nucleatum carrying fadA may be more closely related to the development of gingivitis and periodontal disease compared with orthodontic gingivitis. PMID:24416378

  2. Pulmonary rehabilitation.

    PubMed

    Troosters, Thierry; Demeyer, Heleen; Hornikx, Miek; Camillo, Carlos Augusto; Janssens, Wim

    2014-03-01

    Pulmonary rehabilitation is a therapy that offers benefits to patients with chronic obstructive pulmonary disease that are complementary to those obtained by pharmacotherapy. The main objective of pulmonary rehabilitation is to restore muscle function and exercise tolerance, reverse other nonrespiratory consequences of the disease, and help patients to self-manage chronic obstructive pulmonary disease and its exacerbations and symptoms. To do so, a multidisciplinary program tailored to the patient in terms of program content, exercise prescription, and setting must be offered. Several settings and programs have shown to spin off in significant immediate results. The challenge lies in maintaining the benefits outside the program. PMID:24507849

  3. Pulmonary fibrosis: pathogenesis, etiology and regulation

    PubMed Central

    Wilson, MS; Wynn, TA

    2009-01-01

    Pulmonary fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The etiology of pulmonary fibrotic diseases is varied, with an array of triggers including allergens, chemicals, radiation and environmental particles. However, the cause of one of the most common pulmonary fibrotic conditions, idiopathic pulmonary fibrosis (IPF), is still unclear. This review examines common mechanisms of pulmonary wound-healing responses following lung injury, and highlights the pathogenesis of some of the most widespread pulmonary fibrotic diseases. A three phase model of wound repair is reviewed that includes; (1) injury; (2) inflammation; and (3) repair. In most pulmonary fibrotic conditions dysregulation at one or more of these phases has been reported. Chronic inflammation can lead to an imbalance in the production of chemokines, cytokines, growth factors, and disrupt cellular recruitment. These changes coupled with excessive pro-fibrotic IL-13 and/or TGFβ1 production can turn a well-controlled healing response into a pathogenic fibrotic response. Endogenous regulatory mechanisms are discussed including novel areas of therapeutic intervention. Restoring homeostasis to these dysregulated healing responses, or simply neutralizing the key pro-fibrotic mediators may prevent or slow the progression of pulmonary fibrosis. PMID:19129758

  4. Inflammation induced loss of skeletal muscle.

    PubMed

    Londhe, Priya; Guttridge, Denis C

    2015-11-01

    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  5. In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

    PubMed Central

    Qazi, Y; Kheirkhah, A; Blackie, C; Cruzat, A; Trinidad, M; Williams, C; Korb, D R; Hamrah, P

    2015-01-01

    Purpose The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. Methods A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. Results Despite clinical improvement (TBUT: 6.4±1.2 s to 10.1±2.1 s, P=0.03; MGYLS: 3.5±0.8 glands to 7.0±1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6±110.1 cells/mm2; untreated MGD EIC=522.6±104.7 cells/mm2, P=0.69; responsive MGD EIC=194.9±119.4 cells/mm2, P<0.01; normals EIC=123.7±19.2 cells/mm2, P< 0.001), but not the cornea (refractory MGD DC=60.9±28.3 cells/mm2; normals DC=25.9±6.3 cells/mm2; P=0.43). EIC did not correlate with TBUT (Rs=−0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P<0.001) and TBUT (Rs=−0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen. Conclusion MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy. PMID:26088680

  6. Role of inflammation in cardiopulmonary health effects of PM

    SciTech Connect

    Donaldson, Ken . E-mail: ken.donaldson@ed.ac.uk; Mills, Nicholas; MacNee, William; Robinson, Simon; Newby, David

    2005-09-01

    The relationship between increased exposure to PM and adverse cardiovascular effects is well documented in epidemiological studies. Inflammation in the lungs, caused by deposited particles, can be seen as a key process that could mediate adverse effects on the cardiovascular system. There are at least three potential pathways that could lead from pulmonary inflammation to adverse cardiovascular effects. Firstly, inflammation in the lung could lead to systemic inflammation, which is well known to be linked to sudden death from cardiovascular causes. Systemic inflammation can lead to destabilization by activation of inflammatory processes in atheromatous plaques. Secondly, inflammation can cause an imbalance in coagulation factors that favor propagation of thrombi if thrombosis is initiated. Thirdly, inflammation could affect the autonomic nervous system activity in ways that could lead to alterations in the control of heart rhythm which could culminate in fatal dysrhythmia.

  7. Exposure to cigarette smoke downregulates β2-adrenergic receptor expression and upregulates inflammation in alveolar macrophages.

    PubMed

    Wang, Wei; Li, Xiaoguang; Xu, Jie

    2015-01-01

    Cigarette smoke-triggered inflammation is important in the pathophysiology of chronic obstructive pulmonary disease (COPD). β2-Adrenergic receptor (β2-AR) is abundantly expressed on inflammatory cells, which is associated with inflammation regulation. To observe alterations in inflammation, pathological changes in lung tissues, and detect changes in β2-AR expression, rats were exposed for 4 months to cigarette smoke. Pathological changes were observed in lung tissue sections. The levels of inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF), and lung tissues were measured using enzyme-linked immunosorbent assay (ELISA). Nuclear factor (NF)-κB activity was detected by electrophoretic mobility shift assay (EMSA). Exposure to this regimen of cigarette smoke induced peribronchial and perivascular lymphocytic aggregates and parenchymal accumulation of macrophages in rats. EMSA demonstrated that smoke exposure enhanced NF-κB activation in rats' alveolar macrophages (AMs). Compared with the control group, smoke exposure induced a notable increase in TNF-α and IL-1β in BALF, lung tissues, and a decrease of β2-AR expression of AMs. The expression of β2-AR from AMs was inversely correlated with TNF-α and IL-1β levels of BALF. These data demonstrated that chronic smoke-triggered lung inflammation was accompanied by down-regulation of β2-AR in rat lungs' AMs.

  8. Association of Sand Dust Particles with Pulmonary Function and Respiratory Symptoms in Adult Patients with Asthma in Western Japan Using Light Detection and Ranging: A Panel Study.

    PubMed

    Watanabe, Masanari; Noma, Hisashi; Kurai, Jun; Shimizu, Atsushi; Sano, Hiroyuki; Kato, Kazuhiro; Mikami, Masaaki; Ueda, Yasuto; Tatsukawa, Toshiyuki; Ohga, Hideki; Yamasaki, Akira; Igishi, Tadashi; Kitano, Hiroya; Shimizu, Eiji

    2015-10-16

    Light detection and ranging (LIDAR) can estimate daily volumes of sand dust particles from the East Asian desert to Japan. The objective of this study was to investigate the relationship between sand dust particles and pulmonary function, and respiratory symptoms in adult patients with asthma. One hundred thirty-seven patients were included in the study. From March 2013 to May 2013, the patients measured their morning peak expiratory flow (PEF) and kept daily lower respiratory symptom diaries. A linear mixed model was used to estimate the correlation of the median daily levels of sand dust particles, symptoms scores, and PEF. A heavy sand dust day was defined as an hourly concentration of sand dust particles of >0.1 km(-1). By this criterion, there were 8 heavy sand dust days during the study period. Elevated sand dust particles levels were significantly associated with the symptom score (0.04; 95% confidence interval (CI); 0.03, 0.05), and this increase persisted for 5 days. There was no significant association between PEF and heavy dust exposure (0.01 L/min; 95% CI, -0.62, 0.11). The present study found that sand dust particles were significantly associated with worsened lower respiratory tract symptoms in adult patients with asthma, but not with pulmonary function.

  9. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS).

    PubMed

    Schuller, Simone; Callanan, John J; Worrall, Sheila; Francey, Thierry; Schweighauser, Ariane; Kohn, Barbara; Klopfleisch, Robert; Posthaus, Horst; Nally, Jarlath E

    2015-06-01

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG (n=26), IgM (n=25) and leptospiral antigens (n=26). Three general staining patterns for IgG/IgM were observed in lungs of dogs with LPHS with most tissues showing more than one staining pattern: (1) alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3) staining of intra-alveolar fluid. Healthy control lung showed no staining, whereas haemorrhagic lung from dogs not infected with Leptospira showed staining of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens were not detected. We conclude that deposition of IgG/IgM is demonstrable in the majority of canine lungs with naturally occurring LPHS, similar to what has been described in other species. Our findings suggest involvement of the host humoral immunity in the pathogenesis of LPHS and provide further evidence to support the dog as a natural disease model for human LPHS. PMID:25963899

  10. Association of Sand Dust Particles with Pulmonary Function and Respiratory Symptoms in Adult Patients with Asthma in Western Japan Using Light Detection and Ranging: A Panel Study

    PubMed Central

    Watanabe, Masanari; Noma, Hisashi; Kurai, Jun; Shimizu, Atsushi; Sano, Hiroyuki; Kato, Kazuhiro; Mikami, Masaaki; Ueda, Yasuto; Tatsukawa, Toshiyuki; Ohga, Hideki; Yamasaki, Akira; Igishi, Tadashi; Kitano, Hiroya; Shimizu, Eiji

    2015-01-01

    Light detection and ranging (LIDAR) can estimate daily volumes of sand dust particles from the East Asian desert to Japan. The objective of this study was to investigate the relationship between sand dust particles and pulmonary function, and respiratory symptoms in adult patients with asthma. One hundred thirty-seven patients were included in the study. From March 2013 to May 2013, the patients measured their morning peak expiratory flow (PEF) and kept daily lower respiratory symptom diaries. A linear mixed model was used to estimate the correlation of the median daily levels of sand dust particles, symptoms scores, and PEF. A heavy sand dust day was defined as an hourly concentration of sand dust particles of >0.1 km−1. By this criterion, there were 8 heavy sand dust days during the study period. Elevated sand dust particles levels were significantly associated with the symptom score (0.04; 95% confidence interval (CI); 0.03, 0.05), and this increase persisted for 5 days. There was no significant association between PEF and heavy dust exposure (0.01 L/min; 95% CI, −0.62, 0.11). The present study found that sand dust particles were significantly associated with worsened lower respiratory tract symptoms in adult patients with asthma, but not with pulmonary function. PMID:26501307

  11. Hepatic Cryoablation, But Not Radiofrequency Ablation, Results in Lung Inflammation

    PubMed Central

    Chapman, William C.; Debelak, Jacob P.; Wright Pinson, C.; Washington, M. Kay; Atkinson, James B.; Venkatakrishnan, Annapurna; Blackwell, Timothy S.; Christman, John W.

    2000-01-01

    Objective To compare the effects of 35% hepatic cryoablation with a similar degree of radiofrequency ablation (RFA) on lung inflammation, nuclear factor κB (NF-κB) activation, and production of NF-κB dependent cytokines. Summary Background Data Multisystem injury, including acute lung injury, is a severe complication associated with hepatic cryoablation of 30% to 35% or more of liver parenchyma, but this complication has not been reported with RFA. Methods Sprague-Dawley rats underwent 35% hepatic cryoablation or RFA and were killed at 1, 2, and 6 hours. Liver and lung tissue were freeze-clamped for measurement of NF-κB activation, which was detected by electrophoretic mobility shift assay. Serum concentrations of tumor necrosis factor α and macrophage inflammatory protein 2 were measured by enzyme-linked immunosorbent assay. Histologic studies of pulmonary tissue and electron microscopy of ablated liver tissue were compared among treatment groups. Results Histologic lung sections after cryoablation showed multiple foci of perivenular inflammation, with activated lymphocytes, foamy macrophages, and neutrophils. In animals undergoing RFA, inflammatory foci were not present. NF-κB activation was detected at 1 hour in both liver and lung tissue samples of animals undergoing cryoablation but not after RFA, and serum cytokine levels were significantly elevated in cryoablation versus RFA animals. Electron microscopy of cryoablation-treated liver tissue demonstrated disruption of the hepatocyte plasma membrane with extension of intact hepatocyte organelles into the space of Disse; RFA-treated liver tissue demonstrated coagulative destruction of hepatocyte organelles within an intact plasma membrane. To determine the stimulus for systemic inflammation, rats treated with cryoablation had either immediate resection of the ablated segment or delayed resection after a 15-minute thawing interval. Immediate resection of the cryoablated liver tissue prevented NF

  12. Unilateral Pulmonary Agenesis and Gastric Duplication Cyst: A Rare Association

    PubMed Central

    Skokic, Fahrija; Hotic, Nesad; Husaric, Edin; Radoja, Gordana; Muratovic, Selma; Dedic, Nermina

    2013-01-01

    Lung agenesis and gastric duplication cysts are both rare congenital anomalies. Gastric duplication cysts can present with nausea, vomiting, hematemesis, or vague abdominal pain. Unilateral pulmonary agenesis can present with respiratory distress which usually occurs due to retention of bronchial secretions and inflammations. We report the unique case of right pulmonary agenesis associated with gastric duplication cyst. PMID:23844300

  13. [Radiographic assessment of pulmonary hypertension: Methodical aspects].

    PubMed

    Korobkova, I Z; Lazutkina, V K; Nizovtsova, L A; Riden, T V

    2015-01-01

    Pulmonary hypertension is a menacing complication of a number of diseases, which is responsible for high mortality rates and considerably poorer quality of life in a patient. The timely detection for pulmonary hypertension allows timely initiation of treatment, thus improvement in prognosis in the patient. Chest X-ray is the most commonly used radiographic technique for various causes. Physicians' awareness about the radiographic manifestations of pulmonary hypertension may contribute to the earlier detection of this severe disease. Owing to the natural contrast of reflected structures, a chest X-ray film gives a unique opportunity to assess pulmonary circulation vessels, to reveal the signs of pulmonary hypertension, and to estimate trends in the course of the disease. The paper details a procedure for analysis and the normal radiographic anatomy of pulmonary circulation vessels, gives the present classification of pulmonary hypertension, and sets forth its X-ray semiotics. PMID:26552229

  14. [Radiographic assessment of pulmonary hypertension: Methodical aspects].

    PubMed

    Korobkova, I Z; Lazutkina, V K; Nizovtsova, L A; Riden, T V

    2015-01-01

    Pulmonary hypertension is a menacing complication of a number of diseases, which is responsible for high mortality rates and considerably poorer quality of life in a patient. The timely detection for pulmonary hypertension allows timely initiation of treatment, thus improvement in prognosis in the patient. Chest X-ray is the most commonly used radiographic technique for various causes. Physicians' awareness about the radiographic manifestations of pulmonary hypertension may contribute to the earlier detection of this severe disease. Owing to the natural contrast of reflected structures, a chest X-ray film gives a unique opportunity to assess pulmonary circulation vessels, to reveal the signs of pulmonary hypertension, and to estimate trends in the course of the disease. The paper details a procedure for analysis and the normal radiographic anatomy of pulmonary circulation vessels, gives the present classification of pulmonary hypertension, and sets forth its X-ray semiotics.

  15. A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include

  16. The Pathobiology of Chronic Thromboembolic Pulmonary Hypertension.

    PubMed

    Lang, Irene M; Dorfmüller, Peter; Vonk Noordegraaf, Anton

    2016-07-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a late sequel of venous thromboembolism that cannot be completely reproduced in animal models. The prevalence of CTEPH in humans is estimated at roughly 17-20 per million; however, partly because up to 50% of patients with CTEPH never experience symptomatic pulmonary embolism, precise numbers on the incidence and prevalence are not known. Because CTEPH is diagnosed at a median age of 63 years in patients who often have other concomitant cardiovascular disease or lung disease, assessment of pathophysiology in patients can be challenging, We do know that CTEPH is a dual vascular disorder. Stenoses, webs, and occlusions predominate in large and medium-sized pulmonary arteries at the sites of previous pulmonary emboli. A "secondary vasculopathy" resembling the pulmonary arteriopathy encountered in other forms of pulmonary hypertension predominates in low-resistance vessels. Anastomoses between bronchial artery branches and precapillary pulmonary arterioles appear during evolution of the disease. Other acquired vascular connections between bronchial arteries and pulmonary veins may trigger venous remodeling. Current concepts regarding the pathophysiology of CTEPH include contributions of hyperactive coagulation (e.g., high coagulation factor VIII, combined coagulation defects, dysfibrinogenemias), insufficient anticoagulation, non-O blood groups, and misguided thrombus resolution (e.g., infection, inflammation, dysfunctional innate immunity, abnormal circulating phospholipids). Current research focuses on the question as to whether a genetic predisposition leads to misguided vascular healing after pulmonary thromboembolism in susceptible individuals. PMID:27571003

  17. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens.

    PubMed

    Sali, Michela; De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Delogu, Giovanni; Giagulli, Cinzia

    2016-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance.

  18. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens

    PubMed Central

    De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Giagulli, Cinzia

    2015-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance. PMID:26491178

  19. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  20. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  1. [Pulmonary rehabilitation].

    PubMed

    Senjyu, Hideaki

    2016-05-01

    Pulmonary rehabilitation commenced in Japan in 1957. However, the development of pulmonary rehabilitation took a long time due to the lack of the necessary health and medical services. Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. The benefits of pulmonary rehabilitation include a decrease in breathlessness and an improvement in exercise tolerance. It is important that the gains in exercise tolerance lead to an increase in daily physical activity. PMID:27254948

  2. Pulmonary hypertension

    MedlinePlus

    ... that damage the lungs, such as scleroderma and rheumatoid arthritis Birth defects of the heart Blood clots in the lung ( pulmonary embolism ) Heart failure Heart valve disease HIV infection Low oxygen levels in the blood ...

  3. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis See also: Aspergillosis Symptoms You may not have ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Update Date 8/31/2014 Updated by: Jatin ...

  4. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  5. Value of systematic intervention for chronic obstructive pulmonary disease in a regional Japanese city based on case detection rate and medical cost

    PubMed Central

    Tawara, Yuichi; Senjyu, Hideaki; Tanaka, Kenichiro; Tanaka, Takako; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Honda, Sumihisa; Sawai, Terumitsu

    2015-01-01

    Objective We established a COPD taskforce for early detection, diagnosis, treatment, and intervention. We implemented a pilot intervention with a prospective and longitudinal design in a regional city. This study evaluates the usefulness of the COPD taskforce and intervention based on COPD case detection rate and per capita medical costs. Method We distributed a questionnaire to all 8,878 inhabitants aged 50–89 years, resident in Matsuura, Nagasaki Prefecture in 2006. Potentially COPD-positive persons received a pulmonary function test and diagnosis. We implemented ongoing detection, examination, education, and treatment interventions, performed follow-up examinations or respiratory lessons yearly, and supported the health maintenance of each patient. We compared COPD medical costs in Matsuura and in the rest of Nagasaki Prefecture using data from 2004 to 2013 recorded by the association of Nagasaki National Health Insurance Organization, assessing 10-year means and annual change. Results As of 2014, 256 people have received a definitive diagnosis of COPD; representing 31% of the estimated total number of COPD patients. Of the cases detected, 87.5% were mild or moderate in severity. COPD medical costs per patient in Matsuura were significantly lower than the rest of Nagasaki Prefecture, as was rate of increase in cost over time. Conclusion The COPD program in Matsuura enabled early detection and treatment of COPD patients and helped to lower the associated burden of medical costs. The success of this program suggests that a similar program could reduce the economic and human costs of COPD morbidity throughout Japan. PMID:26347397

  6. Detection and Quantification of Mycobacterium tuberculosis in the Sputum of Culture-Negative HIV-infected Pulmonary Tuberculosis Suspects: A Proof-of-Concept Study

    PubMed Central

    Madico, Guillermo; Mpeirwe, Moses; White, Laura; Vinhas, Solange; Orr, Beverley; Orikiriza, Patrick; Miller, Nancy S.; Gaeddert, Mary; Mwanga-Amumpaire, Juliet; Palaci, Moises; Kreiswirth, Barry; Straight, Joe; Dietze, Reynaldo; Boum, Yap; Jones-López, Edward C.

    2016-01-01

    Rationale Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease. Methods We evaluated the Totally Optimized PCR (TOP) TB assay, a new molecular test that we hypothesize is more sensitive than culture. After pre-clinical studies, we estimated TOP’s per-patient sensitivity and specificity in a convenience sample of 261 HIV-infected pulmonary TB suspects enrolled into a TB diagnostic study in Mbarara, Uganda against MGIT culture, Xpert MTB/RIF and a composite reference standard. We validated results with a confirmatory PCR used for sequencing M. tuberculosis. Measurements and Results Using culture as reference, TOP had 100% sensitivity but 35% specificity. Against a composite reference standard, the sensitivity of culture (27%) and Xpert MTB/RIF (27%) was lower than TOP (99%), with similar specificity (100%, 98% and 87%, respectively). In unadjusted analyses, culture-negative/TOP-positive patients were more likely to be older (P<0·001), female (P<0·001), have salivary sputum (P = 0·05), sputum smear-negative (P<0.001) and less advanced disease on chest radiograph (P = 0.05). M. tuberculosis genotypes identified in sputum by DNA sequencing exhibit differential growth in culture. Conclusions These findings suggest that the TOP TB assay is accurately detecting M. tuberculosis DNA in the sputum of culture-negative tuberculosis suspects. Our results require prospective validation with clinical outcomes. If the operating characteristics of the TOP assay are confirmed in future studies, it will be justified as a “TB rule out” test. PMID:27391604

  7. Evaluation of a Multiplex Real-Time PCR Assay for Detecting Major Bacterial Enteric Pathogens in Fecal Specimens: Intestinal Inflammation and Bacterial Load Are Correlated in Campylobacter Infections.

    PubMed

    Wohlwend, Nadia; Tiermann, Sacha; Risch, Lorenz; Risch, Martin; Bodmer, Thomas

    2016-09-01

    A total of 1,056 native or Cary-Blair-preserved stool specimens were simultaneously tested by conventional stool culturing and by enteric bacterial panel (EBP) multiplex real-time PCR for Campylobacter jejuni, Campylobacter coli, Salmonella spp., and shigellosis disease-causing agents (Shigella spp. and enteroinvasive Escherichia coli [EIEC]). Overall, 143 (13.5%) specimens tested positive by PCR for the targets named above; 3 coinfections and 109 (10.4%) Campylobacter spp., 17 (1.6%) Salmonella spp., and 20 (1.9%) Shigella spp./EIEC infections were detected. The respective positive stool culture rates were 75 (7.1%), 14 (1.3%), and 7 (0.7%). The median threshold cycle (CT) values of culture-positive specimens were significantly lower than those of culture-negative ones (CT values, 24.3 versus 28.7; P < 0.001), indicating that the relative bacterial load per fecal specimen was significantly associated with the culture results. In Campylobacter infections, the respective median fecal calprotectin concentrations in PCR-negative/culture-negative (n = 40), PCR-positive/culture-negative (n = 14), and PCR-positive/culture-positive (n = 15) specimens were 134 mg/kg (interquartile range [IQR], 30 to 1,374 mg/kg), 1,913 mg/kg (IQR, 165 to 3,813 mg/kg), and 5,327 mg/kg (IQR, 1,836 to 18,213 mg/kg). Significant differences were observed among the three groups (P < 0.001), and a significant linear trend was identified (P < 0.001). Furthermore, the fecal calprotectin concentrations and CT values were found to be correlated (r = -0.658). Our results demonstrate that molecular screening of Campylobacter spp., Salmonella spp., and Shigella spp./EIEC using the BD Max EBP assay will result in timely diagnosis and improved sensitivity. The determination of inflammatory markers, such as calprotectin, in fecal specimens may aid in the interpretation of PCR results, particularly for enteric pathogens associated with mucosal damage and colonic inflammation. PMID:27307458

  8. Pulmonary Immunostimulation with MALP-2 in Influenza Virus-Infected Mice Increases Survival after Pneumococcal Superinfection

    PubMed Central

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D.; Suttorp, Norbert

    2015-01-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  9. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  10. DNA Damage and Pulmonary Hypertension

    PubMed Central

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  11. Detection of Aspergillus fumigatus in a rat model of invasive pulmonary aspergillosis by real-time nucleic acid sequence-based amplification.

    PubMed

    Zhao, Yanan; Park, Steven; Warn, Peter; Shrief, Raghdaa; Harrison, Elizabeth; Perlin, David S

    2010-04-01

    Rapid and sensitive detection of Aspergillus from clinical samples may facilitate the early diagnosis of invasive pulmonary aspergillosis (IPA). A real-time nucleic acid sequence-based amplification (NASBA) method was investigated by use of an inhalational rat model of IPA. Immunosuppressed male Sprague-Dawley rats were exposed to Aspergillus fumigatus spores for an hour in an aerosol chamber. Bronchoalveolar lavage (BAL) fluid, lung tissues, and whole blood were collected from five infected rats at 1, 24, 48, 72, and 96 h postinfection and five uninfected rats at the end of the experiment. Total nucleic acid (TNA) was extracted on an easyMAG instrument. A primer-molecular beacon set targeting 28S rRNA was designed to detect Aspergillus spp. The results were compared to those of quantitative PCR (qPCR) (18S rDNA) and quantitative culture. The analytical sensitivity of the real-time NASBA assay was <1 CFU/assay. A linear range of detection was demonstrated over 5 log units of conidia (10 to 10(5) spores). Both NASBA and qPCR showed a progressive increase in lung tissue burdens, while the CFU counts were stable over time. The fungal burdens in BAL fluid were more variable and not indicative of a progressive infection. The results of both real-time assays correlated well for both sample types (r = 0.869 and P < 0.0001 for lung tissue, r = 0.887 and P < 0.0001 for BAL fluid). For all whole-blood specimens, NASBA identified Aspergillus-positive samples in the group from which samples were collected at 72 h postinfection (three of five samples) and the group from which samples were collected at 96 h postinfection (five of five samples), but no positive results were obtained by culture or PCR. Real-time NASBA is highly sensitive and useful for the detection of Aspergillus in an experimental model of IPA. PMID:20129972

  12. Detection of Aspergillus fumigatus in a rat model of invasive pulmonary aspergillosis by real-time nucleic acid sequence-based amplification.

    PubMed

    Zhao, Yanan; Park, Steven; Warn, Peter; Shrief, Raghdaa; Harrison, Elizabeth; Perlin, David S

    2010-04-01

    Rapid and sensitive detection of Aspergillus from clinical samples may facilitate the early diagnosis of invasive pulmonary aspergillosis (IPA). A real-time nucleic acid sequence-based amplification (NASBA) method was investigated by use of an inhalational rat model of IPA. Immunosuppressed male Sprague-Dawley rats were exposed to Aspergillus fumigatus spores for an hour in an aerosol chamber. Bronchoalveolar lavage (BAL) fluid, lung tissues, and whole blood were collected from five infected rats at 1, 24, 48, 72, and 96 h postinfection and five uninfected rats at the end of the experiment. Total nucleic acid (TNA) was extracted on an easyMAG instrument. A primer-molecular beacon set targeting 28S rRNA was designed to detect Aspergillus spp. The results were compared to those of quantitative PCR (qPCR) (18S rDNA) and quantitative culture. The analytical sensitivity of the real-time NASBA assay was <1 CFU/assay. A linear range of detection was demonstrated over 5 log units of conidia (10 to 10(5) spores). Both NASBA and qPCR showed a progressive increase in lung tissue burdens, while the CFU counts were stable over time. The fungal burdens in BAL fluid were more variable and not indicative of a progressive infection. The results of both real-time assays correlated well for both sample types (r = 0.869 and P < 0.0001 for lung tissue, r = 0.887 and P < 0.0001 for BAL fluid). For all whole-blood specimens, NASBA identified Aspergillus-positive samples in the group from which samples were collected at 72 h postinfection (three of five samples) and the group from which samples were collected at 96 h postinfection (five of five samples), but no positive results were obtained by culture or PCR. Real-time NASBA is highly sensitive and useful for the detection of Aspergillus in an experimental model of IPA.

  13. Pulmonary embolism

    SciTech Connect

    Dunnick, N.R.; Newman, G.E.; Perlmutt, L.M.; Braun, S.D.

    1988-11-01

    Pulmonary embolism is a common medical problem whose incidence is likely to increase in our aging population. Although it is life-threatening, effective therapy exists. The treatment is not, however, without significant complications. Thus, accurate diagnosis is important. Unfortunately, the clinical manifestations of pulmonary embolism are nonspecific. Furthermore, in many patients the symptoms of an acute embolism are superimposed on underlying chronic heart or lung disease. Thus, a high index of suspicion is needed to identify pulmonary emboli. Laboratory parameters, including arterial oxygen tensions and electrocardiography, are as nonspecific as the clinical signs. They may be more useful in excluding another process than in diagnosing pulmonary embolism. The first radiologic examination is the chest radiograph, but the clinical symptoms are frequently out of proportion to the findings on the chest films. Classic manifestations of pulmonary embolism on the chest radiograph include a wedge-shaped peripheral opacity and a segmental or lobar diminution in vascularity with prominent central arteries. However, these findings are not commonly seen and, even when present, are not specific. Even less specific findings include cardiomegaly, pulmonary infiltrate, elevation of a hemidiaphragm, and pleural effusion. Many patients with pulmonary embolism may have a normal chest radiograph. The chest radiograph is essential, however, for two purposes. First, it may identify another cause of the patient's symptoms, such as a rib fracture, dissecting aortic aneurysm, or pneumothorax. Second, a chest radiograph is essential to interpretation of the radionuclide V/Q scan. The perfusion scan accurately reflects the perfusion of the lung. However, a perfusion defect may result from a variety of etiologies. Any process such as vascular stenosis or compression by tumor may restrict blood flow. 84 references.

  14. Protective Effects of Diallyl Sulfide on Ovalbumin-Induced Pulmonary Inflammation of Allergic Asthma Mice by MicroRNA-144, -34a, and -34b/c-Modulated Nrf2 Activation.

    PubMed

    Ho, Cheng-Ying; Lu, Chi-Cheng; Weng, Chia-Jui; Yen, Gow-Chin

    2016-01-13

    Allergic airway disorder is characterized by an increase in the level of reactive oxygen species (ROS). The induction of inflammation and hyperresponsiveness by an allergen was ameliorated by antioxidants in vivo. This study investigated the protective effects and underlying mechanism of diallyl sulfide (DAS) on ovalbumin (OVA)-induced allergic asthma of BALB/c mice. The animals were intraperitoneally sensitized by inhaling OVA to induce chronic airway inflammation. By administering DAS, a decrease of the infiltrated inflammatory cell counts and the levels of IL-4 and IL-10 in bronchoalveolar lavage fluid as well as the OVA-specific immunoglobulin E levels in sera were observed. DAS also effectively inhibited OVA-induced inflammatory cell infiltration and mucus hypersecretion in lung tissue. Several OVA-induced inflammatory factors (ROS, 8-hydroxy-2'-deoxyguanosine, 8-iso-prostaglandin F2α, and NF-κB) were inhibited by DAS. In addition, DAS increased OVA inhalation-reduced levels of Nrf2 activation by regulating microRNA-144, -34a and -34b/c. Together, the pathogenesis of OVA-induced asthma is highly associated with oxidative stress, and DAS may be an effective supplement to alleviate this disease.

  15. First Description of a New Disease in Rainbow Trout (Oncorhynchus mykiss (Walbaum)) Similar to Heart and Skeletal Muscle Inflammation (HSMI) and Detection of a Gene Sequence Related to Piscine Orthoreovirus (PRV).

    PubMed

    Olsen, Anne Berit; Hjortaas, Monika; Tengs, Torstein; Hellberg, Hege; Johansen, Renate

    2015-01-01

    In fall 2013, anorexia, lethargy and mortalities up to 10-12,000 dead fish per week were observed in rainbow trout Oncorhynchus mykiss in three fresh water hatcheries (salinity 0-1 ‰) on the west coast of Norway. The fish (25-100 g) showed signs of circulatory failure with haemorrhages, ascites and anaemia. The histopathological findings comprised inflammation of the heart and red muscle and liver necrosis. The affected fish had a common origin. Disease and mortalities were also observed up to four months after sea water transfer. Microbiological examination did not reveal presence of any known pathogens. Based on histopathological similarities to heart and skeletal inflammation (HSMI) in Atlantic salmon, associated with piscine orthoreovirus (PRV), extended investigations to detect a virus within the family Reoviridae were conducted. By the use of primer sets targeting the PRV genome, a sequence with 85% identity to a part of segment S1 of PRV was obtained. Further analysis showed that the virus sequence could only be aligned with PRV and no other reoviruses both on amino acid and nucleotide level. Two PCR assays were developed for specific detection of the virus. High amounts of the virus were detected in diseased fish at all affected farms and low amounts were detected in low prevalence at the broodfish farms. Further investigations are needed to determine if the virus is associated with the new disease in rainbow trout and to further characterize the virus with respect to classification, relationship with PRV, virulence, pathology and epidemiology. PMID:26176955

  16. Pulmonary Manifestations among Patients with Primary Biliary Cirrhosis

    PubMed Central

    Koksal, Deniz; Koksal, Aydin Seref; Gurakar, Ahmet

    2016-01-01

    Abstract Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease caused by diffuse inflammation, destruction and fibrosis of the intrahepatic bile ducts, ultimately leading to cirrhosis, portal hypertension and liver failure. The pathogenesis of PBC is incompletely understood, but current data suggest roles for genetic susceptibility and environmental factors. PBC is often thought of as an organ-specific autoimmune disease, which mainly targets the liver; however, lung tissue is also a site for autoimmune involvement of PBC. The pulmonary manifestations of PBC include abnormalities in gas transfer and pulmonary function, subclinical alveolitis, interstitial lung disease, granulomatous lung disease, airway disease, pulmonary hypertension, pulmonary hemorrhage and pleural effusion. PMID:27777894

  17. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

  18. [Pulmonary Langerhans cell histiocytosis].

    PubMed

    Popper, H H

    2015-09-01

    Pulmonary Langerhans cell histiocytosis is regarded as a reactive proliferation of the dendritic Langerhans cell population stimulated by chronic tobacco-derived plant proteins due to incomplete combustion but can also occur in childhood as a tumor-like systemic disease. Currently, both these forms cannot be morphologically distinguished. In the lungs a nodular proliferation of Langerhans cells occurs in the bronchial mucosa and also peripherally in the alveolar septa with an accompanying infiltration by eosinophilic granulocytes and destruction of the bronchial wall. Langerhans cells can be selectively detected with antibodies against CD1a and langerin. In the reactive isolated pulmonary form, abstinence from tobacco smoking in most patients leads to regression of infiltration and improvement of symptoms. In high-resolution computed tomography (HRCT) the small star-like scars can still be detected even after complete cessation of tobacco smoking.

  19. Pulmonary Function Reduction in Diabetes With and Without Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kinney, Gregory L.; Black-Shinn, Jennifer L.; Wan, Emily S.; Make, Barry; Regan, Elizabeth; Lutz, Sharon; Soler, Xavier; Silverman, Edwin K.; Crapo, James; Hokanson, John E.

    2014-01-01

    OBJECTIVE Diabetes damages major organ systems through disrupted glycemic control and increased inflammation. The effects of diabetes on the lung have been of interest for decades, but the modest reduction in pulmonary function and its nonprogressive nature have limited its investigation. A recent systematic review found that diabetes was associated with reductions in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide of the lung and increased FEV1/FVC. They reported pooled results including few smokers. This study will examine measures of pulmonary function in participants with extensive smoking exposure. RESEARCH DESIGN AND METHODS We examined pulmonary function in participants with a >10–pack-year history of smoking with and without diabetes with and without chronic obstructive pulmonary disease (COPD). We measured pulmonary function, exercise capacity, and pulmonary-related quality of life in 10,129 participants in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study. RESULTS Participants with diabetes were observed to have reduced pulmonary function after controlling for known risk factors and also significant reductions in exercise capacity and quality of life across functional stages of COPD. CONCLUSIONS Pulmonary function in patients with ≥10 pack-years of smoking and diabetes is reduced, and this decrease is associated with significant reductions in activity-related quality of life and exercise capacity. PMID:24026562

  20. [Pulmonary toxicity of manufactured nanomaterials].

    PubMed

    Morimoto, Yasuo

    2012-05-01

    We introduced the report on the pulmonary toxicity of manufactured nanomaterials as a national project in Japan conducted by the New Energy and Industrial Technology Development Organization (NEDO project). Well-characterized and well-dispersed industrial nanomaterials were used in this project. Using multiwall carbon nanotubes (MWCNTs), we conducted intratracheal instillation and inhalation studies. At a low dose (0.2 mg/rat) and a high dose (1 mg/rat) of almost individual MWCNTs, transient and persistent inflammatory responses were induced in the lungs following intratracheal instillation. Well-dispersed MWCNTs at a low concentration (0.37 mg/m3) did not induce pulmonary inflammation. Using single-wall carbon nanotubes (SWCNTs), we also conducted both studies. At low (0.2 mg/rat) and high doses (0.4 mg/rat) of well-dispersed SWCNTs, persistent inflammatory responses were induced in the lungs following intratracheal instillation. Well-dispersed MWCNTs at low and high concentrations (0.03 mg/m3 and 0.13 mg/m3, respectively) did not induce pulmonary inflammation. On the basis of these data from mainly inhalation studies, the acceptable exposure concentration of carbon nanotubes is proposed to be 0.03 mg/m3 in Japan.

  1. The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease

    PubMed Central

    Wang, Qing; Guo, Yi-Zhan; Zhang, Yi-Tao; Xue, Jiao-Jie; Chen, Zhi-Chong; Cheng, Shi-Yao; Ou, Mao-De; Cheng, Kang-Lin; Zeng, Wei-Jie

    2016-01-01

    Background Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. Methods Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group. Results Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group. Conclusions Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the

  2. Detection of septal coronary collaterals by color flow Doppler mapping is a marker for anomalous origin of a coronary artery from the pulmonary artery.

    PubMed

    Frommelt, Michele A; Miller, Elaine; Williamson, Jeff; Bergstrom, Sarita

    2002-03-01

    Between August 1991 and September 2000, 15 patients received a diagnosis of the anomalous origin of the coronary artery from the pulmonary artery, at the Children's Hospital of Wisconsin. All were evaluated initially by transthoracic echocardiography, with subsequent diagnosis confirmation at cardiac catheterization and/or surgery. Seven of the 15 patients were referred in infancy (mean age 4.3 months) with symptoms of congestive heart failure. The remaining 8 patients were older (mean age 7.0 years) at the time of diagnosis, and 7 of those 8 patients were clinically asymptomatic and were referred for evaluation of a heart murmur and/or cardiomegaly on chest radiograph. One older patient, previously healthy, was referred at age 18 for an episode of sudden death while playing basketball. All the older asymptomatic patients had echocardiographic detection of multiple unusual color flow Doppler signals within the ventricular septum, believed to represent septal coronary collaterals, which raised suspicion of a coronary artery abnormality and led to more detailed imaging of the coronary artery anatomy. In the younger infants with congestive heart failure, septal coronary collaterals were less frequent, but did aid in the diagnosis of an anomalous coronary artery when present.

  3. PULMONARY TOXICOLOGY

    EPA Science Inventory

    Pulmonary disease and dysfunction exact a tremendous health burden on society. In a recent survey of lung disease published by the American Lung Association in 2012, upwards of 10 million Americans were diagnosed with chronic bronchitis while over 4 million Americans had emphysem...

  4. Pulmonary ascariasis.

    PubMed

    Mukerjee, C M; Thompson, J E

    1979-07-28

    A case of pulmonary ascariasis is reported for the first time in Australia. Because of increasing immigration from countries which have a high incidence of ascariasis (especially those of South-East Asia), and increasing travel to Asian countries, the awareness of this infestation as a cause of respiratory disease may be of great importance. PMID:40103

  5. Pulmonary schistosomiasis.

    PubMed

    Hill, I R; Turk, E P

    1980-09-01

    Two cases are reported of the incidental finding of pulmonary schistosomiasis in the victims of a fatal aircraft accident. The presence of this disease had no bearing on the causation of the accident, but it gives insight into the potential hazards of dissemination of diseases by travellers. The finding also emphasises the value of routine postmortems and histology in all aircraft accident victims.

  6. Sex differences in the pulmonary circulation: implications for pulmonary hypertension

    PubMed Central

    Martin, Yvette N.

    2014-01-01

    Pulmonary arterial hypertension (PAH), a form of pulmonary hypertension, is a complex disease of multifactorial origin. While new developments regarding pathophysiological features and therapeutic options in PAH are being reported, one important fact has emerged over the years: there is a sex difference in the incidence of this disease such that while there is a higher incidence in females, disease outcomes are much worse in males. Accordingly, recent attention has been focused on understanding the features of sex differences in the pulmonary circulation and the contributory mechanisms, particularly sex hormones and their role in the pathological and pathophysiological features of PAH. However, to date, there is no clear consensus whether sex hormones (particularly female sex steroids) are beneficial or detrimental in PAH. In this review, we highlight some of the most recent evidence regarding the influence of sex hormones (estrogen, testosterone, progesterone, dehydroepiandrosterone) and estrogen metabolites on key pathophysiological features of PAH such as proliferation, vascular remodeling, vasodilation/constriction, and inflammation, thus setting the stage for research avenues to identify novel therapeutic target for PAH as well as potentially other forms of pulmonary hypertension. PMID:24610923

  7. Pulmonary blue bodies.

    PubMed

    Koss, M N; Johnson, F B; Hochholzer, L

    1981-03-01

    Pulmonary blue bodies are intra-alveolar laminated basophilic concretions of uncertain etiology. Blue bodies were studied in lung biopsy specimens from 10 patients. The patients ranged in age from 47 to 69 years and were predominantly men. Three had a history of overt exposure to environmental dusts such as sawdust and asbestos, and two showed occasional ferruginous bodies in the lung, raising the possibility of pneumoconiosis. In eight cases there was interstitial pneumonitis, which resembled desquamative interstitial pneumonia by light microscopy but which was often seen to be patchy and asymmetrically distributed in the lung by chest x-ray examination. Of two other patients, one had xanthogranulomatous inflammation and the other, necrotizing granulomatous inflammation. Light and electron microscopic, histochemical, microchemical, and x-ray diffraction studies of blue bodies were also performed. Calcium carbonate is a major component of blue bodies and is responsible for their birefringence in unstained sections and ready solubility in acid solutions. Blue bodies also contain a mucopolysaccharide matrix and iron. We offer the hypothesis that blue bodies (calcium carbonate) are a product of histiocytic catabolism.

  8. Detection and follow-up of chronic obstructive pulmonary disease (COPD) and risk factors in the Southern Cone of Latin America. the pulmonary risk in South America (PRISA) study

    PubMed Central

    2011-01-01

    Background The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition. Methods/Design PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken. Discussion There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary

  9. Disrupted pulmonary vascular development and pulmonary hypertension in transgenic mice overexpressing transforming growth factor-alpha.

    PubMed

    Le Cras, Timothy D; Hardie, William D; Fagan, Karen; Whitsett, Jeffrey A; Korfhagen, Thomas R

    2003-11-01

    Pulmonary vascular disease plays a major role in morbidity and mortality in infant and adult lung diseases in which increased levels of transforming growth factor (TGF)-alpha and its receptor EGFR have been associated. The aim of this study was to determine whether overexpression of TGF-alpha disrupts pulmonary vascular development and causes pulmonary hypertension. Lung-specific expression of TGF-alpha in transgenic mice was driven with the human surfactant protein (SP)-C promoter. Pulmonary arteriograms and arterial counts show that pulmonary vascular development was severely disrupted in TGF-alpha mice. TGF-alpha mice developed severe pulmonary hypertension and vascular remodeling characterized by abnormally extensive muscularization of small pulmonary arteries. Pulmonary vascular development was significantly improved and pulmonary hypertension and vascular remodeling were prevented in bi-transgenic mice expressing both TGF-alpha and a dominant-negative mutant EGF receptor under the control of the SP-C promoter. Vascular endothelial growth factor (VEGF-A), an important angiogenic factor produced by the distal epithelium, was decreased in the lungs of TGF-alpha adults and in the lungs of infant TGF-alpha mice before detectable abnormalities in pulmonary vascular development. Hence, overexpression of TGF-alpha caused severe pulmonary vascular disease, which was mediated through EGFR signaling in distal epithelial cells. Reductions in VEGF may contribute to the pathogenesis of pulmonary vascular disease in TGF-alpha mice.

  10. Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujishima, Kei; Yatera, Kazuhiro; Yamamoto, Kazuhiro

    2016-01-01

    Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation. PMID:26828483

  11. Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity.

    PubMed

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujishima, Kei; Yatera, Kazuhiro; Yamamoto, Kazuhiro

    2016-01-27

    Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.

  12. Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia.

    PubMed

    Miyazato, Takako; Ishikawa, Takaki; Michiue, Tomomi; Maeda, Hitoshi

    2012-07-01

    Drowning involves complex fatal factors, including asphyxiation and electrolyte/osmotic disturbances, as well as hypothermia in cold water. The present study investigated the molecular pathology of pulmonary injury due to drowning, using lung specimens from forensic autopsy cases of drowning (n = 21), acute mechanical asphyxia due to neck compression and smothering (n = 24), and hypothermia (cold exposure, n = 11), as well as those of injury (n = 23), intoxication (n = 13), fire fatality (n = 18), and acute cardiac death (n = 9) for comparison. TaqMan real-time reverse transcription polymerase chain reaction was used to quantify messenger RNA (mRNA) expressions of pulmonary surfactant-associated proteins A and D (SP-A and SP-D), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10. SP-A and SP-D mRNA levels were lower for drowning, mechanical asphyxiation, fire fatality, and acute cardiac deaths than for hypothermia and injury. TNF-α, IL-1β, and IL-10 mRNA levels were higher for drowning or for drowning and injury than for other groups; there was no significant difference between fire fatality, involving airway injury due to inhalation of hot/irritant gases, and other control groups. These observations suggest characteristic molecular biological patterns of pulmonary injury involving suppression of pulmonary surfactants and activation of early-phase mediators of inflammation in drowning, with high mRNA expression levels of pulmonary surfactants in fatal hypothermia; however, there was no significant difference among these markers in immunohistochemical detection, except for SP-A. These mRNA expressions can be used as markers of pulmonary injury to assist in investigations of the pathophysiology of drowning and fatal hypothermia in combination with other biochemical and biological markers.

  13. Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury.

    PubMed

    Gao, Wei; Yuan, Cheng; Zhang, Jingying; Li, Lingling; Yu, Like; Wiegman, Coen H; Barnes, Peter J; Adcock, Ian M; Huang, Mao; Yao, Xin

    2015-12-01

    COPD (chronic obstructive pulmonary disease) is associated with sustained inflammation, excessive injury, and accelerated lung aging. Human Klotho (KL) is an anti-aging protein that protects cells against inflammation and damage. In the present study, we quantified KL expression in the lungs of COPD patients and in an ozone-induced mouse model of COPD, and investigated the mechanisms that control KL expression and function in the airways. KL distribution and levels in human and mouse airways were measured by immunohistochemistry and Western blotting. The effect of CSE (cigarette smoke extract) on KL expression was detected in human bronchial epithelial cells. Moreover, the effect of KL on CSE-mediated inflammation and hydrogen peroxide-induced cellular injury/apoptosis was determined using siRNAs. KL expression was decreased in the lungs of smokers and further reduced in patients with COPD. Similarly, 6 weeks of exposure to ozone decreased KL levels in airway epithelial cells. CSE and TNFα (tumour necrosis factor α) decreased KL expression and release from airway epithelial cells, which was associated with enhanced pro-inflammatory cytokine expression. Moreover, KL depletion increased cell sensitivity to cigarette smoke-induced inflammation and oxidative stress-induced cell damage. These effects involved the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase) and Nrf2 (nuclear factor erythroid 2-related factor 2) pathways. Reduced KL expression in COPD airway epithelial cells was associated with increased oxidative stress, inflammation and apoptosis. These data provide new insights into the mechanisms associated with the accelerated lung aging in COPD development. PMID:26201096

  14. Gallium-67 and pulmonary complications of amiodarone

    SciTech Connect

    Lecklitner, M.L.; Johnson, D.R.; Hughes, J.J.

    1988-11-01

    A 66-year-old white man with amiodarone pneumonitis is presented. The diagnosis was made with the aid of Ga-67 imaging, which is a sensitive method of detecting amiodarone pulmonary toxicity in patients with symptomatic pulmonary infiltrates on chest radiographs. Ga-67 imaging is especially useful in distinguishing amiodarone pneumonitis from congestive heart failure.

  15. Pain related inflammation analysis using infrared images

    NASA Astrophysics Data System (ADS)

    Bhowmik, Mrinal Kanti; Bardhan, Shawli; Das, Kakali; Bhattacharjee, Debotosh; Nath, Satyabrata

    2016-05-01

    Medical Infrared Thermography (MIT) offers a potential non-invasive, non-contact and radiation free imaging modality for assessment of abnormal inflammation having pain in the human body. The assessment of inflammation mainly depends on the emission of heat from the skin surface. Arthritis is a disease of joint damage that generates inflammation in one or more anatomical joints of the body. Osteoarthritis (OA) is the most frequent appearing form of arthritis, and rheumatoid arthritis (RA) is the most threatening form of them. In this study, the inflammatory analysis has been performed on the infrared images of patients suffering from RA and OA. For the analysis, a dataset of 30 bilateral knee thermograms has been captured from the patient of RA and OA by following a thermogram acquisition standard. The thermograms are pre-processed, and areas of interest are extracted for further processing. The investigation of the spread of inflammation is performed along with the statistical analysis of the pre-processed thermograms. The objectives of the study include: i) Generation of a novel thermogram acquisition standard for inflammatory pain disease ii) Analysis of the spread of the inflammation related to RA and OA using K-means clustering. iii) First and second order statistical analysis of pre-processed thermograms. The conclusion reflects that, in most of the cases, RA oriented inflammation affects bilateral knees whereas inflammation related to OA present in the unilateral knee. Also due to the spread of inflammation in OA, contralateral asymmetries are detected through the statistical analysis.

  16. Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

    PubMed Central

    Sarnat, Jeremy A.; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U.; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E.; Flanders, W. Dana; Mirabelli, Maria C.; Zora, Jennifer E.; Bergin, Michael H.; Yip, Fuyuen

    2015-01-01

    Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p < 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. PMID:24906070

  17. In Vivo Detection of Hyperoxia-Induced Pulmonary Endothelial Cell Death Using 99mTc-Duramycin

    PubMed Central

    Audi, Said H.; Jacobs, Elizabeth R.; Zhao, Ming; Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

    2014-01-01

    Introduction: 99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Methods: Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Results: Lung DU uptake increased significantly (p < 0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r2 = 0.82, p = 0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Conclusions: Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. PMID:25218023

  18. [Pulmonary melioidosis].

    PubMed

    Perret, J L; Vidal, D; Thibault, F

    1998-12-01

    Melioidosis is most frequently encountered in pulmonary localization. Melioidosis is an infectious disease caused by Burkholderia pseudomallei first described by Whitmore in 1912 in Burma. B. pseudomallei is a Gram negative rod belonging to the Pseudomonadaceae family. Soil and water are the natural reservoirs for the germ which is a specific pathogen for several mammal species. Long endemic in Southeast Asia and several tropical zones, B. pseudomallei has recently been found in temperate zones, including France. Human contamination occurs via the transcutaneous route and often leads to dormant inapparent infection. Many conditions, such as diabetes, renal lithiasis, various circumstances of immunodepression or stress, facilitate clinical manifestations which vary greatly. Pulmonary manifestations may be acute and extensive, producing a torpid pseudo-tuberculous condition or a variety of clinical and radiological features mimicking other diseases. Bacteriological and serological tests may be negative. Exposure in an endemic zone, the notion of a favorable context, weight loss, cavitary images on successive chest x-rays and the presence of extra-pulmonary localizations may be suggestive. Ceftazidime or the amoxicillin-clavulanic acid combination are indicated, but mortality in acute forms still reaches 40%. Relapse can be expected if the treatment duration is too short. PMID:10100350

  19. Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia

    PubMed Central

    Balany, Jherna; Bhandari, Vineet

    2015-01-01

    The concerted interaction of genetic and environmental factors acts on the preterm human immature lung with inflammation being the common denominator leading to the multifactorial origin of the most common chronic lung disease in infants – ­bronchopulmonary dysplasia (BPD). Adverse perinatal exposure to infection/inflammation with added insults like invasive mecha nical ventilation, exposure to hyperoxia, and sepsis causes persistent immune dysregulation. In this review article, we have attempted to analyze and consolidate current knowledge about the role played by persistent prenatal and postnatal inflammation in the pathogenesis of BPD. While some parameters of the early inflammatory response (neutrophils, cytokines, etc.) may not be detectable after days to weeks of exposure to noxious stimuli, they have already initiated the signaling pathways of the inflammatory process/immune cascade and have affected permanent defects structurally and functionally in the BPD lungs. Hence, translational research aimed at prevention/amelioration of BPD needs to focus on dampening the inflammatory response at an early stage to prevent the cascade of events leading to lung injury with impaired healing resulting in the pathologic pulmonary phenotype of alveolar simplification and dysregulated vascularization characteristic of BPD. PMID:26734611

  20. Molecular Imaging of Folate Receptor β–Positive Macrophages during Acute Lung Inflammation

    PubMed Central

    Zaynagetdinov, Rinat; Yull, Fiona E.; Polosukhin, Vasiliy V.; Gleaves, Linda A.; Tanjore, Harikrishna; Young, Lisa R.; Peterson, Todd E.; Manning, H. Charles; Prince, Lawrence S.; Blackwell, Timothy S.

    2015-01-01

    Characterization of markers that identify activated macrophages could advance understanding of inflammatory lung diseases and facilitate development of novel methodologies for monitoring disease activity. We investigated whether folate receptor β (FRβ) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FRβ expression was markedly increased in lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and was markedly attenuated after depletion of macrophages. Using flow cytometry, we identified the cells responsible for uptake of cyanine 5–conjugated folate as FRβ+ interstitial macrophages and pulmonary monocytes, which coexpressed markers associated with an M1 proinflammatory macrophage phenotype. These findings were confirmed using a second model of acute lung inflammation generated by inducible transgenic expression of an NF-κB activator in airway epithelium. Using CC chemokine receptor 2–deficient mice, we found that FRβ+ macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein-1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate-based molecular imaging can be used as a noninvasive approach to detect classically activated monocytes/macrophages recruited to the lungs during acute inflammation. PMID:25375039

  1. Indirect detection of pulmonary nodule on low-pass filtered and original x-ray images during limited and unlimited display times

    NASA Astrophysics Data System (ADS)

    Pietrzyk, Mariusz W.; McEntee, Mark; Evanoff, Michael G.; Brennan, Patrick C.

    2012-02-01

    Aim: This study evaluates the assumption that global impression is created based on low spatial frequency components of posterior-anterior chest radiographs. Background: Expert radiologists precisely and rapidly allocate visual attention on pulmonary nodules chest radiographs. Moreover, the most frequent accurate decisions are produced in the shortest viewing time, thus, the first hundred milliseconds of image perception seems be crucial for correct interpretation. Medical image perception model assumes that during holistic analysis experts extract information based on low spatial frequency (SF) components and creates a mental map of suspicious location for further inspection. The global impression results in flagged regions for detailed inspection with foveal vision. Method: Nine chest experts and nine non-chest radiologists viewed two sets of randomly ordered chest radiographs under 2 timing conditions: (1) 300ms; (2) free search in unlimited time. The same radiographic cases of 25 normal and 25 abnormal digitalized chest films constituted two image sets: low-pass filtered and unfiltered. Subjects were asked to detect nodules and rank confidence level. MRMC ROC DBM analyses were conducted. Results: Experts had improved ROC AUC while high SF components are displayed (p=0.03) or while low SF components were viewed under unlimited time (p=0.02) compared with low SF 300mSec viewings. In contrast, non-chest radiologists showed no significant changes when high SF are displayed under flash conditions compared with free search or while low SF components were viewed under unlimited time compared with flash. Conclusion: The current medical image perception model accurately predicted performance for non-chest radiologists, however chest experts appear to benefit from high SF features during the global impression.

  2. Comparison of sensitivity and reading time for the use of computer aided detection (CAD) of pulmonary nodules at MDCT as concurrent or second reader

    NASA Astrophysics Data System (ADS)

    Beyer, F.; Zierott, L.; Fallenberg, E. M.; Juergens, K.; Stoeckel, J.; Heindel, W.; Wormanns, D.

    2006-03-01

    Purpose: To compare sensitivity and reading time when using CAD as second reader resp. concurrent reader. Materials and Methods: Fifty chest MDCT scans due to clinical indication were analysed independently by four radiologists two times: First with CAD as concurrent reader (display of CAD results simultaneously to the primary reading by the radiologist); then after a median of 14 weeks with CAD as second reader (CAD results were shown after completion of a reading session without CAD). A prototype version of Siemens LungCAD (Siemens,Malvern,USA) was used. Sensitivities and reading times for detecting nodules >=4mm of concurrent reading, reading without CAD and second reading were recorded. In a consensus conference false positive findings were eliminated. Student's T-Test was used to compare sensitivities and reading times. Results: 108 true positive nodules were found. Mean sensitivity was .68 for reading without CAD, .68 for concurrent reading and .75 for second reading. Differences of sensitivities were significant between concurrent and second reading (p<.001) resp. reading without CAD and second reading (p=.001). Mean reading time for concurrent reading was significant shorter (274s) compared to reading without CAD (294s;p=.04) and second reading (337sp<.001). New work to be presented: To our knowledge this is the first study that compares sensitivities and reading times between use of CAD as concurrent resp. second reader. Conclusion: CAD can either be used to speed up reading of chest CT cases for pulmonary nodules without loss of sensitivity as concurrent reader -OR (and not AND) to increase sensitivity and reading time as second reader.

  3. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  4. Toxicogenomic analysis of susceptibility to inhaled urban particulate matter in mice with chronic lung inflammation

    PubMed Central

    Thomson, Errol M; Williams, Andrew; Yauk, Carole L; Vincent, Renaud

    2009-01-01

    Background Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter. Results Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF)-α under the control of the surfactant protein C promoter and wildtype littermates (C57BL/6 background) were exposed by inhalation for 4 h to particulate matter (0 or 42 mg/m3 EHC-6802) and euthanized 0 or 24 h post-exposure. The low alveolar dose of particles (16 μg) did not provoke an inflammatory response in the lungs of wildtype mice, nor exacerbate the chronic inflammation in TNF animals. Real-time PCR confirmed particle-dependent increases of CYP1A1 (30–100%), endothelin-1 (20–40%), and metallothionein-II (20–40%) mRNA in wildtype and TNF mice (p < 0.05), validating delivery of a biologically-effective dose. Despite detection of striking genotype-related differences, including activation of immune and inflammatory pathways consistent with the TNF-induced pathology, and time-related effects attributable to stress from nose-only exposure, microarray analysis failed to identify effects of the inhaled particles. Remarkably, the presence of chronic inflammation did not measurably amplify the transcriptional response to particulate matter. Conclusion Our data support the hypothesis that health effects of acute exposure to urban particles are dominated by activation of specific physiological response cascades rather than widespread changes in gene expression. PMID:19284582

  5. Inflammation in Tendon Disorders.

    PubMed

    Speed, Cathy

    2016-01-01

    The role of inflammation in tendon disorders has long been a subject of considerable debate. Developments in our understanding of the basic science of inflammation have provided further insight into its potential role in specific forms of tendon disease, and the circumstances that may potentiate this. Such circumstances include excessive mechanical stresses on tendon and the presence of systemic inflammation associated with chronic diseases. In this chapter a brief review of the basic science of inflammation is provided and the influence that it may play on tendons is discussed. PMID:27535263

  6. Neurogenic inflammation and colliquative lymphadenitis with persistent orthopox virus DNA detection in a human case of cowpox virus infection transmitted by a domestic cat.

    PubMed

    Hobi, S; Mueller, R S; Hill, M; Nitsche, A; Löscher, T; Guggemos, W; Ständer, S; Rjosk-Dendorfer, D; Wollenberg, A

    2015-08-01

    Cowpox viruses are orthopoxviruses that may survive in the environment for years. Rodents are regarded as the primary hosts, but transmission to other species has been reported. This report describes a cowpox virus infection in a cat with subsequent transmission to its owner leading to protracted, atypical and severe clinical signs. A young cat presented with multiple crusts and plaques on the neck, muzzle and tail base. The owner developed an erythematous lesion with elevated margins, central necrosis and crust formation below the left breast, a neurogenic inflammation, enlarged regional lymph nodes, a colliquative lymphadenitis and concomitant flu-like symptoms. Cultures were taken at the first visit from the cat's lesional skin and the patient's skin, and polymerase chain reaction with sequencing of the haemagglutinin region of both were positive for cowpox virus. The patient was treated with various antibiotics and methylprednisolone and was in clinical remission after 7 months.

  7. Simple pulmonary eosinophilia

    MedlinePlus

    Pulmonary infiltrates with eosinophilia; Loffler syndrome; Eosinophilic pneumonia; Pneumonia - eosinophilic ... simple pulmonary eosinophilia is a severe type of pneumonia called acute idiopathic eosinophilic pneumonia.

  8. A Pulmonary Sequestered Segment with an Aberrant Pulmonary Arterial Supply: A Case of Unique Anomaly

    PubMed Central

    Kim, Minchul; An, Jin Kyung; Jung, Yoon Young; Choi, Yun Sun

    2016-01-01

    We presented a rare case of a 64-year-old man with a combined anomaly of the bronchus and pulmonary artery that was detected incidentally. Computed tomography showed a hyperlucent, aerated sequestered segment of the right lower lung with an independent ectopic bronchus, which had no connection to the other airway. The affected segment was supplied by its own aberrant pulmonary artery branch from the right pulmonary trunk. This anomaly cannot be classified with any of the previously reported anomalies. PMID:26957918

  9. Pulmonary toxicity in mice following exposure to cerium chloride.

    PubMed

    Hong, Jie; Yu, Xiaohong; Pan, Xiaoyu; Zhao, Xiaoyang; Sheng, Lei; Sang, Xuezi; Lin, Anan; Zhang, Chi; Zhao, Yue; Gui, Suxin; Sun, Qingqing; Wang, Ling; Hong, Fashui

    2014-06-01

    The widespread application of lanthanoids (Lns) in manufacturing industries has raised occupational and environmental health concerns about the possible increased health risks to humans exposed to Lns in their working and living environments. Numerous studies have shown that exposures to Ln cause pulmonary injury in animals, but very little is known about the molecular mechanisms of the pulmonary inflammation caused by cerium chloride (CeCl3) exposure. In this study, we evaluated the oxidative stress and molecular mechanism underlying with the pulmonary inflammation associated with chronic lung toxicity in mice treated with nasally instilled CeCl3 for 90 consecutive days. Our findings suggest that significant cerium accumulated in the lung, leading the obvious increase of the lung indices, significant increases in inflammatory cells and levels of lactate dehydrogenase, alkaline phosphate, and total protein, overproduction of reactive oxygen species and peroxidation of lipids, reduced antioxidant capacity, and pulmonary inflammation. CeCl3 exposure also activated nuclear factor κB, increased the expression of tumor necrosis factor α, cyclooxygenase-2, heme oxygenase 1, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 18, interleukin 1β, and CYP1A1. However, CeCl3 reduced the expression of nuclear factor κB (NF-κB)-inhibiting factor and heat shock protein 70. These findings suggest that the pulmonary inflammation caused by CeCl3 in mice is closely associated with oxidative stress and inflammatory cytokine expression. PMID:24736977

  10. Inhibition of Acute Lung Injury by TNFR-Fc through Regulation of an Inflammation-Oxidative Stress Pathway

    PubMed Central

    Yujie, Hu; Weifeng, Li; Zhenhui, Guo; Wenjie, Huang

    2016-01-01

    Background Acute lung injury (ALI), characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema, and associated with a proteinaceous alveolar exudate, is a leading cause of morbidity and mortality. Currently, inflammation-oxidative stress interaction between TNF-α and NF-κB was identified as a key pathway of ALI. We hypothesized that a TNFR-Fc fusion protein would have beneficial effects in experimental ALI, and sought to test this idea in mice by blocking TNF-α. Methods and Results Intratracheal instillation of lipopolysaccharide (LPS) into the lungs of ALI mice led to histiocyte apoptosis, and detection of serum and bronchoalveolar lavage fluid (BALF) cytokines, feedback between NF-κB and TNF-α, lung albumin leakage, lung damage, IκB kinase (IKK) and NF-κB activation, I-κB degradation, and oxidative injury. LPS administration raised pulmonary inflammation as reflected by increased inflammatory cytokines, alveoli protein concentration, and ALI scores. IKK is phosphorylated following LPS challenge, leading to I-κB degradation and NF-κB p65 phosphorylation. Furthermore, NF-κB is translocated into the nucleus and up-regulates TNF-α gene transcription. Infusion of TNFR-Fc 24h before LPS challenge significantly abrogated the increase of inflammatory cytokines, especially serum TNF-α concentration, as well as pulmonary alveoli protein levels, and diminished IKK and NF-κB activation and I-κB degradation. The nuclear translocation of NF-κB was inhibited, following by down-regulation of TNF-α gene transcription. In addition, LPS intratracheal instillation induced marked oxidative damage, such as a decrease in total anti-oxidation products and an increase in malondialdehyde (MDA), as well as up-regulation of oxidation enzymes. Histologic analysis and apoptosis scores revealed that the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-α blockade. Conclusion Treatment with LPS alone

  11. Pulmonary hypertension and pulmonary artery dissection

    PubMed Central

    Corrêa, Ricardo de Amorim; Silva, Luciana Cristina dos Santos; Rezende, Cláudia Juliana; Bernardes, Rodrigo Castro; Prata, Tarciane Aline; Silva, Henrique Lima

    2013-01-01

    Pulmonary artery dissection is a fatal complication of long-standing pulmonary hypertension, manifesting as acute, stabbing chest pain, progressive dyspnea, cardiogenic shock, or sudden death. Its incidence has been underestimated, and therapeutic options are still scarce. In patients with pulmonary hypertension, new chest pain, acute chest pain, or cardiogenic shock should raise the suspicion of pulmonary artery dissection, which can result in sudden death. PMID:23670510

  12. [Pulmonary hyalinizing granuloma mimicking pulmonary carcinoma].

    PubMed

    Uçvet, Ahmet; Tözüm, Halil; Gürsoy, Soner; Gülle, Ali Alper; Yaldiz, Sadik; Aydoğdu Dinç, Zekiye

    2006-01-01

    Pulmonary hyalinizing granuloma is a rare fibrosing nodular disease of the lung characterized by solitary or multiple pulmonary nodules. They can occur after inflammatory or post-inflammatory changes. A 60 years old asymptomatic patient admitted to our clinic because of a solid mass of 6 cm in his routine chest radiography. A lobectomy was performed and the histological diagnosis was reported as pulmonary hyalinizing granuloma. This case, mimicking pulmonary carcinoma, is rarely found in the literature. PMID:16615022

  13. Spindle cell sarcoma of pulmonary artery mimicking thromboembolism with lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Pattabiraman, Vr; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2014-10-01

    Pulmonary artery sarcoma (PAS), although rare, must be considered in the differential diagnosis of pulmonary thromboembolism (PTE). This tumor is highly malignant and the prognosis is very poor. As much as the standardized uptake values (SUVs) at fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) have helped in differentiating between benign and malignant tumors, visualization of a low-attenuation filling defect within a pulmonary artery on contrast-enhanced chest computed tomography (CT) can be suggestive of a malignancy, such as PAS, if the lesion shows high FDG uptake at PET. We present a case of PAS that showed high FDG uptake on integrated FDG PET/CT and with lung metastasis. Patient underwent endoscopic bronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA), which confirmed spindle cell sarcoma.

  14. Spindle cell sarcoma of pulmonary artery mimicking thromboembolism with lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Pattabiraman, VR; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan

    2014-01-01

    Pulmonary artery sarcoma (PAS), although rare, must be considered in the differential diagnosis of pulmonary thromboembolism (PTE). This tumor is highly malignant and the prognosis is very poor. As much as the standardized uptake values (SUVs) at fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) have helped in differentiating between benign and malignant tumors, visualization of a low-attenuation filling defect within a pulmonary artery on contrast-enhanced chest computed tomography (CT) can be suggestive of a malignancy, such as PAS, if the lesion shows high FDG uptake at PET. We present a case of PAS that showed high FDG uptake on integrated FDG PET/CT and with lung metastasis. Patient underwent endoscopic bronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA), which confirmed spindle cell sarcoma. PMID:25400365

  15. Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... CDC.gov . Hantavirus Share Compartir Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS) Diagnosing HPS Diagnosing HPS in ... of patients that develop HPS from New World Hantaviruses recover completely. No chronic infection has been detected ...

  16. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms. PMID:3533597

  17. Detection of Intrathoracic Bleeding by 99mTc-Labeled Red Blood Cell SPECT/CT After Wedge Biopsy of Pulmonary Angiosarcoma.

    PubMed

    Provost, Karine; Charest, Mathieu

    2016-09-01

    A 52-y-old man presenting with dyspnea and a massive effusion in the right pleural cavity underwent wedge biopsies of pulmonary lesions found on thoracic CT, leading to a diagnosis of pleural angiosarcoma. Bleeding developed postoperatively and was investigated using pulmonary CT angiography, which failed to identify a site of active bleeding. (99m)Tc-labeled red blood cell (RBC) SPECT/CT of the chest was performed, and the site was rapidly located. To our knowledge, this is the first case reported in the literature of localization of intrathoracic bleeding using (99m)Tc-RBC SPECT/CT. PMID:27363446

  18. Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema.

    PubMed

    Tanaka, Ken-Ichiro; Tanaka, Yuta; Miyazaki, Yuri; Namba, Takushi; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru

    2011-09-01

    No medication exists that clearly improves the mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions, play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn- SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leukocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema, and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of proinflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smoke-induced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in the inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.

  19. Pulmonary haemodynamics in obstructive sleep apnoea.

    PubMed

    Marrone, Oreste; Bonsignore, Maria Rosaria

    2002-06-01

    In patients with obstructive sleep apnoea syndrome (OSAS), pulmonary haemodynamics can show both transient perturbations during sleep and permanent alterations. During sleep, repeated fluctuations in pulmonary artery pressure and pulmonary wedge pressure, coincident with apnoeas, can be observed. Calculation of transmural pressure values is preferable to intravascular pressures in OSAS, due to the marked swings in intrathoracic pressure associated with obstructive apnoeas. Pulmonary artery pressure may progressively increase during sleep, particularly in close sequences of highly desaturating apnoeas. Apnoea-induced hypoxia appears as the most important determinant of this pulmonary artery pressure behaviour. Stroke volume and cardiac output during obstructive apnoeas show changes mainly related to intrathoracic pressure variations. Permanent precapillary pulmonary hypertension at rest is observed in <50% OSAS patients, and is poorly reversible after OSAS treatment. It correlates best with diurnal respiratory function parameters. However, the finding of pulmonary hypertension in some patients with near normal diurnal lung function led to suggest that sleep respiratory disorders may contribute to permanent pulmonary haemodynamic impairment in predisposed subjects. Knowledge on right ventricle hypertrophy in OSAS is inconsistent. As to right ventricle failure, it is clinically evident in subjects with associated lung disease or morbid obesity, while it may be detected instrumentally in subjects without such alterations, presumably as effect of apnoeas themselves. Besides, it appears more fully reversible after long-term OSAS treatment than pulmonary hypertension. PMID:12531120

  20. Macrophages in Vascular Inflammation: Origins and Functions.

    PubMed

    Decano, Julius L; Mattson, Peter C; Aikawa, Masanori

    2016-06-01

    Macrophages influence various processes of cardiovascular inflammation. Whether they are of embryonic or post-natal hematopoietic origin, their balance in differential activation may direct the course of inflammation. Accelerated macrophage activation and accumulation through a pro-inflammatory signaling pathway may result in extensive tissue damage, adverse repair, and worsened clinical outcomes. Attenuation of such a mechanism and/or promotion of the anti-inflammatory macrophage activation may lead to early resolution of inflammation. Elucidating multiple novel mechanisms of monocyte and macrophage activation leads to a better understanding of their roles in vascular inflammation. In turn, this begets better therapeutic target identification and biomarker discovery. Combined with increasingly sensitive and specific imaging techniques, we continue to push back early detection and monitoring to provide us with a greater window for disease modification. The potential success of cytokine-targeted therapy will be solid proof of the inflammatory hypothesis of atherothrombosis. PMID:27125207

  1. [Novel immunopathological approaches to pulmonary arterial hypertension].

    PubMed

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition. PMID:21536178

  2. Sterile inflammation in acute liver injury: myth or mystery?

    PubMed

    Woolbright, Benjamin L; Jaeschke, Hartmut

    2015-01-01

    Inflammation during liver injury normally serves as a mechanism for cleaning up debris and as a stimulant for regeneration. However, aberrant levels of inflammation can provoke further liver injury and inhibit regeneration through the release of damaging reactive oxygen species. Considerable effort has gone into understanding the mechanisms that control the switch between healthy and pathological inflammation. The identification of a receptor system that detects damage-associated molecular patterns and stimulates inflammation has led to the idea of sterile inflammation. This article will focus on the role of sterile inflammation during liver injury in three models where sterile inflammation has been presumed to mediate a portion of the injury mechanism and its potential relevance for the human pathophysiology. PMID:26186639

  3. Morphological characteristics of potentially malignant pulmonary nodules in high-risk male smokers detected in lung cancer screening trial in Cracow, Poland.

    PubMed

    Kiszka, K; Rudnicka-Sosin, L; Tomaszewska, R; Urbańczyk-Zawadzka, M; Krupiński, M; Pikul, P; Podsiadło, K; Pasowicz, M; Vliegenthart, R; Oudkerk, M; Miszalski-Jamka, T

    2013-06-01

    The purpose of this paper was to present morphological characteristics of potentially malignant nodules revealed in a group of male smokers aged 50-74 with a very high risk for developing lung cancer estimated in the study for lung cancer screening in Cracow (Poland). Nine hundred male smokers aged 50 to 74 years were invited to the study and were asked in questionnaires about e.g. smoking exposure history. Exclusion criteria included e.g. positive cancer history and chest computed tomography (CT) examination in the previous year. Based on CT results and characteristics of pulmonary nodules subjects were classified to group A (low risk), group B (indeterminate) and group C (high-risk individuals - required work-up). Final diagnosis was based on pathological results of postoperative material. Thirty-nine males of mean age 63.4 (standard deviation (SD): 6.69 years) revealed 41 potentially malignant pulmonary nodules in baseline screening. In 14 subjects 16 type C pulmonary nodules were histologically proved. Nine nodules were found to be benign lesions, while 7 nodules revealed malignant lung cancer: 5 cases of adenocarcinoma and 2 cases of adenosquamous carcinoma. We determined morphological characteristics of potentially malignant pulmonary nodules in 39 high-risk male smokers and proved lung cancer in 7 subjects.

  4. Inflammation and haemostasis.

    PubMed

    Margetic, Sandra

    2012-01-01

    Inflammation and haemostasis are interrelated pathophysiologic processes that considerably affect each other. In this bidirectional relationship, inflammation leads to activation of the haemostatic system that in turn also considerably influences inflammatory activity. Such, the haemostatic system acts in concert with the inflammatory cascade creating an inflammation-haemostasis cycle in which each activated process promotes the other and the two systems function in a positive feedback loop. The extensive crosstalk between immune and haemostatic systems occurs at level of all components of the haemostatic system including vascular endothelial cells, platelets, plasma coagulation cascade, physiologic anticoagulants and fibrinolytic activity. During inflammatory response, inflammatory mediators, in particular proinflammatory cytokines, play a central role in the effects on haemostatic system by triggering its disturbance in a number of mechanisms including endothelial cell dysfunction, increased platelet reactivity, activation of the plasma coagulation cascade, impaired function of physiologic anticoagulants and suppressed fibrinolytic activity. The two examples of pathophysiologic processes in which the tight interdependent relationship between inflammation and haemostasis considerably contribute to the pathogenesis and/or progression of disease are systemic inflammatory response to infection or sepsis and acute arterial thrombosis as a consequence of ruptured atherosclerotic plaque. Close links between inflammation and haemostasis help explain the prothrombotic tendency in these two clinical conditions in which inflammation shifts the haemostatic activity towards procoagulant state by the ability of proinflammatory mediators to activate coagulation system and to inhibit anticoagulant and fibrinolytic activities. This review summarizes the current knowledge of the complex interactions in the bidirectional relationship between inflammation and haemostasis.

  5. Postoperative Acute Pulmonary Embolism Following Pulmonary Resections

    PubMed Central

    Shonyela, Felix Samuel; Liu, Bo; Jiao, Jia

    2015-01-01

    Postoperative acute pulmonary embolism after pulmonary resections is highly fatal complication. Many literatures have documented cancer to be the highest risk factor for acute pulmonary embolism after pulmonary resections. Early diagnosis of acute pulmonary embolism is highly recommended and computed tomographic pulmonary angiography is the gold standard in diagnosis of acute pulmonary embolism. Anticoagulants and thrombolytic therapy have shown a great success in treatment of acute pulmonary embolism. Surgical therapies (embolectomy and inferior vena cava filter replacement) proved to be lifesaving but many literatures favored medical therapy as the first choice. Prophylaxis pre and post operation is highly recommended, because there were statistical significant results in different studies which supported the use of prophylaxis in prevention of acute pulmonary embolism. Having reviewed satisfactory number of literatures, it is suggested that thoroughly preoperative assessment of patient conditions, determining their risk factors complicating to pulmonary embolism and the use of appropriate prophylaxis measures are the key options to the successful minimization or eradication of acute pulmonary embolism after lung resections. PMID:26354232

  6. Lung preservation: pulmonary flush route affects bronchial mucosal temperature and expression of IFN-gamma and Gro in regional lymph nodes.

    PubMed

    Roe, David W; Fehrenbacher, John W; Niemeier, Michael R; Zieger, Michael; Labarrere, Carlos; Wilkes, David S

    2005-05-01

    Optimal lung preservation via flush of the pulmonary vasculature minimizes early graft failure post-lung transplantation. We hypothesized that the route of pulmonary flush has differential effects on thermal gradients in the lung and expression of inflammatory mediators. Swine underwent antegrade flush (AG) via pulmonary artery; AG/RG: antegrade + retrograde flush via pulmonary veins or AG/BA: antegrade + bronchial artery flush via bronchial artery. Temperatures were recorded in bronchial mucosa and peribronchial lymph nodes. RT-PCR was utilized to detect cytokine gene expression in the nodes. AG/BA flush resulted in greatest cooling of bronchial mucosa and lymph nodes (p < 0.001). The route of flush did not affect expression of RANTES, MCP-1, IL-8, IL-1beta, TNF-alpha or IL-6. However, expression of Gro was reduced 4-h post-preservation in all groups. Only AG/BA resulted in decreased IFN-gamma transcripts. These data show that, compared to AG or AG/RG, AG/BA flush results in the greatest cooling of lung compartments and down regulates lymph node expression of a cytokine and chemokine that have key roles in inflammation and immunity. These data suggest that pulmonary flush via AG/BA during donor harvest may be optimal to decrease the risk of early graft failure.

  7. Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice.

    PubMed

    Shi, Keyun; Jiang, Jianzhong; Ma, Tieliang; Xie, Jing; Duan, Lirong; Chen, Ruhua; Song, Ping; Yu, Zhixin; Liu, Chao; Zhu, Qin; Zheng, Jinxu

    2014-01-01

    Our objective was to investigate the pathogenesis pathways of idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental lung fibrosis were used. CHIP assay was executed to find the link between Smad3 and IL-31, and the expressions of TGF-β1, Smad3, IL-31 and STAT1 were detected to find whether they were similar with each other. We found that in the early injury or inflammation of the animal model, BLM promoted the development of inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF-β1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region, followed by the activation of JAK-STAT pathways. The inhibitor of TGF-β1 receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM-induced mouse model that involves the TGF-β, IL-31 and JAKs/STATs pathway.

  8. [Inflammation and diabetes].

    PubMed

    Löbner, K; Füchtenbusch, M

    2004-09-01

    The focus of current diabetes research is the clarification of the pathogenetic relationships between subclinical inflammation, diabetes and arteriosclerosis. Even minimal disturbances in glucose tolerance are associated with a chronic, generalized inflammatory reaction that links components of the metabolic syndrome and contributes to the development of diabetic complications as well as to the development and progression of arteriosclerosis. The most important mediators and markers of this inflammation cascade are NF-kappaB, TNF-alpha, IL-6, CRP and PAI-1. For the treatment of subclinical inflammation, substances with anti-inflammatory properties such as statins or ACE inhibitors are of increasing importance.

  9. Estrogens, inflammation and cognition.

    PubMed

    Au, April; Feher, Anita; McPhee, Lucy; Jessa, Ailya; Oh, Soojin; Einstein, Gillian

    2016-01-01

    The effects of estrogens are pleiotropic, affecting multiple bodily systems. Changes from the body's natural fluctuating levels of estrogens, through surgical removal of the ovaries, natural menopause, or the administration of exogenous estrogens to menopausal women have been independently linked to an altered immune profile, and changes to cognitive processes. Here, we propose that inflammation may mediate the relationship between low levels of estrogens and cognitive decline. In order to determine what is known about this connection, we review the literature on the cognitive effects of decreased estrogens due to oophorectomy or natural menopause, decreased estrogens' role on inflammation--both peripherally and in the brain--and the relationship between inflammation and cognition. While this review demonstrates that much is unknown about the intersection between estrogens, cognition, inflammation, we propose that there is an important interaction between these literatures.

  10. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung

    PubMed Central

    Hwang, Ji Young; Randall, Troy D.; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity. PMID:27446088

  11. Vitamin D and inflammation

    PubMed Central

    Cannell, John J; Grant, William B; Holick, Michael F

    2014-01-01

    Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints. PMID:26413186

  12. Orbital inflammation: Corticosteroids first.

    PubMed

    Dagi Glass, Lora R; Freitag, Suzanne K

    2016-01-01

    Orbital inflammation is common, and may affect all ages and both genders. By combining a thorough history and physical examination, targeted ancillary laboratory testing and imaging, a presumptive diagnosis can often be made. Nearly all orbital inflammatory pathology can be empirically treated with corticosteroids, thus obviating the need for histopathologic diagnosis prior to initiation of therapy. In addition, corticosteroids may be effective in treating concurrent systemic disease. Unless orbital inflammation responds atypically or incompletely, patients can be spared biopsy.

  13. Epidemic inflammation: pondering obesity.

    PubMed

    Nathan, Carl

    2008-01-01

    Over the past two decades, inflammation has been recognized as a major driver in the pathogenesis of several common diseases, including atherosclerosis, diabetes, cancer, and asthma. Over the same period, there has been a steep rise in the incidence of obesity, a major risk factor for these disorders. Inflammation of adipose tissue is now recognized to accompany obesity and contribute to its sequelae. Thus, whereas obesity is primarily a disorder of energy balance, it may be helpful to consider it also as a form of epidemic inflammation that predisposes to other forms of epidemic inflammation. It is a fundamental biologic challenge to understand how a positive energy balance and inflammation are linked. This work reviews evidence that reactive oxygen and nitrogen intermediates (ROI and RNI) help drive chronic inflammation in the obese. This is proposed to be a maladaptive instance of our evolved dependence on ROI and RNI for both homeostatic signaling and host defense. ROI and RNI are well suited for these seemingly contradictory dual functions by their metabolic origin, high diffusibility in water and lipid, atomic specificity, and large number of molecular targets. When we eat so much and work so little that we repeatedly generate reactive compounds at levels normally reserved for emergencies, we treat our own cells like invading microbes.

  14. Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas aeruginosa-induced pneumonia in rats.

    PubMed

    Cornet, Alexander D; Hofstra, Jorrit J; Vlaar, Alexander P; van den Boogaard, Floor E; Roelofs, Joris J; van der Poll, Tom; Levi, Marcel; Groeneveld, A B Johan; Schultz, Marcus J

    2011-10-01

    Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia. Inhibitors of coagulation could exert lung-protective effects via anticoagulant (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could also affect host defense. In this randomized controlled in vivo laboratory study, rats were challenged intratracheally with Pseudomonas aeruginosa, inducing pneumonia, and randomized to local treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin, or danaparoid. Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-AT complexes and fibrin degradation products and decreased pulmonary levels plasminogen activator activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of thrombin-AT complexes increased, and systemic levels of plasminogen activator activity decreased. Although rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. Nebulization of rh-APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial clearance or inflammation, in a rat model of P. aeruginosa pneumonia. PMID:21897338

  15. Experimental pulmonary paracoccidioidomycosis in mice: morphology and correlation of lesions with humoral and cellular immune response.

    PubMed

    Defaveri, J; Rezkallah-Iwasso, M T; de Franco, M F

    1982-01-15

    The present paper describes a murine model for pulmonary paracoccidioidomycosis injecting 6 X 10(5) yeast forms of Paracoccidioides brasiliensis (Pb) by the direct intratracheal route. The sequential histopathology of lung and dissemination lesions together with humoral (immunodiffusion test) and cellular immune response (footpad test and macrophage inhibition factor assay - MIF assay) were investigated since the 1st to the 360th day after infection. All infected animal showed pulmonary Pbmycosis up to Day 30; onwards the lesions subsided being found only in one mouse at Day 360. Dissemination lesions were observed in paratracheal and cervical lymph nodes in 9 out of 68 infected animals. Histologically early lesions were rich in polymorphonuclear cells and evolved to a macrophage desquamative pneumonitis at Day 15 and to typical epithelioid granulomata from Day 30 up to Day 360. Specific precipitating antibodies were first detected 15 days after infection, peaked from Day 30 to 60 and were not observed at Day 360. Significant cell-mediated immunity to Pb was noted at Day 15 with the peak reaction at Day 60 and 90. The intratracheal route represents a highly effective way of infecting mouse with Pb. This experimental pulmonary Pbmycosis is a granulomatous inflammation which courses with specific humoral and cellular immune response. It may be a good tool for further investigation in the pathogenesis and natural history of the disease.

  16. Effect of hypoxia on lung gene expression and proteomic profile: insights into the pulmonary surfactant response

    PubMed Central

    Olmeda, Bárbara; Umstead, Todd M.; Silveyra, Patricia; Pascual, Alberto; López-Barneo, José; Phelps, David S.; Floros, Joanna; Pérez-Gil, Jesús

    2014-01-01

    Exposure of lung to hypoxia has been previously reported to be associated with significant alterations in the protein content of bronchoalveolar lavage (BAL) and lung tissue. In the present work we have used a proteomic approach to describe the changes in protein complement induced by moderate long-term hypoxia (rats exposed to 10% O2 for 72 hours) in BAL and lung tissue, with a special focus on the proteins associated with pulmonary surfactant, which could indicate adaptation of this system to limited oxygen availability. The analysis of the general proteomic profile indicates a hypoxia-induced increase in proteins associated with inflammation both in lavage and lung tissue. Analysis at mRNA and protein levels revealed no significant changes induced by hypoxia on the content in surfactant proteins or their apparent oligomeric state. In contrast, we detected a hypoxia-induced significant increase in the expression and accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as well as an accumulation of hemoglobin both in BAL and associated with surface-active membranes of the pulmonary surfactant complex. Evaluation of pulmonary surfactant surface activity from hypoxic rats showed no alterations in its spreading ability, ruling out inhibition by increased levels of serum or inflammatory proteins. PMID:24576641

  17. Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive ana...

  18. Pathogenic mechanism of second hand smoke induced inflammation and COPD

    PubMed Central

    Birru, Rahel L.; Di, Y. Peter

    2012-01-01

    Second hand smoke (SHS) introduces thousands of toxic chemicals into the lung, including carcinogens and oxidants, which cause direct airway epithelium tissue destruction. It can also illicit indirect damage through its effect on signaling pathways related to tissue cell repair and by the abnormal induction of inflammation into the lung. After repeated exposure to SHS, these symptoms can lead to the development of pulmonary inflammatory disorders, including chronic obstructive pulmonary disease (COPD). COPD is a severe pulmonary disease characterized by chronic inflammation and irreversible tissue destruction. There is no causal cure, as the mechanism behind the development and progression of the disease is still unknown. Recent discoveries implicate genetic predisposition associated with inflammatory response contributed to the development of COPD, linked to irregular innate and adaptive immunity, as well as a risk factor for cancer. The use of animal models for both cigarette smoke (CS) and SHS associated in vivo experiments has been crucial in elucidating the pathogenic mechanisms and genetic components involved in inflammation-related development of COPD. PMID:22973236

  19. The Role of Peroxisome Proliferator-Activated Receptors in Pulmonary Vascular Disease

    PubMed Central

    Nisbet, Rachel E.; Sutliff, Roy L.; Hart, C. Michael

    2007-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that regulate diverse physiological processes ranging from lipogenesis to inflammation. Recent evidence has established potential roles of PPARs in both systemic and pulmonary vascular disease and function. Existing treatment strategies for pulmonary hypertension, the most common manifestation of pulmonary vascular disease, are limited by an incomplete understanding of the underlying disease pathogenesis and lack of efficacy indicating an urgent need for new approaches to treat this disorder. Derangements in pulmonary endothelial-derived mediators and endothelial dysfunction have been shown to play a pivotal role in pulmonary hypertension pathogenesis. Therefore, the following review will focus on selected mediators implicated in pulmonary vascular dysfunction and evidence that PPARs, in particular PPARγ, participate in their regulation and may provide a potential novel therapeutic target for the treatment of pulmonary hypertension. PMID:17710111

  20. Pulmonary endarterectomy after pulmonary infectious embolisms

    PubMed Central

    Heiberg, Johan; Ilkjær, Lars B.

    2013-01-01

    Pulmonary endarterectomy (PEA) is a well-established procedure in the treatment of chronic thromboembolic pulmonary hypertension (CTPH). The procedure is known to increase functional outcome and to raise the 5-year survival rate. We report 2 cases of pulmonary valve endocarditis and secondary embolisms causing sustained pulmonary hypertension. Both were treated with PEA. In none of the cases, a cleavage between the thrombotic masses and the vessel wall was obtainable, and both attempts were therefore inadequate. Based on our reports, we recommend not attempting PEA in cases of CTPH after infectious embolisms. PMID:23248168

  1. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  2. [Connective tissue and inflammation].

    PubMed

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  3. A study of magnesium deficiency in human and experimental pulmonary hypertension.

    PubMed

    Chaumais, Marie-Camille; Lecerf, Florence; Fattal, Soly; Savale, Laurent; Günther, Sven; Huertas, Alice; Montani, David; Perros, Frederic; Humbert, Marc; German-Fattal, Michèle

    2012-03-01

    Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure above 25 mmHg. Pulmonary vasoconstriction, cellular proliferation, inflammation, and oxidative stress are involved in the pathophysiology of PH. Since hypomagnesemia was reported to promote endothelial cell dysfunction leading to inflammation and oxidative stress, we investigated the potential involvement of magnesium (Mg) deficiency in experimental and human PH. Our results indicate that Mg deficiency has no impact on hypoxia-induced PH development or severity, and that no reduction in Mg plasma concentration was observed in patients with severe pulmonary arterial hypertension. Thus, hypomagnesemia does not appear to play a role in the pathophysiology of experimental and human pulmonary hypertension. PMID:22433438

  4. Familial Pulmonary Fibrosis

    MedlinePlus

    ... are here: Health Information > Condition Information Familial Pulmonary Fibrosis: Overview When two or more members within the ... Associate Professor View full profile More Familial Pulmonary Fibrosis Information Forms Causes Genetic Counseling Print Page Email ...

  5. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...

  6. Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... this page: About CDC.gov . Hantavirus Share Compartir Hantavirus Pulmonary Syndrome (HPS) Severe HPS. Image courtesy D. ... the workers showed evidence of infection or illness. Hantavirus Pulmonary Syndrome (HPS) Topics Transmission Where HPS is ...

  7. Who Needs Pulmonary Rehabilitation?

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... other symptoms. Examples of interstitial lung diseases include sarcoidosis and idiopathic pulmonary fibrosis . Cystic fibrosis (CF). CF ...

  8. Physiological mechanisms of pulmonary hypertension.

    PubMed

    MacIver, David H; Adeniran, Ismail; MacIver, Iain R; Revell, Alistair; Zhang, Henggui

    2016-10-01

    Pulmonary hypertension is usually related to obstruction of pulmonary blood flow at the level of the pulmonary arteries (eg, pulmonary embolus), pulmonary arterioles (idiopathic pulmonary hypertension), pulmonary veins (pulmonary venoocclusive disease) or mitral valve (mitral stenosis and regurgitation). Pulmonary hypertension is also observed in heart failure due to left ventricle myocardial diseases regardless of the ejection fraction. Pulmonary hypertension is often regarded as a passive response to the obstruction to pulmonary flow. We review established fluid dynamics and physiology and discuss the mechanisms underlying pulmonary hypertension. The important role that the right ventricle plays in the development and maintenance of pulmonary hypertension is discussed. We use principles of thermodynamics and discuss a potential common mechanism for a number of disease states, including pulmonary edema, through adding pressure energy to the pulmonary circulation. PMID:27659877

  9. Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity.

    PubMed

    Hasday, Jeffrey D; Garrison, Allen; Singh, Ishwar S; Standiford, Theodore; Ellis, Garrettson S; Rao, Srinivas; He, Ju-Ren; Rice, Penny; Frank, Mariah; Goldblum, Simeon E; Viscardi, Rose M

    2003-06-01

    Febrile-range hyperthermia (FRH) improves survival in experimental infections by accelerating pathogen clearance, but may also increase collateral tissue injury. We hypothesized that FRH would worsen the outcome of inflammation stimulated by a non-replicating agonist and tested this hypothesis in a murine model of pulmonary oxygen toxicity. Using a conscious, temperature-controlled mouse model, we showed that maintaining a core temperature at FRH (39 degrees C to 40 degrees C) rather than at euthermic levels (36.5 degrees C to 37 degrees C) during hyperoxia exposure accelerated lethal pulmonary vascular endothelial injury, reduced the inspired oxygen threshold for lethality, induced expression of granulocyte-colony stimulating factor, and expanded the circulating neutrophil pool. In these same mice, FRH augmented pulmonary expression of the ELR(+) CXC chemokines, KC and LPS-induced CXC chemokine, enhanced recruitment of neutrophils, and changed the histological pattern of lung injury to a neutrophilic interstitial pneumonitis. Immunoblockade of CXC receptor-2 abrogated neutrophil recruitment, reduced pulmonary vascular injury, and delayed death. These combined data demonstrate that FRH may enlist distinct mediators and effector cells to profoundly shift the host response to a defined injurious stimulus, in part by augmenting delivery of neutrophils to sites of inflammation, such as may occur in infections. In certain conditions, such as in the hyperoxic lung, this process may be deleterious.

  10. Lung Cancer Risk Following Detection of Pulmonary Scarring by Chest Radiography in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Yu, Ying-Ying; Pinsky, Paul F.; Caporaso, Neil E.; Chatterjee, Nilanjan; Baumgarten, Mona; Langenberg, Patricia; Furuno, Jon P.; Lan, Qing; Engels, Eric A.

    2010-01-01

    Background Fibrotic scars are frequently found in proximity to lung cancer at the time of cancer diagnosis. However, the nature of the relationship between pulmonary scarring and lung cancer remains uncertain. Our objective was to test whether localized pulmonary scarring is associated with increased lung cancer risk. Methods Cohort analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We included 66 863 cancer-free trial participants aged 55 to 74 years, who received a baseline chest radiographic examination and were followed up subsequently for up to 12 years. We used proportional hazards models to estimate hazard ratios (HRs) for lung cancer associated with scarring, adjusting for age, sex, race, and cigarette smoking, and in relation to laterality of scarring. The main outcome measure was incident lung cancer. Results Scarring was present on the baseline chest radiograph for 5041 subjects (7.5%). Scarring was associated with elevated lung cancer risk (809 lung cancer cases [HR, 1.5; 95% confidence interval {CI}, 1.2-1.8]). This association was specific for cancer in the lung ipsilateral to the scar (HR, 1.8; 95% CI, 1.4-2.4) and absent for contralateral cancer (HR, 0.9; 95% CI, 0.7-1.2). Ipsilateral lung cancer risk was elevated throughout the follow-up period (interval-specific HRs, 1.6, 2.0, 2.1, and 1.7 during 0.01-2.00, 2.01-4.00, 4.01-6.00, and 6.01-12.00 years after baseline chest radiography, respectively). Conclusions The relationship between pulmonary scarring and lung cancer was specific to the same lung and extended over time. These findings are consistent with the hypothesis that localized inflammatory processes associated with scarring promote the subsequent development of lung cancer. PMID:19029496

  11. Association Between Pulmonary Uptake of Fluorodeoxyglucose Detected by Positron Emission Tomography Scanning After Radiation Therapy for Non-Small-Cell Lung Cancer and Radiation Pneumonitis

    SciTech Connect

    Mac Manus, Michael P.; Ding Zhe; Hogg, Annette; Herschtal, Alan; Binns, David; Ball, David L.; Hicks, Rodney J.

    2011-08-01

    Purpose: To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis. Methods and Materials: In 88 consecutive patients, {sup 18}F-FDG-positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score. Results: There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis. Conclusions: The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. {sup 18}F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.

  12. Inflammation and cancer

    PubMed Central

    Coussens, Lisa M.; Werb, Zena

    2009-01-01

    Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development. PMID:12490959

  13. Quercetin, Inflammation and Immunity

    PubMed Central

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-01-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  14. Quercetin, Inflammation and Immunity.

    PubMed

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-03-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  15. Dual left anterior descending artery with anomalous origin of long LAD from pulmonary artery - rare coronary anomaly detected on computed tomography coronary angiography

    PubMed Central

    Vohra, Aditi; Narula, Harneet

    2016-01-01

    Dual left anterior descending artery is a rare coronary artery anomaly showing two left anterior descending arteries. Short anterior descending artery usually arises from the left coronary artery, while long anterior descending artery has anomalous origin and course. Dual left anterior descending artery with origin of long anterior descending artery from the pulmonary artery (ALCAPA) is a very rare coronary artery anomaly which has not been reported previously in the literature. We present the computed tomography coronary angiographic findings of this rare case in a young female patient who presented with atypical chest pain. PMID:27413266

  16. Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis.

    PubMed Central

    Jang, An-Soo

    2002-01-01

    There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR. PMID:12482998

  17. Pulmonary hyalinizing granuloma.

    PubMed

    Gans, S J; van der Elst, A M; Straks, W

    1988-04-01

    A patient with pulmonary hyalinizing granuloma (PHG) is presented. PHG is a rare disease with very specific histological characteristics. Roentgenograms display multiple bilateral pulmonary nodules which may be cavitated. Evidence exists that the nodules are the result of an exaggerated chronic immune response. The course of the disease is generally favourable. PHG should be considered in patients showing multiple bilateral pulmonary nodules. PMID:2456228

  18. Diagnostic Value of Dual-Source Computerized Tomography Combined with Perfusion Imaging for Peripheral Pulmonary Embolism

    PubMed Central

    Mao, Xijin; Wang, Shanshan; Jiang, Xingyue; Zhang, Lin; Xu, Wenjian

    2016-01-01

    Background Pulmonary embolism has become the third most common cardiovascular disease, which can seriously harm human health. Objectives To investigate the diagnostic value of dual-source computerized tomography (CT) and perfusion imaging for peripheral pulmonary embolism. Patients and Methods Thirty-two patients with suspected pulmonary embolism underwent dual-source CT exams. To compare the ability of pulmonary embolism detection software (PED) with CT pulmonary angiography (CTPA) in determining the presence, numbers, and locations of pulmonary emboli, the subsequent images were reviewed by two radiologists using both imaging modalities. Also, the diagnostic consistency between PED and CTPA images and dual-energy pulmonary perfusion imaging (DEPI) for segmental pulmonary embolism was compared. Results CTPA images revealed 50 (7.81%) segmental and 56 (4.38%) sub-segmental pulmonary embolisms, while the PED images showed 68 (10.63%) segmental and 94 (7.34%) sub-segmental pulmonary embolisms. Thus, the detection rate on PED images for peripheral pulmonary embolism was significantly higher than that of the CTPA images (P < 0.05). There was good consistency for diagnosing segmental pulmonary embolism between PED and CTPA and DEPI (kappa = 0.85). The sensitivity and specificity of DEPI images for the diagnosis of pulmonary embolism were 91.7% and 97.5%, respectively. Conclusion PED software of dual-source CT combined with perfusion imaging can significantly improve the detection rate of peripheral pulmonary embolism.

  19. Effect of Pregnancy Serum on Experimental Inflammation

    PubMed Central

    Persellin, R. H.; Vance, S. E.; Peery, A.

    1974-01-01

    Experimental inflammation induced in the rat by injection of carrageenin was suppressed by prior administration of pooled serum obtained from pregnant human females. Inflammatory oedema in the rat hind paw measured by a plethysmograph was inhibited 81% by 10 ml of pregnancy serum pool and the effect was dose related. Non-pregnant female serum was inhibitory to a lesser degree and no anti-inflammatory action was detected using cord serum. Although adrenal corticosteroid hormones could modify this inflammatory model, their presence in the serum pools could not account for the effects observed. Since carrageenin is sequestered within phagolysosomes and provokes release of their inflammation-inducing contents, it is suggested that the protective effect of pregnancy serum on carrageenin inflammation is mediated via lysosomal stabilization. PMID:4835795

  20. Recurrent pulmonary hyalinizing granuloma.

    PubMed

    Arruda, Guilherme D'Andréa Saba; Carvalho, Paulo César Ribeiro de; Andrade, Mara Patrícia Guilhermino de; Cusmanich, Maurício Campos; Bandeira, Gustavo; Tozaki, Felipe Shigueo Passos

    2010-01-01

    We report the case of a 61-year-old male patient who underwent surgical excision of a lung mass for anatomopathological study. The patient had previously presented with fever, dry cough, and chest pain, together with lung masses detected by chest X-ray, and had undergone thoracotomy for diagnostic investigation on two occasions (1976 and 1981), although a conclusive diagnosis had not been made. A CT scan of the chest revealed large masses with areas of calcification in both lung fields. The anatomopathological study was consistent with pulmonary hyalinizing granuloma. In the postoperative period, the patient experienced several episodes of bronchospasm, which was reversible with the use of symptomatic medication. At this writing, the patient was receiving maintenance therapy with prednisone (40 mg/day) and had shown clinical improvement. PMID:21085833