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Sample records for acute pulmonary inflammation

  1. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  2. Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

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    Menk M

    2018-05-01

    Full Text Available Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2 receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21 might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9, a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9, and a control group that received mechanical ventilation only (control, n=9. Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6

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

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    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...

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

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    Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden)

    2016-10-15

    We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-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 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-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 24 h, 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 24 h but did not influence the AHR. Inhalation of Cl{sub 2} 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 Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment

  5. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  6. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

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    Ken-Ichiro Inoue

    2011-01-01

    Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

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

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    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. Copyright © 2014 the American Physiological Society.

  8. Cytokine–Ion Channel Interactions in Pulmonary Inflammation

    Science.gov (United States)

    Hamacher, Jürg; Hadizamani, Yalda; Borgmann, Michèle; Mohaupt, Markus; Männel, Daniela Narcissa; Moehrlen, Ueli; Lucas, Rudolf; Stammberger, Uz

    2018-01-01

    The lungs conceptually represent a sponge that is interposed in series in the bodies’ systemic circulation to take up oxygen and eliminate carbon dioxide. As such, it matches the huge surface areas of the alveolar epithelium to the pulmonary blood capillaries. The lung’s constant exposure to the exterior necessitates a competent immune system, as evidenced by the association of clinical immunodeficiencies with pulmonary infections. From the in utero to the postnatal and adult situation, there is an inherent vital need to manage alveolar fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability edema. Whereas a wealth of literature exists on the physiological basis of fluid and solute reabsorption by ion channels and water pores, only sparse knowledge is available so far on pathological situations, such as in microbial infection, acute lung injury or acute respiratory distress syndrome, and in the pulmonary reimplantation response in transplanted lungs. The aim of this review is to discuss alveolar liquid clearance in a selection of lung injury models, thereby especially focusing on cytokines and mediators that modulate ion channels. Inflammation is characterized by complex and probably time-dependent co-signaling, interactions between the involved cell types, as well as by cell demise and barrier dysfunction, which may not uniquely determine a clinical picture. This review, therefore, aims to give integrative thoughts and wants to foster the unraveling of unmet needs in future research. PMID:29354115

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

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    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

    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.

  10. G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

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    Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

    2016-01-01

    Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

  11. Pulmonary inflammation and crystalline silica in respirable coal ...

    Indian Academy of Sciences (India)

    Unknown

    This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities. [Kuempel E D, Attfield M D, Vallyathan V, Lapp N L, Hale J M, Smith R J and Castranova V 2003 Pulmonary inflammation and ...

  12. Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

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    Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

    2012-01-01

    Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

  13. Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.

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    Zhang, Minlong; Wang, Li; Dong, Mingqing; Li, Zhichao; Jin, Faguang

    2014-10-28

    Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.

  14. Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Munthe-Fog, Lea

    2016-01-01

    acute lung and systemic inflammation induce recruitment of lectins in humans. METHODS: Fifteen healthy volunteers received LPS intravenously (IV) or in a lung subsegment on two different occasions. Volunteers were evaluated by consecutive blood samples and by bronchoalveolar lavage 2, 4, 6, 8, or 24h...... acute phase response with an increase in CRP (precruitment...

  15. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

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    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls

  16. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

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    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  17. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

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    Bengtson, Stefan; Knudsen, Kristina Bram; Kyjovska, Zdenka O.

    2017-01-01

    assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  19. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

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    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  20. Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs.

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    Foudi, Nabil; Badi, Aouatef; Amrane, Mounira; Hodroj, Wassim

    2017-12-01

    Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E 2 and PGI 2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE 2 , KCl, sodium nitroprusside, and acetylcholine. Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI 2 analogs through the impairment of cAMP pathway.

  1. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    DEFF Research Database (Denmark)

    Saber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction...... epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk...

  2. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

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    Izziki Mohamed

    2009-01-01

    Full Text Available Abstract Background Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH. Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6. Methods To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/- and wild-type (IL-6+/+ mice exposed to hypoxia for 2 weeks. Results Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. Conclusion These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

  3. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2012-07-01

    The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.

  4. Pulmonary edema in acute carbon monoxide poisoning

    International Nuclear Information System (INIS)

    Kim, Kun Sang; Chang, Kee Hyun; Lee, Myung Uk

    1974-01-01

    Acute carbon monoxide poisoning has frequently occurred in Korean, because of the coal briquette being widely used as fuel in Korean residences. Carbon monoxide poisoning has been extensively studied, but it has been sparsely reported that pulmonary edema may develop in acute CO poisoning. We have noticed nine cases of pulmonary edema in acute CO poisoning last year. Other possible causes of pulmonary edema could be exclude in all cases but one. The purpose of this paper is to describe nine cases of pulmonary edema complicated in acute CO poisoning and discuss the pathogenesis and the prognosis

  5. Pulmonary edema in acute carbon monoxide poisoning

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    Kim, Kun Sang; Chang, Kee Hyun; Lee, Myung Uk [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Acute carbon monoxide poisoning has frequently occurred in Korean, because of the coal briquette being widely used as fuel in Korean residences. Carbon monoxide poisoning has been extensively studied, but it has been sparsely reported that pulmonary edema may develop in acute CO poisoning. We have noticed nine cases of pulmonary edema in acute CO poisoning last year. Other possible causes of pulmonary edema could be exclude in all cases but one. The purpose of this paper is to describe nine cases of pulmonary edema complicated in acute CO poisoning and discuss the pathogenesis and the prognosis.

  6. Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.

    Directory of Open Access Journals (Sweden)

    M Carme Coll Ferrer

    Full Text Available 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.

  7. [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

    Science.gov (United States)

    Sánchez Marteles, Marta; Urrutia, Agustín

    2014-03-01

    Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index 30 mmHg) and absent or reduced diuresis (acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  8. Rosette nanotubes show low acute pulmonary toxicity in vivo

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    W Shane Journeay

    2008-10-01

    Full Text Available W Shane Journeay1, Sarabjeet S Suri1, Jesus G Moralez2, Hicham Fenniri2, Baljit Singh11Immunology Research Group, Toxicology Graduate Program and Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada; 2National Institute of Nanotechnology, National Research Council (NINT-NRC and Department of Chemistry, University of Alberta, 11421 Saskatchewan Drive, Edmonton, AB, T6G 2M9, CanadaAbstract: Nanotubes are being developed for a large variety of applications ranging from electronics to drug delivery. Common carbon nanotubes such as single-walled and multi-walled carbon nanotubes have been studied in the greatest detail but require solubilization and removal of catalytic contaminants such as metals prior to being introduced to biological systems for medical application. The present in vivo study characterizes the degree and nature of inflammation caused by a novel class of self-assembling rosette nanotubes, which are biologically inspired, naturally water-soluble and free of metal content upon synthesis. Upon pulmonary administration of this material we examined responses at 24 h and 7d post-exposure. An acute inflammatory response is triggered at 50 and 25 μg doses by 24 h post-exposure but an inflammatory response is not triggered by a 5 μg dose. Lung inflammation observed at a 50 μg dose at 24 h was resolving by 7d. This work suggests that novel nanostructures with biological design may negate toxicity concerns for biomedical applications of nanotubes. This study also demonstrates that water-soluble rosette nanotube structures represent low pulmonary toxicity, likely due to their biologically inspired design, and their self-assembled architecture.Keywords: nanotoxicology, biocompatibility, nanomedicine, pulmonary drug delivery, lung inflammation

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

    Directory of Open Access Journals (Sweden)

    Nascimento ESP

    2015-03-01

    Full Text Available Eloisa Sanches Pereira do Nascimento,1 Luciana Maria Malosá Sampaio,1 Fabiana Sobral Peixoto-Souza,1 Fernanda Dultra Dias,1 Evelim Leal Freitas Dantas Gomes,1 Flavia Regina Greiffo,2 Ana Paula Ligeiro de Oliveira,2 Roberto Stirbulov,3 Rodolfo Paula Vieira,2 Dirceu Costa11Laboratory of Functional Respiratory Evaluation (LARESP, 2Laboratory of Pulmonary and Exercise Immunology (LABPEI, Nove de Julho University (UNINOVE, São Paulo, SP, Brazil; 3Department of Pneumology, Santa Casa University Hospital, São Paulo, SP, BrazilAbstract: 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

  10. The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.

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    Duraisamy Kempuraj

    Full Text Available Acute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown.In duct ligation-induced acute pancreatitis in mice and rats, we found that (a IL-33 concentration was increased in the pancreas; (b mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c plasma histamine and pancreatic substance P concentrations were increased; and (d pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α. Also, IL-33 activated ERK in human pancreatic tissue.As exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation

  11. Acute and subacute pulmonary toxicity caused by a single intratracheal instillation of colloidal silver nanoparticles in mice: pathobiological changes and metallothionein responses.

    Science.gov (United States)

    Kaewamatawong, Theerayuth; Banlunara, Wijit; Maneewattanapinyo, Pattwat; Thammachareon, Chuchaat; Ekgasit, Sanong

    2014-01-01

    To study the acute and subacute pulmonary toxicity of colloidal silver nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alterations were determined 1, 3, 7, 15, and 30 days after instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF indices during the acute period; however, these changes gradually regressed in a time-dependent manner. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. Superoxide dismutase and metallothionein expression occurred in particle-laden macrophages and alveolar epithelial cells, which correlated to lung lesions in mice treated with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient moderate acute lung inflammation and tissue damage. Oxidative stress may underlie the induction of injury to lung tissue. Moreover, the expression of metallothionein in tissues indicated the protective response to exposure to Ag-NPs.

  12. CT pulmonary angiography findings that predict 30-day mortality in patients with acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Bach, Andreas Gunter, E-mail: mail@andreas-bach.de [Department of Radiology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Germany); Nansalmaa, Baasai; Kranz, Johanna [Department of Radiology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Germany); Taute, Bettina-Maria [Department of Internal Medicine, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Germany); Wienke, Andreas [Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Magdeburger-Str. 8, 06112 Halle (Germany); Schramm, Dominik; Surov, Alexey [Department of Radiology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Germany)

    2015-02-15

    Highlights: • In patients with acute pulmonary embolism contrast reflux in inferior vena cava is significantly stronger in non-survivors (odds ratio 3.29; p < 0.001). • This finding is independent from the following comorbidities: heart insufficiency and pulmonary hypertension. • Measurement of contrast reflux is a new and robust radiologic method for predicting 30-day mortality in patients with acute pulmonary embolism. • Measurement of contrast reflux is a better predictor of 30-day mortality after acute pulmonary embolism than any other existing radiologic predictor. This includes thrombus distribution, and morphometric measurements of right ventricular dysfunction. - Abstract: Purpose: Standard computed tomography pulmonary angiography (CTPA) can be used to diagnose acute pulmonary embolism. In addition, multiple findings at CTPA have been proposed as potential tools for risk stratification. Therefore, the aim of the present study is to examine the prognostic value of (I) thrombus distribution, (II) morphometric parameters of right ventricular dysfunction, and (III) contrast reflux in inferior vena cava on 30-day mortality. Material and methods: In a retrospective, single-center study from 06/2005 to 01/2010 365 consecutive patients were included. Inclusion criteria were: presence of acute pulmonary embolism, and availability of 30-day follow-up. A review of patient charts and images was performed. Results: There were no significant differences between the group of 326 survivors and 39 non-survivors in (I) thrombus distribution, and (II) morphometric measurements of right ventricular dysfunction. However, (III) contrast reflux in inferior vena cava was significantly stronger in non-survivors (odds ratio 3.29; p < 0.001). Results were independent from comorbidities like heart insufficiency and pulmonary hypertension. Conclusion: Measurement of contrast reflux is a new and robust method for predicting 30-day mortality in patients with acute pulmonary

  13. Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation.

    Science.gov (United States)

    Lane-Cordova, Abbi D; Ranadive, Sushant M; Kappus, Rebecca M; Cook, Marc D; Phillips, Shane A; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Fernhall, Bo

    2016-12-01

    Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

  14. Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

    International Nuclear Information System (INIS)

    Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

    2009-01-01

    Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

  15. The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

    Directory of Open Access Journals (Sweden)

    Nemmar A

    2017-04-01

    Full Text Available Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Al-Khod, Sultanate of Oman Abstract: Cerium oxide nanoparticles (CeO2 NPs, used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours effect of intratracheal (IT instillation of either CeO2 NPs (0.1 or 0.5 mg/kg or saline (control on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice. CeO2 NPs induced a significant increase of neutrophils into the bronchoalveolar lavage (BAL fluid with an elevation of tumor necrosis factor α (TNFα and a decrease in the activity of the antioxidant catalase. Lung sections of mice exposed to CeO2 NPs showed a dose-dependent infiltration of inflammatory cells consisting of macrophages and neutrophils. Similarly, the plasma levels of C-reactive protein and TNFα were significantly increased, whereas the activities of catalase and total antioxidant were significantly decreased. Interestingly, CeO2 NPs significantly and dose dependently induced a shortening of the thrombotic occlusion time in pial arterioles and venules. Moreover, the plasma concentrations of fibrinogen and plasminogen activator inhibitor-1 were significantly elevated by CeO2 NPs. The direct addition of CeO2 NPs (1, 5, or 25 µg/mL to mouse whole blood, collected from the inferior vena cava, in vitro neither caused significant platelet aggregation nor affected prothrombin time or partial

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  18. Acute pulmonary parenchymal densities in the adult

    International Nuclear Information System (INIS)

    Murphy, C.H.; Murphy, M.R.

    1987-01-01

    The thrust of the radiographic interpretation is to correlate the often non-specific appearance of any parenchymal density with its time-table of development, rate of change, distribution, and the patient's clinical status. Although this chapter contains separate sections on each major cause of acute pulmonary opacification, the intent of the chapter overall is their differential diagnosis. Before beginning to deal with acute pulmonary densities, it is stressed that acute densities can only be differentiated from chronic ones by reviewing preoperative or pre-existing studies. Without the baseline comparison film or reliable presumption of prior normalcy, the acuteness of a parenchymal density may not be apparent until later examinations reveal change or resolution. Also, as discussed is baseline pathology that is altered by the portable technique can be terribly confusing when attempting to evaluate a single isolated film in an acute clinical situation

  19. The acute pulmonary oedema in the intensive-care ward

    International Nuclear Information System (INIS)

    Marciniak, R.; Aronski, A.

    1989-01-01

    760 patients suffering from acute pulmonary oedema were treated between 1980 and 1986 at the Institute of Anaesthesiology of the Medical Academy in Wroclaw. The radiological image of the pulmonary oedema was subdivided into three forms (hilar, hilar and perihilar, and hilar with massive plane-shaped infiltrates). In the treatment of acute pulmonary oedema in the intensive-care ward a thorough diagnostic programme is mandatory after the immediately necessary measures have been taken. (orig.) [de

  20. Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

    Science.gov (United States)

    Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

    2016-01-01

    Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

  1. Inflammation: a trigger for acute coronary syndrome

    International Nuclear Information System (INIS)

    SAGER, Hendrik B.; NAHRENDORF, Matthias

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis’ most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes.

  2. Evaluation of pulmonary artery flow in acute massive pulmonary thromboembolism with MRI

    International Nuclear Information System (INIS)

    Li Yongzhong; Li Kuncheng; Zhao Xigang; Zhao Hong

    2004-01-01

    Objective: To probe into the value of MR imaging in evaluating the pulmonary artery hemodynamics and pulmonary artery pressure in acute massive pulmonary embolism. Methods: MR studies were performed in 21 patients with acute massive pulmonary embolism (diagnosed by contrast enhanced MR pulmonary angiography) and 20 healthy volunteers. The pulmonary artery hemodynamic parameters, such as the diameters of main and right pulmonary artery, peak velocity, average velocity, flow volume, flow patterns, and ejection acceleration time in main pulmonary artery were measured. The findings in patients and volunteers were compared. The hemodynamic parameters in patients were correlated with mean pulmonary artery pressure acquired with right heart catheterization. Results: The diameters of main pulmonary artery (2.93 vs 2.52 cm) and right pulmonary artery (2.49 vs 1.92 cm) in patients and volunteers showed significant differences (t=3.55, P<0.01 and t=4.19, P<0.01, respectively); Peak velocity (85.29 vs 100.63 cm/s), average velocity (11.00 vs 17.12 cm/s), flow volume (89.15 vs 98.96 ml/s), and ejection acceleration time (105.09 vs 163.85 ms) in main pulmonary artery were significantly different between patients and volunteers (t values were 2.89, 6.37, 2.21, and 9.46, respectively; P values were 0.01, <0.01, 0.03, and <0.01, respectively). The peak velocity-time curve of main pulmonary artery acquired with velocity encoded cine of MR in patients demonstrated earlier and lower peak velocity as well as abnormal retrograde flow. In addition, linear correlations were seen between the mean pulmonary pressure and the diameter of main pulmonary artery (r=0.62, P=0.001), diameter of right pulmonary artery (r=0.63, P=0.001), and ejection acceleration time (r=-0.55, P=0.005). Conclusion: MR imaging is a promising technique not only for the detection of pulmonary thromboemboli but also for the evaluation of hemodynamic parameters in pulmonary hypertension. (author)

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

    Directory of Open Access Journals (Sweden)

    Tudorache E

    2015-09-01

    Full Text Available Emanuela Tudorache,1 Cristian Oancea,1 Claudiu Avram,2 Ovidiu Fira-Mladinescu,1 Lucian Petrescu,3 Bogdan Timar4 1Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, 2Physical Education and Sport Faculty, West University of Timisoara, 3Department of Cardiology, University of Medicine and Pharmacy “Victor Babes”, 4Department of Biostatistics and Medical Informatics, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania 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

  4. Grouping nanomaterials to predict their potential to induce pulmonary inflammation

    NARCIS (Netherlands)

    Braakhuis, Hedwig M; Oomen, Agnes G; Cassee, Flemming R

    2016-01-01

    The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in

  5. Rapid Onset Acute Epiglottitis Leading to Negative Pressure Pulmonary Edema

    Directory of Open Access Journals (Sweden)

    V Saraswat

    2007-01-01

    Full Text Available Pulmonary edema is a potentially life-threatening complication of acute airway obstruction. It develops rapidly, without warning, in young healthy individuals. Two forms of post-obstructive pulmonary edema (POPE (also known as negative pressure pulmonary edema, NPPE have been identified. POPE I follows sudden, severe upper airway obstruction. POPE II occurs following surgical relief of chronic upper airway obstruction. Treatment for both is supportive. Full and rapid recovery can be expected with appropriate management. A case report of a middle aged man with acute onset epiglottitis who developed negative pressure pulmonary edema after intubation is presented. The report includes a brief discussion on etiology, clinical features and management dilemma of acute upper airway obstruction.

  6. The establishment of animal model of acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

    2008-01-01

    Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

  7. [Bronchial inflammation during chronic bronchitis, importance of fenspiride].

    Science.gov (United States)

    Melloni, B

    2002-09-01

    PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): Chronic inflammation of the upper airways, pulmonary parenchyma and pulmonary vasculature is the characteristic feature of COPD. Two mechanisms besides inflammation are also involved: oxidative stress and imbalance between proteinases and antiproteinases. Cellular infiltration of the upper airways involved neutrophils, macrophages, T lymphocytes and eosinophils. Inflammatory mediators appear to play a crucial role in the interaction between inflammation and obstruction. PROPERTIES OF FENSPIRIDE: A nonsteroidal drug, fenspiride, exhibits interesting properties documented in vitro: anti-bronchoconstriction activity, anti-secretory activity, and anti-inflammatory activity (reduction in the activity of phospholipase A2 and release of proinflammatory leukotriens). Two french clinical trials have studied the efficacy of fenspiride in patients with acute excerbation or stable COPD and have demonstrated an improvement in the group treated with fenspiride compared with the placebo group.

  8. Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Michael R Wilson

    2010-07-01

    Full Text Available Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO using a mouse model of lipopolysaccharide (LPS-induced pulmonary inflammation.Mice were exposed to 0-500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow.When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40-50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space.Overall, these data confirm some protective role for inhaled CO during pulmonary inflammation, although this required a dose that produced carboxyhemoglobin values close to potentially toxic levels for humans, and increased lung permeability.

  9. Acute pulmonary infections

    International Nuclear Information System (INIS)

    Juhl, J.H.

    1987-01-01

    Acute pulmonary infection may be caused by a variety of organisms. In some instances they produce a reasonably characteristic, gross pathologic pattern and, therefore, a recognizable roentgenographic pattern. In the subsequent discussions the most common gross anatomic findings in the pneumonias of various causes as reflected in chest roentgenograms will be described. The roentgenographic manifestations of pulmonary infections are so varied that the pattern observed often gives us little information regarding the causative organism. Therefore, in each instance it should be remembered that roentgenographic findings must be correlated with clinical, bacteriological, and laboratory data to ascertain the correct etiologic diagnosis upon which treatment is based. The role of the radiologist is to locate and define the extent of the disease and any complicating findings such as lung abscess and pleural effusion or empyema

  10. Acute pulmonary embolism in helical computed tomography

    International Nuclear Information System (INIS)

    Paslawski, M.

    2005-01-01

    Pulmonary embolism is a common condition in which diagnostic and therapeutic delays contribute to substantial morbidity and mortality. Clinical diagnosis is difficult because the signs and symptoms re unspecific, and a differential diagnosis is extensive, including pneumonia or bronchitis, asthma, myocardial infraction, pulmonary edema, anxiety, dissection of the aorta, pericardial tamponade, lung cancer, primary pulmonary hypertension, rib fracture, and pneumothorax. The purpose of the study was to present the use of CT in diagnosing acute pulmonary embolism. A group of 23 patients with clinically suspected pulmonary embolism underwent CT examination with a helical CT scanner (Somatom Emotion, Siemens) before and after administration of 150 ml of Ultravist. Pulmonary embolism was found in the CT examinations of 13 patients. In two of these it was a central filling defect. Amputation of the artery was found in one. Parietal filling defect in three patients formed an acute angle with the vessel walls. Saddle emboli appearing as filling defects in the contrast column that hung over vessel bifurcations was found in two patients. In five patients,emboli were found in small segmental arteries. CT provides information not only on the pulmonary arteries, but also on the lung parenchyma, hila, mediastinum, and the heart. Alternative findings may be identified by CT chest examination, stablishing alternative diagnoses, including pulmonary disorders (such as pneumonia or fibrosis), pleural abnormalities, and cardiovascular disease (such as aortic dissection or pericardial tamponade). Another advantage of the CT is its widespread availability.(author)

  11. Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

    Science.gov (United States)

    Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

    2018-02-01

    Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

  12. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

    Science.gov (United States)

    Gehlen, Heidrun

    2016-01-01

    Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature. PMID:28053371

  13. Acute Toxic Myocarditis and Pulmonary Oedema Developing from Scorpion Sting

    Directory of Open Access Journals (Sweden)

    Cem Sahin

    2015-03-01

    Full Text Available The majority of scorpion stings are generally seen with a set of simple clinical findings, such as pain, oedema, numbness, and tenderness in the area of the sting. However, occasionally events, such as toxic myocarditis, acute heart failure, acute pulmonary oedema, and Acute Respiratory Distress Syndrome (ARDS, which occur in scorpion sting cases are a significant problem which determine mortality and morbidity. The case presented here was a 38-year-old man who developed acute toxic myocarditis, acute heart failure, and acute pulmonary oedema following a scorpion sting on the 3rd finger of his right hand.

  14. Acute pulmonary admissions following implementation of a national workplace smoking ban.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-09-01

    The implementation of workplace smoking bans has contributed to a significant reduction in the incidence of acute coronary syndrome admissions, but their influence on adult acute pulmonary disease admissions is unclear. We sought to assess the impact of a national smoking ban on nationwide admissions of individuals of working age with acute pulmonary illness.

  15. Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

    Science.gov (United States)

    Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

    2017-01-01

    Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

  16. Bufei Huoxue Capsule Attenuates PM2.5-Induced Pulmonary Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Yue Jing

    2017-01-01

    Full Text Available Atmospheric fine particulate matter 2.5 (PM 2.5 may carry many toxic substances on its surface and this may pose a public health threat. Epidemiological research indicates that cumulative ambient PM2.5 is correlated to morbidity and mortality due to pulmonary and cardiovascular diseases and cancer. Mitigating the toxic effects of PM2.5 is therefore highly desired. Bufei Huoxue (BFHX capsules have been used in China to treat pulmonary heart disease (cor pulmonale. Thus, we assessed the effects of BFHX capsules on PM2.5-induced pulmonary inflammation and the underlying mechanisms of action. Using Polysearch and Cytoscape 3.2.1 software, pharmacological targets of BFHX capsules in atmospheric PM2.5-related respiratory disorders were predicted and found to be related to biological pathways of inflammation and immune function. In a mouse model of PM2.5-induced inflammation established with intranasal instillation of PM2.5 suspension, BFHX significantly reduced pathological response and inflammatory mediators including IL-4, IL-6, IL-10, IL-8, TNF-α, and IL-1β. BFHX also reduced keratinocyte growth factor (KGF, secretory immunoglobulin A (sIgA, and collagen fibers deposition in lung and improved lung function. Thus, BFHX reduced pathological responses induced by PM2.5, possibly via regulation of inflammatory mediators in mouse lungs.

  17. Differential role of the Fas/Fas ligand apoptotic pathway in inflammation and lung fibrosis associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia and acute respiratory distress syndrome.

    Science.gov (United States)

    Lopez, Andrea D; Avasarala, Sreedevi; Grewal, Suman; Murali, Anuradha K; London, Lucille

    2009-12-15

    Bronchiolitis obliterans organizing pneumonia (BOOP) and acute respiratory distress syndrome (ARDS) are two clinically and histologically distinct syndromes sharing the presence of an inflammatory and fibrotic component. Apoptosis via the Fas/Fas ligand (FasL) pathway plays an important role in the development of acute lung injury and fibrosis characteristic of these and other pulmonary inflammatory and fibrotic syndromes. We evaluated the role of apoptosis via the Fas/FasL pathway in the development of pulmonary inflammation and fibrosis in reovirus 1/L-induced BOOP and ARDS. CBA/J mice were intranasally inoculated with saline, 1 x 10(6) (BOOP), or 1 x 10(7) (ARDS) PFU reovirus 1/L, and evaluated at various days postinoculation for in situ apoptosis by TUNEL analysis and Fas/FasL expression. Our results demonstrate the presence of apoptotic cells and up-regulation of Fas/FasL expression in alveolar epithelium and in infiltrating cells during the inflammatory and fibrotic stages of both reovirus 1/L-induced ARDS and BOOP. Treatment of mice with the caspase 8 inhibitor, zIETD-fmk, inhibited apoptosis, inflammation, and fibrotic lesion development in reovirus 1/L-induced BOOP and ARDS. However, CBA/KlJms-Fas(lpr-cg)/J mice, which carry a point mutation in the Fas cytoplasmic region that abolishes the ability of Fas to transduce an apoptotic signal, do not develop pulmonary inflammation and fibrotic lesions associated with reovirus 1/L-induced BOOP, but still develop inflammation and fibrotic lesions associated with reovirus 1/L-induced ARDS. These results suggest a differential role for the Fas/FasL apoptotic pathway in the development of inflammation and fibrotic lesions associated with BOOP and ARDS.

  18. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  19. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  20. Digital subtraction angiography (DSA) for acute pulmonary emboli

    International Nuclear Information System (INIS)

    Witte, H.; Grabbe, E.; Buecheler, E.

    1983-01-01

    The results of 49 DSAs (in 29 patients) are presented; these were performed for the diagnosis or follow-up of pulmonary emboli. The direct or indirect signs of pulmonary emboli, known to occur during conventional pulmonary angiography, were used as diagnostic criteria. In 47 examinations it was possible to make or to exclude the diagnosis unequivocally. The advantages of DSA make it desirable to use this method as the first form of examination in the diagnosis of acute, but not immediately life-threatening, pulmonary emboli. (orig.) [de

  1. Suppression of Th17-polarized airway inflammation by rapamycin.

    Science.gov (United States)

    Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

    2017-11-10

    Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

  2. Differential Role of the Fas/Fas Ligand Apoptotic Pathway in Inflammation and Lung Fibrosis Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia and Acute Respiratory Distress Syndrome1

    Science.gov (United States)

    Lopez, Andrea D.; Avasarala, Sreedevi; Grewal, Suman; Murali, Anuradha K.; London, Lucille

    2010-01-01

    Bronchiolitis obliterans organizing pneumonia (BOOP) and acute respiratory distress syndrome (ARDS) are two clinically and histologically distinct syndromes sharing the presence of an inflammatory and fibrotic component. Apoptosis via the Fas/Fas ligand (FasL) pathway plays an important role in the development of acute lung injury and fibrosis characteristic of these and other pulmonary inflammatory and fibrotic syndromes. We evaluated the role of apoptosis via the Fas/FasL pathway in the development of pulmonary inflammation and fibrosis in reovirus 1/L-induced BOOP and ARDS. CBA/J mice were intranasally inoculated with saline, 1 × 106 (BOOP), or 1 × 107 (ARDS) PFU reovirus 1/L, and evaluated at various days postinoculation for in situ apoptosis by TUNEL analysis and Fas/FasL expression. Our results demonstrate the presence of apoptotic cells and up-regulation of Fas/FasL expression in alveolar epithelium and in infiltrating cells during the inflammatory and fibrotic stages of both reovirus 1/L-induced ARDS and BOOP. Treatment of mice with the caspase 8 inhibitor, zIETD-fmk, inhibited apoptosis, inflammation, and fibrotic lesion development in reovirus 1/L-induced BOOP and ARDS. However, CBA/KlJms-Faslpr-cg/J mice, which carry a point mutation in the Fas cytoplasmic region that abolishes the ability of Fas to transduce an apoptotic signal, do not develop pulmonary inflammation and fibrotic lesions associated with reovirus 1/L-induced BOOP, but still develop inflammation and fibrotic lesions associated with reovirus 1/L-induced ARDS. These results suggest a differential role for the Fas/FasL apoptotic pathway in the development of inflammation and fibrotic lesions associated with BOOP and ARDS. PMID:20007588

  3. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A following Acute Repeated Inhalation Exposure

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts

    2014-01-01

    Full Text Available Introduction Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. Methods The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m 3 , five hours per day, over nine work days, or filtered air (control. At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. Results No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following metha-choline (MCh inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP responses to these agents; however, the baseline heart rate (HR and HR responses to isoproterenol (ISO were significantly elevated at one-day post exposure

  4. Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

    Science.gov (United States)

    Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

    2014-04-01

    Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

  5. Tomographic findings of acute pulmonary toxoplasmosis in immunocompetent patients.

    Science.gov (United States)

    de Souza Giassi, Karina; Costa, Andre Nathan; Apanavicius, Andre; Teixeira, Fernando Bin; Fernandes, Caio Julio Cesar; Helito, Alfredo Salim; Kairalla, Ronaldo Adib

    2014-11-25

    Toxoplasmosis is one of the most common human zoonosis, and is generally benign in most of the individuals. Pulmonary involvement is common in immunocompromised subjects, but very rare in immunocompetents and there are scarce reports of tomographic findings in the literature. The aim of the study is to describe three immunocompetent patients diagnosed with acute pulmonary toxoplasmosis and their respective thoracic tomographic findings. Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology. From 2009 to 2013, three patients were diagnosed with acute respiratory failure secondary to acute toxoplasmosis. The patients were two female and one male, and were 38, 56 and 36 years old. Similarly they presented a two-week febrile illness and progressive dyspnea before admission. Laboratory tests demonstrated lymphocytosis, slight changes in liver enzymes and high inflammatory markers. Tomographic findings were bilateral smooth septal and peribronchovascular thickening (100%), ground-glass opacities (100%), atelectasis (33%), random nodules (33%), lymph node enlargement (33%) and pleural effusion (66%). All the patients improved their symptoms after treatment, and complete resolution of tomographic findings were found in the followup. These cases provide a unique description of the presentation and evolution of pulmonary tomographic manifestations of toxoplasmosis in immunocompetent patients. Toxoplasma pneumonia manifests with fever, dyspnea and a non-productive cough that may result in respiratory failure. In animal models, changes were described as interstitial pneumonitis with focal infiltrates of neutrophils that can finally evolve into a pattern of diffuse alveolar damage with focal necrosis. The tomographic findings are characterized as ground glass opacities, smooth septal and marked peribronchovascular thickening; and may mimic pulmonary congestion

  6. Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment

    NARCIS (Netherlands)

    Slofstra, S. H.; Groot, A. P.; Maris, N. A.; Reitsma, P. H.; Cate, H. Ten; Spek, C. A.

    2006-01-01

    BACKGROUND AND PURPOSE: Intravenous administration of recombinant human activated protein C (rhAPC) is known to reduce lipopolysaccharide (LPS)-induced pulmonary inflammation by attenuating neutrophil chemotaxis towards the alveolar compartment. Ideally, one would administer rhAPC in pulmonary

  7. Multidetector-row computed tomography management of acute pulmonary embolism

    International Nuclear Information System (INIS)

    Yasui, Takahiro; Tanabe, Nobuhiro; Terada, Jiro

    2007-01-01

    The purpose of this study was to evaluate the usefulness and safety of multidetector-row computed tomography (MDCT) pulmonary angiography and indirect venography management of acute pulmonary embolism (PE), including indication for inferior vena cava (IVC) filter. Seventy-one consecutive patients who were clinically suspected of PE and underwent 16-slice MDCT pulmonary angiography and indirect venography were enrolled. Management included indication of IVC filter for patients with extensive deep venous thrombosis (DVT) in submassive or massive PE. A right ventricular to left ventricular short-axis diameter by MDCT >1.0 was judged as submassive PE. All patients were followed for 1 year. MDCT identified 50 patients with venous thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7 patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the right atrium died of recurrence. No other patients died of PE. Management based on MDCT pulmonary angiography combined with indirect venography is considered to be safe and reliable in patients with suspected acute PE. (author)

  8. Acute inflammation in horizontal incompletely impacted third molar with radiolucency in the elderly

    Directory of Open Access Journals (Sweden)

    Minoru Yamaoka

    2009-07-01

    Full Text Available Minoru Yamaoka, Yusuke Ono, Masahiro Takahashi, Masahide Ishizuka, Takayuki Uchihashi, Kouichi Yasuda, Takashi Uematsu, Kiyofumi FurusawaMatsumoto Dental University, Oral and Maxillofacial Surgery, Shiojiri, Nagano, JapanAbstract: Although radiolucency has been shown as a risk of infection, the poorly understood effects of aging on radiolucency correlate with acute pericoronitis, which has a high risk of infection extending any complications. We reviewed the records of 346 consecutive patients aged more than 41 years to evaluate whether pericoronal radiolucency below the crown in mandibular horizontal incompletely impacted third molars is related to acute inflammation. The frequency of acute inflammation in teeth with pericoronal radiolucency below the crown was similar to that in teeth without; however, the odds ratio of acute inflammation exhibited in women aged more than 61 years compared to women aged 41–50 years was 9.77 (95% confidence interval [CI]: 1.67–57.29; P <<0.05, and in women aged more than 61 years compared to women aged 51–60 years was 26.25 (95% CI: 2.94–234.38; P < 0.01. The odds ratio of severe acute inflammation exhibited in men aged more than 61 years compared to men aged 41–50 years was 16.67 (95% CI: 1.76–158.27; P < 0.01. These odds ratios indicate an association of acute pericoronitis, including the severe forms of acute inflammation that result from pericoronitis, with pericoronal radiolucency below the crown in the elderly.Keywords: radiolucency, mandible, third molar, acute inflammation, aging

  9. Awara (Astrocaryum vulgare M.) pulp oil: chemical characterization, and anti-inflammatory properties in a mice model of endotoxic shock and a rat model of pulmonary inflammation.

    Science.gov (United States)

    Bony, Emilie; Boudard, Frédéric; Brat, Pierre; Dussossoy, Emilie; Portet, Karine; Poucheret, Patrick; Giaimis, Jean; Michel, Alain

    2012-01-01

    Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the broncho-alveolar lavages. These results suggest that awara pulp oil administration can efficiently counteract an acute and chronic inflammatory response in vivo that is probably mediated by fatty acids and minor compounds. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Acute effects of cigarette smoke on inflammation and oxidative stress : a review

    NARCIS (Netherlands)

    van der Vaart, H; Postma, DS; Timens, W; Ten Hacken, NHT

    Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human,

  11. Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

    Science.gov (United States)

    Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

    1984-03-01

    Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

  12. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A(®)) Following Acute Repeated Inhalation Exposure.

    Science.gov (United States)

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m(3), five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. In summary, acute

  13. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  14. The axonal guidance receptor neogenin promotes acute inflammation.

    Directory of Open Access Journals (Sweden)

    Klemens König

    Full Text Available Neuronal guidance proteins (NGP were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/- demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/- to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

  15. Effects of vagus nerve stimulation and vagotomy on systemic and pulmonary inflammation in a two-hit model in rats.

    Directory of Open Access Journals (Sweden)

    Matthijs Kox

    Full Text Available Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit may be potentiated by mechanical ventilation (MV, second hit. Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX and vagus nerve stimulation (VNS on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg or moderate (15 mL/kg tidal volumes was initiated, or animals were left breathing spontaneously (SP. After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP, but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM, and resulted in decreased pO(2 (p<0.05 compared to sham-operated animals. VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.

  16. Radioiodine uptake in inactive pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Bakheet, S.M.; Powe, J.; Al Suhaibani, H.; Hammami, M.M.; Bazarbashi, M.

    1999-01-01

    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.)

  17. High‑risk pulmonary embolism in a patient with acute dissecting ...

    African Journals Online (AJOL)

    2016-04-07

    Apr 7, 2016 ... Key words: Acute dissection of an aneurysm, anticoagulant therapy, pulmonary ... On admission, the physical examination revealed cyanosis, .... myocardial infarction and type B acute aortic dissection – A case report. Adv.

  18. Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury.

    Science.gov (United States)

    Wolthuis, Esther K; Choi, Goda; Dessing, Mark C; Bresser, Paul; Lutter, Rene; Dzoljic, Misa; van der Poll, Tom; Vroom, Margreeth B; Hollmann, Markus; Schultz, Marcus J

    2008-01-01

    Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

  19. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  20. Negative spiral CT in acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, T.; Olausson, A. [Karolinska Hospital, Stockholm (Sweden). Dept. of Thoracic Radiology; Johnsson, H. [Karolinska Hospital, Stockholm (Sweden). Dept. of Internal Medicine; Nyman, U. [County Hospital, Trelleborg (Sweden). Dept. of Radiology; Aspelin, P. [Huddinge Univ. Hospital (Sweden). Dept. of Radiology

    2002-09-01

    Purpose: To retrospectively evaluate the clinical outcome of non-anticoagulated patients with clinically suspected acute pulmonary embolism (PE) and no symptoms or signs of deep venous thrombosis (DVT) following a negative contrast medium-enhanced spiral CT of the pulmonary arteries (s-CTPA). Material and Methods: During a 24-month period, 739 of 751 patients underwent s-CTPA with acceptable diagnostic quality for clinically suspected acute PE. All patients who had a CT study not positive for PE were followed up with a questionnaire, a telephone interview and review of all medical reports, including autopsies and death certificates for any episodes of venous thromboembolism (VTE) during a 3-month period. Results: PE was diagnosed in 158 patients. Of the remaining 581 patients with a negative s-CTPA, 45 patients were lost to follow-up. 88 patients were excluded because of anticoagulation treatment (cardiac disorder n=32, chronic VTE or acute symptomatic DVT n=31, PE diagnosed at pulmonary angiography n=1, thrombus prophylaxis during diagnostic work-up or other reasons than VTE n=24) and 7 patients undergoing lower extremity venous studies because of symptoms of DVT (all negative). Thus, 441 patients with a negative s-CTPA and no DVT symptoms, venous studies or anticoagulant treatment constituted the follow-up cohort. Four of these patients had proven VTE (all PE) during the 3-month follow-up period. Two of the PE episodes contributed to the patient's death. Conclusion: Patients with clinically suspected acute PE, no symptoms or signs of DVT and a negative single slice s-CTPA using 3-5 mm collimation, may safely be left without anticoagulation treatment unless they are critically ill, have a limited cardiopulmonary reserve and/or if a high clinical suspicion remains.

  1. Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

    Science.gov (United States)

    Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

    2002-09-01

    The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

  2. Effects of asphalt fume condensate exposure on acute pulmonary responses

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.Y.C.; Barger, M.W.; Castranova, V. [Health Effects Lab. Div., National Inst. for Occupational Safety and Health, Morgantown, WV (United States); Kriech, A.J. [Heritage Research Group, Indianapolis, IN (United States)

    2000-10-01

    The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. Methods: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-{alpha} and IL-1 production by AM were assayed to monitor AM function. Results: In vitro AFC exposure at <200 {mu}g/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-{alpha} release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control

  3. Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation.

    Science.gov (United States)

    An, Gary

    2008-05-27

    One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure. ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems. A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents

  4. Rapid Onset Acute Epiglottitis Leading to Negative Pressure Pulmonary Edema

    OpenAIRE

    V Saraswat; P V Madhu; Suresh S Kumar

    2007-01-01

    Pulmonary edema is a potentially life-threatening complication of acute airway obstruction. It develops rapidly, without warning, in young healthy individuals. Two forms of post-obstructive pulmonary edema (POPE) (also known as negative pressure pulmonary edema, NPPE) have been identified. POPE I follows sudden, severe upper airway obstruction. POPE II occurs following surgical relief of chronic upper airway obstruction. Treatment for both is supportive. Full and rapid recovery can be expecte...

  5. Acute pulmonary edema after near strangulation

    International Nuclear Information System (INIS)

    Shumaker, D.; Kottamasu, S.; Preston, G.; Treloar, D.

    1988-01-01

    We report a case of acute, noncardiogenic pulmonary edema in an 11 year old boy who suffered strangulation during an altercation. The clinical presentation was characterized by moderate respiratory distress and hemoptysis. Both the radiographic and clinical findings resolved during the three day admission which followed. A review of the literature is presented, and possible pathogenesis is discussed. (orig.)

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

    Science.gov (United States)

    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...

  7. Influence of fitness and age on the endothelial response to acute inflammation.

    Science.gov (United States)

    Schroeder, Elizabeth C; Lane-Cordova, Abbi D; Ranadive, Sushant M; Baynard, Tracy; Fernhall, Bo

    2018-04-16

    What is the central question of the study? The purpose of this study was to determine the effect of age and fitness on the vascular response to acute inflammation in younger and older adults. What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function following acute inflammation: older moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications of further supporting the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with aging. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger (YA) and 62 older (OA) adults. We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilation (FMD), augmentation index (AIx@75), carotid elastic modulus (Ep) and inflammatory markers were measured before and 24-hours after vaccination. VO 2 peak was measured via a treadmill test. Fit was defined as a VO 2 peak greater than the age- and sex-determined 50 th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (p fit: 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit: 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24h (p fit OA did not reduce FMD at 24h (5.5 ± 0.4 to 5.2 ± 0.5%, p > 0.05). The reduction in FMD in YA was similar between fitness groups (p > 0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. AIx@75 and Ep did not

  8. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Woodruff PG

    2012-11-01

    Full Text Available Richard K Albert,1 John Connett,2 Jeffrey L Curtis,3,4 Fernando J Martinez,3 MeiLan K Han,3 Stephen C Lazarus,5 Prescott G Woodruff51Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO, 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, 4Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, 5Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USABackground: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Methods: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Results: Samples were obtained from 1037 subjects (91% in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.Conclusion: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin

  9. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    Science.gov (United States)

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p  0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. CT and pathologic correlation acute miliary pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Yang Jing; Ma Daqing; Zhang Yansong; Guan Yansheng; Yang Jun; Liu Weihua

    2011-01-01

    Objective: To elucidate the CT characteristics and pathology of acute miliary pulmonary tuberculosis (AMPT). Methods: The CT features of AMPT in 25 cases were analyzed retrospectively, and the CT features in HIV-seronegative and HIV-seropositive patients were compared by 2-sided exact probability Chi-square test. Two lung specimens were inflated and fixed by Heitzman's method. HRCT scans, gross specimen section (80-150 μm) and histologic section (5 μm) were performed on dry lung specimens and CT-pathologic correlation was conducted. The distribution of micronodules in the secondary lobule on HRCT and pathology in one specimen was evaluated by Chi-square test. Results: Twenty five patients with AMPT were included in this study, including 11 HIV-seropositive patients and 14 HIV- seronegative patients. HRCT showed diffuse micronodules randomly distributed throughout both lungs in 25 patients, and ground-glass opacity (17 patients) was the predominant complicated finding. Coalescence of nodules and consolidation in HIV-seropositive patients (5 and 6 patients) were markedly higher than that in HIV-seronegative patients (none). In lung specimens, most nodules located in the lung parenchyma between the central bronchovascular bundle and the perilobular structures (792 and 560 nodules), which located in the interlobular septum pathologically. The distribution of micronodules in the secondary lobule showed on HRCT (1060 nodules) and pathology (864 nodules) was not significantly difference (χ 2 =2.814, P>0.05) . HRCT showed ground-glass opacities when ARDS occurred, which were pulmonary edema, inflammation and hyaline membrane on alveolar wall pathologically. Conclusions: The HRCT characteristic of nodule distribution in AMPT is random. ARDS should be suspected when diffuse ground-glass opacities appear on HRCT. (authors)

  11. Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

    Science.gov (United States)

    Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

    2015-04-01

    Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  12. A clinical study on the interventional treatment of acute pulmonary embolism

    International Nuclear Information System (INIS)

    Yu Xixiang; Zhang Minghua; Ci Xiao; Wang Chunmei; Lin Xiaojie; Si Tongguo; Huang Linfen; Feng Xiaofeng

    2004-01-01

    Objective: To evaluate the effectiveness of interventional procedures in the treatment of acute pulmonary embolism (PE). Methods: Pulmonary arterial thrombolytic therapy, suction and fragmentation of thromhi, anti-spasm, and balloon dilation were performed in eighteen cases with clinically highly suspected PE confirmed by emergent pulmonary artery angiography beforehand. Wedged pulmonary arterial pressure, pulmonary recanalization rate, the display ratio of distal pulmonary capillary net, blood gas analysis, blood oxygen saturation, and the improvement of clinical symptoms and signs were used for evaluation of the effectiveness. Seventeen of the alive cases with dislodgement of deep vein thrombi of the lower extremities were confirmed for the formation of PE and then thrombolytic treatment of the thrombotic deep vein was performed after the placement of inferior vena cava filter. Results: Pulmanory artery angiographies showed embolism of the pulmonary arterial trunks or more than two of the branches. The post-treatment pulmonary patency reached 80%-90% in three cases, 90%-95% in eleven cases and 100% in five cases. The display ratio of distal pulmonary capillary net was over 90% in all the cases. Wedged pulmonary arterial pressure decreased to below 25 mmHg in thirteen cases, and to 25-30 mmHg in five cases. Blood oxygen saturation rate improved immediately to 90%-95% in ten cases and to 95%-100% in eight cases. Cough, hemoptysis, dyspnea, and chest pain were completely relieved in thirteen cases and significantly relieved in five cases. Digestive track bleeding was complicated in one case. Conclusions: Pulmonary artery angiography is the golden standard for the diagnosis of pulmonary embolism. Interventional therapy is very effective for acute pulmonary embolism, which can significantly reduce the mortality rate. (authors)

  13. Surgical treatment of acute pulmonary embolism--a 12-year retrospective analysis

    DEFF Research Database (Denmark)

    Lehnert, Per; Møller, Christian H; Carlsen, Jørn

    2012-01-01

    Surgical embolectomy for acute pulmonary embolism (PE) is considered to be a high risk procedure and therefore a last treatment option. We wanted to evaluate the procedures role in modern treatment of acute PE....

  14. Radiolucency below the crown of mandibular horizontal incompletely impacted third molars and acute inflammation in men with diabetes

    Directory of Open Access Journals (Sweden)

    Minoru Yamaoka

    2009-05-01

    Full Text Available Minoru Yamaoka, Yusuke Ono, Masahide Ishizuka, Kouichi Yasuda, Takashi Uematsu, Kiyofumi FurusawaOral and Maxillofacial Surgery, Matsumoto Dental University, Shiojiri, Nagano 399-0781, JapanAbstract: Although mandibular third molar has a high risk of infection extending any complications, the influence of diabetes on radiolucency and acute inflammation in pericoronitis remains unclear. The present study was to evaluate whether radiolucency below the crown is related to acute inflammation in mandibular horizontal incompletely impacted third molars and to review the records of 140 men more than 45 years with and without diabetes. The odds ratio of exhibiting acute inflammation was 3.38 (95% CI: 1.13–10.16, p < 0.05 and that of exhibiting severe acute inflammation was 15.38 (95% CI: 3.56–66.49, p < 0.0001, indicating an association of acute pericoronitis in diabetes. The frequency of radiolucency below the crown and below the root in diabetics was similar to that in nondiabetics. However, the odds ratio of exhibiting both radiolucency below the crown and acute inflammation under the diabetic condition was 4.85 (95% CI: 1.60–14.73, p < 0.01, whereas that of diabetics showing both radiolucency below the root and acute inflammation was 0.46 (95% CI: 0.06–3.74, p = 0.74. Radiolucency below the crown and acute inflammation were associated with diabetes, but that below root and acute inflammation were not associated with diabetes, indicating that the region below the crown carries susceptibility to acute pericoronitis, whereas the periodontium shows a protective effect against acute pericoronitis.Keywords: radiolucency, acute inflammation, mandible, third molar, diabetes, periodontium

  15. Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    Full Text Available Acute exacerbation (AE is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF. In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF. Keywords: Idiopathic pulmonary fibrosis, Acute exacerbation, AE-IPF, Triggered AE, Aspergillus infection

  16. Resolution of sonographic B-lines as a measure of pulmonary decongestion in acute heart failure.

    Science.gov (United States)

    Martindale, Jennifer L

    2016-06-01

    Objective noninvasive measures of dyspnea in patients with acute heart failure are lacking. In this review, we describe lung ultrasound as a tool to estimate the degree of pulmonary congestion in patients presenting with acute heart failure and to monitor therapeutic efficacy. Serial semiquantitative measures of sonographic B-lines in acute heart failure patients can be converted to pulmonary edema scores obtained at admission and hospital discharge. These scores provide prognostic information for short-term clinical outcomes. Lung ultrasound has the potential to measure changes in pulmonary edema during acute heart failure management and improve risk stratification. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Acute fibrinous organising pneumonia: a manifestation of trimethoprim-sulfamethoxazole pulmonary toxicity.

    Science.gov (United States)

    Jamous, Fady; Ayaz, Syed Zain; Choate, Jacquelyn

    2014-10-29

    A 50-year-old man was treated with trimethoprim-sulfamethoxazole (TMP-SMX) for acute arthritis of his right big toe. Within a few days, he developed dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. Symptoms improved with discontinuation of the antibiotic but worsened again with its reintroduction. An open lung biopsy was performed. We describe the workup performed and the factors that pointed to a final diagnosis of TMP-SMX-related pulmonary toxicity in the form of acute fibrinous organising pneumonia. 2014 BMJ Publishing Group Ltd.

  18. Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation.

    Science.gov (United States)

    Li, Qian; Guo, Zhenhong; Xu, Xiongfei; Xia, Sheng; Cao, Xuetao

    2008-10-01

    The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.

  19. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

    Science.gov (United States)

    Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

    1999-12-01

    Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

  20. Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox.

    Science.gov (United States)

    Eapen, Mathew Suji; Myers, Stephen; Walters, Eugene Haydn; Sohal, Sukhwinder Singh

    2017-10-01

    Chronic obstructive pulmonary disease (COPD) is primarily an airway condition, which mainly affects cigarette smokers and presents with shortness of breath that is progressive and poorly reversible. In COPD research, there has been a long held belief that airway disease progression is due to inflammation. Although this may be true in the airway lumen with innate immunity activated by the effect of smoke or secondary to infection, the accurate picture of inflammatory cells in the airway wall, where the pathophysiological COPD remodeling occurs, is uncertain and debatable. Areas covered: The current review provides a comprehensive literature survey of the changes in the main inflammatory cells in human COPD patients and focuses on contrarian views that affect the prevailing dogma on inflammation. The review also delves into the role of oxidative stress and inflammasomes in modulating the immune response in COPD. Further, the effects of inflammation in affecting the epithelium, fibroblasts, and airway remodeling are discussed. Expert commentary: Inflammation as a driving force for airway wall damage and remodelling in early COPD is at the very least 'oversimplified' and is likely to be misleading. This has serious implications for rational thinking about the illness, including pathogenesis and designing therapy.

  1. Pulmonary hypertension due to acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    S.A. Ñamendys-Silva

    2014-10-01

    Full Text Available Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS, to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46% who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%. The most common cause of ARDS was pneumonia (56.3%. The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit.

  2. Mitochondrial Complex IV Subunit 4 Isoform 2 Is Essential for Acute Pulmonary Oxygen Sensing.

    Science.gov (United States)

    Sommer, Natascha; Hüttemann, Maik; Pak, Oleg; Scheibe, Susan; Knoepp, Fenja; Sinkler, Christopher; Malczyk, Monika; Gierhardt, Mareike; Esfandiary, Azadeh; Kraut, Simone; Jonas, Felix; Veith, Christine; Aras, Siddhesh; Sydykov, Akylbek; Alebrahimdehkordi, Nasim; Giehl, Klaudia; Hecker, Matthias; Brandes, Ralf P; Seeger, Werner; Grimminger, Friedrich; Ghofrani, Hossein A; Schermuly, Ralph T; Grossman, Lawrence I; Weissmann, Norbert

    2017-08-04

    Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as a critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and the mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing, remain unresolved. To investigate the role of the pulmonary-specific isoform 2 of subunit 4 of the mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling. Isolated ventilated and perfused lungs from Cox4i2 -/- mice lacked acute HPV. In parallel, pulmonary arterial smooth muscle cells (PASMCs) from Cox4i2 -/- mice showed no hypoxia-induced increase of intracellular calcium. Hypoxia-induced superoxide release which was detected by electron spin resonance spectroscopy in wild-type PASMCs was absent in Cox4i2 -/- PASMCs and was dependent on cysteine residues of Cox4i2. HPV could be inhibited by mitochondrial superoxide inhibitors proving the functional relevance of superoxide release for HPV. Mitochondrial hyperpolarization, which can promote mitochondrial superoxide release, was detected during acute hypoxia in wild-type but not Cox4i2 -/- PASMCs. Downstream signaling determined by patch-clamp measurements showed decreased hypoxia-induced cellular membrane depolarization in Cox4i2 -/- PASMCs compared with wild-type PASMCs, which could be normalized by the application of hydrogen peroxide. In contrast, chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling were not or only slightly affected by Cox4i2 deficiency, respectively. Cox4i2 is essential for acute but not chronic pulmonary oxygen sensing by triggering mitochondrial hyperpolarization and release of mitochondrial superoxide which, after conversion

  3. Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

    Science.gov (United States)

    Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

    2014-03-01

    Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis. Copyright © 2012 Elsevier España, S.L. y SEMICYUC. All rights reserved.

  4. P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

    Science.gov (United States)

    Müller, Tobias; Fay, Susanne; Vieira, Rodolfo Paula; Karmouty-Quintana, Harry; Cicko, Sanja; Ayata, Cemil Korcan; Zissel, Gernot; Goldmann, Torsten; Lungarella, Giuseppe; Ferrari, Davide; Di Virgilio, Francesco; Robaye, Bernard; Boeynaems, Jean-Marie; Lazarowski, Eduardo R.; Blackburn, Michael R.; Idzko, Marco

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF. PMID:28878780

  5. P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Tobias Müller

    2017-08-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF.

  6. Dual energy CT pulmonary blood volume assessment in acute pulmonary embolism - correlation with D-dimer level, right heart strain and clinical outcome

    International Nuclear Information System (INIS)

    Bauer, Ralf W.; Frellesen, Claudia; Schell, Boris; Lehnert, Thomas; Jacobi, Volkmar; Vogl, Thomas J.; Kerl, J.M.; Renker, Matthias; Ackermann, Hanns; Schoepf, U.J.

    2011-01-01

    To investigate the role of perfusion defect (PD) size on dual energy CT pulmonary blood volume assessment as predictor of right heart strain and patient outcome and its correlation with d-dimer levels in acute pulmonary embolism (PE). 53 patients with acute PE who underwent DECT pulmonary angiography were retrospectively analyzed. Pulmonary PD size caused by PE was measured on DE iodine maps and quantified absolutely (VolPD) and relatively to the total lung volume (RelPD). Signs of right heart strain (RHS) on CT were determined. Information on d-dimer levels and readmission for recurrent onset of PE and death was collected. D-dimer level was mildly (r = 0.43-0.47) correlated with PD size. Patients with RHS had significantly higher VolPD (215 vs. 73 ml) and RelPD (9.9 vs. 2.9%) than patients without RHS (p 5% RelPD, while no such events were found for patients with <5% RelPD. Pulmonary blood volume on DECT in acute PE correlates with RHS and appears to be a predictor of patient outcome in this pilot study. (orig.)

  7. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.

    Directory of Open Access Journals (Sweden)

    Paméla Gasse

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+ γδ T cells and to a lesser extent by CD4αβ(+ T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

  8. Influence of pre-existing inflammation on the outcome of acute coronary syndrome

    DEFF Research Database (Denmark)

    Odeberg, J.; Freitag, M.; Forssell, Henrik

    2016-01-01

    Objectives: Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were...... that a pre-existing low-grade inflammation may dispose towards MI over UA....

  9. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice

    NARCIS (Netherlands)

    Khedoe, P.P.S.J.; Wong, M.C.; Wagenaar, G.T.M.; Plomp, J.J.; Eck, M. van; Havekes, L.M.; Rensen, P.C.N.; Hiemstra, P.S.; Berbée, J.F.P.

    2013-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore,

  10. Adrenergic and steroid hormone modulation of ozone-induced pulmonary injury and inflammation

    Science.gov (United States)

    Rationale: We have shown that acute ozone inhalation promotes activation of the sympathetic and hypothalamic-pituitary-adrenal (HPA) axis leading to release of cortisol and epinephrine from the adrenals. Adrenalectomy (ADREX) inhibits ozone-induced pulmonary vascular leakage and ...

  11. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured.Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  12. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  13. Acute pulmonary embolism. Part 1: Epidemiology and diagnosis

    NARCIS (Netherlands)

    Douma, Renée A.; Kamphuisen, Pieter W.; Büller, Harry R.

    2010-01-01

    Pulmonary embolism (PE) is a frequently occurring, acute, and potentially fatal condition. Numerous risk factors for PE, both inherited and acquired, have been identified. Adequate diagnosis is mandatory to prevent PE-related morbidity and mortality on the one hand, and unnecessary treatment on the

  14. Pulmonary CT findings in acute mercury vapour exposure

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Manabu; Sato, Kimihiko; Heianna, Jyouiti; Hirano, Yoshinori; Omachi, Kohiti; Izumi, Jyunichi; Watarai, Jiro

    2001-01-01

    AIM: We describe the pulmonary computed tomography (CT) findings in acute mercury poisoning. MATERIALS AND METHODS: Initial (n= 8) and follow-up (n= 6) chest CT examinations in eight patients exposed to mercury vapour while cutting pipes in a sulphuric acid plant were reviewed. Of the eight patients, two were asymptomatic and had normal CT results, two were asymptomatic but had abnormalities on CT, and four had both acute symptoms and positive CT results. The patients were all men whose ages ranged from 37 to 54 years (mean, 49 years). RESULTS: Poorly defined nodules were present in five of six patients with positive CT findings, present alone in two patients or as part of a mixed pattern in three. They were random in distribution. Alveolar consolidation (n= 3) and areas of ground-glass opacity (n= 4) were observed and were more prominent in the most severely affected patients with the highest blood and urine level of mercury, predominantly in the upper and/or middle zone. These abnormal findings on CT resolved with (n= 1) or without (n= 5) steroid therapy. Pathological findings (n= 1) demonstrated acute interstitial changes predominantly with oedema. CONCLUSION: We report CT findings in eight patients acutely exposed to mercury vapour. The pulmonary injury was reversible on CT in these cases. Hashimoto, M. (2001)

  15. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.

    2015-01-01

    by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 m...

  16. Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

    Science.gov (United States)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

    Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

  17. Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

    Directory of Open Access Journals (Sweden)

    An Gary

    2008-05-01

    Full Text Available Abstract Background One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure. Results and Discussion ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems Conclusion A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior

  18. The acute pulmonary oedema in the intensive-care ward. Das akute Lungenoedem auf der Intensivstation

    Energy Technology Data Exchange (ETDEWEB)

    Marciniak, R.; Aronski, A. (Akademia Medyczna, Wroclaw (Poland))

    1989-07-01

    760 patients suffering from acute pulmonary oedema were treated between 1980 and 1986 at the Institute of Anaesthesiology of the Medical Academy in Wroclaw. The radiological image of the pulmonary oedema was subdivided into three forms (hilar, hilar and perihilar, and hilar with massive plane-shaped infiltrates). In the treatment of acute pulmonary oedema in the intensive-care ward a thorough diagnostic programme is mandatory after the immediately necessary measures have been taken. (orig.).

  19. Thallium pulmonary scintigraphy. Relationship to pulmonary fluid volumes during left atrial hypertension and the acute release of pressure

    International Nuclear Information System (INIS)

    Slutsky, R.A.

    1984-01-01

    To evaluate the relationship between thallium-201 lung activity and pulmonary fluid volumes, we compared thallium pulmonary scintigrams with measures of intravascular (PBV), extravascular (EVLW) and total lung water (TLW) during gradual left atrial (LA) hypertension and then serially after the acute release of pressure. The study group was composed of nine mongrel dogs who were each studied at seven levels of elevated LA pressure, and then every 15 minutes for 2 hours after the acute release of pressure. During LA pressure (congestion phase) elevation, lung counts (normalized for myocardial activity), correlated best with TLW (r . .91), rather than PBV (r . .84) or EVLW (r . .81). After the release of pressure (recovery phase), lung counts correlated well with EVLW (r . .92) and TLW (r . .82), but not with PBV (r . .28). Postmortem lung counts from 197 separate lung sections correlated well with the corresponding wet weight/dry weight ratio from that section (r . .81). Thus, we conclude that changes in pulmonary thallium emissions during cardiogenic pulmonary edema relate to corresponding changes in pulmonary fluid volumes. During congestion, the confounding effects of nonlinear increases in EVLW and PBV make thallium emissions more a marker of TLW than either the intravascular or extravascular pulmonary fluid compartment. After pressure release, PBV immediately returns to normal, at which time EVLW and pulmonary emissions correlate closely. These latter data, more applicable to postexercise stress thallium data, lend support to the hypothesis that elevated pulmonary emissions during postexercise thallium scintigrams reflect elevations in EVLW that develop during exercise

  20. Dual energy CT pulmonary blood volume assessment in acute pulmonary embolism - correlation with D-dimer level, right heart strain and clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Ralf W.; Frellesen, Claudia; Schell, Boris; Lehnert, Thomas; Jacobi, Volkmar; Vogl, Thomas J.; Kerl, J.M. [Clinic of the Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Renker, Matthias [Clinic of the Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Medical University of South Carolina, Heart and Vascular Center, Ashley River Tower, Charleston, SC (United States); Ackermann, Hanns [Clinic of the Goethe University, Department of Biostatistics and Mathematical Modelling, Frankfurt (Germany); Schoepf, U.J. [Medical University of South Carolina, Heart and Vascular Center, Ashley River Tower, Charleston, SC (United States)

    2011-09-15

    To investigate the role of perfusion defect (PD) size on dual energy CT pulmonary blood volume assessment as predictor of right heart strain and patient outcome and its correlation with d-dimer levels in acute pulmonary embolism (PE). 53 patients with acute PE who underwent DECT pulmonary angiography were retrospectively analyzed. Pulmonary PD size caused by PE was measured on DE iodine maps and quantified absolutely (VolPD) and relatively to the total lung volume (RelPD). Signs of right heart strain (RHS) on CT were determined. Information on d-dimer levels and readmission for recurrent onset of PE and death was collected. D-dimer level was mildly (r = 0.43-0.47) correlated with PD size. Patients with RHS had significantly higher VolPD (215 vs. 73 ml) and RelPD (9.9 vs. 2.9%) than patients without RHS (p < 0.003). There were 2 deaths and 1 readmission due of PE in 18 patients with >5% RelPD, while no such events were found for patients with <5% RelPD. Pulmonary blood volume on DECT in acute PE correlates with RHS and appears to be a predictor of patient outcome in this pilot study. (orig.)

  1. Acute Pulmonary Edema in an Eclamptic Pregnant Patient: A Rare Case of Takotsubo Syndrome.

    Science.gov (United States)

    Karamchandani, Kunal; Bortz, Brandon; Vaida, Sonia

    2016-09-23

    BACKGROUND Acute pulmonary edema in a pregnant patient is associated with significant morbidity and mortality. Takotsubo syndrome, or stress-induced cardiomyopathy, is a rare cause of acute pulmonary edema in a pregnant patient, especially prior to delivery of the fetus. CASE REPORT We describe a case of a pregnant patient who presented with acute pulmonary edema and eclampsia and was found to have Takotsubo syndrome. To the best of our knowledge, eclampsia as a precipitating factor for Takotsubo syndrome has not been described in literature. CONCLUSIONS Clinicians taking care of pregnant patients should be aware of the potential link between eclampsia and Takotsubo cardiomyopathy. Prompt correction of the precipitating cause along with supportive management as described is the key to a successful outcome.

  2. Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung Injury and Inflammation.

    Science.gov (United States)

    Li, Lili; Zhang, Sheng; Xin, Yanfei; Sun, Junying; Xie, Feng; Yang, Lin; Chen, Zhiqin; Chen, Hao; Liu, Fang; Xuan, Yaoxian; You, Zhenqiang

    2018-01-26

    Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

  3. Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

    Science.gov (United States)

    Retamal, Jaime; Hurtado, Daniel; Villarroel, Nicolás; Bruhn, Alejandro; Bugedo, Guillermo; Amato, Marcelo Britto Passos; Costa, Eduardo Leite Vieira; Hedenstierna, Göran; Larsson, Anders; Borges, João Batista

    2018-06-01

    It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. University animal research laboratory. Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals

  4. Widening of coronary sinus in CT pulmonary angiography indicates right ventricular dysfunction in patients with acute pulmonary embolism

    International Nuclear Information System (INIS)

    Staskiewicz, Grzegorz; Czekajska-Chehab, Elzbieta; Trojanowska, Agnieszka; Drop, Andrzej; Przegalinski, Jerzy; Tomaszewski, Andrzej; Torres, Kamil; Torres, Anna; Maciejewski, Ryszard

    2010-01-01

    Right ventricular dysfunction (RVD) may occur in the course of acute pulmonary embolism (PE). Patients with RVD need more intensive treatment, and the prognosis is more severe. The aim of this study was to evaluate the usefulness of the measurement of the coronary sinus in the assessment of RVD in patients with acute PE and to compare it with other indicators of RVD. Retrospective assessment of 55 CT pulmonary angiography examinations with signs of acute PE was performed. Pulmonary artery systolic pressure (PASP) was echocardiographically assessed in all patients, and RVD was defined as PASP values greater than 30 mmHg. CT measurements included the size of the heart ventricles, mediastinal vessels and the width of the coronary sinus. Median width of the coronary sinus was 16 mm (range 12-24 mm) in patients with increased PASP and 10 mm (range 7-22 mm) in patients with normal PASP (p = 0.001). Best cut-off value was assessed to be 12.5 mm, with sensitivity 94% and specificity 75%. It was characterised by the largest area under ROC curve (0.82) among analysed parameters. Width of the coronary sinus seems to be a promising parameter for identification of RVD in patients with acute PE. A prospective study should be undertaken to further assess its clinical and prognostic applicability. (orig.)

  5. Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

    2017-09-01

    Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  6. Grouping nanomaterials to predict their potential to induce pulmonary inflammation.

    Science.gov (United States)

    Braakhuis, Hedwig M; Oomen, Agnes G; Cassee, Flemming R

    2016-05-15

    The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. [Acute onset pulmonary toxicity associated to amiodarone].

    Science.gov (United States)

    Ferreira, Pedro Gonçalo; Saraiva, Fátima; Carreira, Cláudia

    2012-01-01

    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome.

  8. Acrolein - a pulmonary hazard.

    Science.gov (United States)

    Bein, Kiflai; Leikauf, George D

    2011-09-01

    Acrolein is a respiratory irritant that can be generated during cooking and is in environmental tobacco smoke. More plentiful in cigarette smoke than polycyclic aromatic hydrocarbons (PAH), acrolein can adduct tumor suppressor p53 (TP53) DNA and may contribute to TP53-mutations in lung cancer. Acrolein is also generated endogenously at sites of injury, and excessive breath levels (sufficient to activate metalloproteinases and increase mucin transcripts) have been detected in asthma and chronic obstructive pulmonary disease (COPD). Because of its reactivity with respiratory-lining fluid or cellular macromolecules, acrolein alters gene regulation, inflammation, mucociliary transport, and alveolar-capillary barrier integrity. In laboratory animals, acute exposures have lead to acute lung injury and pulmonary edema similar to that produced by smoke inhalation whereas lower concentrations have produced bronchial hyperreactivity, excessive mucus production, and alveolar enlargement. Susceptibility to acrolein exposure is associated with differential regulation of cell surface receptor, transcription factor, and ubiquitin-proteasome genes. Consequent to its pathophysiological impact, acrolein contributes to the morbidly and mortality associated with acute lung injury and COPD, and possibly asthma and lung cancer. Copyright © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Pulmonary hydatid cyst in a pregnant patient causing acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Hijazi Mohammed

    2007-01-01

    Full Text Available A 21-year-old primigravida, at 32 weeks of gestation, presented with acute onset of respiratory failure and circulatory shock. Chest imaging showed findings suggestive of ruptured hydatid cyst, which was confirmed by histology post-thoracotomy. Tissue cultures from the removed cyst grew Mycobacterium tuberculosis also. She was successfully managed in the intensive care unit and was then discharged home on antituberculosis medications in addition to albendazole after prolonged hospitalization and a need for chest tube for bronchopleural fistula. Acute respiratory failure and anaphylactic shock secondary to ruptured pulmonary hydatid cyst and superimposed pulmonary tuberculosis in a pregnant lady should be considered in patients living in endemic areas.

  10. Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Harkema, J.R.; Sun, J.D.; Henderson, R.F.

    1988-01-01

    The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O 3 for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O 3 had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O 3 had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O 3 had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O 3 concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

  11. Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkiss, J A; Harkema, J R; Sun, J D; Henderson, R F

    1988-12-01

    The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O{sub 3} for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O{sub 3} had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O{sub 3} had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O{sub 3} had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O{sub 3} concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

  12. Carboxyhemoglobin and methemoglobin levels as prognostic markers in acute pulmonary embolism.

    Science.gov (United States)

    Kakavas, Sotirios; Papanikolaou, Aggeliki; Ballis, Evangelos; Tatsis, Nikolaos; Goga, Christina; Tatsis, Georgios

    2015-04-01

    Carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels have been associated with a poor outcome in patients with various pathological conditions including cardiovascular diseases. Our aim was to retrospectively assess the prognostic value of arterial COHb and MetHb in patients with acute pulmonary embolism (PE). We conducted a retrospective study of 156 patients admitted in a pulmonary clinic due to acute PE. Measured variables during emergency department evaluation that were retrospectively analyzed included the ratio of the partial pressure of oxygen in arterial blood to the fraction of oxygen in inspired gas, Acute Physiology and Chronic Health Evaluation II score, risk stratification indices, and arterial blood gases. The association between arterial COHb and MetHb levels and disease severity or mortality was evaluated using bivariate tests and logistic regression analysis. Arterial COHb and MetHb levels correlated with Acute Physiology and Chronic Health Evaluation II and pulmonary severity index scores. Furthermore, arterial COHb and MetHb levels were associated with troponin T and N-terminal pro-B-type natriuretic peptide levels. In univariate logistic regression analysis, COHb and MetHb levels were both significantly associated with an increased risk of death. However, in multivariate analysis, only COHb remained significant as an independent predictor of in-hospital mortality. Our preliminary data suggest that arterial COHb and MetHb levels reflect the severity of acute PE, whereas COHb levels are independent predictors of in hospital death in patients in this clinical setting. These findings require further prospective validation. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ladefoged Ole

    2009-01-01

    Full Text Available Abstract 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.

  14. Intermittent hypoxia simulating obstructive sleep apnea causes pulmonary inflammation and activates the Nrf2/HO-1 pathway.

    Science.gov (United States)

    Wang, Yeying; Chai, Yanling; He, Xiaojie; Ai, Li; Sun, Xia; Huang, Yiling; Li, Yongxia

    2017-10-01

    Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA damages multiple organs and tissues, including the cardiovascular and cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA-induced damage is earliest and greatest to the pulmonary tissue. The present study established a rat OSA model of differing severity by inducing intermittent hypoxia with different concentrations of O 2 and it was determined that OSA caused a severe oxidative stress response and pulmonary inflammation in a dose-dependent manner. OSA increased serum levels of C-reactive protein and 8-isoprostane and elevated the expression of malondialdehyde, tumor necrosis factor α, interleukin (IL)-1β and IL-6 in the pulmonary tissue. Furthermore, the expression of two important antioxidants, superoxide dismutase and glutathione, was downregulated following intermittent hypoxia. By contrast, levels of cylooxygenase 2 and inducible nitric oxide synthase, which are crucial in the antioxidative response, increased. In addition, OSA activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (OH)-1 antioxidative signaling pathway. Finally, all increases and decreases in levels of inflammatory and antioxidative substances were dependent on oxygen concentrations. Therefore, the present study demonstrated that OSA, simulated by intermittent hypoxia, caused an oxidative stress response and pulmonary inflammation, and activated the canonical antioxidative Nrf2/HO-1 signaling pathway in a dose-dependent manner. These results may facilitate the development of clinical therapies to treat pulmonary diseases caused by OSA.

  15. Successful Treatment of Free-Floating Right Ventricular Thrombus with Acute Pulmonary Embolism

    Directory of Open Access Journals (Sweden)

    Sanjay Singhal

    2015-01-01

    Full Text Available Acute pulmonary embolism with floating right intra-ventricular thrombus is a rare phenomena associated with poor prognosis. Here, we are presenting a case of 35-year-young male with no co-morbid illness diagnosed to have right ventricular thrombus with bilateral pulmonary embolism, which was managed successfully with thrombolytic therapy.

  16. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina

    2006-01-01

    There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current

  17. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Directory of Open Access Journals (Sweden)

    Takeshi Tohyama

    Full Text Available Lipopolysaccharide (LPS induces acute inflammation, activates sympathetic nerve activity (SNA and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP, examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis.Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg. We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection.In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.. In contrast, AP increased initially (until 75 min, then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP.LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and

  18. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Science.gov (United States)

    Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

    2018-01-01

    Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed

  19. Value of the ventilation/perfusion scan in acute pulmonary embolism: Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED)

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    To determine the sensitivities and specificities of ventilation/perfusion lung scans for acute pulmonary embolism, a random sample of 933 of 1,493 patients was studied prospectively. Nine hundred thirty-one underwent scintigraphy and 755 underwent pulmonary angiography; 251 (33%) of 755 demonstrated pulmonary embolism. Almost all patients with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism. Of 116 patients with high-probability scans and definitive angiograms, 102 (88%) had pulmonary embolism, but only a minority with pulmonary embolism had high-probability scans. Of 322 with intermediate-probability scans and definitive angiograms, 105 (33%) had pulmonary embolism. Follow-up and angiography together suggest pulmonary embolism occurred among 12% of patients with low-probability scans. Clinical assessment combined with the ventilation/perfusion scan established the diagnosis or exclusion of pulmonary embolism only for a minority of patients--those with clear and concordant clinical and ventilation/perfusion scan findings

  20. [Clinical features and management of acute myositis in idiopathic orbital inflammation].

    Science.gov (United States)

    Halimi, E; Rosenberg, R; Wavreille, O; Bouckehove, S; Franquet, N; Labalette, P

    2013-09-01

    Acute myositis is the second most common component of non-specific orbital inflammation. We will describe its clinical features and natural history. This is a retrospective study of 10 cases. The diagnosis of acute myositis was based on clinical and imaging criteria. Our study includes five men and five women. The average age was 35.8 years (17-59 years). Clinical symptoms were: pain increased on eye movement (10/10), diplopia (4/10), proptosis (6/10), visual loss (3/10), lid edema (6/10), conjunctival hyperemia (7/10), anterior scleritis (2/10), episcleritis (2/10), chemosis (4/10), upper lid retraction (1/10), limitation of eye movement (3/10), fundus abnormalities (2/10). Imaging showed thickening of one or more extraocular muscles (10/10). Recovery was complete with anti-inflammatory therapy in six patients. Three patients experienced recurrence, and one patient had a clinical rebound upon tapering the treatment. Acute myositis can be defined by pain on eye movement, signs of inflammation, and extraocular muscle thickening on imaging. If the clinical presentation is typical, histopathological analysis can be deferred but remains necessary in cases of poor response to treatment, chronic duration or suspicion of tumor infiltration. The diagnosis of acute myositis may be suspected in the presence of consistent, well-defined clinical signs. Contiguous inflammation is often associated. Treatment is based on steroids or non-steroidal treatment anti-inflammatory therapy, administered alone or consecutively. Recurrences are frequent but do not alter the final prognosis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Pulmonary Hypertension and Pulmonary Vasodilators.

    Science.gov (United States)

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.

    Science.gov (United States)

    Benson, Sven; Brinkhoff, Alexandra; Lueg, Larissa; Roderigo, Till; Kribben, Andreas; Wilde, Benjamin; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Elsenbruch, Sigrid

    2017-12-11

    Experimental endotoxemia is a translational model to study inflammatory mechanisms involved in the pathophysiology of mood disorders including depression. Disturbed affective cognition constitutes a core aspect in depression, but has never been studied in the context of inflammation. We combined experimental endotoxemia with an established experimental mood induction procedure to assess the interaction between acute inflammation and sad mood and their effects on affective cognition. In this randomized cross-over study, N = 15 healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study day and placebo an otherwise identical study day. The affective Go/Nogo task was conducted after experimental induction of neutral and sad mood. Inflammatory markers were assessed hourly. Endotoxin application induced a transient systemic inflammation, characterized by increased leukocyte counts, TNF-alpha and interleukin-6 plasma concentrations (all p sadness ratings, with highest ratings when sad mood was induced during inflammation (p sad vs. neutral mood) × 2 (sad vs. happy Go/Nogo target words) factorial design, we observed a significant target × endotoxin condition interaction (p sad targets during endotoxemia. Additionally, we found a valence × mood interaction (p sad targets in sad mood. In summary, acute inflammation and sad mood are risk factors for disturbed affective cognition. The results may reflect a mood-congruency effect, with prolonged and sustained processing of mood-congruent information during acute inflammation, which may contribute to depression risk.

  3. Diagnosing acute pulmonary embolism with computed tomography: imaging update.

    Science.gov (United States)

    Devaraj, Anand; Sayer, Charlie; Sheard, Sarah; Grubnic, Sisa; Nair, Arjun; Vlahos, Ioannis

    2015-05-01

    Acute pulmonary embolism is recognized as a difficult diagnosis to make. It is potentially fatal if undiagnosed, yet increasing referral rates for imaging and falling diagnostic yields are topics which have attracted much attention. For patients in the emergency department with suspected pulmonary embolism, computed tomography pulmonary angiography (CTPA) is the test of choice for most physicians, and hence radiology has a key role to play in the patient pathway. This review will outline key aspects of the recent literature regarding the following issues: patient selection for imaging, the optimization of CTPA image quality and dose, preferred pathways for pregnant patients and other subgroups, and the role of CTPA beyond diagnosis. The role of newer techniques such as dual-energy CT and single-photon emission-CT will also be discussed.

  4. Alternative and Natural Therapies for Acute Lung Injury and Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Vipul J. Patel

    2018-01-01

    Full Text Available Introduction. Acute respiratory distress syndrome (ARDS is a complex clinical syndrome characterized by acute inflammation, microvascular damage, and increased pulmonary vascular and epithelial permeability, frequently resulting in acute respiratory failure and death. Current best practice for ARDS involves “lung-protective ventilation,” which entails low tidal volumes and limiting the plateau pressures in mechanically ventilated patients. Although considerable progress has been made in understanding the pathogenesis of ARDS, little progress has been made in the development of specific therapies to combat injury and inflammation. Areas Covered. In recent years, several natural products have been studied in experimental models and have been shown to inhibit multiple inflammatory pathways associated with acute lung injury and ARDS at a molecular level. Because of the pleiotropic effects of these agents, many of them also activate antioxidant pathways through nuclear factor erythroid-related factor 2, thereby targeting multiple pathways. Several of these agents are prescribed for treatment of inflammatory conditions in the Asian subcontinent and have shown to be relatively safe. Expert Commentary. Here we review natural remedies shown to attenuate lung injury and inflammation in experimental models. Translational human studies in patients with ARDS may facilitate treatment of this devastating disease.

  5. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

    DEFF Research Database (Denmark)

    Poulsen, Sarah Søs; Knudsen, Kristina Bram; Jackson, Petra

    2017-01-01

    of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BLI6J mice pulmonary exposed to 0, 6, 18 or 54 lag MWCNT/mouse. Plasma levels...... of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saal and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater...... limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length...

  6. Prognostic impact of pleural effusion in acute pulmonary embolism.

    Science.gov (United States)

    Kiris, Tuncay; Yazıcı, Selçuk; Koc, Ali; Köprülü, Cinar; Ilke Akyildiz, Zehra; Karaca, Mustafa; Nazli, Cem; Dogan, Abdullah

    2017-07-01

    Background Pulmonary embolism (PE) is a common and life-threatening condition associated with considerable morbidity and mortality. Pleural effusion occurs in about one in three cases; however, data on its prognostic value are scarce. Purpose To investigate the association between pleural effusion and both 30-day and long-term mortality in patients with acute PE. Material and Methods We retrospectively evaluated 463 patients diagnosed with acute PE using computed tomography pulmonary angiography (CTPA). Echocardiographic, demographic, and laboratory data were collected. The study population was divided into two groups: patients with and without pleural effusions. Pleural effusion detected on CT was graded as small, moderate, and large according to the amount of effusion. The predictors of 30-day and long-term total mortality were analyzed. Results Pleural effusions were found in 120 patients (25.9%). After the 30-day follow-up, all-cause mortality was higher in acute PE patients with pleural effusions than in those without (23% versus 9%, P pleural effusions had significantly higher incidence of long-term total mortality than those without pleural effusions (55% versus 23%, P pleural effusion was an independent predictor of 30-day and long-term mortality (odds ratio [OR], 2.154; 95% confidence interval [CI], 1.186-3.913; P = 0.012 and OR, 1.591; 95% CI, 1.129-2.243; P = 0.008, respectively). Conclusion Pleural effusion can be independently associated with both 30-day and long-term mortality in patients with acute PE.

  7. Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

    2011-01-01

    with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc....... in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more...... than 1.2‐fold (adjusted P‐value changes in the expression of genes associated...

  8. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tashkin DP

    2018-01-01

    Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

  9. Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema.

    Science.gov (United States)

    Wei, Jingjing; Zhao, Hui; Fan, Guoquan; Li, Jianqiang

    2015-09-18

    Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage. To assess the capacity of bilirubin to protect against smoke-induced emphysema. Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPD participants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione. Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema. Copyright © 2015. Published by Elsevier Inc.

  10. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

  11. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  12. HELICOBACTER PYLORI-ASSOCIATED INFLAMMATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    O. N. Pavlov

    2014-07-01

    Full Text Available The aim – assessment of the prevalence of seropositivity to Helicobacter pylori infection and laboratory comparative study of the peripheralblood in patients depending on the course of coronary heart disease (CHD.Materials and methods. Observation of 100 patients with coronary artery disease and 40 control patients is presented. Investigation indicatorsof clinical blood tests, biochemical blood analysis and determination of immunoglobulin antibody titer against Helicobacter pylori.Results. In patients with coronary artery disease signs of systemic inflammation associated with the development of acute coronary syndrome are marked with increased antibody titers to infection Helicobacter pylori.Conclusion. A history of coronary artery disease in patients with Helicobacter pylori-associated gastroduodenal pathology should be considered as a factor that increases the likelihood of unstable coronary desease course. Detected in patients with coronary artery disease signs of systemic inflammation with an increase in titer of antibodies to Helicobacter pylori infection associated with development of acute coronary syndrome.

  13. The role of inflammation and interleukin-1 in acute cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Galea J

    2013-08-01

    Full Text Available James Galea,1 David Brough21Manchester Academic Health Sciences Center, Brain Injury Research Group, Clinical Sciences Building, Salford Royal Foundation Trust, Salford, UK; 2Faculty of Life Sciences, University of Manchester, AV Hill Building, Manchester, UKAbstract: Acute cerebrovascular disease can affect people at all stages of life, from neonates to the elderly, with devastating consequences. It is responsible for up to 10% of deaths worldwide, is a major cause of disability, and represents an area of real unmet clinical need. Acute cerebrovascular disease is multifactorial with many mechanisms contributing to a complex pathophysiology. One of the major processes worsening disease severity and outcome is inflammation. Pro-inflammatory cytokines of the interleukin (IL-1 family are now known to drive damaging inflammatory processes in the brain. The aim of this review is to discuss the recent literature describing the role of IL-1 in acute cerebrovascular disease and to provide an update on our current understanding of the mechanisms of IL-1 production. We also discuss the recent literature where the effects of IL-1 have been targeted in animal models, thus reviewing potential future strategies that may limit the devastating effects of acute cerebrovascular disease.Keywords: cerebral ischemia, stroke, inflammation, microglia, interleukin-1, caspase-1

  14. Pathophysiology of acute mountain sickness and high altitude pulmonary oedema

    DEFF Research Database (Denmark)

    Sutton, J R; Lassen, N

    1979-01-01

    We review the evidence that acute mountain sickness (AMS) and high altitude pulmonary oedema (HAPO) occur together more often than is realized. We hypothesize that AMS and HAPO have a common pathophysiological basis: both are due to increased pressure and flow in the microcirculation, causing...

  15. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease.

    LENUS (Irish Health Repository)

    McNicholas, Walter T

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea\\/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea\\/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and\\/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell\\/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.

  16. Hypercalcemia and acute pancreatitis in a male patient with acute promyelocytic leukemia and pulmonary tuberculosis.

    Science.gov (United States)

    Abdullah, Ali S; Adel, Ahmad M; Hussein, Radwa M; Abdullah, Mohammed Aj; Yousaf, Anil; Mudawi, Deena; Mohamed, Shehab F; Nashwan, Abdulqadir J; Soliman, Dina; Ibrahim, Feryal; Yassin, Mohamed A

    2018-04-03

    We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

  17. Comparison of Serum Leptin Levels in Pulmonary Tuberculosis Patients with Acute Pneumonia Patients and Healthy Individuals

    Directory of Open Access Journals (Sweden)

    M. Naderi

    2017-10-01

    Full Text Available Aims: Leptin is one of the most important fat-derived hormones. Several studies have shown that serum leptin levels in systemic inflammatory diseases are reduced. The aim of this study was to evaluate the serum leptin levels in three groups: patients with active pulmonary tuberculosis (TB, patients with non-pulmonary infections (acute pneumonia and normal people. Materials & Methods: In this cross-sectional study, in 2010, 40 patients with active pulmonary TB (case group and 40 patients with non-pulmonary infections (positive control group admitted to Boo-Ali hospital in Zahedan and 40 healthy subjects (negative control group were selected using easy access and serum leptin levels were evaluated by ELISA. Data were analyzed by SPSS 18 software and one-way ANOVA. Findings: The mean of serum leptin levels in patients with non-pulmonary infections (p=0.030 and in patients with active pulmonary TB (p=0.004 were significantly lower than normal group, but the mean of serum leptin levels in patients with active pulmonary TB and patients with non-pulmonary infections were not significantly different (p=0.555. Conclusion: Serum leptin levels are lower in patients with active pulmonary tuberculosis and in patients with non-pulmonary infections than in normal people, but there is no difference between patients with active pulmonary tuberculosis and patients with non-pulmonary infections. Therefore, serum leptin levels are not an appropriate marker for the differentiation of active pulmonary tuberculosis from pulmonary infections (acute pneumonia.

  18. Therapeutic management of acute pulmonary embolism.

    Science.gov (United States)

    Tromeur, Cécile; Van Der Pol, Liselotte M; Couturaud, Francis; Klok, Frederikus A; Huisman, Menno V

    2017-08-01

    Acute pulmonary embolism (PE) is a potentially fatal manifestation of venous thromboembolism. Prompt anticoagulant treatment is crucial for PE patients, which can decrease morbidity and mortality. Risk assessment is the cornerstone of the therapeutic management of PE. It guides physicians to the most appropriate treatment and selects patients for early discharge or home treatment. Areas covered: Here, we review the current treatments of acute PE according to contemporary risk stratification strategies, highlighting each step of PE therapeutic management. Expert commentary: Currently, direct oral anticoagulants (DOACs) represent the first-line therapy of patients presenting with non-high risk PE with a better risk-benefit ratios than vitamin K antagonists (VKAs) due to lower risk of major bleeding. Only high-risk patients with PE who present in shock should be treated with systematic thrombolysis, while surgical thrombectomy or catheter direct thrombolysis (CDT) should only be considered when thrombolysis is contraindicated because of too high bleeding risk.

  19. A case of acute exacerbation of idiopathic pulmonary fibrosis after proton beam therapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Nagano, Tatsuya; Kotani, Yoshikazu; Fujii, Osamu

    2012-01-01

    There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis. (author)

  20. A fatal case of acute pulmonary embolism caused by right ventricular masses of acute lymphoblastic lymphoma-leukemia in a 13 year old girl

    Directory of Open Access Journals (Sweden)

    Yu Mi Ko Ko

    2012-07-01

    Full Text Available We report a case of a 13-year-old girl with acute lymphoblastic lymphoma- leukemia, who presented with a cardiac metastasis in the right ventricle, resulting in a pulmonary embolism. At the time of her leukemia diagnosis, a cardiac mass was incidentally found. The differential diagnosis for this unusual cardiac mass included cardiac tumor, metastasis, vegetation, and thrombus. Empirical treatment was initiated, including anticoagulation and antibiotics. She underwent plasmapheresis and was administered oral prednisolone for her leukemia. Five days later, she experienced sudden hemodynamic collapse and required extracorporeal membrane oxygenation insertion and emergency surgery. These interventions proved futile, and the patient died. Pathology revealed that the cardiac mass comprised an aggregation of small, round, necrotic cells consistent with leukemia. This is the first known case of acute lymphoblastic leukemia presenting as a right ventricular mass, with consequent fatal acute pulmonary embolism. A cardiac mass in a child with acute leukemia merits investigation to rule out every possible etiology, including vegetation, thrombus, and even a mass of leukemic cells, which could result in the fatal complication of pulmonary embolism.

  1. Acute hemodynamic response to vasodilators in primary pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Kulkarni H

    1996-01-01

    Full Text Available Acute hemodynamic effects of high flow oxygen (O2 inhalation, sublingual isosorbide dinitrate (ISDN, intravenous aminophylline (AMN and sublingual nifedipine (NIF were studied in 32 patients with primary pulmonary hypertension (PPH. In 30 out of 32 patients the basal ratio of pulmonary to systemic vascular resistance (Rp/Rs was > 0.5 (mean = 0.77 +/- 0.20. Oxygen caused significant decrease in the mean resistance ratio to 0.68 +/- 0.20 (p = 0.005. ISDN, AMN and NIF caused increase in the resistance ratio to 0.79 +/- 0.26; 0.78 +/- 0.26; and 0.80 +/- 0.23 respectively. O2, ISDN, AMN and NIF caused a fall of Rp/Rs in 21 (65.6%, 10 (31.2%, 10(31.2% and 9(28.1% patients respectively. Thus, of the four drugs tested high flow O2 inhalation resulted in fall of Rp/Rs in two thirds of patients whereas ISDN, AMN and NIF caused a mean rise in Rp/Rs. One third of patients did respond acutely to the latter three drugs. Acute hemodynamic studies are useful before prescribing vasodilators in patients with PPH since more of the commonly used drugs like ISDN, AMN, NIF could have detrimental hemodynamic responses in some patients. However, great caution should be exercised before performing hemodynamic study as the procedure has definite mortality and morbidity.

  2. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

    International Nuclear Information System (INIS)

    Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J.

    2016-01-01

    Ozone (O 3 )-related cardiorespiratory effects are a growing public health concern. Ground level O 3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O 3 -induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O 3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O 3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O 2 ) or hypoxia (10.0% O 2 ), followed by a 4-h exposure to either 1 ppm O 3 or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O 3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O 3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O 3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O 3 -induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive pulmonary disease (COPD). • It is unknown if comorbid

  3. [PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

    Science.gov (United States)

    Fedorkiv, M B

    2015-06-01

    Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%.

  4. High‑risk pulmonary embolism in a patient with acute dissecting ...

    African Journals Online (AJOL)

    In the last decades, an increased incidence of pulmonary embolism (PE) and acute dissection (AD) of aortic aneurysms has been registered mostly due to increased availability of advanced imaging techniques. They seldom occur concomitantly in the same patient. In this paper, we present the clinical challenges and ...

  5. Medical image of the week: acute amiodarone pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Mazursky K

    2015-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 71 year old man with a medical history significant for chronic obstructive pulmonary disease, coronary artery disease with post-operative status coronary artery bypass grafting, heart failure with reduced ejection fraction (25% and atrial fibrillation/flutter underwent an elective ablation of the tachyarrhythmia at another facility and was prescribed amiodarone post procedure. He started complaining of cough and dyspnea one day post procedure and was empirically treated with 2 weeks of broad spectrum antibiotics. He subsequently was transferred to our facility due to worsening symptoms. He also complained of nausea, anorexia with resultant weight loss since starting amiodarone, which was stopped 5 days prior to transfer. Infectious work up was negative. On arrival to our facility, he was diagnosed with small sub-segmental pulmonary emboli, pulmonary edema and possible acute amiodarone toxicity. His was profoundly hypoxic requiring high flow nasal cannula or 100% non-rebreather mask at all times. His symptoms persisted despite ...

  6. Aspiration, Localized Pulmonary Inflammation, and Predictors of Early-Onset Bronchiolitis Obliterans Syndrome after Lung Transplantation

    Science.gov (United States)

    Fisichella, P Marco; Davis, Christopher S; Lowery, Erin; Ramirez, Luis; Gamelli, Richard L; Kovacs, Elizabeth J

    2014-01-01

    BACKGROUND We hypothesized that immune mediator concentrations in the bronchoalveolar fluid (BALF) are predictive of bronchiolitis obliterans syndrome (BOS) and demonstrate specific patterns of dysregulation, depending on the presence of acute cellular rejection, BOS, aspiration, and timing of lung transplantation. STUDY DESIGN We prospectively collected 257 BALF samples from 105 lung transplant recipients. The BALF samples were assessed for absolute and differential white blood cell counts and 34 proteins implicated in pulmonary immunity, inflammation, fibrosis, and aspiration. RESULTS There were elevated BALF concentrations of interleukin (IL)-15, IL-17, basic fibroblast growth factor, tumor necrosis factor–α, and myeloperoxidase, and reduced concentrations of α1-antitrypsin, which were predictive of early-onset BOS. Patients with BOS had an increased percentage of BALF lymphocytes and neutrophils, with a reduced percentage of macrophages (p < 0.05). The BALF concentrations of IL-1β; IL-8; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; neutrophil elastase; and pepsin were higher in patients with BOS (p < 0.05). Among those with BOS, BALF concentrations of IL-1RA; IL-8; eotaxin; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; myeloperoxidase; and neutrophil elastase were positively correlated with time since transplantation (p < 0.01). Those with worse grades of acute cellular rejection had an increased percentage of lymphocytes in their BALF (p < 0.0001) and reduced BALF concentrations of IL-1β, IL-7, IL-9, IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, and vascular endothelial growth factor (p ≤ 0.001). Patients with aspiration based on detectable pepsin had increased percentage of neutrophils (p < 0.001) and reduced BALF concentrations of IL-12 (p < 0.001). CONCLUSIONS The BALF levels

  7. Acute Pulmonary Oedema after Removal of Sand Bag at the End of Open Cholecystectomy due to Unknown Cause

    Directory of Open Access Journals (Sweden)

    Pramod Gupta

    2008-01-01

    Full Text Available Pulmonary oedema developes acutely during perioperative period and is usually due to unknown cause,but this life threatening complication if managed on time ,leads to rapid and full recovery. Here a case of 70 year old man is reported who developed acute pulmonary oedema after conclusion of surgery due to unknown cause.

  8. [Echocardiography in acute pulmonary embolism. Not a routine method but useful in the diagnosis of simultaneous hemodynamic disorders].

    Science.gov (United States)

    Kierkegaard, A

    1998-08-19

    Echocardiographic diagnosis of acute pulmonary embolism as illustrated by three case reports is discussed in the article. Acute pulmonary embolism was diagnosed by demonstration of right heart strain in one case, of long vermiform thrombi floating in the right atrium in another, and in the third case by demonstration of a long thrombus lodged in the foramen ovale, astride the atrial septum, and with its ends floating in either atrium. Thus, as echocardiography enables pulmonary embolism to be diagnosed by demonstration either of right heart strain or of intracardial thrombi, it is a useful diagnostic tool in cases of haemodynamic compromise, though it does not detect minor pulmonary embolism.

  9. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  10. Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

    Science.gov (United States)

    CHOI, Gil Soon; OAK, Chulho; CHUN, Bong-Kwon; WILSON, Donald; JANG, Tae Won; KIM, Hee-Kyoo; JUNG, Mannhong; TUTKUN, Engin; PARK, Eun-Kee

    2014-01-01

    Titanium dioxide (TiO2) is increasingly widely used in industrial, commercial and home products. TiO2 aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO2. One ml of 10, 50 and 250 µg of P25 TiO2 was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO2 exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO2 exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO2 and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO2 showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO2 exposure. P25 TiO2 induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO2 induces lung inflammation in rabbits which is associated with eosinophilic inflammation. PMID:24705802

  11. Acute Pulmonary Edema Caused by a Giant Atrial Myxoma

    Directory of Open Access Journals (Sweden)

    Andrea Fisicaro

    2013-01-01

    Full Text Available Atrial myxoma is the most common primary cardiac tumor. Its clinical presentation spreads from asymptomatic incidental mass to serious life-threatening cardiovascular complications. We report the case of a 44-year-old man with evening fever and worsening dyspnea in the last weeks, admitted to our hospital for acute pulmonary edema. The cardiac auscultation was very suspicious for mitral valve stenosis, but the echocardiography revealed a huge atrial mass with a diastolic prolapse into mitral valve orifice causing an extremely high transmitral gradient pressure. Awareness of this uncommon acute presentation of atrial myxoma is necessary for timely diagnosis and prompt surgical intervention.

  12. Acute, massive pulmonary embolism with right heart strain and hypoxia requiring emergent tissue plasminogen activator (TPA infusion

    Directory of Open Access Journals (Sweden)

    Jonathan Patane

    2017-04-01

    Full Text Available History of present illness: A 63-year-old male presented to the emergency department with shortness of breath. He had a history of prostate cancer and two previous pulmonary embolisms, but was not currently on blood thinners. He had no associated chest pain at the time of presentation, but endorsed hemoptysis. Vital signs were significant for a heart rate of 88, blood pressure 145/89, oxygen saturation in the mid-70’s on room air which increased to mid-80’s on 15L facemask. His exam was significant for clear lung sounds bilaterally. He immediately underwent chest x-ray which showed no acute abnormalities. A bedside ultrasound was performed which showed evidence of right ventricular and atrial dilation, consistent with right heart strain. Given that the patient’s oxygen saturations improved to 88% on 15L facemask, the patient was felt to be stable enough for CT angiography. Significant findings: CT angiogram showed multiple large acute pulmonary emboli, most significantly in the distal right main pulmonary artery (image 1 and 2. Additional pulmonary emboli were noted in the bilateral lobar, segmental, and subsegmental levels of all lobes. There was a peripheral, wedge-shaped consolidation surrounded by groundglass changes in the posterolateral basal right lower lobe that was consistent with a small lung infarction (image 3. Discussion: The patient underwent in the Emergency Department a tissue plasminogen activator (TPA infusion of alteplase 100 mg over 2 hours for his massive acute pulmonary embolisms. Throughout his TPA infusion his oxygen saturations became improved to mid-90’s and his shortness of breath symptoms began improving. His troponin returned at 0.15 ng/mL, suggesting right heart strain. He was admitted to the ICU for continued monitoring and treatment. An acute, massive pulmonary embolism is described as having more than 50% occlusion of pulmonary blood flow.1 The main causes of hypoxia includes ventilation

  13. Grouping nanomaterials to predict their potential to induce pulmonary inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Braakhuis, Hedwig M., E-mail: hedwig.braakhuis@rivm.nl [National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, PO Box 616, 6200 MD Maastricht (Netherlands); Oomen, Agnes G. [National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Cassee, Flemming R. [National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Institute of Risk Assessment Sciences, Utrecht University, PO Box 80.163, 3508 TD Utrecht (Netherlands)

    2016-05-15

    The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined. - Highlights: • Grouping of nanomaterials helps to gather information in an efficient way with the aim to aid risk assessment. • Different ways of grouping nanomaterials for their risk assessment after inhalation are

  14. Grouping nanomaterials to predict their potential to induce pulmonary inflammation

    International Nuclear Information System (INIS)

    Braakhuis, Hedwig M.; Oomen, Agnes G.; Cassee, Flemming R.

    2016-01-01

    The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined. - Highlights: • Grouping of nanomaterials helps to gather information in an efficient way with the aim to aid risk assessment. • Different ways of grouping nanomaterials for their risk assessment after inhalation are

  15. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    International Nuclear Information System (INIS)

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  16. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  17. H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Hong-Xia Zhang

    2016-12-01

    Full Text Available Background: Hydrogen sulfide (H2S, known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI induced by endotoxemia. Methods: Male ICR mice were divided in six groups: (1 Control group; (2 GYY4137treatment group; (3 L-NAME treatment group; (4 lipopolysaccharide (LPS treatment group; (5 LPS with GYY4137 treatment group; and (6 LPS with L-NAME treatment group. The lungs were analysed by histology, NO production in the mouse lungs determined by modified Griess (Sigma-Aldrich reaction, cytokine levels utilizing commercialkits, and protein abundance by Western blotting. Results: GYY4137, a slowly-releasing H2S donor, improved the histopathological changes in the lungs of endotoxemic mice. Treatment with NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase (NOS inhibitor, increased anti-oxidant biomarkers such as thetotal antioxidant capacity (T-AOC and theactivities of catalase (CAT and superoxide dismutase (SOD but decreased a marker of peroxynitrite (ONOO- action and 3-nitrotyrosine (3-NT in endotoxemic lung. L-NAME administration also suppressed inflammation in endotoxemic lung, as evidenced by the decreased pulmonary levels of interleukin (IL-6, IL-8, and myeloperoxidase (MPO and the increased level of anti-inflammatory cytokine IL-10. GYY4137 treatment reversed endotoxin-induced oxidative/nitrative stress, as evidenced by a decrease in malondialdehyde (MDA, hydrogenperoxide (H2O2 and 3-NT and an increase in the antioxidant biomarker ratio of reduced/oxidized glutathione(GSH/GSSG ratio and T-AOC, CAT and SOD activity. GYY4137 also attenuated endotoxin-induced lung inflammation. Moreover, treatment with GYY4137 inhibited inducible NOS (iNOS expression and nitric oxide (NO production in the

  18. [Chronic obstructive pulmonary disease: 2. Short-term prognostic scores for acute exacerbations].

    Science.gov (United States)

    Junod, Alain F

    2014-01-22

    The chronic obstructive pulmonary disease or COPD is a slowly progressive disease whose course is frequently the subject of acute episodes, of variable severity, although, in general, reversible, called acute exacerbations. In the past five years (between 2008 and 2013), seven prognostic scores have been published to try to assess the short-term risk of these acute exacerbations. Their components and characteristics are analysed and commented upon. An Internet program with a detailed compilation of the main features of these scores (www.medhyg.ch/scoredoc) supplements this review.

  19. Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Jian-Bo Lai

    2016-01-01

    Conclusions: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.

  20. Impact of food supplements on hemoglobin, iron status, and inflammation in children with moderate acute malnutrition

    DEFF Research Database (Denmark)

    Cichon, Bernardette; Fabiansen, Christian; Iuel-Brockdorf, Ann-Sophie Julie D

    2018-01-01

    Background: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective: The objective of this study was to inve......Background: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective: The objective of this study...

  1. Diagnóstico por imagem do tromboembolismo pulmonar agudo Imaging of acute pulmonary thromboembolism

    Directory of Open Access Journals (Sweden)

    C. Isabela S. Silva

    2004-10-01

    Full Text Available O diagnóstico do tromboembolismo pulmonar agudo é baseado na probabilidade clínica, uso do dímero D (quando disponível e na avaliação por imagem. Os principais métodos de imagem utilizados no diagnóstico são representados por cintilografia ventilação-perfusão, angiografia pulmonar e tomografia computadorizada (TC. Na última década vários estudos têm demonstrado que a TC espiral apresenta elevada sensibilidade e especificidade no diagnóstico de tromboembolismo pulmonar agudo. Uma melhor avaliação das artérias pulmonares tornou-se possível com a recente introdução dos equipamentos de TC espirais com multidetectores. Vários pesquisadores têm sugerido que a angiografia pulmonar por TC espiral deve substituir a cintilografia na avaliação de pacientes com suspeita clinica de tromboembolismo pulmonar agudo. Os autores discutem os principais métodos de imagem utilizados no diagnóstico de tromboembolismo pulmonar agudo enfatizando o papel da TC espiral.The diagnosis of acute pulmonary thromboembolism is based on the clinical probability, use of D-dimer (when available and imaging. The main imaging modalities used in the diagnosis are ventilation-perfusion (V/Q, scintigraphy, angiography, and computed tomography (CT. In the last decade several studies have demonstrated that spiral CT has a high sensitivity and specificity in the diagnosis of acute pulmonary thromboembolism. The evaluation of the pulmonary arteries has further improved with the recent introduction of multidetector spiral CT scanners. Various investigators have suggested that spiral CT pulmonary angiography should replace scintigraphy in the assessment of patients whose symptoms are suggestive of acute PE. This article discusses the role of the various imaging modalities in the diagnosis of acute pulmonary thromboembolism with emphasis on the role of spiral CT.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

    Methyl iodide-131 (CH 3 I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH 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 3 I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory

  3. The clinical implication of serum cyclophilin A in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Zhang M

    2018-01-01

    Full Text Available Ming Zhang,1 Jingjing Tang,1 Jiafeng Yin,2 Xiaoying Wang,3 Xiangli Feng,1 Xia Yang,1 Hu Shan,1 Qiuhong Zhang,1 Jie Zhang,1 Yali Li1 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 2Department of Laboratory Examination, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 3Health Examination Center, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China Background: Cyclophilin A (CyPA is a secreted molecule that is regulated by inflammatory stimuli. Although inflammation has an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD, little is known regarding the relationship between serum CyPA and COPD. Methods: Ninety-three COPD patients with acute exacerbation were enrolled in the study and were reassessed during the convalescence phase. Eighty-eight controls were matched for age, gender, body mass index, smoking index and comorbidity. The basic clinical information and pulmonary function of all participants were collected. Serum levels of CyPA and other inflammation indexes were further measured. Results: Serum CyPA was significantly increased in convalescent COPD patients compared to healthy controls, and further elevated in COPD patients with acute exacerbation. Serum CyPA positively correlated with serum interleukin-6, matrix metalloproteinase-9 and high-sensitivity C-reactive protein in both the exacerbation and convalescence phases of COPD. Furthermore, it negatively correlated with percent value of forced expiratory volume in 1 second (FEV1% predicted and FEV1/forced vital capacity in convalescent COPD patients. Conclusion: These results suggest that serum CyPA can be used as a potential inflammatory biomarker for COPD and assessment of serum CyPA may reflect the severity of inflammation in COPD. Keywords: cyclophilin A, chronic obstructive pulmonary disease

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

    Directory of Open Access Journals (Sweden)

    Sivakumar Periasamy

    2016-03-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  6. Temporary interventional pneumonectomy used as an emergency treatment for acute massive pulmonary embolism: the initial experimental results

    International Nuclear Information System (INIS)

    Fan Yong; Liu Yang; Wu Qi; Li Ping; Tian Jing; Bao Guijun; He Nengshu

    2009-01-01

    Objective: To evaluate regional airway obstruction with balloon catheter in stabilizing the vital signs in experimental animals suffered from acute massive pulmonary embolism. Methods: Pulmonary embolism of right lung artery by using auto-blood clots or detachable latex balloons was established in 27 healthy sheep. When the blood oxygen saturation decreased by 25% compared to that before the procedure, the placement of balloon catheter in corresponding right main bronchus was carried out in 18 sheep (study group). Five sheep were used as control group. The blood oxygen saturation in the remaining four sheep did not reach the intervention level. The pulmonary arterial pressure, the peripheral arterial pressure, the central venous pressure, the heart rate, the blood oxygen saturation, the arterial partial pressure of oxygen as well as of carbon dioxide were invasively determined. Results: The experimental model of acute massive pulmonary embolism was successfully established in 23 sheep. After the establishment of pulmonary embolism, increased heart rate, tachypnea, a decrease of ≥ 25% in blood oxygen saturation within 30 minutes and a rise in pulmonary arterial pressure were detected. After the placement of balloon catheter in study group, a reduction of the pulmonary arterial pressure and an elevation of the blood oxygen saturation as well as the arterial partial pressure of oxygen rose were observed.The difference between study group and control group was statistically significant (P<0.05). Conclusion: The result of this animal experiment indicates that obstruction of airway with balloon can be served as a first aid for acute massive pulmonary embolism, which can stabilizes the animal's vital signs and, therefore, can help gain precious time for the follow-up thrombolysis treatment. (authors)

  7. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Chi Chou

    2015-01-01

    Full Text Available Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group, sham-operation (Sham, or sham plus caffeine (n=12 in each group. To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.. Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05. These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

  8. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.

    Science.gov (United States)

    Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D

    2014-10-01

    Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Reproducibility of multi-detector spiral computed tomography in detection of sub-segmental acute pulmonary embolism

    International Nuclear Information System (INIS)

    Brunot, S.; Corneloup, O.; Latrabe, V.; Montaudon, M.; Laurent, F.

    2005-01-01

    The aim of this study was to evaluate the inter-observer and intra-observer agreement of the diagnosis of sub-segmental acute pulmonary embolism (PE) in an inpatient population explored by 16 slice multi-detector spiral computed tomography (MDCT). Four hundred consecutive inpatients were referred for MDCT for the clinical suspicion of acute PE. One hundred and seventy seven (44.2%) had a known cardio-respiratory disease at the time of examination. Inter-observer and intra-observer agreements for the diagnosis of acute PE and of sub-segmental acute PE were assessed blind and independently by three experienced readers and by kappa statistics. Seventy-five patients were diagnosed as having acute PE findings (19.5%), and clots were located exclusively within sub-segmental arteries in nine patients (12%). When clots were limited to sub-segmental or more distal branches of the pulmonary arteries, kappa values were found to be moderate (0.56) to very good (0.85) for the diagnosis of sub-segmental acute PE, whereas for the diagnosis of acute PE in the whole population, kappa values ranged from 0.84 to 0.97. Intra-observer agreement was found to be perfect (kappa=1). MDCT is a reproducible technique for the diagnosis of sub-segmental acute PE as well as for acute PE. In this inpatient population, sub-segmental acute PE was not a rare event. (orig.)

  10. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

    Science.gov (United States)

    Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

    2017-09-01

    Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats

  11. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice.

    Directory of Open Access Journals (Sweden)

    Sarah S Poulsen

    Full Text Available Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs has been linked to an increased risk of developing cardiovascular disease in addition to the well-documented physicochemical-dependent adverse lung effects. A proposed mechanism is through a strong and sustained pulmonary secretion of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BL/6J mice pulmonary exposed to 0, 6, 18 or 54 μg MWCNT/mouse. Plasma levels of acute phase response proteins serum amyloid A1/2 (SAA1/2 and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saa1 and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater and lasted longer than hepatic Saa1 mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length resulted in lowered SAA1/2 plasma levels. Increased SAA3 protein levels were positively related to dose and content of Mn, Mg and Co on day 1, whereas oxidation and diameter of the MWCNTs were protective on day 28 and 92, respectively. The results of this study reveal very differently controlled pulmonary and hepatic acute phase responses after MWCNT exposure. As the responses were influenced by the physicochemical properties of the MWCNTs, this study provides the first step

  12. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

    International Nuclear Information System (INIS)

    Zhang, Da-Gang; Zhang, Cheng; Wang, Jun-Xian; Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Tao, Li; Wang, Jian-Qing; Chen, Xi; Xu, De-Xiang

    2017-01-01

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl 4 )-induced acute liver injury. Mice were intraperitoneally injected with CCl 4 (0.15 ml/kg). In CCl 4 + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl 4 . As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl 4 -induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl 4 -induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl 4 -induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl 4 -induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl 4 -induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl 4 -induced acute liver injury. These results suggest that OCA protects against CCl 4 -induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl 4 -induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl 4 -induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

  13. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Da-Gang [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Wang, Jun-Xian [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua [Department of Toxicology, Anhui Medical University, Hefei 230032 (China); Lu, Yan; Tao, Li; Wang, Jian-Qing [Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei 230032 (China)

    2017-01-01

    The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.

  14. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J., E-mail: mcampen@salud.unm.edu

    2016-08-15

    Ozone (O{sub 3})-related cardiorespiratory effects are a growing public health concern. Ground level O{sub 3} can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O{sub 3}-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O{sub 3} pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O{sub 3} exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O{sub 2}) or hypoxia (10.0% O{sub 2}), followed by a 4-h exposure to either 1 ppm O{sub 3} or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O{sub 3} exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O{sub 3} exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O{sub 3} exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O{sub 3}-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive

  15. Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

    Directory of Open Access Journals (Sweden)

    Spyridon Loridas

    2013-08-01

    Full Text Available Reactive oxygen or nitrogen species (ROS, RNS and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.. Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM, at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc. play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5 are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis.

  16. Inflammation of vertebral bone associated with acute calcific tendinitis of the longus colli muscle

    Energy Technology Data Exchange (ETDEWEB)

    Mihmanli, I.; Kanberoglu, K. [Dept. of Radiology, Istanbul Univ. (Turkey); Karaarslan, E. [Intermed Medical Center, Nisantasi, Istanbul (Turkey)

    2001-12-01

    We present a case of acute retropharyngeal calcific tendinitis with characteristic findings on radiographic, computed tomography, and magnetic resonance imaging (MRI). To our knowledge, this is the first acute retropharyngeal calcific tendinitis report having inflammation of both the vertebra itself and the longus colli muscle diagnosed on MRI. In patients with neck pain, acute retropharyngeal calcific tendinitis should be kept in mind in the differential diagnosis, even if these patients had vertebral pathological signals on MRI. (orig.)

  17. Inflammation of vertebral bone associated with acute calcific tendinitis of the longus colli muscle

    International Nuclear Information System (INIS)

    Mihmanli, I.; Kanberoglu, K.; Karaarslan, E.

    2001-01-01

    We present a case of acute retropharyngeal calcific tendinitis with characteristic findings on radiographic, computed tomography, and magnetic resonance imaging (MRI). To our knowledge, this is the first acute retropharyngeal calcific tendinitis report having inflammation of both the vertebra itself and the longus colli muscle diagnosed on MRI. In patients with neck pain, acute retropharyngeal calcific tendinitis should be kept in mind in the differential diagnosis, even if these patients had vertebral pathological signals on MRI. (orig.)

  18. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation

    Czech Academy of Sciences Publication Activity Database

    Kremserová, Silvie; Perečko, Tomáš; Souček, Karel; Klinke, A.; Baldus, S.; Eiserich, J.P.; Kubala, Lukáš

    2016-01-01

    Roč. 2016, Č. 2016 (2016), č. článku 5219056. ISSN 1942-0900 R&D Projects: GA ČR GCP305/12/J038 Institutional support: RVO:68081707 Keywords : nitrotyrosine formation * airway inflammation * mouse neutrophils * apoptosis Subject RIV: BO - Biophysics Impact factor: 4.593, year: 2016

  19. Paramedic identification of acute pulmonary edema in a metropolitan ambulance service.

    Science.gov (United States)

    Williams, Teresa A; Finn, Judith; Celenza, Antonio; Teng, Tiew-Hwa; Jacobs, Ian G

    2013-01-01

    Acute pulmonary edema (APE) is a common cause of acute dyspnea. In the prehospital setting, it is often difficult to differentiate APE from other causes of shortness of breath (SOB). Radiography and echocardiography aid in the identification of APE but are often not available. There is little information on how accurately ambulance paramedics identify patients with APE. Objectives. This study aimed to 1) describe the prehospital clinical presentation and management of patients with a clinical diagnosis of APE and 2) compare the accuracy of coding of APE by paramedics against the emergency department (ED) medical discharge diagnosis. This study included a retrospective cohort of all patients who had episodes identified as APE by ambulance paramedics and were transported to a metropolitan hospital ED in 2011. Two databases were used: an ambulance database and the Emergency Department Information System. The ED medical discharge diagnosis (using International Statistical Classification of Diseases and Related Problems, 10th Revision, Australian Modification [ICD-10-AM] codes) was used as the comparator with paramedic-assigned problem codes for APE. The outcomes for the study were the positive predictive value, i.e., the proportion of patients identified as having APE in the ambulance database who also had an ED discharge diagnosis of APE, and the sensitivity of paramedic identification of APE, i.e., the proportion of patients with an ED discharge diagnosis of APE that were correctly identified as APE by the ambulance paramedics. Four hundred ninety-five patients were transported to an ED with APE identified by the paramedics as the primary problem code. Shortness of breath, crepitations, high systolic blood pressure, and chest pain were the most common presenting signs and symptoms. Pink frothy sputum was rare (3% of patient episodes of APE). One hundred eighty-six patients received an ED discharge diagnosis of APE, i.e., a positive predictive value of 41%. Of 631 ED

  20. Serial Sonographic Assessment of Pulmonary Edema in Patients With Hypertensive Acute Heart Failure.

    Science.gov (United States)

    Martindale, Jennifer L; Secko, Michael; Kilpatrick, John F; deSouza, Ian S; Paladino, Lorenzo; Aherne, Andrew; Mehta, Ninfa; Conigiliaro, Alyssa; Sinert, Richard

    2018-02-01

    Objective measures of clinical improvement in patients with acute heart failure (AHF) are lacking. The aim of this study was to determine whether repeated lung sonography could semiquantitatively capture changes in pulmonary edema (B-lines) in patients with hypertensive AHF early in the course of treatment. We conducted a feasibility study in a cohort of adults with acute onset of dyspnea, severe hypertension in the field or at triage (systolic blood pressure ≥ 180 mm Hg), and a presumptive diagnosis of AHF. Patients underwent repeated dyspnea and lung sonographic assessments using a 10-cm visual analog scale (VAS) and an 8-zone scanning protocol. Lung sonographic assessments were performed at the time of triage, initial VAS improvement, and disposition from the emergency department. Sonographic pulmonary edema was independently scored offline in a randomized and blinded fashion by using a scoring method that accounted for both the sum of discrete B-lines and degree of B-line fusion. Sonographic pulmonary edema scores decreased significantly from initial to final sonographic assessments (P < .001). The median percentage decrease among the 20 included patient encounters was 81% (interquartile range, 55%-91%). Although sonographic pulmonary edema scores correlated with VAS scores (ρ = 0.64; P < .001), the magnitude of the change in these scores did not correlate with each other (ρ = -0.04; P = .89). Changes in sonographic pulmonary edema can be semiquantitatively measured by serial 8-zone lung sonography using a scoring method that accounts for B-line fusion. Sonographic pulmonary edema improves in patients with hypertensive AHF during the initial hours of treatment. © 2017 by the American Institute of Ultrasound in Medicine.

  1. Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

    2017-01-15

    Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed.

  2. Acute pulmonary oedema: clinical characteristics, prognostic factors, and in-hospital management.

    Science.gov (United States)

    Parissis, John T; Nikolaou, Maria; Mebazaa, Alexandre; Ikonomidis, Ignatios; Delgado, Juan; Vilas-Boas, Fabio; Paraskevaidis, Ioannis; Mc Lean, Antony; Kremastinos, Dimitrios; Follath, Ferenc

    2010-11-01

    Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). ALARM-HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in-hospital mortality (7.4 vs. 6.0%, P = 0.057) compared with ADHF patients (n = 1911, 38.5%), and APE patients exhibited higher systolic blood pressures (P chronic renal disease (P renal function, and history may identify high-risk APE patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rusu, Mirabela, E-mail: mirabela.rusu@gmail.com; Wang, Haibo; Madabhushi, Anant [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 (United States); Golden, Thea; Gow, Andrew [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08854 (United States)

    2015-08-15

    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

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

    International Nuclear Information System (INIS)

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

    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

  5. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism

    NARCIS (Netherlands)

    Tulevski, I. I.; Hirsch, A.; Sanson, B. J.; Romkes, H.; van der Wall, E. E.; van Veldhuisen, D. J.; Büller, H. R.; Mulder, B. J.

    2001-01-01

    Right ventricular (RV) function is of major prognostic significance in patients with acute pulmonary embolism (PE). The aim of the present study was to evaluate the role of neurohormone plasma brain natriuretic peptide (BNP) in assessing RV function in patients with acute PE. BNP levels were

  6. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism

    NARCIS (Netherlands)

    Tulevski, I.I.; Hirsch, A; Sanson, BJ; Romkes, H; van der Wall, EE; van Veldhuisen, DJ; Buller, HR; Mulder, BJM

    Right ventricular (RV) function is of major prognostic significance in patients with acute pulmonary embolism (PE). The aim of the present study was to evaluate the role of neurohormone plasma brain natriuretic peptide (BNP) in assessing RV function in patients with acute PE. BNP levels were

  7. 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

    Energy Technology Data Exchange (ETDEWEB)

    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. [University Extremo Catarinense, Criciuma (Brazil)

    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.

  8. Reproducibility of a novel model of murine asthma-like pulmonary inflammation.

    Science.gov (United States)

    McKinley, L; Kim, J; Bolgos, G L; Siddiqui, J; Remick, D G

    2004-05-01

    Sensitization to cockroach allergens (CRA) has been implicated as a major cause of asthma, especially among inner-city populations. Endotoxin from Gram-negative bacteria has also been investigated for its role in attenuating or exacerbating the asthmatic response. We have created a novel model utilizing house dust extract (HDE) containing high levels of both CRA and endotoxin to induce pulmonary inflammation (PI) and airway hyperresponsiveness (AHR). A potential drawback of this model is that the HDE is in limited supply and preparation of new HDE will not contain the exact components of the HDE used to define our model system. The present study involved testing HDEs collected from various homes for their ability to cause PI and AHR. Dust collected from five homes was extracted in phosphate buffered saline overnight. The levels of CRA and endotoxin in the supernatants varied from 7.1 to 49.5 mg/ml of CRA and 1.7-6 micro g/ml of endotoxin in the HDEs. Following immunization and two pulmonary exposures to HDE all five HDEs induced AHR, PI and plasma IgE levels substantially higher than normal mice. This study shows that HDE containing high levels of cockroach allergens and endotoxin collected from different sources can induce an asthma-like response in our murine model.

  9. The central role of hypothalamic inflammation in the acute illness response and cachexia.

    Science.gov (United States)

    Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

    2016-06-01

    When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Clinical and radiological characterization of the pulmonary commitment for acute toxoplasmosis disseminated in nine immunocompetent patients

    International Nuclear Information System (INIS)

    Salinas, Jorge E; Pino, Luis Eduardo

    2008-01-01

    The acute toxoplasmosis in the immunocompetent individual generally has a benign and autoresolutive course. However, in patient coming from wild area severe cases of visceral commitment, the most frequent in them, the pulmonary commitment has been reported. The clinical and radiological description of nine individuals members of the military forces of Colombia, with acute toxoplasmosis and pulmonary commitment was carried. 55% of the cases presented dysnea functional class II/IV; 33% functional class III/IV and only 1/9 patients presented functional class IV/IV. The most common radiological image was the uni focal or multifocal consolidation pulmonary (66%), and in smaller frequency the presence of having infiltrated reticular, reticulo nodular and pleural effusion. The entirety of the patients evolved in satisfactory form, two of them with support with noninvasive ventilation.

  11. The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies.

    Science.gov (United States)

    Bollen, Jessica; Trick, Leanne; Llewellyn, David; Dickens, Chris

    2017-03-01

    The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Severe pulmonary hypertension associated with the acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome.

    Science.gov (United States)

    Rooney, Kris A; Thomas, Neal J

    2010-01-01

    To evaluate pulmonary hypertension associated with acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome. Guillain-Barré syndrome consists of a group of autoimmune disorders that generally manifest as symmetric, progressive, ascending paralysis. There are five subtypes of Guillain-Barré syndrome, and autonomic involvement has been described in all subtypes, including cardiovascular, vasomotor, or pseudomotor dysfunction of both the sympathetic and parasympathetic systems. Case report. Tertiary care pediatric intensive care unit. Three-yr-old female patient. None. Serial measurements of pulmonary artery pressure. We report the case of a young girl with acute motor sensory axonal neuropathy who presented with severe cardiovascular collapse secondary to severe pulmonary hypertension. In this patient, multiple factors may have played a role in the development of pulmonary hypertension including autonomic dysfunction, hypoventilation, and immobility as a risk for thrombosis and pulmonary emboli. It is possible that many other individuals suffering from severe forms of Guillain-Barré syndrome, especially those with significant autonomic dysfunction, may actually have undiagnosed and therefore untreated pulmonary hypertension. Therefore, it is recommended that clinicians caring for critically ill children with Guillain-Barré syndrome have a high index of suspicion for pulmonary hypertension and consider echocardiography if there are clinical signs of this potentially fatal process.

  13. Recurrent acute pulmonary oedema after aortic and mitral valve surgery due to trachea malacia and obstructive sleep apnoea syndrome

    NARCIS (Netherlands)

    Sankatsing, S. U. C.; Hanselaar, W. E. J. J.; van Steenwijk, R. P.; Van der Sloot, J. A. P.; Broekhuis, E.; Kok, W. E. M.

    2008-01-01

    In this report we describe a patient with recurrent episodes of acute pulmonary oedema after aortic and mitral valve surgery. The first episode of pulmonary oedema was caused by mitral valve dysfunction. The second episode of pulmonary oedema was not clearly associated with a mitral valve problem,

  14. Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

    Science.gov (United States)

    Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

    2018-04-15

    Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

  15. Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    David M Brass

    Full Text Available Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress.

  16. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    Science.gov (United States)

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice.

  17. Skin condition and its relationship to systemic inflammation in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Majewski, Sebastian; Pietrzak, Anna; Tworek, Damian; Szewczyk, Karolina; Kumor-Kisielewska, Anna; Kurmanowska, Zofia; Górski, Paweł; Zalewska-Janowska, Anna; Piotrowski, Wojciech Jerzy

    2017-01-01

    The systemic (extrapulmonary) effects and comorbidities of chronic obstructive pulmonary disease (COPD) contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), were measured in serum using commercially available enzyme-linked immunosorbent assays. There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level ( P skin measured. The mean levels of hsCRP and IL-6 in serum were significantly higher in COPD patients and healthy smokers in comparison with healthy never-smokers. There were significant correlations between skin temperature and serum hsCRP ( R =0.40; P =0.02) as well as skin temperature and serum IL-6 ( R =0.49; P =0.005) in smokers. Stratum corneum hydration correlated significantly with serum TNF-α ( R =0.37; P =0.01) in COPD patients. Differences noted in several skin biophysical properties and biomarkers of systemic inflammation between COPD patients, smokers, and healthy never-smokers may suggest a possible link between smoking-driven, low-grade systemic inflammation, and the overall skin condition.

  18. Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism

    NARCIS (Netherlands)

    de Groot, M. R.; Turkstra, F.; van Marwijk Kooy, M.; Oostdijk, A. H.; van Beek, E. J.; Büller, H. R.

    2000-01-01

    The main purpose of ventilation scanning, as adjunct to perfusion lung scintigraphy, in acute pulmonary embolism is to allow for the classification of segmental perfusion defects as mismatched, which is generally accepted as proof for the presence of pulmonary embolism. We examined whether this

  19. Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.

    Science.gov (United States)

    Shah, Ravi; Yeri, Ashish; Das, Avash; Courtright-Lim, Amanda; Ziegler, Olivia; Gervino, Ernest; Ocel, Jeffrey; Quintero-Pinzon, Pablo; Wooster, Luke; Bailey, Cole Shields; Tanriverdi, Kahraman; Beaulieu, Lea M; Freedman, Jane E; Ghiran, Ionita; Lewis, Gregory D; Van Keuren-Jensen, Kendall; Das, Saumya

    2017-12-01

    Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health. NEW & NOTEWORTHY How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community. Copyright © 2017 the American Physiological Society.

  20. Milano summer particulate matter (PM10 triggers lung inflammation and extra pulmonary adverse events in mice.

    Directory of Open Access Journals (Sweden)

    Francesca Farina

    Full Text Available Recent studies have suggested a link between particulate matter (PM exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS, cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17 for a putative pro-carcinogenic marker (Cyp1B1 and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1 and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO. Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity

  1. Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography

    International Nuclear Information System (INIS)

    Suzuki, Hidemi; Sekine, Yasuo; Yoshida, Shigetoshi

    2011-01-01

    In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n=9) and nonexacerbation (n=19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P<0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P<0.05). Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors. (author)

  2. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    Science.gov (United States)

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  3. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    Directory of Open Access Journals (Sweden)

    Claire Serena

    2014-01-01

    Full Text Available We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  4. Guidance Cue Netrin-1 and the Regulation of Inflammation in Acute and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Punithavathi Ranganathan

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a common problem in the hospital setting and intensive care unit. Despite improved understanding, there are no effective therapies available to treat AKI. A large body of evidence strongly suggests that ischemia reperfusion injury is an inflammatory disease mediated by both adaptive and innate immune systems. Cell migration also plays an important role in embryonic development and inflammation, and this process is highly regulated to ensure tissue homeostasis. One such paradigm exists in the developing nervous system, where neuronal migration is mediated by a balance between chemoattractive and chemorepulsive signals. The ability of the guidance molecule netrin-1 to repulse or abolish attraction of neuronal cells expressing the UNC5B receptor makes it an attractive candidate for the regulation of inflammatory cell migration. Recent identification of netrin-1 as regulators of immune cell migration has led to a large number of studies looking into how netrin-1 controls inflammation and inflammatory cell migration. This review will focus on recent advances in understanding netrin-1 mediated regulation of inflammation during acute and chronic kidney disease and whether netrin-1 and its receptor activation can be used to treat acute and chronic kidney disease.

  5. Predicting in-hospital death during acute presentation with pulmonary embolism to facilitate early discharge and outpatient management.

    Directory of Open Access Journals (Sweden)

    Jerrett K Lau

    Full Text Available Pulmonary embolism continues to be a significant cause of death. The aim was to derive and validate a risk prediction model for in-hospital death after acute pulmonary embolism to identify low risk patients suitable for outpatient management.A confirmed acute pulmonary embolism database of 1,426 consecutive patients admitted to a tertiary-center (2000-2012 was analyzed, with odd and even years as derivation and validation cohorts respectively. Risk stratification for in-hospital death was performed using multivariable logistic-regression modelling. Models were compared using receiver-operating characteristic-curve and decision curve analyses.In-hospital mortality was 3.6% in the derivation cohort (n = 693. Adding day-1 sodium and bicarbonate to simplified Pulmonary Embolism Severity Index (sPESI significantly increased the C-statistic for predicting in-hospital death (0.71 to 0.86, P = 0.001. The validation cohort yielded similar results (n = 733, C-statistic 0.85. The new model was associated with a net reclassification improvement of 0.613, and an integrated discrimination improvement of 0.067. The new model also increased the C-statistic for predicting 30-day mortality compared to sPESI alone (0.74 to 0.83, P = 0.002. Decision curve analysis demonstrated superior clinical benefit with the use of the new model to guide admission for pulmonary embolism, resulting in 43 fewer admissions per 100 presentations based on a risk threshold for admission of 2%.A risk model incorporating sodium, bicarbonate, and the sPESI provides accurate risk prediction of acute in-hospital mortality after pulmonary embolism. Our novel model identifies patients with pulmonary embolism who are at low risk and who may be suitable for outpatient management.

  6. Fatal acute pulmonary injury associated with everolimus.

    Science.gov (United States)

    Depuydt, Pieter; Nollet, Joke; Benoit, Dominique; Praet, Marleen; Caes, Frank

    2012-03-01

    To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

  7. Role of PGC-1α in acute and low-grade inflammation

    DEFF Research Database (Denmark)

    Olesen, Jesper

    The aim of the present thesis was to examine the role of the exercise-induced transcriptional co-activator, PGC-1α, in acute and low-grade inflammation. To investigate this, the following three hypotheses were tested: 1) Skeletal muscle PGC-1α plays an important role in acute LPS-induced systemic...... in skeletal muscle showed a greater fold increase in plasma TNFα than WT mice, when stimulated with LPS. Taken together, these results suggest that skeletal muscle PGC-1α is required for a robust LPS-induced TNFα response. Study II demonstrated that plasma TNFα and IL-6 as well as liver TNFα mRNA and protein...

  8. Deciphering the complexity of acute inflammation using mathematical models.

    Science.gov (United States)

    Vodovotz, Yoram

    2006-01-01

    Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

  9. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  10. Investigation of Acute Pulmonary Deficits Associated with Biomass Fuel Cookstove Emissions in Rural Bangladesh

    Directory of Open Access Journals (Sweden)

    Danielle N. Medgyesi

    2017-06-01

    Full Text Available The use of solid biomass fuels in cookstoves has been associated with chronic health impacts that disproportionately affect women worldwide. Solid fuel stoves that use wood, plant matter, and cow dung are commonly used for household cooking in rural Bangladesh. This study investigates the immediate effects of acute elevated cookstove emission exposures on pulmonary function. Pulmonary function was measured with spirometry before and during cooking to assess changes in respiratory function during exposure to cookstove emissions for 15 females ages 18–65. Cookstove emissions were characterized using continuous measurements of particulate matter (PM2.5—aerodynamic diameter <2.5 μm concentrations at a 1 s time resolution for each household. Several case studies were observed where women ≥40 years who had been cooking for ≥25 years suffered from severe pulmonary impairment. Forced expiratory volume in one second over forced vital capacity (FEV1/FVC was found to moderately decline (p = 0.06 during cooking versus non-cooking in the study cohort. The study found a significant (α < 0.05 negative association between 3- and 10-min maximum PM2.5 emissions during cooking and lung function measurements of forced vital capacity (FVC, forced expiratory volume in one second (FEV1, and FEV1/FVC obtained during cooking intervals. This study found that exposure to biomass burning emissions from solid fuel stoves- associated with acute elevated PM2.5 concentrations- leads to a decrease in pulmonary function, although further research is needed to ascertain the prolonged (e.g., daily, for multiple years impacts of acute PM2.5 exposure on immediate and sustained respiratory impairment.

  11. Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-12-01

    Full Text Available Abstract Background Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs following inhalation of UfCPs (24 h, 172 μg·m-3, to assess whether compromised animals (SHR exhibit a different response pattern compared to the previously studied healthy rats (WKY. Methods Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1, blood coagulation (tissue factor, plasminogen activator inhibitor-1, and endothelial function (endothelin-1, and endothelin receptors A and B were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF. Results Increased BP and heart rate (HR by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary and blood (systemic were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p Conclusion Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction

  12. How inflammation underlies physical and organ function in acutely admitted older medical patients

    DEFF Research Database (Denmark)

    Klausen, Henrik Hedegaard; Bodilsen, Ann Christine; Petersen, Janne

    2017-01-01

    OBJECTIVES: To investigate whether systemic inflammation in acutely admitted older medical patients (age >65 years) is associated with physical performance and organ dysfunction. Organ dysfunction´s association with physical performance, and whether these associations are mediated by systemic...... inflammation was assessed by suPAR, TNFα, and IL-6. Associations were investigated by regression analyses adjusted for age, sex, cognitive impairment, CRP, and VitalPAC Modified Early Warning Score. RESULTS: A total of 369 patients were evaluated. In adjusted analyses, suPAR and TNFα was associated with both...

  13. Prevalence of acute epiglottitis and its association with pulmonary tuberculosis in adults in a tertiary care hospital of Nepal

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    Thapa, Narmaya

    2008-12-01

    Full Text Available Introduction: Acute epiglottitis is a relatively uncommon disease in both children and adults. It can be a serious life threatening disease because of its potential for sudden upper airway obstruction. Objective: To determine the prevalence of acute epiglottitis and to find out its association with Pulmonary Tuberculosis. Methods: All cases of acute epiglottitis admitted in ENT and Head and Neck Surgery ward of TUTH, Kathmandu, Nepal, from April 2001 to September 2007, were enrolled. Routine investigations including x-rays and blood cultures were done. The patients were further investigated to rule out the presence of Pulmonary Tuberculosis.The standard treatment protocol we used included Injection Ampicillin 500 mg intravenously six hourly for 72 hours followed by oral Ampicillin 500mg for 7 days, with analgesics and intravenous steroid (Hydrocortisone 200mg if required. Study Design: Prospective longitudinal study. Results: Majority of the patients presented with a history sore throat (83.3%, dysphagia (78.6% and odynophagia (78.6%. On examination all the patients were found to have swollen and congested epiglottis. Positive "Thumb sign" on plain X-ray soft tissue neck lateral view was found in almost all the patients (95.2%. Four patients presented with stridor and patient needed emergency tracheostomy. None of the investigations done to detect Pulmonary Tuberculosis was found to be positive. Conclusion: Acute epiglottitis is a rare disease which now occurs more commonly in adults. The annual prevalence of Acute Epiglottitis in adult in TUTH is 4.8 per 1000. This study did not find any association of acute epiglottitis with pulmonary tuberculosis.

  14. Effects of Asian dust event particles on inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats

    International Nuclear Information System (INIS)

    Lei, Y.-C.; Chan, C.-C.; Wang, P.-Y.; Lee, C.-T.; Cheng, T.-J.

    2004-01-01

    The health impact of dust events from China has become a concern within China and in its neighboring countries. Previous epidemiological studies have demonstrated an association between particulate matter exposure and cardiopulmonary mortality. Here, we use pulmonary hypertensive rat models to examine inflammation markers in the lung and in peripheral blood after exposure to Asian dust storm particles. Using a nose-only inhalation system, eight pulmonary hypertensive rats were exposed to concentrated ambient particles (CAPs) from an actual Asian dust storm that took place between March 18 and 19, 2002; four control rats were also exposed to room air. Four rats exposed to CAPs of 315.6 μg/m 3 for 6 h were classified as the low-exposure group, and another four rats exposed to CAPs of 684.5 μg/m 3 for 4.5 h were classified as the high-exposure group. The animals were sacrificed 36 h after exposure. Inflammation markers in the peripheral blood and in the bronchoalveolar lavage (BAL) were analyzed, and IL-6 in BAL was also determined using ELISA. White blood cell counts in peripheral blood increased with increased CAP exposure levels (P<0.001, test for trend). In BAL analysis, total cell numbers and the proportion of neutrophil also increased with increased CAP levels (P<0.001, test for trend for both markers). Positive dose-response relationships between CAP exposure and total protein (P<0.05) and between CAPs and LDH activity (P<0.05) were also observed. Moreover, IL-6 protein in BAL increasing with CAP levels (P<0.05, test for trend) was demonstrated. Our results revealed that exposure to particulate matters during an Asian dust storm could increase lung inflammation and injury in pulmonary hypertensive rats. Further studies are needed to determine the components of dust storm particles that may contribute to the particle toxicity

  15. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

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    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

  16. Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants.

    Science.gov (United States)

    Gisslen, Tate; Alvarez, Manuel; Wells, Casey; Soo, Man-Ting; Lambers, Donna S; Knox, Christine L; Meinzen-Derr, Jareen K; Chougnet, Claire A; Jobe, Alan H; Kallapur, Suhas G

    2016-03-23

    To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes. This is a prospective observational study: subjects were mothers delivering at 32-36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected. Twenty-four per cent of 32-36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity. Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Diagnosis and management of acute exacerbation of chronic obstructive pulmonary disease [digest].

    Science.gov (United States)

    Holden, Van; Slack, Donald; McCurdy, Michael T; Shah, Nirav G; Gupta, Nachi; Nusbaum, Jeffrey

    2017-10-20

    Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a clinical diagnosis that is based on changes in dyspnea, cough, and/or sputum production in a COPD patient; however, patients presenting with an acute exacerbation may be undiagnosed or have a variety of comorbid conditions that can complicate diagnosis. This issue presents strategies and algorithms for the early use of evidence-based interventions, including appropriate use of antibiotics, bronchodilators, and corticosteroids, along with noninvasive ventilation with capnography, to minimize morbidity and mortality associated with this disease. [Points & Pearls is a digest of Emergency Medicine Practice.].

  18. The primary experimental study of self-made percutaneous catheterized thrombectomy device for acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Zhao Shijun; Ma Junshan; Yang Jianping

    2008-01-01

    Objective: To evaluate efficacy, feasibility and safety of the self-made percutaneous catheterized thrombectomy divice in animal model for thrombus removal. Methods: Seven dogs were selected, with acute massive pulmonary embolism animal models created by injecting thrombi into the pulmonary arterial trunk via percutaneous femoral vein approach. After half an hours the catheter sheath was inserted into the occluded pulmonary artery through right femoral vein in 5 dogs, left femoral vein in 1 dog and right internal jugular vein in another one. The procedure began to remove the thrombi with simultaneous recording the thrombectomy time and the blood volume drainage. Blood gass was tested before and after embolization together with those of thrombi removement, continuously monitored pulmonary arterial pressure and intermittently performed angiography. The mean time form vascular recanalization to euthanasia was 2 hours, and then the lung specimens were resected for histological examination. Results: One animal died of pulmonary arterial penetration during thrombi removal, but others were all alive by the end of the test. Mean time of removing thrombi was 2.4 minutes with mean volume blood drainage of 84 ml. Angiograms showed the approximately complete patency of the pulmonary arterial trunk after reopening of occlusion but still with remnont thrombi within distal branches and arterial pressure with blood gas returned to normal level. Pathology revealed the recanalization of pulmonary arterial trunk but with thromi still staying in the distal branches, and effusion around the arteries. Conclusions: The self-made percutaneous catheterized thrombectomy device is effective, feasible and comparatively safe in the treatment of acute massive pulmonary embolism in this primary test. (authors)

  19. Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

    Science.gov (United States)

    Jiang, Jun-Xia; Zhang, Shui-Juan; Shen, Hui-Juan; Guan, Yan; Liu, Qi; Zhao, Wei; Jia, Yong-Liang; Shen, Jian; Yan, Xiao-Feng; Xie, Qiang-Min

    2017-07-01

    Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear. In this study, we investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or 16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute inflammation. The lungs of mice exposed to CS showed an increase in the release of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an accumulation of inflammatory cells, indicating high Rac1 activity. The exposure of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1 ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS-exposed mice. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the infiltration of neutrophils and macrophages into the alveolar spaces. Selective inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with CS-mediated inflammation. Rac1 may be a promising therapeutic target for the treatment of CS-induced pulmonary inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Role of Hydrogen Sulfide in the Pathology of Inflammation

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    Madhav Bhatia

    2012-01-01

    Full Text Available Hydrogen sulfide (H2S is a well-known toxic gas that is synthesized in the human body from the amino acids cystathionine, homocysteine, and cysteine by the action of at least two distinct enzymes: cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H2S has emerged as a novel and increasingly important biological mediator. Imbalances in H2S have also been shown to be associated with various disease conditions. However, defining the precise pathophysiology of H2S is proving to be a complex challenge. Recent research in our laboratory has shown H2S as a novel mediator of inflammation and work in several groups worldwide is currently focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions, such as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive pulmonary disease (COPD. Active research on the role of H2S in inflammation will unravel the pathophysiology of its actions in inflammatory conditions and may help develop novel therapeutic approaches for several, as yet incurable, disease conditions.

  1. Sarcoidosis-associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long-term effect of sildenafil

    DEFF Research Database (Denmark)

    Milman, Nils; Svendsen, Claus Bo; Iversen, Martin

    2009-01-01

    Abstract Background: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. Objectives: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil...

  2. Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: New Horizons in the Interventional Management of Pulmonary Embolism.

    Science.gov (United States)

    Rivers-Bowerman, Michael D; Zener, Rebecca; Jaberi, Arash; de Perrot, Marc; Granton, John; Moriarty, John M; Tan, Kong T

    2017-09-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed potential complication of acute or recurrent pulmonary thromboembolic disease. Multiple studies suggest that up to 5% of patients with acute pulmonary thromboembolic disease go on to develop CTEPH. The prognosis of untreated CTEPH is poor, but advances in medical and surgical treatments over the past few decades have improved patient outcomes. The gold standard and curative treatment for CTEPH is pulmonary endarterectomy; however, some patients are inoperable and others who have undergone pulmonary endarterectomy experience persistent or recurrent pulmonary hypertension despite medical therapy. In recent years, balloon pulmonary angioplasty has emerged as a primary and adjunctive treatment for these CTEPH patients at expert or specialized centers. This review outlines an approach to balloon pulmonary angioplasty for CTEPH, including clinical presentation and evaluation; patient selection and indications; treatment planning; equipment and technique; overcoming technical challenges; recognition and management of complications; postprocedural care and clinical follow-up; and expected outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Impacts of acute severe pulmonary regurgitation on right ventricular geometry and contractility assessed by tissue-Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; K. Iversen, Kasper; G Vejlstrup, Niels

    2010-01-01

    AIMS: Little is known of the impact of acute right ventricular (RV) volume overload on RV function. We assessed the impact of acute severe pulmonary regurgitation (PR) on global and regional RV function by applying novel quantitative echocardiographic markers of myocardial performance in an animal...

  4. Impacts of acute severe pulmonary regurgitation on right ventricular geometry and contractility assessed by tissue-Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Iversen, Kasper K; Vejlstrup, Niels G

    2010-01-01

    Little is known of the impact of acute right ventricular (RV) volume overload on RV function. We assessed the impact of acute severe pulmonary regurgitation (PR) on global and regional RV function by applying novel quantitative echocardiographic markers of myocardial performance in an animal model....

  5. Scorpion-related cardiomyopathy and acute pulmonary edema in a child who is stung by Leiurus abdullahbayrami

    Directory of Open Access Journals (Sweden)

    Mehmet Dokur

    2017-09-01

    Full Text Available Venom of Leiurus abdullahbayrami (Scorpiones: Buthidae is an extremely toxic one and it stimulates voltage-gated sodium and potassium channels. In case of a stung by this scorpion; excessive catecholamine release occur and it impairs left ventricle contractility and consequently a heart failure occurs (scorpion sting-related cardiomyopathy. In addition to this cardiac-induced acute pulmonary, edema may occur in severe cases too. An 11-year-old male child who was stung by a scorpion (species: Leiurus abdullahbayrami consulted to the Emergency Room. Even after 7 h of scorpion envenomation he was confused and having hallucinations. Besides he was dyspneic, tachycardic, hypotensive and got worse in overall situation due to cardiogenic pulmonary edema. These clinical findings are concordant with the Level III scorpion envenomation (major systemic manifestations. Positive inotropic agents, diuretics and antiagregant agents used on supportive therapy in his treatment. After 2 weeks he get recovered and discharged from the pediatric intensive care unit. This research is conducted by thinking emergency physicians should learn that Leiurus abdullahbayrami envenomation can cause scorpion-related cardiomyopathy and acute pulmonary edema especially in children. Keywords: Leiurus, Scorpionism, Cardiomyopathy, Pulmonary edema

  6. Oleanolic acid acetate attenuates polyhexamethylene guanidine phosphate-induced pulmonary inflammation and fibrosis in mice.

    Science.gov (United States)

    Kim, Min-Seok; Han, Jin-Young; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Lee, Seung Woong; Rho, Mun-Chual; Lee, Kyuhong

    2018-06-01

    Oleanolic acid acetate (OAA), triterpenoid compound isolated from Vigna angularis (azuki bean), has been revealed anti-inflammatory in several studies. We investigated the effects of OAA against polyhexamethylene guanidine phosphate (PHMG-P)-induced pulmonary inflammation and fibrosis in mice. OAA treatment effectively alleviated PHMG-P-induced lung injury, including the number of total and differential cell in BAL fluid, histopathological lesions and hydroxyproline content in a dose dependent manner. Moreover, OAA treatment significantly decreased the elevations of IL-1β, IL-6, TNF-α, TGF-β1, and fibronectin, and the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the lungs of PHMG-P-treated mice. Cytokines are known to be key modulators in the inflammatory responses that drive progression of fibrosis in injured tissues. The activation of NLRP3 inflammasome has been reported to be involved in induction of inflammatory cytokines. These results indicate that OAA may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG-P. Copyright © 2018. Published by Elsevier B.V.

  7. January 2015 Phoenix pulmonary journal club: noninvasive ventilation in acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Mathew M

    2015-01-01

    Full Text Available No abstract available. Article truncated after 150 words. Noninvasive positive pressure ventilation has expanded its role in the treatment of both chronic and acute respiratory failure. Its initial use in conditions such as obstructive sleep apnea, neuromuscular disease and tracheobronchomalacia, have been shown to improve quality of life and reduce mortality. Over the past 20 years studies have looked at using noninvasive ventilation in the management of acute respiratory failure from pulmonary edema, asthma and COPD exacerbations. During this month's journal club we reviewed 3 articles evaluating the efficacy of noninvasive ventilation in acute respiratory failure. Gupta D, Nath A, Agarwal R, Behera D. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010;55(5:536-43. [PubMed] This was a small unblinded randomized controlled trial (RCT looking at the efficacy using noninvasive ventilation (NIV in acute asthma. A total of 53 patients were included and divided into 2 groups of 28 patients ...

  8. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty...

  9. Acute Arterial Hypertension in Acute Pulmonary Edema: Mostly a Trigger or an Associated Phenomenon?

    Science.gov (United States)

    Figueras, Jaume; Bañeras, Jordi; Peña-Gil, Carlos; Masip, Josep; Barrabés, José A; Rodriguez Palomares, Jose; Garcia-Dorado, David

    2016-10-01

    The role of acute arterial hypertension in acute pulmonary edema (APE) as an associated or triggering phenomenon has been poorly investigated and is relevant to patient management. This was a prospective observational study of clinical, electrocardiographic, and echocardiographic characteristics of patients with APE. Potential triggers, including acute coronary syndrome (ACS), rapid atrial fibrillation (AF) (≥ 120 bpm in AF), fever > 38°C or volume overload, isolated acute hypertension (systolic blood pressure ≥ 170 mm Hg), and unknown factors were investigated. There were 742 patients, 578 with coronary artery disease (78%), 116 with valvular heart disease or cardiomyopathy (16%), and 47 without identifiable heart disease (6%). ACS was present in 482 (65%) patients (silent in 154 of them), AF was present in 76 (10%) patients, fever/volume overload was present in 62 (8%) patients, acute hypertension was present in 50 (7%) patients, and no apparent trigger was seen in 72 (10%) patients. Admission hypertension occurred in 260 patients (35%): 155 (60%) with ACS (silent in 49 [32%]), 36 (14%) with AF, 19 (7%) with fever/volume overload, and 59 (19%) as an isolated trigger. Similar results were obtained when analyzing patients using coronary angiography (467 patients [63%]). Acute hypertension was present more frequently in patients with severe hypoventilation (arterial Pco 2 > 60 mm Hg) than in those without (57% vs 29%; P acute hypertension is often present but mainly as an associated/reactive phenomenon and seems favoured by severe hypoventilation. Silent myocardial ischemia/necrosis deserves systematic investigation because it is not rare that it may be the underlying cause of APE. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  10. Investigating suspected acute pulmonary embolism - what are hospital clinicians thinking?

    International Nuclear Information System (INIS)

    McQueen, A.S.; Worthy, S.; Keir, M.J.

    2008-01-01

    Aims: To assess local clinical knowledge of the appropriate investigation of suspected acute pulmonary embolism (PE) and this compare with the 2003 British Thoracic Society (BTS) guidelines as a national reference standard. Methods: A clinical questionnaire was produced based on the BTS guidelines. One hundred and eight-six participants completed the questionnaires at educational sessions for clinicians of all grades, within a single NHS Trust. The level of experience amongst participants ranged from final year medical students to consultant physicians. Results: The clinicians were divided into four groups based on seniority: Pre-registration, Junior, Middle, and Senior. Forty-six point eight percent of all the clinicians correctly identified three major risk factors for PE and 25.8% recognized the definition of the recommended clinical probability score from two alternatives. Statements regarding the sensitivity of isotope lung imaging and computed tomography pulmonary angiography (CTPA) received correct responses from 41.4 and 43% of participants, respectively, whilst 81.2% recognized that an indeterminate ventilation-perfusion scintigraphy (V/Q) study requires further imaging. The majority of clinicians correctly answered three clinical scenario questions regarding use of D-dimers and imaging (78, 85, and 57.5%). There was no statistically significant difference between the four groups for any of the eight questions. Conclusions: The recommended clinical probability score was unfamiliar to all four groups of clinicians in the present study, and the majority of doctors did not agree that a negative CTPA or isotope lung scintigraphy reliably excluded PE. However, questions based on clinical scenarios received considerably higher rates of correct responses. The results indicate that various aspects of the national guidelines on suspected acute pulmonary embolism are unfamiliar to many UK hospital clinicians. Further research is needed to identify methods to improve

  11. Undiagnosed chronic obstructive pulmonary diseases in patients admittet to an acute assessment unit

    DEFF Research Database (Denmark)

    Eikhof, Karin Dam; Olsen, Kristine R; Wrengler, NCH

    2017-01-01

    Introduction: Chronic obstructive pulmonary disease (COPD) is very prevalent worldwide, yet underdiagnosed. Aim: This study investigates feasibility of performing spirometry in patients in need of acute hospital admission as well as the prevalence of undiagnosed COPD in the same cohort. Methods....../3 was in GOLD group A. In total, 75% of the patients with airflow obstruction at the initial examination remained obstructive. Conclusion: Performing spirometry in patients in need of acute hospital admission is feasible, abnormal findings are common, and COPD is the most prevalent diagnosis....

  12. Pulmonary effects after acute inhalation of oil dispersant (COREXIT EC9500A) in rats.

    Science.gov (United States)

    Roberts, Jenny R; Reynolds, Jeffrey S; Thompson, Janet A; Zaccone, Eric J; Shimko, Michael J; Goldsmith, William T; Jackson, Mark; McKinney, Walter; Frazer, David G; Kenyon, Allison; Kashon, Michael L; Piedimonte, Giovanni; Castranova, Vincent; Fedan, Jeffrey S

    2011-01-01

    COREXIT EC9500A (COREXIT) was used to disperse crude oil during the 2010 Deepwater Horizon oil spill. While the environmental impact of COREXIT has been examined, the pulmonary effects are unknown. Investigations were undertaken to determine whether inhaled COREXIT elicits airway inflammation, alters pulmonary function or airway reactivity, or exerts pharmacological effects. Male rats were exposed to COREXIT (mean 27 mg/m(3), 5 h). Bronchoalveolar lavage was performed on d 1 and 7 postexposure. Lactate dehydrogenase (LDH) and albumin were measured as indices of lung injury; macrophages, neutrophils, lymphocytes, and eosinophils were quantified to evaluate inflammation; and oxidant production by macrophages and neutrophils was measured. There were no significant effects of COREXIT on LDH, albumin, inflammatory cell levels or oxidant production at either time point. In conscious animals, neither breathing frequency nor specific airway resistance were altered at 1 hr, 1 d and 7 d postexposure. Airway resistance responses to methacholine (MCh) aerosol in anesthetized animals were unaffected at 1 and 7 d postexposure, while dynamic compliance responses were decreased after 1 d but not 7 d. In tracheal strips, in the presence or absence of MCh, low concentrations of COREXIT (0.001% v/v) elicited relaxation; contraction occurred at 0.003-0.1% v/v. In isolated, perfused trachea, intraluminally applied COREXIT produced similar effects but at higher concentrations. COREXIT inhibited neurogenic contractile responses of strips to electrical field stimulation. Our findings suggest that COREXIT inhalation did not initiate lung inflammation, but may transiently increase the difficulty of breathing.

  13. Diesel exhaust induced pulmonary and cardiovascular impairment: The role of hypertension intervention

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Thomas, Ronald F.; Ledbetter, Allen D.; Schladweiler, Mette C.; Bass, Virginia; Krantz, Q. Todd; King, Charly [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Nyska, Abraham [Tel Aviv University, Tel Aviv (Israel); Richards, Judy E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Andrews, Debora [Research Core Unit, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711 (United States); Gilmour, M. Ian [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States)

    2013-04-15

    Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or L-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500 μg/m{sup 3}), 4 h/day for 2 days or 5 days/week for 4 weeks. Acute and 4-week gas and DE exposures increased neutrophils and γ-glutamyl transferase (γ-GT) activity in lavage fluid of WKY and SH rats. DE (4 weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-α, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while L-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF γ-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by L-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-α, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers. - Highlights: ► Acute diesel exhaust exposure induces pulmonary inflammation in healthy rats. ► In hypertensive rats diesel exhaust effects are seen only after long term exposure. ► Normalizing blood pressure reverses lung protein leakage caused by diesel exhaust. ► Normalizing blood pressure reverses

  14. The content of mucin MUC-2, -3 and -4 antigens in the bronchial mucosa membrane of chronic obstructive pulmonary disease patients during acute exacerbation - initial report.

    Science.gov (United States)

    Kovalenko, Svetlana; Dorofieiev, Andrey

    2017-01-01

    Changes in mucin production and dyscrinia are common features of inflammation in chronic obstructive pulmonary disease (COPD). Immunohistochemical assessment of MUC-2, MUC-3, MUC-4 expression in the integumentary epithelium, goblet cells, the epithelium of mucous glands and stroma fusiform cells of the bronchial mucosa of COPD patients during an infectious and noninfectious exacerbation was performed. 30 patients with stage III COPD were enrolled to the study. Patients were divided into 2 groups: group A - 14 patients with non-infectious acute exacerbation of COPD (AECOPD) and group B - 16 patients with infectious AECOPD. Fiberoptic bronchoscopy (FBS) and in vivo bronchial biopsy of bronchial mucosa were implemented to determine the extent and nature of bronchial inflammation. The optical density of specific color in bronchial structures was assessed using immunohistochemical staining to MUC-2, -3 and -4 antigens by means of primary monoclonal antibodies to these proteins, and visualization system Dako EnVision + System, Peroxidase (AEC). We detected that in different types of bronchial mucosa epithelial cells, during acute infectious exacerbation, a decrease of antigens MUC-2 and MUC-3 expression of a various degree may occur. This phenomenon in the stroma fusiform cells in AECOPD may be a sign of epithelial-mesenchymal transition, that may play a role in the development of an inflammatory process and progression of fibrosis in COPD.

  15. Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille; Dadrich, Monika; Hauser, Kai; Abdollahi, Amir; Groene, Hermann-Josef; Angel, Peter; Huber, Peter E.

    2010-01-01

    Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results: We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.

  16. [Acute asthma attacks introduced by anesthesia before nasal endoscopic surgery].

    Science.gov (United States)

    Lü, Xiaofei; Han, Demin; Zhou, Bing; Ding, Bin

    2004-05-01

    In order to pay our attention to the perioperative treatment before nasal endoscopic surgery. Three patients with asthma accompanied chronic sinusitis were analyzed systemically, who had undergone acute attacks of asthma introduced by anesthesia. Anesthetic drugs and instruments can lead to acute attacks of asthma, because sinusitis with asthma means allergic airway inflammation, broncho-hyperreactivity and lower compensatory pulmonary function. Then all of the 3 cases had missed the preoperative treatment. Anesthetic drugs and instruments can lead to acute attacks of asthma. The perioperative treatment before nasal endoscopic surgery is very important for the prevention of the occurrences of this severe complication. Except emergency, the operation should be can celled for avoiding the acute attack of asthma introduced by anesthesia.

  17. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Dahl, Morten; Lange, Peter

    2012-01-01

    Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities.......Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities....

  18. Curcumin use in pulmonary diseases: State of the art and future perspectives.

    Science.gov (United States)

    Lelli, Diana; Sahebkar, Amirhossein; Johnston, Thomas P; Pedone, Claudio

    2017-01-01

    Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis. These effects may be relevant for several pulmonary diseases that are characterized by abnormal inflammatory responses, such as asthma or chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests that curcumin may have a role in the treatment of lung cancer. The evidence for the use of curcumin in pulmonary disease is still sparse and has mostly been obtained using either in vitro or animal models. The most important issue with the use of curcumin in humans is its poor bioavailability, which makes it necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of this review is to summarize the available evidence on curcumin's effectiveness in pulmonary diseases, including lung cancer, and to provide our perspective on future research with curcumin so as to improve its pharmacological effects, as well as provide additional evidence of curcumin's efficacy in the treatment of pulmonary diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting

    Directory of Open Access Journals (Sweden)

    Ozge Korkmaz

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located, and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9; second group (thrombus in main pulmonary artery branches; n = 71; third group (thrombus in pulmonary artery segmental branches; n = 34; and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8. RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009 and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033 remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

  20. Low triiodothyronine: A new facet of inflammation in acute ischemic stroke.

    Science.gov (United States)

    Ma, Lili; Zhu, Dongliang; Jiang, Ying; Liu, Yingying; Ma, Xiaomeng; Liu, Mei; Chen, Xiaohong

    2016-07-01

    Patients with acute ischemic stroke (AIS) frequently experience low free triiodothyronine (fT3) concentrations. Inflammation is recognized as a key contributor to the pathophysiology of stroke. Previous studies, however, did not simultaneously evaluate fT3 and inflammation biomarkers in AIS patients. Markers of inflammation, including serum concentrations of C-reactive protein (CRP) and albumin, and fT3 were assessed retrospectively in 117 patients. Stroke severity was measured on the National Institutes of Health Stroke Scale (NIHSS). Regression analyses were performed to adjust for confounders. Serum fT3 concentrations were significantly lower in moderate AIS patients than those in mild AIS patients (P<0.001). fT3 concentration also positively correlated with serum albumin concentration (r=0.358, P<0.001) and negatively correlated with log10CRP concentration (r=-0.341, P<0.001), NIHSS score (r=-0.384, P<0.001). Multiple regression analysis showed that CRP, albumin concentrations and NIHSS score were independently correlated with fT3 concentration. Binary logistic regression analysis showed that fT3 concentration was an independent factor correlated with NIHSS score, the area under the receiver operating characteristic curve was 0.712 (95% CI, 0.618-0.805). Low fT3 concentrations may be involved in the pathogenic pathway linking inflammation to stroke severity in AIS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study.

    Science.gov (United States)

    Gimber, Lana Hirai; Travis, R Ing; Takahashi, Jayme M; Goodman, Torrey L; Yoon, Hyo-Chun

    2009-01-01

    Pulmonary computed tomography angiography (CTA) and the Wells criteria both have interobserver variability in the assessment of pulmonary embolism (PE). Quantitative D-dimer assay findings have been shown to have a high negative predictive value in patients with low pretest probability of PE. Evaluate roles for clinical probability and CTA in Emergency Department (ED) patients suspected of acute PE but having a low serum D-dimer level. Prospective observational study of ED patients with possible PE who underwent pulmonary CTA and had D-dimer levels tiebreaker. Pulmonary CTA findings positive for acute embolism should be viewed with caution, especially if the suspected PE is in a distal segmental or subsegmental artery in a patient with a serum D-dimer level of

  2. Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.

    Science.gov (United States)

    Hirasawa, Noriyasu; Goi, Yoshiaki; Tanaka, Rina; Ishihara, Kenji; Ohtsu, Hiroshi; Ohuchi, Kazuo

    2010-06-15

    The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation. (c) 2009 Wiley Periodicals, Inc.

  3. Boussignac continuous positive airway pressure for the management of acute cardiogenic pulmonary edema: prospective study with a retrospective control group

    Directory of Open Access Journals (Sweden)

    Aarts Leon PHJ

    2007-12-01

    Full Text Available Abstract Background Continuous positive airway pressure (CPAP treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP system that does not need a mechanical ventilator. Methods BCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of Results During the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78% were treated at the coronary care unit of which 66 (61% were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47% needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately € 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment. Conclusion At the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings.

  4. Acute pulmonary edema associated with propofol: an unusual complication.

    Science.gov (United States)

    Waheed, Mian Adnan; Oud, Lavi

    2014-11-01

    Propofol is frequently used in the emergency department to provide procedural sedation for patients undergoing various procedures and is considered to be safe when administered by trained personnel. Pulmonary edema after administration of propofol has rarely been reported. We report a case of a 23-year-old healthy male who developed acute cough, hemoptysis and hypoxia following administration of propofol for splinting of a foot fracture. Chest radiography showed bilateral patchy infiltrates. The patient was treated successfully with supportive care. This report emphasizes the importance of this potentially fatal propofol-associated complication and discusses possible underlying mechanisms and related literature.

  5. Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    2010-01-01

    Full Text Available The anti-inflammatory activity of licorice (LE and roated licorice (rLE extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

  6. Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice.

    Science.gov (United States)

    Hazarika, Surovi; Van Scott, Michael R; Lust, Robert M; Wingard, Christopher J

    2010-01-01

    Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intraperitoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K+ depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6±3.9% and 97.7±1.2% to 32±4% and 51±6%, respectively (p<0.05). The sensitivity to acetylcholine was likewise reduced (EC₅₀=0.26±0.05 μM vs. 1.09±0.16 μM, p<0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    van Dijk, Wouter D; Akkermans, Reinier; Heijdra, Yvonne; Weel, Chris van; Schermer, Tjard R J; Scheepers, Paul T J; Lenders, Jacques W M

    2013-04-01

    The evidence on the acute effects of smoking on biomarkers is limited. Our aim was to study the acute effect of smoking on disease-related biomarkers. The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and plasma fibrinogen and its association with disease severity was studied by challenging 31 chronic obstructive pulmonary disease patients with cigarette smoking and repeatedly measuring these biomarkers before and after smoking. Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95% CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation coefficient between the hs-CRP change and chronic obstructive pulmonary disease severity was 0.25 (p = 0.06). Fibrinogen and hs-CRP increased directly after smoking in the chronic obstructive pulmonary disease patients. Their association with disease risk and/or progression remains to be demonstrated.

  8. Idiopathic pulmonary fibrosis: evolving concepts.

    Science.gov (United States)

    Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. A 64-year old man who sustained many episodes of acute cardiogenic pulmonary edema successfully treated with Boussignac continuous positive airway pressure : A case report

    NARCIS (Netherlands)

    Dieperink, Willem; van der Horst, Iwan C. C.; Nannenberg-Koops, Jaqueline W.; Brouwer, Henk W.; Jaarsma, T.; Nieuwland, Wybe; Zijlstra, Felix; Nijsten, Maarten W. N.

    2007-01-01

    Continuous positive airway pressure (CPAP) is standard treatment for patients with acute cardiogenic pulmonary edema. We describe a patient who had 21 episodes of acute cardiogenic pulmonary edema due to very poor patient compliance. This 64-year old man had end-stage congestive heart failure based

  10. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Acute liver failure (ALF is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT. BT triggers/induces systemic inflammatory responses syndrome (SIRS, which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  11. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure.

    Science.gov (United States)

    Yang, Runkuan; Zou, Xiaoping; Tenhunen, Jyrki; Tønnessen, Tor Inge

    2017-01-01

    Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  12. Logistic regression model for identification of right ventricular dysfunction in patients with acute pulmonary embolism by means of computed tomography

    International Nuclear Information System (INIS)

    Staskiewicz, Grzegorz; Czekajska-Chehab, Elżbieta; Uhlig, Sebastian; Przegalinski, Jerzy; Maciejewski, Ryszard; Drop, Andrzej

    2013-01-01

    Purpose: Diagnosis of right ventricular dysfunction in patients with acute pulmonary embolism (PE) is known to be associated with increased risk of mortality. The aim of the study was to calculate a logistic regression model for reliable identification of right ventricular dysfunction (RVD) in patients diagnosed with computed tomography pulmonary angiography. Material and methods: Ninety-seven consecutive patients with acute pulmonary embolism were divided into groups with and without RVD basing upon echocardiographic measurement of pulmonary artery systolic pressure (PASP). PE severity was graded with the pulmonary obstruction score. CT measurements of heart chambers and mediastinal vessels were performed; position of interventricular septum and presence of contrast reflux into the inferior vena cava were also recorded. The logistic regression model was prepared by means of stepwise logistic regression. Results: Among the used parameters, the final model consisted of pulmonary obstruction score, short axis diameter of right ventricle and diameter of inferior vena cava. The calculated model is characterized by 79% sensitivity and 81% specificity, and its performance was significantly better than single CT-based measurements. Conclusion: Logistic regression model identifies RVD significantly better, than single CT-based measurements

  13. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    Li Jianjun

    2012-09-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

  14. Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

    Science.gov (United States)

    Yeh, D Y-W; Yang, Y-C; Wang, J-J

    2015-05-01

    Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

    Science.gov (United States)

    Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

    2005-01-01

    Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

  16. Rarity of isolated pulmonary embolism and acute aortic syndrome occurring outside of the field of view of dedicated coronary CT angiography

    International Nuclear Information System (INIS)

    Lee, Hwa Yeon; Song, In Sup; Yoo, Seung Min; Rho, Ji Young; Moon, Jae Youn; Kim, In Jai; Lim, Sang Wook; Sung, Jung Hoon; Cha, Dong Hun; White, Charles S.

    2011-01-01

    Background Although triple rule-out CT angiography (TRO) to simultaneously evaluate acute coronary syndrome (ACS), pulmonary embolism (PE), and acute aortic syndrome (AAS) is increasingly used in many institutions, TRO is inevitably associated with increased radiation exposure due to extended z-axis coverage compared with dedicated coronary CT angiography (DCTA). Purpose To determine the frequency of exclusion of findings of AAS, PE, and significant incidental non-cardiac pathology that may be the cause of acute chest pain when using a restricted DCTA field of view (FOV). Material and Methods We retrospectively reviewed CT images and charts of 103 patients with acute PE and 50 patients with AAS. Either non-ECG gated dedicated pulmonary or aortic CT angiography was performed using 16- or 64-slice multidetector CT (MDCT). We analyzed the incidence of isolated PE, AAS, or significant non-cardiac pathology outside of DCTA FOV (i.e. from tracheal carina to the base of heart). Results There were two cases of isolated PE (2/103, 1.9%) excluded from the FOV of DCTA. One case of PE was isolated to the subsegmental pulmonary artery in the posterior segment of the right upper lobe. In the second case, pulmonary embolism in the left main pulmonary artery was located out of the FOV of DCTA because the left main pulmonary artery was retracted upwardly by fibrotic scar in the left upper lobe due to prior tuberculosis. There was no case of AAS and significant non-cardiac pathology excluded from the FOV of DCTA. AAS (n = 50) consisted of penetrating atherosclerotic ulcer (n = 7), intramural hematoma (n = 5) and aortic dissection (n = 38). Conclusion As isolated PE, AAS, and significant non-cardiac pathology outside of the DCTA FOV rarely occur, DCTA may replace TRO in the evaluation of patients with non-specific acute chest pain and a low pre-test probability of PE or aortic dissection

  17. Rarity of isolated pulmonary embolism and acute aortic syndrome occurring outside of the field of view of dedicated coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwa Yeon; Song, In Sup (Dept. of Diagnostic Radiology Chung-Ang Univ. College of Medicine, Seoul (Korea, Republic of)); Yoo, Seung Min; Rho, Ji Young (Dept. of Diagnostic Radiology CHA Medical Univ. Hospital, Bundang (Korea, Republic of)), email: smyoo68@hanmail.net; Moon, Jae Youn; Kim, In Jai; Lim, Sang Wook; Sung, Jung Hoon; Cha, Dong Hun (Dept. of Cardiology CHA Medical Univ. Hospital, Bundang (Korea, Republic of)); White, Charles S. (Dept. of Diagnostic Radiology Univ. of Maryland, Baltimore (United States))

    2011-05-15

    Background Although triple rule-out CT angiography (TRO) to simultaneously evaluate acute coronary syndrome (ACS), pulmonary embolism (PE), and acute aortic syndrome (AAS) is increasingly used in many institutions, TRO is inevitably associated with increased radiation exposure due to extended z-axis coverage compared with dedicated coronary CT angiography (DCTA). Purpose To determine the frequency of exclusion of findings of AAS, PE, and significant incidental non-cardiac pathology that may be the cause of acute chest pain when using a restricted DCTA field of view (FOV). Material and Methods We retrospectively reviewed CT images and charts of 103 patients with acute PE and 50 patients with AAS. Either non-ECG gated dedicated pulmonary or aortic CT angiography was performed using 16- or 64-slice multidetector CT (MDCT). We analyzed the incidence of isolated PE, AAS, or significant non-cardiac pathology outside of DCTA FOV (i.e. from tracheal carina to the base of heart). Results There were two cases of isolated PE (2/103, 1.9%) excluded from the FOV of DCTA. One case of PE was isolated to the subsegmental pulmonary artery in the posterior segment of the right upper lobe. In the second case, pulmonary embolism in the left main pulmonary artery was located out of the FOV of DCTA because the left main pulmonary artery was retracted upwardly by fibrotic scar in the left upper lobe due to prior tuberculosis. There was no case of AAS and significant non-cardiac pathology excluded from the FOV of DCTA. AAS (n = 50) consisted of penetrating atherosclerotic ulcer (n = 7), intramural hematoma (n = 5) and aortic dissection (n = 38). Conclusion As isolated PE, AAS, and significant non-cardiac pathology outside of the DCTA FOV rarely occur, DCTA may replace TRO in the evaluation of patients with non-specific acute chest pain and a low pre-test probability of PE or aortic dissection

  18. Effects of inhaled corticosteroids on airway inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Jen R

    2012-09-01

    Full Text Available Rachel Jen,1 Stephen,1 Rennard,2 Don D Sin1,31Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada; 2Internal Medicine Section of Pulmonary and Critical Care, Nebraska Medical Center, Omaha, NE, USA; 3Institute of Heart and Lung Health and the UBC James Hogg Research Center, St Paul's Hospital, Vancouver, BC, CanadaBackground: Chronic obstructive pulmonary disease (COPD is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.Methods: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1, then a random effects model was used to pool the original data; otherwise, a fixed effects model was used.Results: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n = 102 participants and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval. The five studies used bronchoalveolar lavage fluid (n = 309, which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval. ICS on the other hand

  19. Severe pulmonary compromise in an immunocompetent patient with acute disseminated toxoplasmosis: A Case Report

    International Nuclear Information System (INIS)

    Salinas, Jorge; Pino, Luis; Lopez Consuelo

    2008-01-01

    Introduction: The acute toxoplasmosis in the immunocompetent patient, unlike of the positive HIV patient, it is characterizes for prolonged fever, lymph node and nonspecific infectious symptoms, generally with benign course and without systemic commitment. This pathology acquired a very importance in the pregnancy people, where the primary infection can to derivates in the congenital transmission of the illness with irreversible sequels in newborn. Nevertheless, the travel of the people to inhospitable woodsy areas, and the contact with wild-type strain of toxoplasma gondii, to be permitted a new expression of the illness in the immunocompetent patient, with pulmonary, cardiovascular and central nervous system manifestations. They are a high risk for the patient life's. In this study, one case of severe pulmonary commitment for toxoplasma gondii in immunocompetent patient is review; he is admitted to Internal Medicine Service of the Militar Central Hospital's in Bogota. He has a favorable evolution and adequate survival. Objective: To describe the clinical characteristics and follow-up of one patient with severe pulmonary commitment caused by toxoplasma gondii. Design: Case report. Materials and methods: The clinical records of the one patient who was hospitalized in the Militar Central Hospital's in Bogota was reviewed and described. Afterwards, the existing literature on Acute toxoplasmosis in immunocompetent patient was reviewed in PubMed, MD consult and OVID databases. Conclusions: The toxoplasma gondii infection's in immunocompetent patient generally has a benign course without systemic manifestations; nevertheless, the exposure to wild-type strain can to be related with severe pulmonary commitment.

  20. STING Signaling Promotes Inflammation in Experimental Acute Pancreatitis.

    Science.gov (United States)

    Zhao, Qinglan; Wei, Yi; Pandol, Stephen J; Li, Lingyin; Habtezion, Aida

    2018-05-01

    Acute pancreatitis (AP) is characterized by severe inflammation and acinar cell death. Transmembrane protein 173 (TMEM173 or STING) is a DNA sensor adaptor protein on immune cells that recognizes cytosolic nucleic acids and transmits signals that activate production of interferons and the innate immune response. We investigated whether leukocyte STING signaling mediates inflammation in mice with AP. We induced AP in C57BL/6J mice (control) and C57BL/6J-Tmem173gt/J mice (STING-knockout mice) by injection of cerulein or placement on choline-deficient DL-ethionine supplemented diet. In some mice, STING signaling was induced by administration of a pharmacologic agonist. AP was also induced in C57BL/6J mice with bone marrow transplants from control or STING-knockout mice and in mice with disruption of the cyclic GMP-AMP synthase (Cgas) gene. Pancreata were collected, analyzed by histology, and acini were isolated and analyzed by flow cytometry, quantitative polymerase chain reaction, immunoblots, and enzyme-linked immunosorbent assay. Bone-marrow-derived macrophages were collected from mice and tested for their ability to detect DNA from dying acinar cells in the presence and absence of deoxyribonuclease (DNaseI). STING signaling was activated in pancreata from mice with AP but not mice without AP. STING-knockout mice developed less severe AP (less edema, inflammation, and markers of pancreatic injury) than control mice, whereas mice given a STING agonist developed more severe AP than controls. In immune cells collected from pancreata, STING was expressed predominantly in macrophages. Levels of cGAS were increased in mice with vs without AP, and cGAS-knockout mice had decreased edema, inflammation, and other markers of pancreatic injury upon induction of AP than control mice. Wild-type mice given bone marrow transplants from STING-knockout mice had less pancreatic injury and lower serum levels of lipase and pancreatic trypsin activity following induction of AP than

  1. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  2. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    International Nuclear Information System (INIS)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-01-01

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  3. Paradoxical embolization via a patent foramen ovale following acute pulmonary embolism

    International Nuclear Information System (INIS)

    Thomas, D.V.; Bynevelt, V.; Price, R.

    2005-01-01

    The foramen ovale is usually obliterated following establishment of the adult circulation but remains patent in 25% of individuals. This potential communication between the venous and arterial circulations can allow thromboembolic material to bypass the lungs and enter the systemic circulation. We report two cases of paradoxical embolization through a patent foramen ovale following acute large pulmonary embolism (PE) and discuss the factors that predispose to paradoxical embolization following PE Copyright (2005) Blackwell Publishing Asia Pty Ltd

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

    Science.gov (United States)

    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. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  6. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

    Science.gov (United States)

    Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

    2017-05-01

    Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.

  7. Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Cassee, Flemming R.

    2018-01-01

    in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential...... studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monse et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well...

  8. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  9. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Nozomi Yabuuchi

    2016-12-01

    Full Text Available High mortality of acute kidney injury (AKI is associated with acute lung injury (ALI, which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS, in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5, in bilateral nephrectomy (BNx-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr, blood urea nitrogen (BUN and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.

  10. [Unilateral acute pulmonary edema and ischemic myocardial process: a case report].

    Science.gov (United States)

    Bentaleb, A; Tagu, P; Vascaut, L

    2008-08-01

    Unilateral acute pulmonary oedema (APO) is a rare radioclinical finding. It occurs secondary to multiple specific and rare pathological processes. Functional ischemic mitral regurgitation (FIMR) secondary to myocardial necrosis is one of the rare aetiologies involved in its pathogenesis. This concerns a 94-year-old male patient with a history of myocardial infarction who presented with a clinical picture of unilateral APO secondary to functional mitral regurgitation as a complication of myocardial necrosis. In addition to the clinical presentation and unilateral radiological findings, the diagnosis was based essentially on the electrocardiographic tracing, as well as changes in cardiac enzyme levels and transthoracic echocardiogram coupled with Doppler tissue imaging. This resulted after ruling out many differential diagnoses. Unilateral APO secondary to functional mitral regurgitation often presents diagnostic challenges and problems of initial management for the clinician. There are multiple aetiologies of acute unilateral pulmonary oedema, namely mechanical (re-expansion), lesional, vascular, bronchial obstructions, as well as iatrogenic causes, as is the case with some lung transplantations. As with all cases of APO, the treatment is based mainly on diuretics with high-flow oxygen therapy in association with an anticoagulant, which is usually effectively combined with a platelet aggregation inhibiting drug and sometimes with vasodilators and beta-blockers. Surgical treatment with valvuloplasty or valvular replacement appears to be the most effective means for preventing relapse.

  11. Low Tidal Volume Reduces Lung Inflammation Induced by Liquid Ventilation in Piglets With Severe Lung Injury.

    Science.gov (United States)

    Jiang, Lijun; Feng, Huizhen; Chen, Xiaofan; Liang, Kaifeng; Ni, Chengyao

    2017-05-01

    Total liquid ventilation (TLV) is an alternative treatment for severe lung injury. High tidal volume is usually required for TLV to maintain adequate CO 2 clearance. However, high tidal volume may cause alveolar barotrauma. We aim to investigate the effect of low tidal volume on pulmonary inflammation in piglets with lung injury and under TLV. After the establishment of acute lung injury model by infusing lipopolysaccharide, 12 piglets were randomly divided into two groups, TLV with high tidal volume (25 mL/kg) or with low tidal volume (6 mL/kg) for 240 min, respectively. Extracorporeal CO 2 removal was applied in low tidal volume group to improve CO 2 clearance and in high tidal volume group as sham control. Gas exchange and hemodynamic status were monitored every 30 min during TLV. At the end of the study, pulmonary mRNA expression and plasmatic concentration of interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured by collecting lung tissue and blood samples from piglets. Arterial blood pressure, PaO 2 , and PaCO 2 showed no remarkable difference between groups during the observation period. Compared with high tidal volume strategy, low tidal volume resulted in 76% reduction of minute volume and over 80% reduction in peak inspiratory pressure during TLV. In addition, low tidal volume significantly diminished pulmonary mRNA expression and plasmatic level of IL-6 and IL-8. We conclude that during TLV, low tidal volume reduces lung inflammation in piglets with acute lung injury without compromising gas exchange. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  12. Pulmonary exposure to carbonaceous nanomaterials and sperm quality

    DEFF Research Database (Denmark)

    Skovmand, Astrid; Lauvas, Anna Jacobsen; Christensen, Preben

    2018-01-01

    . Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI...... inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model.Methods: Effects on sperm quality after pulmonary inflammation induced by carbonaceous...... flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA.Results: Neutrophil numbers in the bronchoalveolar fluid showed...

  13. Comparative effects of acute O2 breathing and terbutaline in patients with chronic obstructive pulmonary disease. A combined hemodynamic and radionuclide study

    International Nuclear Information System (INIS)

    Tschopp, J.M.; Gabathuler, J.; Righetti, A.; Junod, A.F.

    1985-01-01

    The acute effects of terbutaline (T) and breathing 100% O 2 (O 2 ) on gas exchange, pulmonary hemodynamics and radionuclide angiography were evaluated in 15 patients with severe chronic obstructive pulmonary disease (COPD). O 2 breathing resulted in a decrease in mean pulmonary artery pressure (PAP) and cardiac index (CI) without changing pulmonary vascular resistance index (PVRI) or right and left ventricular ejection fractions (RVEF,LVEF). On the other hand, T administration was followed by a decrease in PVRI, and increase in CI, RVEF and LVEF. These effects of T were maintained during exersice. Although RVEF was inversely correlated with basal levels of PAP or PVRI, acute changes in pulmonary hemodynamics were not correlated with significant changes on RVEF. These results suggest that T may be useful in the treatment of patients with COPD prone to develop cor pulmonale. However, the long-term benefit of this treatment remains to be established. (author)

  14. Early invasive pulmonary aspergillosis with fatal outcome in a patient with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Gaspar, M.; Poczova, M.; Sladekova, M.; Drgona, L.

    2015-01-01

    Purpose: The main objective of this publication is to highlight the complexity of the issue of care for patients with hemato-oncological disease, with a focus on infectious complication - invasive pulmonary aspergillosis. Case: We present a case report of a 49-year-old patient treated for acute lymphoblastic leukemia. In the early post-transplant period, in spite of combined antimicrobial treatment, an onset of fever and dyspnoea occurred. Because of the clinical condition of our immunosuppressed patient, as well as radiological finding of suspected inflammatory changes in the lung, antibiotic and antifungal therapy was changed. Respiratory symptoms progressed and the state extorted artificial ventilation. Realized bronchoscopy showed structural changes in bronchial mucosa. The results of laboratory analyses of bronchoalveolar lavage testified to fungal infection - pulmonary aspergillosis, with the cultures of Aspergillus flavus. Despite intensive complex treatment, the patient's condition led to multiple organ failure and on the Day D +27 after transplantation physicians stated exitus letalis. Autopsy confirmed invasive pulmonary aspergillosis. Conclusion: Acute leukemia and its treatment is an increased risk of systemic fungal infections in those patients - especially invasive aspergillosis. The fatality rate for invasive aspergillosis in this risk group represents on average 50 %. With this in mind, it is necessary for life-saving to diagnose the infection in time and treat it appropriately. (author)

  15. Effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    Qin Yang

    2017-01-01

    Objective:To study the effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma.Methods: A total of 118 adult patients with bronchial asthma who were treated in our hospital between September 2015 and January 2017 were divided into pure depression group (n=30), pure anxiety group (n=47), depression + anxiety group (n=19) and mental health group (n=22) according to the Self-Rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) score. The differences in the levels of pulmonary function parameters as well as the contents of serum inflammatory factors and airway remodeling indexes were compared among the four groups. Results: FEV1, PEF and FVC levels as well as serum TIMP-1 contents of pure depression group, pure anxiety group and depression + anxiety group were lower than those of mental health group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of mental health group, and FEV1, PEF and FVC levels as well as serum TIMP-1 content of depression + anxiety group were lower than those of pure depression group and pure anxiety group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of pure depression group and pure anxiety group. Conclusion: Anxiety and depression can aggravate the pulmonary function injury, increase airway inflammation and promote airway remodeling process in patients with bronchial asthma.

  16. Acute pulmonary embolism in the era of multi-detector CT: a reality in sub-Saharan Africa

    International Nuclear Information System (INIS)

    Tambe, Joshua; Moifo, Boniface; Fongang, Emmanuel; Guegang, Emilienne; Juimo, Alain Georges

    2012-01-01

    The advantages of multi-detector computed tomography (MDCT) have made it the imaging modality of choice for some patients with suspected cardiothoracic disease, of which pulmonary embolism (PE) is an exponent. The aim of this study was to assess the incidence of PE in patients with clinical suspicion of acute PE using MDCT in a sub-Saharan setting, and to describe the demographic characteristics of these patients. Consecutive records of patients who underwent MDCT pulmonary angiography for suspected acute PE over a two-year period at the Radiology Department of a university-affiliated hospital were systematically reviewed. All MDCT pulmonary angiograms were performed with a 16-detector computed tomography (CT) scanner using real-time bolus tracking technique. Authorization for the study was obtained from the institutional authorities. Forty-one MDCT pulmonary angiograms were reviewed of which 37 were retained. Of the 4 excluded studies, 3 were repeat angiograms and 1 study was not technically adequate. Twelve of 37 patients (32.4%) had CT angiograms that were positive for PE, of which 7 were males. The mean age of these patients was 47.6±10.5 years (age range from 33 to 65 years). Twenty five patients out of 37 (67.6%) had CT angiograms that were negative for PE. Eleven PE-positive patients (91.7%) had at least 1 identifiable thromboembolic risk factor whilst 5 PE-negative patients (20%) also had at least a thromboembolic risk factor. The relative risk of the occurrence of PE in patients with at least a thromboembolic risk factor was estimated at 14.4. Acute PE is a reality in sub-Saharan Africa, with an increased likelihood of MDCT evidence in patients with clinical suspicion of PE who have at least a thromboembolic risk factor. The increasing availability of MDCT will help provide more information on the occurrence of PE in these settings

  17. TRP channels and traffic-related environmental pollution-induced pulmonary disease.

    Science.gov (United States)

    Akopian, Armen N; Fanick, E Robert; Brooks, Edward G

    2016-05-01

    Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease.

  18. Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension.

    Science.gov (United States)

    Santos, Cíntia L; Moraes, Lillian; Santos, Raquel S; Oliveira, Mariana G; Silva, Johnatas D; Maron-Gutierrez, Tatiana; Ornellas, Débora S; Morales, Marcelo M; Capelozzi, Vera L; Jamel, Nelson; Pelosi, Paolo; Rocco, Patricia R M; Garcia, Cristiane S N B

    2012-03-01

    We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI. Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24 h, animals were randomized into subgroups without or with intraabdominal hypertension (15 mmHg) and ventilated with positive end expiratory pressure = 5 cmH(2)O and tidal volume of 6 or 10 ml/kg during 1 h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1β, IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed. With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1β, IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume. Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.

  19. Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Hulya Uzkeser

    2012-01-01

    Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  20. Risk stratification of patients with combined acute pulmonary embolism and pulmonary hypertension using dynamic and regular pulmonary perfusion imaging

    International Nuclear Information System (INIS)

    Wang Xuemei; Wang Jing; Li Guohua; Wang Xiangcheng; Zhang Kaixiu; Liu Caiping

    2010-01-01

    Objective: To stratify the risks of patients with acute pulmonary embolism (APE) and pulmonary hypertension (PH) by dynamic pulmonary perfusion imaging (DPPI) and pulmonary perfusion imaging (PPI). Methods: From October 2007 to February 2009, 20 healthy volunteers (12 males, 8 females; mean age =48.47±13.47 years) and 31 APE patients (21 males, 10 females; mean age =47.68±18.06 years; from October 2007 to July 2009) were included in the study. DPPI and PPI were performed in all subjects. Percentage of perfusion defect scores (PPDs%) were calculated by semi-quantitative analysis of PPI. Risk levels were defined according to PPDs% calculated from PPI: normal (PPDs% =0); very low risk (0 60%). Lung equilibrium time (LET) was calculated on region of interest (ROI) drawn over DPPI. Clinical risk was scored by Aujesky method.The t-test, ANOVA and correlation analysis were used with SPSS 13.0 software. Results: (1) LET in healthy volunteers and APE patients was (12.18±3.28) and (32.90±14.29) s respectively (t = 6.81, P<0.01). (2) The correlation coefficient, coefficient of determination between LET and PPDs% in APE patients were 0.93 and 0.87, respectively. The correlation coefficient between LET and clinical risk score was 0.86. (3) The mean LET of APE patients in very low risk (n =5), low risk (n = 12), moderate risk (n=9), high risk (n=4) and very high risk groups (n=1) were (19.59 ±0.04), (25.03±0.08), (36.07±0.10), (57.15±0.06) and (70±0.00) s, respectively. There was significant difference among APE patients with different risk levels (F =16.78, P<0.01). Conclusions: (1) DPPI was a reliable, convenient and non-invasive method for the evaluation of PH in APE. (2) Combined LET of DPPI and PPDs% of PPI was valuable for risk stratification and prognosis estimation in APE patients. (authors)

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

    Science.gov (United States)

    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...

  2. Tocopherol Supplementation Reduces NO Production and Pulmonary Inflammatory Response to Bleomycin

    Science.gov (United States)

    Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S.; Gow, Andrew J.

    2013-01-01

    Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated. PMID:23669183

  3. Aortic dissection presenting with secondary pulmonary hypertension caused by compression of the pulmonary artery by dissecting hematoma: a case report

    International Nuclear Information System (INIS)

    Kim, Dong Hun; Ryu, Sang Wan; Choi, Yong Sun; Ahn, Byoung Hee

    2004-01-01

    The rupture of an acute dissection of the ascending aorta into the space surrounding the pulmonary artery is an uncommon occurrence. No previous cases of transient pulmonary hypertension caused by a hematoma surrounding the pulmonary artery have been documented in the literature. Herein, we report a case of acute aortic dissection presenting as secondary pulmonary hypertension

  4. Relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism: assessment with breath-hold SPECT-CT pulmonary angiography fusion images.

    Science.gov (United States)

    Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Tokuda, Osamu; Matsunaga, Naofumi

    2008-09-01

    The relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism (PTE) was comprehensively assessed on deep-inspiratory breath-hold (DIBrH) perfusion SPECT-computed tomographic pulmonary angiography (CTPA) fusion images. Subjects were 34 acute PTE patients, who had successfully performed DIBrH perfusion SPECT using a dual-headed SPECT and a respiratory tracking system. Automated DIBrH SPECT-CTPA fusion images were used to assess the relation between lung perfusion defects and intravascular clots detected by CTPA. DIBrH SPECT visualized 175 lobar/segmental or subsegmental defects in 34 patients, and CTPA visualized 61 intravascular clots at variable locations in 30 (88%) patients, but no clots in four (12%) patients. In 30 patients with clots, the fusion images confirmed that 69 (41%) perfusion defects (20 segmental, 45 subsegmental and 4 lobar defects) of total 166 defects were located in lung territories without clots, although the remaining 97 (58%) defects were located in lung territories with clots. Perfusion defect was absent in lung territories with clots (one lobar branch and three segmental branches) in four (12%) of these patients. In four patients without clots, nine perfusion defects including four segmental ones were present. Because of unexpected dissociation between intravascular clots and lung perfusion defects, the present fusion images will be a useful adjunct to CTPA in the diagnosis of acute PTE.

  5. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    DEFF Research Database (Denmark)

    Castellano, J M; Bentsen, A H; Romero, M

    2010-01-01

    , was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern......-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake...... and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center...

  6. Pulmonary manifestations of malaria

    International Nuclear Information System (INIS)

    Rauber, K.; Enkerlin, H.L.; Riemann, H.; Schoeppe, W.; Frankfurt Univ.

    1987-01-01

    We report on the two different types of pulmonary manifestations in acute plasmodium falciparum malaria. The more severe variant shows long standing interstitial pulmonary infiltrates, whereas in the more benign courses only short-term pulmonary edemas are visible. (orig.) [de

  7. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

    Science.gov (United States)

    Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

    2015-12-01

    Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

  8. [Acute pulmonary edema in adult caused by tonsillar hypertrophy following removal of laryngeal mask airway].

    Science.gov (United States)

    Iizuka, Toru; Shimoyama, Naohito; Notoya, Atsuko

    2010-12-01

    Negative pressure pulmonary edema (NPPE) has been described after acute airway obstruction. In the following case, we observed a rare occurrence of pulmonary edema caused by chronic tonsillar hypertrophy in a woman following removal of laryngeal mask airway (LMA). A 38-year-old woman with breast cancer underwent mastectomy under general anesthesia using the LMA. With the patient fully awake, the LMA was removed. Abruptly 7 minutes afterward, she showed signs of intense dyspnea, generalized rhonchus and progressive desaturation, and obstructive tonsillar hypertrophy was noticed. Acute lung edema was suspected and treatment started with oxygen therapy, bronchodilators, intravenous corticoids and loop diuretics. She was then intubated to secure airway and provide adequate ventilation with PEEP. Fortunately, the symptoms progressively remitted satisfactorily, and she was subsequently extubated 18 hours later with no complications. NPPE is an infrequent medical emergency and its early diagnosis and recognition are likely to lead to successful management of this potentially serious complication.

  9. Infection, inflammation and exercise in cystic fibrosis

    Science.gov (United States)

    2013-01-01

    Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF). Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health. In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF. PMID:23497303

  10. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-Yu

    2012-12-01

    Full Text Available Abstract Background Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE. Pulmonary Embolism Severity Index (PESI and simple PESI (sPESI are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events in APE patients, and compare between these two PESIs. Methods MEDLINE and EMBASE database were searched up to June 2012 using the terms “Pulmonary Embolism Severity Index” and “pulmonary embolism”. Summary odds ratio (OR with 95% confidence intervals (CIs for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC used to estimate overall predicting accuracies of prognostic outcomes. Results Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15, PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17 and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41, with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14, 0.09 (95% CI 0.03 to 0.26 and 0.40 (95% CI 0.31 to 0.51, respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16, 0.09 (95% CI 0.04 to 0.21, and 0.30 (95% CI 0.23 to 0.38, respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916, 0.411 (95% CI: 0.407 to 0.415, and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978, 0.374 (95% CI: 0.360 to 0.388, and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0

  11. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

    Science.gov (United States)

    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.

  12. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  13. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    Directory of Open Access Journals (Sweden)

    Huiying Liu

    2016-12-01

    Full Text Available Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1

  14. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury.

    Science.gov (United States)

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen; Bai, Changqing; Niu, Wenkai

    2016-01-01

    Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. It was found that the down-regulation of TNF- α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.

  15. Pulmonary Edema: Classification, Mechanisms of Development, Diagnosis

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2009-01-01

    Full Text Available Pulmonary edema remains a topical problem of modern reanimatology. In clinical practice, there is a need for continuous monitoring of the content of extravascular water in the lung and the pulmonary vascular permeability index for the timely detection and treatment of pulmonary edema. This literature review considers the minor mechanisms of pulmonary extravas-cular water exchange in health and in different types of pulmonary edema (acute lung injury, pneumonia, sepsis, postoperative period, burns, injuries etc., as well as the most accessible current (irradiation and dilution studies permitting an estimate of the level of pulmonary extravascular water and the pulmonary vascular permeability index in clinical practice. Key words: pulmonary edema, acute lung injury, pulmonary extravascular water, pulmonary vascular permeability index.

  16. A dual role for the immune response in a mouse model of inflammation-associated lung cancer

    OpenAIRE

    Dougan, Michael; Li, Danan; Neuberg, Donna; Mihm, Martin; Googe, Paul; Wong, Kwok-Kin; Dranoff, Glenn

    2011-01-01

    Lung cancer is the leading cause of cancer death worldwide. Both principal factors known to cause lung cancer, cigarette smoke and asbestos, induce pulmonary inflammation, and pulmonary inflammation has recently been implicated in several murine models of lung cancer. To further investigate the role of inflammation in the development of lung cancer, we generated mice with combined loss of IFN-γ and the β-common cytokines GM-CSF and IL-3. These immunodeficient mice develop chronic pulmonary in...

  17. Clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease experiencing frequent acute exacerbations

    Directory of Open Access Journals (Sweden)

    Prem Parkash Gupta

    2018-01-01

    Full Text Available Purpose: The present study aimed at clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease (COPD to anticipate future exacerbations. Methods: The study included 80 COPD patients; 40 patients had ≥2 acute exacerbations during preceding 1 year (frequent exacerbation [FECOPD] group and 40 patients had <2 acute exacerbations during preceding 1 year (infrequent exacerbation [I-FECOPD] group. Clinical profile, sputum microbiology, blood gas analysis, spirometric indices, and diffusion capacity (transfer test variables were assessed. Groups' comparison was performed using an independent t-test for numeric scale parameters and Chi-square test for nominal parameters. Pearson's and Spearman's correlation coefficients were derived for numeric scale parameters and numeric nominal parameters, respectively. Multinomial logistic regression analysis was done using SPSS software. Results: FECOPD group contained younger patients than in I-FECOPD group although the difference was not statistically significant. There was no significant difference between two groups regarding smoking pack-years and duration of illness. FECOPD group had significantly more expectoration score and Modified Medical Research Council dyspnea scores. Cough score and wheeze score did not differ significantly between two groups. More patients in FECOPD group (12/40 vs. 4/40 had lower airway bacterial colonization. Arterial blood gas parameters were more deranged in FECOPD group. Spirometric indices (forced expiratory volume during 1st s as well as transfer test (both diffusing capacity for carbon monoxide and transfer coefficient of the lung values were significantly reduced in FECOPD group. Conclusions: The patients in FECOPD group had clinical, spirometric, and transfer test profiling suggestive of a severe COPD phenotype, the recognition will help in predicting future exacerbations and a better management.

  18. Pulmonary exposure to carbonaceous nanomaterials and sperm quality

    DEFF Research Database (Denmark)

    Skovmand, Astrid; Lauvas, Anna Jacobsen; Christensen, Preben

    2018-01-01

    Background: Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung...... inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model.Methods: Effects on sperm quality after pulmonary inflammation induced by carbonaceous...... nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 mu g/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks...

  19. Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide

    International Nuclear Information System (INIS)

    Jakab, G.J.

    1987-01-01

    The effect of acute exposures to NO 2 on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. With S. aureus pulmonary antibacterial defenses were suppressed at NO 2 levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO 2 exposure prior to bacterial challenge) raised the threshold concentration for NO 2 -induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO 2 did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with 32 P-labeled staphylococci

  20. An Unusual Aneurysm of the Main Pulmonary Artery Presenting as Acute Coronary Syndrome

    International Nuclear Information System (INIS)

    Kholeif, Mona A.; El Tahir, Mohamed; Kholeif, Yasser A.; El Watidy, Ahmed

    2006-01-01

    A 70-year old man presented with retrosternal chest pain. His electrocardiogram showed nonspecific T wave changes. Cardiac-specific troponin I (cTnI) was elevated. His condition was managed as acute coronary syndrome, following which he had two minor episodes of hemoptysis. A CT pulmonary angiogram showed no evidence of pulmonary embolism, but a large mass lesion was seen in the mediastinum. Echocardiography and cardiac MRI demonstrated a large solid mass, arising from the right ventricular outflow tract and causing compression of the main pulmonary artery (MPA). The differential diagnosis included pericardial and myocardial tumors and clotted aneurysm of the MPA. At surgery, a clotted aneurysmal sac was identified originating from the MPA and the defect was healed. Aneurysms of the MPA are rare. They most commonly present with dyspnea and chest pain. Compression of surrounding structures produces protean manifestations. A high index of suspicion coupled with imaging modalities establishes the diagnosis. Blunt trauma to the chest, at the time of an accident 4 years previously, may explain this aneurysm. The patient's presentation with chest pain was probably due to compression and/or stretching of surrounding structures. Coronary artery compression simulating acute coronary syndrome has been documented in the literature. The rise in cTnI may have been due to right ventricular strain, as a result of right ventricular outflow obstruction by the aneurysm. This has not been reported previously in the literature. The saccular morphology and narrow neck of the aneurysm predisposed to stagnation leading to clotting of the lumen and healing of the tear, which caused the diagnostic difficulty

  1. Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury

    Science.gov (United States)

    Li, Ji-Guo; Lin, Jia-Ji; Wang, Zhao-Ling; Cai, Wen-Ke; Wang, Pei-Na; Jia, Qian; Zhang, An-Sheng; Wu, Gao-Yi; Zhu, Guo-Xiong; Ni, Long-Xing

    2015-01-01

    Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1β, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1β in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1β and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that

  2. Comparative effects of acute O/sub 2/ breathing and terbutaline in patients with chronic obstructive pulmonary disease. A combined hemodynamic and radionuclide study

    Energy Technology Data Exchange (ETDEWEB)

    Tschopp, J M; Gabathuler, J; Righetti, A; Junod, A F

    1985-01-01

    The acute effects of terbutaline (T) and breathing 100% O/sub 2/(O/sub 2/) on gas exchange, pulmonary hemodynamics and radionuclide angiography were evaluated in 15 patients with severe chronic obstructive pulmonary disease (COPD). O/sub 2/ breathing resulted in a decrease in mean pulmonary artery pressure (PAP) and cardiac index (CI) without changing pulmonary vascular resistance index (PVRI) or right and left ventricular ejection fractions (RVEF,LVEF). On the other hand, T administration was followed by a decrease in PVRI, and increase in CI, RVEF and LVEF. These effects of T were maintained during exercise. Although RVEF was inversely correlated with basal levels of PAP or PVRI, acute changes in pulmonary hemodynamics were not correlated with significant changes on RVEF. These results suggest that T may be useful in the treatment of patients with COPD prone to develop cor pulmonale. However, the long-term benefit of this treatment remains to be established.

  3. Acute Pulmonary Edema Associated With Propofol: An Unusual Complication

    Directory of Open Access Journals (Sweden)

    Mian Adnan Waheed

    2014-11-01

    Full Text Available Propofol is frequently used in the emergency department to provide procedural sedation for patients undergoing various procedures and is considered to be safe when administered by trained personnel. Pulmonary edema after administration of propofol has rarely been reported. We report a case of a 23-year-old healthy male who developed acute cough, hemoptysis and hypoxia following administration of propofol for splinting of a foot fracture. Chest radiography showed bilateral patchy infiltrates. The patient was treated successfully with supportive care. This report emphasizes the importance of this potentially fatal propofol-associated complication and discusses possible underlying mechanisms and related literature. [West J Emerg Med. 2014;15(7:–0.

  4. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

  5. Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

    International Nuclear Information System (INIS)

    Okada, Fumito; Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu

    2009-01-01

    The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

  6. Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Fumito [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan); Oita University Faculty of Medicine, Department of Radiology, Oita (Japan); Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan)

    2009-04-15

    The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

  7. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

    Science.gov (United States)

    Chen, Wenling; Marvizón, Juan Carlos G.

    2009-01-01

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

  8. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

    Science.gov (United States)

    Chen, W; Marvizón, J C G

    2009-06-16

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

  9. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

    2015-11-15

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  10. Mesoporous carbon nanomaterials induced pulmonary surfactant inhibition, cytotoxicity, inflammation and lung fibrosis.

    Science.gov (United States)

    Chen, Yunan; Yang, Yi; Xu, Bolong; Wang, Shunhao; Li, Bin; Ma, Juan; Gao, Jie; Zuo, Yi Y; Liu, Sijin

    2017-12-01

    Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials (MCNs) is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics, energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774A.1 macrophages and lung epithelial A549 cells. Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs. Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis. Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial. Copyright © 2017. Published by Elsevier B.V.

  11. Can a chronic disease management pulmonary rehabilitation program for COPD reduce acute rural hospital utilization?

    Science.gov (United States)

    Rasekaba, T M; Williams, E; Hsu-Hage, B

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) imposes a costly burden on healthcare. Pulmonary rehabilitation (PR) is the best practice to better manage COPD to improve patient outcomes and reduce acute hospital care utilization. To evaluate the impact of a once-weekly, eight-week multidisciplinary PR program as an integral part of the COPD chronic disease management (CDM) Program at Kyabram District Health Services. The study compared two cohorts of COPD patients: CDM-PR Cohort (4-8 weeks) and Opt-out Cohort (0-3 weeks) between February 2006 and March 2007. The CDM-PR Program involved multidisciplinary patient education and group exercise training. Nonparametric statistical tests were used to compare acute hospital care utilization 12 months before and after the introduction of CDM-PR. The number of patients involved in the CDM-PR Cohort was 29 (n = 29), and that in the Opt-out Cohort was 24 (n = 24). The CDM-PR Cohort showed significant reductions in cumulative acute hospital care utilization indicators (95% emergency department presentations, 95% inpatient admissions, 99% length of stay; effect sizes = 0.62-0.66, P 0.05). Total costs associated with the hospital care utilization decreased from $130,000 to $7,500 for the CDM-PR Cohort and increased from $77,700 to $101,200 for the Opt-out Cohort. Participation in the CDM-PR for COPD patients can significantly reduce acute hospital care utilization and associated costs in a small rural health service.

  12. Risk-Adapted Management of Acute Pulmonary Embolism: Recent Evidence, New Guidelines

    Directory of Open Access Journals (Sweden)

    Anja Käberich

    2014-10-01

    Full Text Available Venous thromboembolism (VTE, the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE. Risk stratification is increasingly recognized as a cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function and laboratory biomarkers (indicative of myocardial stress or injury for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.

  13. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

    Science.gov (United States)

    Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

    2012-02-01

    Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. Fundamentals of management of acute postoperative pulmonary hypertension.

    Science.gov (United States)

    Taylor, Mary B; Laussen, Peter C

    2010-03-01

    In the last several years, there have been numerous advancements in the field of pulmonary hypertension as a whole, but there have been few changes in the management of children with pulmonary hypertension after cardiac surgery. Patients at particular risk for postoperative pulmonary hypertension can be identified preoperatively based on their cardiac disease and can be grouped into four broad categories based on the mechanisms responsible for pulmonary hypertension: 1) increased pulmonary vascular resistance; 2) increased pulmonary blood flow with normal pulmonary vascular resistance; 3) a combination of increased pulmonary vascular resistance and increased blood flow; and 4) increased pulmonary venous pressure. In this review of the immediate postoperative management of pulmonary hypertension, various strategies are discussed including medical therapies, monitoring, ventilatory strategies, and weaning from these supports. With early recognition of patients at particular risk for severe pulmonary hypertension, management strategies can be directed at preventing or minimizing hemodynamic instability and thereby prevent the development of ventricular dysfunction and a low output state.

  15. Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

    DEFF Research Database (Denmark)

    Hawkins, Nathaniel M; Huang, Zhen; Pieper, Karen S

    2009-01-01

    ) events associated with chronic obstructive pulmonary disease in 14 703 patients with acute MI enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) trial. Cox proportional hazards models were used to evaluate the relationship between chronic obstructive pulmonary disease and CV outcomes...

  16. Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

    2018-04-01

    There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated

  17. Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

    Science.gov (United States)

    Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

    2003-02-01

    Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the

  18. Pulmonary Artery Dissection: A Fatal Complication of Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Chuanchen Zhang

    2016-01-01

    Full Text Available Pulmonary artery dissection is extremely rare but it is a really life-threatening condition when it happens. Most patients die suddenly from major bleeding or tamponade caused by direct rupture into mediastinum or retrograde into the pericardial sac. What we are reporting is a rare case of a 46-year-old female patient whose pulmonary artery dissection involves both the pulmonary valve and right pulmonary artery. The patient had acute chest pain and severe dyspnea, and the diagnosis of pulmonary artery dissection was confirmed by ultrasonography and CT angiography. Moreover, its etiology, clinical manifestations, and management are also discussed in this article.

  19. Targeting pro-resolution pathways to combat chronic inflammation in COPD.

    Science.gov (United States)

    Bozinovski, Steven; Anthony, Desiree; Vlahos, Ross

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. Paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise COPD airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. Excessive production of leukocyte mobilising cytokines such as CXCL8 (IL-8) and leukotriene B4 (LTB4) in response to environmental stimuli (cigarette smoke and microbial products) are thought to maintain chronic inflammation, in conjunction with inefficient macrophage clearance of microbes and apoptotic neutrophils. In this perspective, we discuss an alternative view on why inflammation persists with a focus on why pro-resolution mediators such as lipoxin A4 (LXA4), D-series resolving and Annexin A1 fail to effectively switch off inflammation in COPD. These pro-resolving mediators converge on the G-protein coupled receptor, ALX/FPR2. This receptor is particularly relevant to COPD as the complex milieu of exogenous and host-derived mediators within the inflamed airways include agonists that potently activate ALX/FPR2, including Serum Amyloid A (SAA) and the cathelicidin, LL-37. There is emerging evidence to suggest that ALX/FPR2 can exist in alternative receptor conformations in an agonist-biased manner, which facilitates alternate functional receptor behaviors. Hence, the development of more stable pro-resolving analogs provides therapeutic opportunities to address ALX/FPR2 conformations to counteract pathogenic signaling and promote non-phlogistic clearance pathways essential for resolution of inflammation.

  20. Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

    Science.gov (United States)

    Akosman, Cengiz; Ordu, Cetin; Eroglu, Elif; Oyan, Basak

    2015-01-01

    Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.

  1. A Rare Cause of Pulmonary Nodules

    Directory of Open Access Journals (Sweden)

    Michael Tsuyoshi Chew

    2016-10-01

    Full Text Available Crohn’s disease is a chronic, idiopathic autoimmune disorder that primarily targets the gastrointestinal (GI system. It is characterized by transmural inflammation of the GI tract that can occur anywhere from the mouth to the anus. Not infrequently, the disease may also have extraintestinal manifestations (EIMs that can affect almost any organ system. It is estimated that EIMs affect up to 36% of patients with Crohn’s disease, but the incidence and prevalence of pulmonary involvement are variable in the literature and may be as low as 0.4%. There are few case reports documenting pulmonary manifestations, as they are often overlooked, especially if respiratory symptoms are present before the diagnosis of GI manifestations, as in the present case. A 44-year-old otherwise healthy woman presented with nonspecific respiratory complaints, recurrent pneumonias, and multiple computed tomography images showing diffuse, migratory, nodular, and consolidative parenchymal lung disease, with a largely unremarkable infectious and rheumatologic evaluation. Lung biopsy revealed necrotizing and nonnecrotizing granulomas, raising concern for sarcoidosis. Subsequent imaging revealed an incidental mass in the cecum. Biopsy of the cecum lesion revealed acute cryptitis, crypt abscess, and a single poorly formed granuloma, suggesting the possibility of Crohn’s disease. In this report, we present a patient whose pulmonary manifestations ultimately led to the diagnosis of Crohn’s disease.

  2. Lung inflammation caused by inhaled toxicants: a review

    Directory of Open Access Journals (Sweden)

    Wong J

    2016-06-01

    Full Text Available John Wong, Bruce E Magun, Lisa J Wood School of Nursing, MGH Institute of Health Professions, Boston, MA, USA Abstract: Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials and those of heavy metals (from paint are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7 may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. Keywords: cigarette, mycotoxin, trichothecene, ricin, inflammasome, macrophage, inhibitors

  3. Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome.

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    Rong Li

    Full Text Available Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1 control group; (2 SA (stable angina group; and (3 ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day and high-statin (atorvastatin, 20 mg/kg/day group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

  4. The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.

    Science.gov (United States)

    Simarro, Maria; Giannattasio, Giorgio; Xing, Wei; Lundequist, Emma-Maria; Stewart, Samantha; Stevens, Richard L; Orduña, Antonio; Boyce, Joshua A; Anderson, Paul J

    2012-08-30

    T-cell intracellular antigen-1 (TIA-1) is a translational repressor that dampens the production of proinflammatory cytokines and enzymes. In this study we investigated the role of TIA-1 in a mouse model of pulmonary inflammation induced by exposure to the allergenic extract (Df) of the house dust mite Dermatophagoides farinae. When intranasally challenged with a low dose of Df, mice lacking TIA-1 protein (Tia-1(-/-)) showed more severe airway and tissue eosinophilia, infiltration of lung bronchovascular bundles, and goblet cell metaplasia than wild-type littermates. Tia-1(-/-) mice also had higher levels of Df-specific IgE and IgG(1) in serum and ex vivo restimulated Tia-1(-/-) lymph node cells and splenocytes transcribed and released more Th2/Th17 cytokines. To evaluate the site of action of TIA-1, we studied the response to Df in bone marrow chimeras. These experiments revealed that TIA-1 acts on both hematopoietic and non-hematopoietic cells to dampen pulmonary inflammation. Our results identify TIA-1 as a negative regulator of allergen-mediated pulmonary inflammation in vivo. Thus, TIA-1 might be an important player in the pathogenesis of bronchial asthma. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Cardiovascular parameters to assess the severity of acute pulmonary embolism with computed tomography

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    Dian-Jiang Zhao; Da-Qing Ma; Wen He; Jian-Jun Wang; Yan Xu; Chun-Shuang Guan (Dept. of Radiology, Beijing Friendship Hospital, Capital Medical Univ., Beijing (China)), e-mail: madaqing@263.net

    2010-05-15

    Background: Computed tomographic pulmonary angiography (CTPA) has been established as a first-line test in the acute pulmonary embolism (APE) diagnostic algorithm, but the assessment of the severity of APE by this method remains to be explored. Purpose: To retrospectively evaluate right ventricular (RV) dysfunction and severity in patients with APE without underlying cardiopulmonary disease using helical computed tomography (CT). Material and Methods: Seventy-three patients (35 men and 38 women) were divided into two groups according to the clinical findings: severe APE (n=22) and non-severe APE (n=51). Pulmonary artery CT obstruction index was calculated according to the location and degree of clots in the pulmonary arteries. Cardiovascular parameters including RV short axis and left ventricular (LV) short axis, RV short axis to LV short axis (RV/LV) ratio, main pulmonary artery, azygous vein, and superior vena cava diameters were measured. Leftward bowing of the interventricular septum, reflux of contrast medium into the inferior vena cava and azygous vein, and bronchial artery dilatation were also recorded. The results were analyzed by Mann-Whitney U test, x2 test, Spearman's rank correlation coefficient, and the area under the receiver operating characteristic curve (Az). Results: CT obstruction index in patients with severe APE (median 43%) was higher than that of patients with non-severe APE (median 20%). Comparison of cardiovascular parameters between patients with severe and non-severe pulmonary embolism showed significant differences in RV short axis, LV short axis, RV/LV ratio, RV wall thickness, main pulmonary artery diameter, azygous vein diameter, leftward bowing of the interventricular septum, and bronchial artery dilatation. The correlation between CT obstruction indexes and cardiovascular parameters was significant. Spearman's rank correlation coefficient was highest between RV/LV ratio and CT obstruction index. Az values were

  6. Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

    2013-06-01

    In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

  7. The relation between international normalized ratio and mortality in acute pulmonary embolism: A retrospective study.

    Science.gov (United States)

    Kırış, Tuncay; Yazıcı, Selcuk; Durmuş, Gündüz; Çanga, Yiğit; Karaca, Mustafa; Nazlı, Cem; Dogan, Abdullah

    2018-01-01

    Acute pulmonary embolism (PE) is a serious clinical disease characterized by a high mortality rate. The aim of this study was to assess the prognostic value of international normalized ratio (INR) in acute PE patients not on anticoagulant therapy. The study included 244 hospitalized acute PE patients who were not receiving previous anticoagulant therapy. Based on their 30-day mortality, patients were categorized as survivors or non-survivors. INR was measured during the patients' admission, on the same day as the diagnosis of PE but before anticoagulation started. Thirty-day mortality occurred in 39 patients (16%). INR was higher in non-survivors than in survivors (1.3±0.4 vs 1.1±0.3, P=.003). In multivariate analysis, INR (HR: 3.303, 95% CI: 1.210-9.016, P=.020) was independently associated with 30-day mortality from PE. Inclusion of INR in a model with simplified pulmonary embolism severity index (sPESI) score improved the area under the receiver operating characteristics (ROC) curve from 0.736 (95% CI: 0.659-0.814) to 0.775 (95% CI: 0.701-0.849) (P=.028). Also, the addition of INR to sPESI score enhanced the net reclassification improvement (NRI=8.8%, P<.001) and integrated discrimination improvement (IDI=0.043, P=.027). Elevated INR may have prognostic value for 30-day mortality in acute PE patients not on anticoagulation. Combining INR with sPESI score improved the predictive value for all-cause mortality. However, further large-scale studies are needed to confirm it's prognostic role. © 2017 Wiley Periodicals, Inc.

  8. Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice.

    Science.gov (United States)

    Oostwoud, L C; Gunasinghe, P; Seow, H J; Ye, J M; Selemidis, S; Bozinovski, S; Vlahos, R

    2016-02-15

    Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.

  9. Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Katja Lakota

    Full Text Available Inflammation in systemic sclerosis (SSc is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA, a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

  10. Potential contribution of phenotypically modulated smooth muscle cells and related inflammation in the development of experimental obstructive pulmonary vasculopathy in rats.

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    Shoichiro Otsuki

    Full Text Available We tested the hypothesis that phenotypically modulated smooth muscle cells (SMCs and related inflammation are associated with the progression of experimental occlusive pulmonary vascular disease (PVD. Occlusive PVD was induced by combined exposure to a vascular endothelial growth factor receptor tyrosine kinase inhibitor Sugen 5416 and hypobaric hypoxia for 3 weeks in rats, which were then returned to ambient air. Hemodynamic, morphometric, and immunohistochemical studies, as well as gene expression analyses, were performed at 3, 5, 8, and 13 weeks after the initial treatment (n = 78. Experimental animals developed pulmonary hypertension and right ventricular hypertrophy, and exhibited a progressive increase in indices of PVD, including cellular intimal thickening and intimal fibrosis. Cellular intimal lesions comprised α smooth muscle actin (α SMA+, SM1+, SM2+/-, vimentin+ immature SMCs that were covered by endothelial monolayers, while fibrous intimal lesions typically included α SMA+, SM1+, SM2+, vimentin+/- mature SMCs. Plexiform lesions comprised α SMA+, vimentin+, SM1-, SM2- myofibroblasts covered by endothelial monolayers. Immature SMC-rich intimal and plexiform lesions were proliferative and were infiltrated by macrophages, while fibrous intimal lesions were characterized by lower proliferative abilities and were infiltrated by few macrophages. Compared with controls, the number of perivascular macrophages was already higher at 3 weeks and progressively increased during the experimental period; gene expression of pulmonary hypertension-related inflammatory molecules, including IL6, MCP1, MMP9, cathepsin-S, and RANTES, was persistently or progressively up-regulated in lungs of experimental animals. We concluded that phenotypically modulated SMCs and related inflammation are potentially associated with the progression of experimental obstructive PVD.

  11. The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Price, Laura C; Dimopoulos, Konstantinos; Marino, Philip; Alonso-Gonzalez, Rafael; McCabe, Colm; Kemnpy, Aleksander; Swan, Lorna; Boutsikou, Maria; Al Zahrani, Ahmed; Coghlan, Gerry J; Schreiber, Benjamin E; Howard, Luke S; Davies, Rachel; Toshner, Mark; Pepke-Zaba, Joanna; Church, Alistair C; Peacock, Andrew; Corris, Paul A; Lordan, James L; Gaine, Sean; Condliffe, Robin; Kiely, David G; Wort, Stephen John

    2017-11-01

    Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten

    2009-01-01

    in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...... receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect....

  13. Pulseless electrical activity in acute massive pulmonary embolism during thrombolytic therapy

    Directory of Open Access Journals (Sweden)

    Han-Hua Yu

    2017-01-01

    Full Text Available We report a case of acute pulmonary embolism with hemodynamic instability diagnosed by a computed tomography pulmonary angiogram. The patient developed pulseless electrical activity during systemic thrombolytic therapy with recombinant tissue plasminogen activator. Successful return of spontaneous circulation was achieved after immediate cardiopulmonary resuscitation with chest compressions for 6 min. His electrocardiogram (ECG on arrival in the emergency department displayed sinus tachycardia, an S wave in lead I, a Q wave in lead III, incomplete right bundle branch block (RBBB, T-wave inversion (TWI in leads V1–V3, ST elevation in leads aVR and V1, and ST depression in leads I, II, III, aVF, and V4–V6. These characteristic ECG changes might have prognostic value for clinical deterioration. He recovered after treatment. After discharge, the ECG showed resolution of TWI in leads V1–V3 and incomplete RBBB, suggesting recovery from right ventricular dysfunction, which was confirmed by an echocardiogram on follow in the outpatient department.

  14. Diagnostic and therapeutic considerations in acute, severe mitral regurgitation: experience in 42 consecutive patients entering the intensive care unit with pulmonary edema.

    Science.gov (United States)

    Horstkotte, D; Schulte, H D; Niehues, R; Klein, R M; Piper, C; Strauer, B E

    1993-09-01

    Forty-two consecutive patients received emergency treatment for acute mitral insufficiency causing pulmonary edema between 1984 and 1992. The underlying diagnoses were acute myocardial infarction (n = 21), acute bacterial endocarditis on the native mitral valve (n = 9), prosthetic endocarditis in the mitral position (n = 4), acute failure of a replacement valve (n = 5), blunt chest trauma (n = 1) and chordal rupture in Marfan's syndrome (n = 2). Dysfunction of the subvalvular apparatus was present in 24 patients, verified by transthoracic echocardiography in 18 (75%) and by transoesophageal echocardiography in all patients in whom this technique was used. There were four cases of outflow strut fracture of a Björk-Shiley mitral prosthesis; a reliable diagnosis was made by fluoroscopy in all patients. Bedside hemodynamic monitoring was found to be unreliable both for differential diagnosis and for the quantitative assessment of the degree of mitral insufficiency. The right ventricular filling pressure was normal in 32/39 patients (82%), and the pulmonary artery and pulmonary capillary pressures elevated in 37/39 (95%). Diagnostically important, high pulmonary capillary v-waves were documented in 13 patients (33%). The left ventricular impedance could be influenced with sodium nitroprussid combined in some cases with dobutamin, and the resultant decrease of the peripheral vascular resistance from 1480 +/- 222 to 702 +/- 86 dyn x sec x cm-5 was followed by a proportionate reduction in the transmitral regurgitant fraction. Three patients died prior to the intended emergency surgical intervention. Emergency surgery was completed in 21 patients with an early mortality of 23.8% (n = 5). Ten patients underwent elective surgery within, and another three later than one year from the onset of the acute symptoms with an early mortality of 7.7% (n = 1). Four patients are alive and clinically well with medical treatment alone.

  15. Acute exacerbations of chronic obstructive pulmonary disease provide a unique opportunity to take care of patients

    Directory of Open Access Journals (Sweden)

    Bianca Beghé

    2013-04-01

    Full Text Available Exacerbation of chronic obstructive pulmonary disease (ECOPD identifies the acute phase of COPD. The COPD patient is often frail and elderly with concomitant chronic diseases. This requires the physician not only looks at specific symptoms or organs, but to consider the patient in all his or her complexity.

  16. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    ) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18......Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP...

  17. Extravascular lung water and pulmonary arterial wedge pressure for fluid management in patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Hu, Wei; Lin, Chang-Wen; Liu, Bing-Wei; Hu, Wei-Hang; Zhu, Ying

    2014-01-16

    Extravascular lung water (EVLW) is a sensitive prognostic indicator of pulmonary edema. Thus, EVLW may be an advantageous method of fluid management. This study aims to evaluate the outcomes of using EVLW and pulmonary artery wedge pressure (PAWP) as strategies for fluid management in patients with acute respiratory distress syndrome (ARDS). Twenty-nine patients were randomly divided into the EVLW and PAWP groups. The survival rate, ICU (Intensive Care Unit) length of stay, duration of mechanical ventilation, acute lung injury scores, and oxygenation index of the EVLW and PAWP groups were compared. No significant difference in the survival rates at 28 and 60 days (d) after treatment was found between the two groups (p = 0.542). The duration of mechanical ventilation and ICU length of stay were significantly lower (p management improved clinical results in patients with ARDS better than PAWP.

  18. Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

    Science.gov (United States)

    McCurdy, BR

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  19. High-voltage zones within the pulmonary vein antra: Major determinants of acute pulmonary vein reconnections after atrial fibrillation ablation.

    Science.gov (United States)

    Nagashima, Koichi; Watanabe, Ichiro; Okumura, Yasuo; Iso, Kazuki; Takahashi, Keiko; Watanabe, Ryuta; Arai, Masaru; Kurokawa, Sayaka; Nakai, Toshiko; Ohkubo, Kimie; Yoda, Shunichi; Hirayama, Atsushi

    2017-08-01

    Recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) is mainly due to PV reconnections. Patient-specific tissue characteristics that may contribute remain unidentified. This study aimed to assess the relationship between the bipolar electrogram voltage amplitudes recorded from the PV-left atrial (LA) junction and acute PV reconnection sites. Three-dimensional LA voltage maps created before an extensive encircling PVI in 47 AF patients (31 men; mean age 62 ± 11 years) were examined for an association between the EGM voltage amplitude recorded from the PV-LA junction and acute post-PVI PV reconnections (spontaneous PV reconnections and/or ATP-provoked dormant PV conduction). Acute PV reconnections were observed in 17 patients (36%) and in 24 (3%) of the 748 PV segments (16 segments per patient) and were associated with relatively high bipolar voltage amplitudes (3.26 ± 0.85 vs. 1.79 ± 1.15 mV, p voltage (137 [106, 166] vs. 295 [193, 498] gs/mV, p voltage and FTI/PV-LA bipolar voltage for acute PV reconnections (areas under the curve: 0.86 and 0.89, respectively); the best cutoff values were >2.12 mV and ≤183 gs/mV, respectively. The PV-LA voltage on the PV-encircling ablation line and FTI/PV-LA voltage were related to the acute post-PVI PV reconnections. A more durable ablation strategy is warranted for high-voltage zones.

  20. Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van Geffen WH

    2018-04-01

    Full Text Available Wouter H van Geffen,1,2 Huib AM Kerstjens2 1Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands; 2Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands Background: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD (AECOPD, but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. Methods: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state at least 42 days later: inspiratory capacity (IC, body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. Results: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01. Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01, and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01. Conclusion: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase. Keywords: COPD, exacerbations of COPD, static hyperinflation, dynamic hyperinflation, severe acute exacerbations of COPD, COPD exacerbation, chronic obstructive pulmonary disease

  1. Pulmonary complications of induction therapy for acute myeloid leukemia in adults. Findings of chest X-rays and computed tomography

    International Nuclear Information System (INIS)

    Kirchner, J.; Huettmann, C.; Jacobi, V.; Boehme, A.

    1998-01-01

    To exclude pulmonary complications, 359 chest radiographs and 50 computed tomographs of the lung were performed in 95 patients suffering from acute myeloid leukemia. The radiological findings were registered, described and correlated with clinical findings in the present study on 2395 days of observation. Results: In summary, 52 patients showed alterations of the lung. Pulmonary hyperhydration was seen in 21 cases, bacterial pneumonia was found in 18 cases, invasive pulmonary aspergillosis was documented in 14 cases, and 5 cases of severe haemorrhage were seen. An unexplained pulmonary edema in 13 patients with interstitial and alveolar infiltrates is considered to be a complication of treatment with cytosine-arabinoside. Conclusion: The results demonstrate that chest X-ray and computed tomography have a high impact in detection and treatment of pulmonary complications following intensive chemotherapy. We may expect the development of diffuse opacity following administration of cytosine-arabinoside in medium-sized doses. (orig.) [de

  2. Pathmorphological investigation of pulmonary infections complications in persons dying from acute radiation sickness after Chernobyl accident

    International Nuclear Information System (INIS)

    Vlasov, P.A.; Kvacheva, Yu.E.

    1993-01-01

    Lungs of 27 persons who participated in liquidation of Chernobyl accident and died from acute radiation sickness were studied histologically. Pulmonary infections were found, including invasion of viral, bacterial and fungal agents. Being depended on hematopoietic function the inflammatory reactions were areactive during postirradiation aplasia and became typical within the recovery beginning

  3. Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

    Science.gov (United States)

    Pillon Barcelos, Rômulo; Freire Royes, Luiz Fernando; Gonzalez-Gallego, Javier; Bresciani, Guilherme

    2017-02-01

    The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

  4. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  5. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  6. Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failure in Trauma and Critical Illness

    Science.gov (United States)

    2017-10-01

    models ); • clinical interventions; • new business creation; and • other. Nothing to report. Nothing to report. Nothing to report. 17...AWARD NUMBER: W81XWH-14-1-0376 TITLE: Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failgure in Trauma...COVERED 22 Sep 2016 - 21 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Acute Pancreatitis as a Model to Predict Transition of Systemic

  7. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

    DEFF Research Database (Denmark)

    Poulsen, Sarah Søs; Knudsen, Kristina Bram; Jackson, Petra

    2017-01-01

    of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saal and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater...... and lasted longer than hepatic Saal mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas...... limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length...

  8. Prognostic stratification of acute pulmonary embolism: Focus on clinical aspects, imaging, and biomarkers

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2009-07-01

    Full Text Available Luca Masotti1, Marc Righini2, Nicolas Vuilleumier3, Fabio Antonelli4, Giancarlo Landini5, Roberto Cappelli6, Patrick Ray71Internal Medicine, 4Clinical Chemistry, Cecina Hospital, Cecina, Italy; 2Division of Angiology and Haemostasis, Department of Internal Medicine, Geneva University Hospital, Switzerland; 3Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals and University of Geneva, Switzerland; 5Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy; 6Thrombosis Center, University of Siena, Siena, Italy; 7Department of Emergency Medicine, Centre Hospitalo-Universitaire Pitié-Salpêtrière, UPMC Paris 6, Paris, FranceAbstract: Pulmonary embolism (PE represents a common disease in emergency medicine and guidelines for diagnosis and treatment have had wide diffusion. However, PE morbidity and mortality remain high, especially when associated to hemodynamic instability or right ventricular dysfunction. Prognostic stratification to identify high risk patients needing to receive more aggressive pharmacological and closer monitoring is of utmost importance. Modern guidelines for management of acute PE are based on risk stratification using either clinical, radiological, or laboratory findings. This article reviews the modern treatment of acute PE, which is customized upon patient prognosis. Accordingly the current risk stratification tools described in the literature such as clinical scores, echocardiography, helical computer tomography, and biomarkers will be reviewed.Keywords: pulmonary embolism, prognosis, troponin, BNP, NT-proBNP, echocardiography, computer tomography

  9. Alterations in the expression of the NF-κB family member RelB as a novel marker of cardiovascular outcomes during acute exacerbations of chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Laura Labonté

    Full Text Available Chronic obstructive pulmonary disease (COPD exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-κB activation. RelB, an NF-κB family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown. Moreover, there is no information on its association with clinical features of COPD. The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation.Data from 48 COPD patients were analyzed. Blood samples were collected from stable-state and exacerbating patients. After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR was performed to assess RelB, Cox-2, IL-8 and IL-1β mRNA expression and their associations with measured clinical variables.Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation. RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1β in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22. Cox-2, IL-8 and IL-1β were significantly associated with clinical features of patients in both stable-state and at exacerbation. There was no association with RelB expression and any clinical features in COPD subjects at stable-state. RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation.RelB mRNA expression is lower than that of the other inflammatory mediators. Expression of Cox-2, IL-8 and IL-1β were related to clinical features in both stable-state and at exacerbation. However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD.

  10. IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema.

    Science.gov (United States)

    Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W; Cua, Daniel J; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko

    2016-11-01

    We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23 -/- ) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23 -/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23 -/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

  11. HRCT in AIDS patients presenting with acute pulmonary conditions

    International Nuclear Information System (INIS)

    Diehl, S.J.; Lehmann, K.J.; Georgi, M.; Thienel, F.

    1997-01-01

    Purpose: The purpose of this study was to assess the clinical value of HRCT of the lung in patients with known HIV-infection and acute lung disease. In a prospective study a HRCT was performed in 31 patients infected with the HIV-1 virus, mainly stage C (CDC), who had acute pulmonary symptoms. Precondition for the HRCT examination was a normal or non-specific chest radiograph. A provoked sputum as well as bronchoscopy with bronchoalveolar lavage and/or transbronchial biopsy were performed concurrently. In 24 out of 31 cases a pathogenic organism was identified. 19 of these 24 patients showed abnormal HRCT findings. The most frequent pathogenic organism was Pneumocystis carinii (n=12). 9 out of these 12 patients (75%) showed pathological HRCT findings consisting of ground-glass opacity. Specific patterns of attenuation could not be worked out except for Pneumocystis carinii infection. Compared to bronchoalveolar lavage, the diagnostic value of HRCT is inferior; it is however helpful in the early stage of disease, when the pathogenic organism has not yet been identified, HRCT may demonstrate parenchymal abnormalities in patients with normal radiographic findings. Compared to bronchoalveolar lavage and induced sputum, HRCT can provide conclusive results within a short time. (orig.) [de

  12. Practical use, effects and complications of prehospital treatment of acute cardiogenic pulmonary edema using the Boussignac CPAP system

    NARCIS (Netherlands)

    E.E. Spijker (Eva Eiske); M. De Bont (Maarten); M. Bax (Matthijs); M. Sandel (Maro)

    2013-01-01

    textabstractBackground: Early use of continuous positive airway pressure (CPAP) has been shown to be beneficial within the setting of acute cardiogenic pulmonary edema (ACPE). The Boussignac CPAP system (BCPAP) was therefore introduced into the protocols of emergency medical services (EMS) in a

  13. Role of ventilation scintigraphy in diagnosis of acute pulmonary embolism: an evaluation using artificial neural networks

    International Nuclear Information System (INIS)

    Evander, Eva; Holst, Holger; Jaerund, Andreas; Wollmer, Per; Edenbrandt, Lars; Ohlsson, Mattias; Aastroem, Karl

    2003-01-01

    The purpose of this study was to assess the value of the ventilation study in the diagnosis of acute pulmonary embolism using a new automated method. Either perfusion scintigrams alone or two different combinations of ventilation/perfusion scintigrams were used as the only source of information regarding pulmonary embolism. A completely automated method based on computerised image processing and artificial neural networks was used for the interpretation. Three artificial neural networks were trained for the diagnosis of pulmonary embolism. Each network was trained with 18 automatically obtained features. Three different sets of features originating from three sets of scintigrams were used. One network was trained using features obtained from each set of perfusion scintigrams, including six projections. The second network was trained using features from each set of (joint) ventilation and perfusion studies in six projections. A third network was trained using features from the perfusion study in six projections combined with a single ventilation image from the posterior view. A total of 1,087 scintigrams from patients with suspected pulmonary embolism were used for network training. The test group consisted of 102 patients who had undergone both scintigraphy and pulmonary angiography. Performances in the test group were measured as area under the receiver operation characteristic curve. The performance of the neural network in interpreting perfusion scintigrams alone was 0.79 (95% confidence limits 0.71-0.86). When one ventilation image (posterior view) was added to the perfusion study, the performance was 0.84 (0.77-0.90). This increase was statistically significant (P=0.022). The performance increased to 0.87 (0.81-0.93) when all perfusion and ventilation images were used, and the increase in performance from 0.79 to 0.87 was also statistically significant (P=0.016). The automated method presented here for the interpretation of lung scintigrams shows a significant

  14. Decision support tool for early differential diagnosis of acute lung injury and cardiogenic pulmonary edema in medical critically ill patients.

    Science.gov (United States)

    Schmickl, Christopher N; Shahjehan, Khurram; Li, Guangxi; Dhokarh, Rajanigandha; Kashyap, Rahul; Janish, Christopher; Alsara, Anas; Jaffe, Allan S; Hubmayr, Rolf D; Gajic, Ognjen

    2012-01-01

    At the onset of acute hypoxic respiratory failure, critically ill patients with acute lung injury (ALI) may be difficult to distinguish from those with cardiogenic pulmonary edema (CPE). No single clinical parameter provides satisfying prediction. We hypothesized that a combination of those will facilitate early differential diagnosis. In a population-based retrospective development cohort, validated electronic surveillance identified critically ill adult patients with acute pulmonary edema. Recursive partitioning and logistic regression were used to develop a decision support tool based on routine clinical information to differentiate ALI from CPE. Performance of the score was validated in an independent cohort of referral patients. Blinded post hoc expert review served as gold standard. Of 332 patients in a development cohort, expert reviewers (κ, 0.86) classified 156 as having ALI and 176 as having CPE. The validation cohort had 161 patients (ALI = 113, CPE = 48). The score was based on risk factors for ALI and CPE, age, alcohol abuse, chemotherapy, and peripheral oxygen saturation/Fio(2) ratio. It demonstrated good discrimination (area under curve [AUC] = 0.81; 95% CI, 0.77-0.86) and calibration (Hosmer-Lemeshow [HL] P = .16). Similar performance was obtained in the validation cohort (AUC = 0.80; 95% CI, 0.72-0.88; HL P = .13). A simple decision support tool accurately classifies acute pulmonary edema, reserving advanced testing for a subset of patients in whom satisfying prediction cannot be made. This novel tool may facilitate early inclusion of patients with ALI and CPE into research studies as well as improve and rationalize clinical management and resource use.

  15. Synchronous advanced pulmonary tuberculosis and acute virus myocarditis mimicked wegener granulomatosis in a 26-year-old man: A case report

    Directory of Open Access Journals (Sweden)

    Pešut Dragica P.

    2016-01-01

    Full Text Available Introduction. Tuberculosis patients are rarely asymptomatic. Acute virus myocarditis presents with a wide range of symptoms, from mild dyspnea or chest pain to cardiogenic shock and death. Case Outline. A 26-year-old Caucasian man non-smoker presented with one-week history of lower extremities’ swelling. The patient’s medical history also revealed a two-day episode of subfebrile temperature with scanty hemoptysis three weeks prior to admission. The episode had not provoked him to seek medical care. Physical examination revealed generalized oedema, and laboratory analysis showed signs of acute renal insufficiency. Enlarged heart and hilar shadows, bilateral massive cavitary pulmonary opacities and pleural effusion were found at chest radiography. Sputum smears were Mycobacteria negative on direct microscopy. Electrocardiogram changes and echocardiography were suggestive of acute myocarditis with dilated cardiomyopathy. IgM titer to adenovirus was positive. Under diuretics, angiotensin-converting-enzyme inhibitor, beta-blocker, antibiotics and bed rest, fast heart compensation and renal function repair were achieved. Radiographic pulmonary changes promptly regressed except for a cavity in the right upper lobe. Bronchial aspirate from the affected lobe was Mycobacteria positive on direct microscopy and culture positive for Mycobacterium tuberculosis. Standard anti-tuberculosis drug regimen led to recovery. Conclusion. In the unusual common existence of two diseases whose presentation initially mimicked Wegener’s granulomatosis, acute dilated cardiomyopathy contributed to pulmonary tuberculosis detection. To prevent diagnostic delay in tuberculosis, further efforts in population education are necessary together with continual medical education. [Projekat Ministarstva nauke Republike Srbije, br. 175095

  16. Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta.

    Science.gov (United States)

    Wahl, S M; Allen, J B; Costa, G L; Wong, H L; Dasch, J R

    1993-01-01

    Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.

  17. Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit

    Science.gov (United States)

    Liu, Qiu-Yue; Han, Fen; Pan, Li-Ping; Jia, Hong-Yan; Li, Qi; Zhang, Zong-De

    2018-01-01

    Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU. PMID:29456674

  18. Effect of delay in hospital presentation on clinical and imaging findings in acute pulmonary thromboembolism.

    Science.gov (United States)

    Jenab, Yaser; Alemzadeh-Ansari, Mohammad Javad; Fehri, Seyedeh Arezoo; Ghaffari-Marandi, Neda; Jalali, Arash

    2014-04-01

    There is limited information on the extent and clinical importance of the delay in hospital presentation of acute pulmonary thromboembolism (PTE). The aim of this study was to investigate the delay in hospital presentation of PTE and its association with clinical and imaging findings in PTE. This prospective study was conducted on patients admitted to our hospital with a diagnosis of acute PTE between September 2007 and September 2011. Relationships between delay in hospital presentation and clinical findings, risk factors, imaging findings, and in-hospital mortality were analyzed. Of the 195 patients enrolled, 84 (43.1%) patients presented 3 days after the onset of symptoms. Patients with chest pain, history of immobility for more than 3 days, recent surgery, and estrogen use had significantly less delayed presentation. Right ventricular dysfunction was significantly more frequent in patients with delayed presentation (odds ratio [OR] = 2.38; 95% confidence interval [CI] 1.27-4.44; p = 0.006); however, no relationship was found between delay in presentation and pulmonary computed tomographic angiography or color Doppler sonography findings. Patients with delayed presentation were at higher risk of in-hospital mortality (OR = 4.32; 95% CI 1.12-16.49; p = 0.021). Our study showed that a significant portion of patients with acute PTE had delayed presentation. Also, patients with delayed presentation had worse echocardiographic findings and higher in-hospital mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide

    International Nuclear Information System (INIS)

    Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T.

    1990-01-01

    Ozone (O 3 ) and nitrogen dioxide (NO 2 ) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O 3 at 0.1, 0.3, or 1 ppm; NO 2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O 3 and 3 ppm NO 2 . Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O 3 . Exposure to 10 ppm NO 2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO 2 and depressed following 3 and 10 ppm. The O 3 /NO 2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O 3 . This study has demonstrated that acute exposure to either O 3 or NO 2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

  20. Inflammation and Rupture of a Congenital Pericardial Cyst Manifesting Itself as an Acute Chest Pain Syndrome.

    Science.gov (United States)

    Aertker, Robert A; Cheong, Benjamin Y C; Lufschanowski, Roberto

    2016-12-01

    We present the case of a 63-year-old woman with a remote history of supraventricular tachycardia and hyperlipidemia, who presented with recurrent episodes of acute-onset chest pain. An electrocardiogram showed no evidence of acute coronary syndrome. A chest radiograph revealed a prominent right-sided heart border. A suspected congenital pericardial cyst was identified on a computed tomographic chest scan, and stranding was noted around the cyst. The patient was treated with nonsteroidal anti-inflammatory drugs, and the pain initially abated. Another flare-up was treated similarly. Cardiac magnetic resonance imaging was then performed after symptoms had resolved, and no evidence of the cyst was seen. The suspected cause of the patient's chest pain was acute inflammation of a congenital pericardial cyst with subsequent rupture and resolution of symptoms.

  1. DNaseI Protects against Paraquat-Induced Acute Lung Injury and Pulmonary Fibrosis Mediated by Mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Guo Li

    2015-01-01

    Full Text Available Background. Paraquat (PQ poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. Methods and Findings. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-β1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNFα, IL-1β, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated. Conclusions. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials.

  2. Fine particulate matter in acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Lei eNi

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress, immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden.

  3. [Acute neurogenic pulmonary edema].

    Science.gov (United States)

    Roquefeuil, B

    1975-01-01

    Neurogenic edema, in the strict sense of the term, has at the present time practically not benefitted from precise hemodynamic investigations in human clinical practice, and owing to this fact, authors still classify them under the heading "mixed edema or of unknown pathogenesis". In contrast with this lack of information in man, animal experimental works are surprising by their coherence and the experimental facility of producing neurogenic edema (cranial hypertension by a small inflatable balloon and cisternal infection of fibrin). If one excludes the now ancient vagal theories (CAMERON 1949; CAMPBELL, 1949) which were never confirmed, all of the most recent experimental works (SARNOFF, 1952; DUCKER, 1968; LUISADA, 1967; MORITZ, 1974) confirm the adrenergic disorder of central origin during neurogenic A.P.E. which from the hemodynamic standpoint is like an authentic hemodynamic A.P.E. with raised left atrial pressure, pulmonary venous pressure and pulmonary capillary pressure.

  4. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

  5. The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.

    Science.gov (United States)

    Algaba-Chueca, Francisco; de-Madaria, Enrique; Lozano-Ruiz, Beatriz; Martínez-Cardona, Claudia; Quesada-Vázquez, Noé; Bachiller, Victoria; Tarín, Fabián; Such, José; Francés, Rubén; Zapater, Pedro; González-Navajas, José M

    Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

    Science.gov (United States)

    Bhargava, Rhea; Janssen, William; Altmann, Christopher; Andrés-Hernando, Ana; Okamura, Kayo; Vandivier, R William; Ahuja, Nilesh; Faubel, Sarah

    2013-01-01

    Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.

  7. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Rhea Bhargava

    Full Text Available Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury, intraperitoneal (IP endotoxin administration (indirect lung injury and, for comparison, intratracheal (IT endotoxin administration (direct lung injury with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation.Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10, BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration], and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping, IP endotoxin (10 µg, or IT endotoxin (80 µg with and without intratracheal (IT IL-6 (25 ng or 200 ng treatment.Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin.IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of

  8. ARDS (Acute Respiratory Distress Syndrome)

    Science.gov (United States)

    ... Also known as What Is ARDS, or acute respiratory distress syndrome, is a lung condition that leads ... treat ARDS. Other Names Acute lung injury Adult respiratory distress syndrome Increased-permeability pulmonary edema Noncardiac pulmonary ...

  9. Acupuncture as an adjunct to pulmonary rehabilitation.

    LENUS (Irish Health Repository)

    Deering, Brenda M

    2012-02-01

    PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and by both systemic and airway inflammation. In COPD, acupuncture has been shown to improve quality-of-life scores and decrease breathlessness; similar findings have also been reported after pulmonary rehabilitation (PR). The hypothesis of this study was that acupuncture in conjunction with pulmonary rehabilitation would improve COPD outcome measures compared to pulmonary rehabilitation alone. METHODS: The design was a randomized prospective study; all subjects had COPD. There were 19 controls, 25 who underwent PR, and 16 who had both acupuncture and PR. The primary outcome measure was a change in measures of systemic inflammation at the end of PR and at 3 month followup. Lung function, including maximum inspiratory pressure (PiMax), quality-of-life scores, functional capacity including steps taken, dyspnea scores, and exercise capacity, were secondary endpoints. RESULTS: After PR, both groups had significantly improved quality-of-life scores, reduced dyspnea scores, improved exercise capacity, and PiMax, but no change in measures of systemic inflammation compared with the controls. There were no differences in most of the outcome measures between the 2 treatment groups except that subjects who had both acupuncture and PR remained less breathless for a longer period. CONCLUSION: The addition of acupuncture to PR did not add significant benefit in most of the outcomes measured.

  10. ECG-gated multislice spiral CT for diagnosis of acute pulmonary embolism

    International Nuclear Information System (INIS)

    Marten, K.; Engelke, C.; Funke, M.; Obenauer, S.; Baum, F.; Grabbe, E.

    2003-01-01

    AIM: The purpose of this study was to determine the feasibility of echocardiogram (ECG)-gated multi-slice CT angiography (MCTA) in patients with clinical suspicion of acute venous thromboembolism (VTE), to investigate the effect of ECG-gating on cardiac motion artefacts, and to determine the diagnostic reader agreement of ECG-gated MCTA in comparison with conventional MCTA. MATERIALS AND METHODS: Forty-eight consecutive patients were prospectively enrolled and randomly underwent ECG-gated (n=25, group 1) or non-ECG-gated (n=23, group 2) eight-slice pulmonary MCTA. Image data were evaluated by three independent chest radiologists with respect to the presence or absence of emboli at different arterial levels (main, lobar, segmental, and subsegmental arteries), and with regard to cardiac motion artefacts. Statistical tests used to calculate inter-observer agreement were weighted κ statistics, extended κ statistics and confidence indices indicating three-reader agreement accuracy. RESULTS: Twenty-seven patients (56.3%) were diagnosed to have pulmonary embolism (13 from group 1, 14 from group 2). Cardiac motion artefacts were significantly more frequent in group 2 (70% in group 2 versus 13% in group 1, p=0.0001). The overall diagnostic agreement was excellent with both MCTA techniques (three-reader confidence index for all vascular territories: 0.76 and 0.84 for groups 1 and 2, respectively (extended κ=0.69 and 0.78, respectively); three-reader confidence index for diagnosis of VTE: 0.94 and 0.85 for groups 1 and 2, respectively (extended κ=0.91 and 0.73, respectively), weighted κ=0.81-0.83 and 0.92-0.95 for groups 1 and 2, respectively, and did not differ significantly between the two groups. In addition there was no significant difference of inter-observer agreement in either group at any assessed pulmonary arterial level. CONCLUSION: ECG-gated pulmonary MCTA is feasible in patients with clinical suspicion of VTE. However, ECG-gated image acquisition did not

  11. Exercise alleviates depression related systemic inflammation in ...

    African Journals Online (AJOL)

    Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients. ... African Health Sciences ... Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory ...

  12. Treatment of presumed acute cardiogenic pulmonary oedema in an ambulance system by nurses using Boussignac continuous positive airway pressure

    NARCIS (Netherlands)

    Dieperink, Willem; Weelink, E. E. M.; van der Horst, I. C. C.; de Vos, R.; Jaarsma, T.; Aarts, L. P. H. J.; Zijlstra, F.; Nijsten, M. W. N.

    Background: Early initiation of continuous positive airway pressure (CPAP) applied by face mask benefits patients with acute cardiogenic pulmonary oedema (ACPE). The simple disposable Boussignac CPAP (BCPAP) has been used in ambulances by physicians. In the Netherlands, ambulances are manned by

  13. [Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

    Science.gov (United States)

    Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

    2006-10-25

    The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (Ppotassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction

  14. Pressure support ventilation vs Continuous positive airway pressure for treating of acute cardiogenic pulmonary edema: A pilot study.

    Science.gov (United States)

    Pagano, Antonio; Numis, Fabio G; Rosato, Valerio; Russo, Teresa; Porta, Giovanni; Bosso, Giorgio; Serra, Claudia; Masarone, Mario; Visone, Giuseppe; Paladino, Fiorella

    2018-04-24

    Non-invasive ventilation is usually adopted as a support to medical therapy in patients with acute pulmonary edema, but which modality between Pressure Support Ventilation (PSV) and Continuous Positive Airway Pressure (CPAP) has better favourable effects is not been yet well known. Aim of this observational study was to provide data on these different non-invasive ventilation modalities in the management of acute cardiogenic pulmonary edema. One-hundred-fifty-three patients consecutively admitted to the Emergency Room of two different Center were enrolled and randomly assigned to CPAP or PSV. Data relative to mortality, need of endotracheal intubation, sequential blood gas analysis were compared. Furthermore, there were no significant differences regarding mortality in the two groups, but patients treated with PSV had a significant lower rate of endotracheal intubation and a higher improvement of blood gas analyses parameters. In conclusion, our data support only a slight advantage in favour to PSV versus CPAP. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Application of transpulmonary thermodilution monitoring (PiCCO in patient with neurogenic pulmonary edema and acute obstructive hydrocephalus due to a central neurocytoma: A case report

    Directory of Open Access Journals (Sweden)

    Ryoichi Iwata

    2017-06-01

    Full Text Available Neurogenic pulmonary edema (NPE is an acute life-threatening complication associated with many forms of central nervous system injury. Its pathophysiology is still debated. We report a patient with acute obstructive hydrocephalus due to a central neurocytoma who also had NPE, for which serial transpulmonary thermodilution monitoring (PiCCO was performed. Insertion of the PiCCO, which provides information about the patient's cardiac output, preload status and amount of lung water, revealed a high pulmonary vascular permeability index (PVPI and low global end-diastolic volume (GEDV without cardiac dysfunction, indicating permeability edema, which led to our changing the therapeutic strategy. Using PiCCO monitoring to balance the preload and extent of pulmonary edema enabled achievement of an optimal cardiac preload for organ perfusion, resulting in normalization of pulmonary edema by day 2. PiCCO facilitates understanding of the mechanism of NPE, guiding the management of fluid balance and the choice of vasopressors in patients with life-threatening NPE.

  16. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

    Science.gov (United States)

    Tan, Wan Shun Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, Wai-Shiu Fred

    2017-12-27

    The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome. This review compiles and analyses recent investigations targeting RAS for the treatment of inflammatory lung diseases. Inhibition of the upstream angiotensin (Ang) I/Ang II/angiotensin receptor type 1 (AT 1 R) pathway and activation of the downstream angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor pathway are two feasible strategies demonstrating efficacies in various pulmonary disease models. More recent studies favor the development of targeting the downstream ACE2/Ang (1-7)/Mas receptor pathway, in which diminazene aceturate, an ACE2 activator, GSK2586881, a recombinant ACE2, and AV0991, a Mas receptor agonist, showed much potential for further development. As the pathogenesis of pulmonary diseases is so complex that RAS modulation may be used alone or in combination with existing drugs like corticosteroids, pirfenidone/nintedanib or endothelin receptor antagonists for different pulmonary diseases. Personalized medicine through genetic screening and phenotyping for angiotensinogen or ACE would aid treatment especially for non-responsive patients. This review serves to provide an update on the latest development in the field of RAS targeting for pulmonary diseases, and offer some insights into future direction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Prognostic factors in acute cardiogenic pulmonary edema.

    Science.gov (United States)

    Le Conte, P; Coutant, V; N'Guyen, J M; Baron, D; Touze, M D; Potel, G

    1999-07-01

    The purpose of this study was to determine the clinical and biological findings at admission in the Department of Emergency Medicine associated with a poor prognosis, and to evaluate early response to treatment as a prognostic factor. It was a prospective cohort study with a 5-month follow-up. One hundred eighty-six patients admitted for acute cardiogenic pulmonary edema were included. Features were analyzed at the admission and on response to initial treatment. The main outcome measure was survival at 2 end-points: hospital discharge, and 5 months of follow-up. Multivariate analysis showed that in-hospital mortality was associated with marbleization (mottling) odd-ratio (OR) = 9.0), low diuresis (OR = 4.0), high breath rate 6 hours after admission (OR = 4.0), and chronic digoxin use (OR = 3.39). Five-month mortality was associated with a bedridden state (OR = 9.0), marbleization (mottling) (OR = 5.5), myocardial infarction (OR = 3), and poor early response to initial treatment (OR = 3.2). In addition to well-known factors, the response to initial treatment evaluated 6 hours after admission was a major determinant of outcome.

  18. What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

    Science.gov (United States)

    Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

    2018-04-01

    Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is

  19. Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

    Directory of Open Access Journals (Sweden)

    Wenxin Chai

    2018-01-01

    Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

  20. Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-10-01

    Full Text Available Abstract Background The avian influenza virus (AIV can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza. Methods We hypothesized that mesenchymal stromal cells (MSCs would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF and serum, and assessed pathological changes to the lungs. Results MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment. Conclusions MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.

  1. Balloon pulmonary valvotomy – Not just a simple balloon dilatation

    Directory of Open Access Journals (Sweden)

    Subhendu Mohanty

    2014-07-01

    Full Text Available Balloon pulmonary valvotomy is the preferred mode of treatment in patients with isolated pulmonary valvar stenosis and has shown good long term results. It is generally considered a safe procedure with few complications. There have been however, case reports of potentially fatal acute severe pulmonary edema occurring after the procedure in some patients. The cause of this complication and its pathophysiology is still not clear. Its occurrence is also infrequent with less than 5 cases reported till now. We report a case of pulmonary valvar stenosis which developed acute severe refractory pulmonary edema immediately after balloon pulmonary valvotomy.

  2. Regional myocardial extraction of a radioiodinated branched chain fatty acid during right ventricular pressure overload due to acute pulmonary hypertension

    International Nuclear Information System (INIS)

    Hurford, W.; Lowenstein, E.; Zapol, W.; Barlai-Kovach, M.; Livni, E.; Elmaleh, D.R.; Strauss, H.W.

    1985-01-01

    To determine whether branched chain fatty acid extraction is reduced during right ventricular (RV) dysfunction due to acute pulmonary artery hypertension, studies were done in 6 anesthetized dogs. Regional branched chain fatty acid extraction was measured by comparing the myocardial uptake of I-125 labeled 15-[p-(iodophenyl)]-3-methylpentadecanoic acid (I-PDA) to myocardial blood flow. Acute pulmonary hypertension was induced by incremental intravenous injection of 100 micron diameter glass beads into six pentobarbital anesthetized, mechanically ventilated dogs. Myocardial blood flow was measured by radiolabeled microspheres both under baseline conditions and during pulmonary hypertension. Mean RV pressure rose from 12 +- 2 (mean +- SEM) to 30 +-3mmHg resulting in a 225 +- 16% increase in RV stroke work. RV ejection fraction, as assessed by gated blood pool scans fell from 39 +- 2 to 18 +- 2%. Left ventricular (LV) pressures, stroke work and ejection fraction were unchanged. Myocardial blood flow increased 132 + 59% in the RV free wall and 67 +- 22% in the RV septum. LV blood flow was unchanged. Despite increased RV work and myocardial blood flow, no differences were noted in the branched chain fatty acid extraction ratios among LV or RV free walls or septum. The authors conclude that early RV dysfunction associated with pulmonary artery hypertension is not due to inadequate myocardial blood flow or branched chain fatty acid extraction

  3. Regional pulmonary edema caused by acute mitral insufficiency after rupture of chordae tendinae with prolaps of the posterior mitral valve

    International Nuclear Information System (INIS)

    Mauser, M.; Wiedemer, B.; Fleischmann, D.; Billmann, P.; Ennker, J.

    2003-01-01

    An unilateral or predominantly lobar pulmonary edema is an unusual clinical or radiological finding, often misdiagnosed as one of the more common causes of focal lung disease. We report 2 cases of a regional pulmonary edema caused by the acute onset of a severe mitral insufficiency after the rupture of chordae tendinae resulting in a prolaps of the posterior mitral leaflet. In both cases the regional pulmonary edema was initially misdiagnosed as a pneumonic infiltration, which delayed the cardiological diagnostical procedures and the surgical intervention. The mechanism of the regional edema is an excentric regurgitation jet into the left atrium, which is usually directed to the orifice of the right upper lobe pulmonary vein which increases the hydrostatic vascular pressure in the corresponding lung segment. For the confirmation of the diagnosis, transesophageal echogradiographye is helpful in documenting the direction of the regurgitant flow and detecting differential gradients between the right and left pulmonary venous systems. The pulmonary infiltrations, which persisted for several weeks, dissappeared within a few days after surgical mitral-valve-reconstruction in both cases. (orig.) [de

  4. Relationship between Inflammation and Cardiovascular Diseases

    OpenAIRE

    Riddhi Patel; Henish Patel; Rachana Sarawade

    2013-01-01

    Inflammation is a part of complex biological response of vascular tissue to harmful stimuli such as pathogens, damaged cells or irritants. Recent advance in basic science have established a fundamental role for inflammation immediating all stages of cardiovascular diseases from initiation, progression and complications. Inflammation is thread linking to cardiovascular diseases. Clinical studies have shown that this emerging biology of inflammation play important role in pathogenesis of acute ...

  5. Correlations between electrocardiogram and biomarkers in acute pulmonary embolism: Analysis of ZATPOL-2 Registry.

    Science.gov (United States)

    Kukla, Piotr; Kosior, Dariusz A; Tomaszewski, Andrzej; Ptaszyńska-Kopczyńska, Katarzyna; Widejko, Katarzyna; Długopolski, Robert; Skrzyński, Andrzej; Błaszczak, Piotr; Fijorek, Kamil; Kurzyna, Marcin

    2017-07-01

    Electrocardiography (ECG) is still one of the first tests performed at admission, mostly in patients (pts) with chest pain or dyspnea. The aim of this study was to assess the correlation between electrocardiographic abnormalities and cardiac biomarkers as well as echocardiographic parameter in patients with acute pulmonary embolism. We performed a retrospective analysis of 614 pts. (F/M 334/280; mean age of 67.9 ± 16.6 years) with confirmed acute pulmonary embolism (APE) who were enrolled to the ZATPOL-2 Registry between 2012 and 2014. Elevated cardiac biomarkers were observed in 358 pts (74.4%). In this group the presence of atrial fibrillation (p = .008), right axis deviation (p = .004), S 1 Q 3 T 3 sign (p electrocardiogram" were as follows: increased heart rate (OR 1.09, 95% CI 1.02-1.17, p = .012), elevated troponin concentration (OR 3.33, 95% CI 1.94-5.72, p = .000), and right ventricular overload (OR 2.30, 95% CI 1.17-4.53, p = .016). Electrocardiographic signs of right ventricular strain are strongly related to elevated cardiac biomarkers and echocardiographic signs of right ventricular overload. ECG may be used in preliminary risk stratification of patient with intermediate- or high-risk forms of APE. © 2017 Wiley Periodicals, Inc.

  6. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

    Directory of Open Access Journals (Sweden)

    Inge Van Hove

    2016-11-01

    Full Text Available Matrix metalloproteinase-3 (MMP-3 is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1, interleukin 6 (Il6, cytokine-inducible nitrogen oxide synthase (Nos2 and tumor necrosis factor α (Tnfα, which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP-1 and (C-X-C motif ligand 1 (CXCL1. These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation.

  7. Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction

    Directory of Open Access Journals (Sweden)

    Surber Mark W

    2010-06-01

    Full Text Available Abstract Background Generalized hypoxic pulmonary vasoconstriction (HPV occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebulization of nitrite and different formulations of acidified sodium nitrite on acute HPV. Methods Ex vivo isolated rabbit lungs perfused with erythrocytes in Krebs-Henseleit buffer (adjusted to 10% hematocrit and in vivo anesthetized catheterized rabbits were challenged with periods of hypoxic ventilation alternating with periods of normoxic ventilation. After baseline hypoxic challenges, vehicle, sodium nitrite or acidified sodium nitrite was delivered via nebulization. In the ex vivo model, pulmonary arterial pressure and nitric oxide concentrations in exhaled gas were monitored. Nitrite and nitrite/nitrate were measured in samples of perfusion buffer. Pulmonary arterial pressure, systemic arterial pressure, cardiac output and blood gases were monitored in the in vivo model. Results In the ex vivo model, nitrite nebulization attenuated HPV and increased nitric oxide concentrations in exhaled gas and nitrite concentrations in the perfusate. The acidified forms of sodium nitrite induced higher levels of nitric oxide in exhaled gas and had longer vasodilating effects compared to nitrite alone. All nitrite formulations increased concentrations of circulating nitrite to the same degree. In the in vivo model, inhaled nitrite inhibited HPV, while pulmonary arterial pressure, cardiac output and blood gases were not affected. All nitrite formulations had similar potency to inhibit HPV. The tested concentration of appeared tolerable. Conclusion Nitrite alone and in acidified forms effectively and similarly attenuates HPV. However, acidified nitrite formulations induce a more pronounced increase in nitric oxide exhalation.

  8. Acute respiratory failure as primary manifestation of antineutrophil cytoplasmic antibodies-associated vasculitis

    Directory of Open Access Journals (Sweden)

    Evdokia Sourla

    2014-07-01

    Full Text Available The systemic vasculitides are multifocal diseases characterized by the presence of blood vessel inflammation in multiple organ systems. Their clinical presentation is variable extending from self-limited illness to critical complications including diffuse alveolar hemorrhage and glomerulonephritis. Alveolar hemorrhage is a lifethreatening manifestation of pulmonary vasculitis that can rapidly progress into acute respiratory failure requiring ventilatory support. We present the case of a 74-year-old patient admitted to the Intensive Care Unit with severe hypoxic respiratory failure and diffuse alveolar infiltrates in chest imaging that was later diagnosed as antineutrophil cytoplasmic antibodies-associated vasculitis. The report highlights the importance of differentiate between alveolar hemorrhage and acute respiratory distress syndrome of other etiology because alveolar hemorrhage is reversible with prompt initiation of treatment.

  9. RUNX1: A Regulator of NF-kB Signaling in Pulmonary Diseases.

    Science.gov (United States)

    Tang, Xiaoju; Sun, Ling; Wang, Gang; Chen, Bojiang; Luo, Fengming

    2018-01-01

    Runt-related transcription factor 1 (RUNX1), a member of the RUNX family, is one of the key regulatory proteins in vertebrates. RUNX1 is involved in embryonic development, hematopoiesis, angiogenesis, tumorigenesis and immune response. In the past few decades, studies mainly focused on the effect of RUNX1 on acute leukemia and cancer. Only few studies about the function of RUNX1 in the pathological process of pulmonary diseases have been reported. Recent studies have demonstrated that RUNX1 is highly expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung and that it plays a critical role in the lipopolysaccharide induced lung inflammation by regulating the NF-kB pathway. RUNX1 participates in the regulation of the NF-kB signaling pathway through interaction with IkB kinase complex in the cytoplasm or interaction with the NF-kB subunit P50. NF-kB is well-known signaling pathway necessary for inflammatory response in the lung. This review is to highlight the RUNX1 structure, isoforms and to present the mechanism that RUNX1 regulates NF-kB. This will illustrate the great potential role of RUNX1 in the inflammation signaling pathway in pulmonary diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. COPD and stroke: are systemic inflammation and oxidative stress the missing links?

    Science.gov (United States)

    Austin, Victoria; Crack, Peter J; Bozinovski, Steven; Miller, Alyson A; Vlahos, Ross

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. © 2016 The Author(s).

  11. High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.

    Science.gov (United States)

    Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J; Presson, Robert G; Petrache, Irina; Kline, Jeffrey; Lahm, Tim

    2017-02-01

    Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.

  12. Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    International Nuclear Information System (INIS)

    Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Hashiba, Masayoshi; Kambara, Tatsunori; Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami; Tomonaga, Taisuke; Myojo, Toshihiko; Yamamoto, Kazuhiro; Kitajima, Shinichi; Horie, Masanori; Kuroda, Etsushi; Morimoto, Yasuo

    2015-01-01

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO 2 ) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO 2 nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO 2 nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO 2 may not lead to chronic, irreversible legions in the lung, and that TiO 2 nanoparticles may not have a high potential for lung disorder

  13. Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Yukiko, E-mail: y-yoshiura@med.uoeh-u.ac.jp; Izumi, Hiroto [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Oyabu, Takako [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Hashiba, Masayoshi; Kambara, Tatsunori [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Tomonaga, Taisuke [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Myojo, Toshihiko [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Horie, Masanori [National Institute of Advanced Industrial Science and Technology (AIST), Health Research Institute (HRI) (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Morimoto, Yasuo [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan)

    2015-06-15

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO{sub 2}) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO{sub 2} may not lead to chronic, irreversible legions in the lung, and that TiO{sub 2} nanoparticles may not have a high potential for lung disorder.

  14. Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers.

    Science.gov (United States)

    Zhu, Xiaojun; Gu, Yishuo; Ma, Wenjun; Gao, Panjun; Liu, Mengxuan; Xiao, Pei; Wang, Hongfei; Chen, Juan; Li, Tao

    2017-12-27

    Refractory ceramic fibers (RCFs) can cause adverse health effects on workers' respiratory system, yet no proper biomarkers have been used to detect early pulmonary injury of RCFs-exposed workers. This study assessed the levels of two biomarkers that are related to respiratory injury in RCFs-exposed workers, and explored their relations with lung function. The exposure levels of total dust and respirable fibers were measured simultaneously in RCFs factories. The levels of TGF-β1 and ceruloplasmin (CP) increased with the RCFs exposure level ( p relations were found between the concentrations of CP and FVC (B = -0.423, p = 0.025), or FEV₁ (B = -0.494, p = 0.014). The concentration of TGF-β1 (B = 0.103, p = 0.001) and CP (B = 8.027, p = 0.007) were associated with respirable fiber exposure level. Occupational exposure to RCFs can impair lung ventilation function and may have the potential to cause pulmonary inflammation and fibrosis. TGF-β1 and CP might be used as sensitive and noninvasive biomarkers to detect lung injury in occupational RCFs-exposed workers. Respirable fiber concentration can better reflect occupational RCFs exposure and related respiratory injuries.

  15. Where Does Inflammation Fit?

    Science.gov (United States)

    Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

    2017-09-01

    This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

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

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-09-01

    Full Text Available Hao Wang,1,2,* Ting Yang,1,2,* Diandian Li,1,2 Yanqiu Wu,1,2 Xue Zhang,1,2 Caishuang Pang,1,2 Junlong Zhang,3 Binwu Ying,3 Tao Wang,1,2 Fuqiang Wen1,2 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work 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

  17. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  18. Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Lange, Peter; Bojesen, Stig Egil

    2014-01-01

    25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk o...... of chronic obstructive pulmonary disease (COPD).......25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk...

  19. Computer-Assisted Detection of Acute Pulmonary Embolism

    NARCIS (Netherlands)

    Wittenberg, R.

    2012-01-01

    Pulmonary embolism (PE) is a common and often potentially life threatening disease. Severe morbidity and mortality can be prevented if PE is diagnosed and treated in time. CT pulmonary angiography (CTPA) has emerged as an effective method for diagnosis of PE, but interpreting a CTPA is complicated

  20. [Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy].

    Science.gov (United States)

    de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

    2014-12-01

    The aim of this study was to assess the pulmonary function of children with acute leukemia. Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(®) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(®)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. The role of serratiopeptidase in the resolution of inflammation

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-05-01

    Full Text Available Inflammation remains a key event during most of the diseases and physiological imbalance. Acute inflammation is an essential physiological event by immune system for a protective measure to remove cause of inflammation and failure of resolution lead to chronic inflammation. Over a period of time, a number of drugs mostly chemical have been deployed to combat acute and chronic inflammation. Recently, enzyme based anti-inflammatory drugs became popular over conventional chemical based drugs. Serratiopeptidase, a proteolytic enzyme from trypsin family, possesses tremendous scope in combating inflammation. Serine protease possesses a higher affinity for cyclooxygenase (COX-I and COX-II, a key enzyme associated with production of different inflammatory mediators including interleukins (IL, prostaglandins (PGs and thromboxane (TXs etc. Currently, arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome, etc. are the leading inflammatory disorders that affected the entire the globe. In order to conquer inflammation, both acute and chronic world, physician mostly relies on conventional drugs. The most common drugs to combat acute inflammation are Nonsteroidal anti-inflammatory drugs (NSAIDs alone and or in combination with other drugs. However, during chronic inflammation, NSAIDs are often used with steroidal drugs such as autoimmune disorders. These drugs possess several limitations such as side effects, ADR, etc. In order to overcome these limitations and complications, enzyme based drugs (anti-inflammatory emerged, and aim for a new high since the last decade. Serine protease, the largest proteolytic family has been reported for several therapeutic applications, including anti-inflammatory. Serratiopeptidase is a leading enzyme which has a very long history in medical as an effective anti-inflammatory drug. Current study emphasizes present scenario and future prospect of serratiopeptidase as an anti-inflammatory drug

  2. Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Shi, Juan; Li, Feng; Luo, Meihui; Wei, Jun

    2017-01-01

    Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema. Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models. Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models. These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments. This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. PMID:28588349

  3. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    Science.gov (United States)

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion

  4. Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

    Directory of Open Access Journals (Sweden)

    Qinlong Liu

    2012-01-01

    Full Text Available Pulmonary complications after liver transplantation (LT often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG and quarter-size grafts (QSG, respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5–18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.

  5. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  6. Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

    Science.gov (United States)

    Buczek, E; Denslow, A; Mateuszuk, L; Proniewski, B; Wojcik, T; Sitek, B; Fedorowicz, A; Jasztal, A; Kus, E; Chmura-Skirlinska, A; Gurbiel, R; Wietrzyk, J; Chlopicki, S

    2018-05-22

    Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI 2 )-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI 2 -dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI 2 production. In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI 2 pathway.

  7. Pulmonary capillary pressure in pulmonary hypertension.

    Science.gov (United States)

    Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

    2005-04-01

    Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

  8. Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis.

    Science.gov (United States)

    Neto, Ary Serpa; Simonis, Fabienne D; Barbas, Carmen S V; Biehl, Michelle; Determann, Rogier M; Elmer, Jonathan; Friedman, Gilberto; Gajic, Ognjen; Goldstein, Joshua N; Linko, Rita; Pinheiro de Oliveira, Roselaine; Sundar, Sugantha; Talmor, Daniel; Wolthuis, Esther K; Gama de Abreu, Marcelo; Pelosi, Paolo; Schultz, Marcus J

    2015-10-01

    Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients. Individual patient data analysis. ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation. Mechanical ventilation with low tidal volume. The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a "low tidal volume group" (tidal volumes ≤ 7 mL/kg predicted body weight), an "intermediate tidal volume group" (> 7 and volume group" (≥ 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52-0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 ± 10.9 vs 13.8 ± 11.6 d; p volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.

  9. Pathogenesis of pulmonary vasculitis

    NARCIS (Netherlands)

    Heeringa, P; Schreiber, A; Falk, RJ; Jennette, JC

    2004-01-01

    Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic

  10. Non-invasive ventilation: comparison of effectiveness, safety, and management in acute heart failure syndromes and acute exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pladeck, T; Hader, C; Von Orde, A; Rasche, K; Wiechmann, H W

    2007-11-01

    Continuous positive airway pressure ventilation (CPAP) and non-invasive positive pressure ventilation (NPPV) are accepted treatments in acute cardiogenic pulmonary edema (ACPE) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of the study was a comparison of effectiveness, safety, and management of NPPV in ACPE and AECOPD trying to find an approach for standard management in intensive care. Thirty patients with acute respiratory failure (14 due to ACPE, 16 due to AECOPD) were prospectively included into the study. If clinical stability could not be achieved by standard therapy (pharmacological therapy and oxygen) patients were treated by non-invasive ventilation (NPPV) using a BiPAP-Vision device in S/T-mode. During the first 90 min after the onset of NPPV respiratory and vital parameters were documented every 30 min. Additional relevant outcome parameters (need for intubation, duration of ICU stay, complications and mortality) were monitored. We found that 85.7% of the ACPE patients and 50.0% of the AECOPD patients were treated successfully with NPPV. Intubation rate was 31.2% in the AECOPD group and 14.3% in the ACPE group. 78.6% of the ACPE patients and 43.8% of the AECOPD patients were regularly discharged from hospital in a good condition. In the first 90 min of NIV, there was a significant amelioration of respiratory and other vital parameters. In ACPE patients there was a significant increase in PaO2 from 58.9 mmHg to 80.6 mmHg and of oxygen saturation (SaO2) from 85.1% to 93.1% without changing the inspiratory O2 concentration. This effect was comparable in the AECOPD group, but only could be achieved by increasing the inspiratory ventilation pressure. In the ACPE group inspiratory ventilation pressure could be reduced. In conclusion, in acute respiratory failure, ACPE patients comparably profit from NPPV as do patients with AECOPD, but the algorithm of titration for non-invasive ventilation pressure is different.

  11. Pulmonary embolism. Clinical relevance, requirements for diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Nowak, F.G.; Halbfass, P.; Hoffmann, E.

    2007-01-01

    In the population the annual incidence of pulmonary embolism amounts to 1.3-2.8 per 1000 at the age of 65-89 years. Mortality reaches about 17% within the first 3 months. Acute pulmonary embolism is characterized by an increase in pulmonary arterial pressure and an impairment of the pulmonary gas exchange. Elevation of the right cardiac pressure up to right heart decompensation may follow. In addition, hypoxemia, hyperventilation, dead space ventilation, right to left shunting, bronchoconstriction, and vasoconstriction may occur. Clinical examination, ECG, laboratory findings such as elevated D-dimer, blood gas analysis, ultrasound examination of the veins of the lower extremities, and transthoracic echocardiography are acutely available diagnostic methods of an emergency department. In addition, extensive diagnostic procedures like pulmonary scintigraphy and pulmonary angiography may be required. The aim is to get a definite diagnosis as quickly as possible to direct therapy. In acute pulmonary embolism with cardiac shock, monitoring and stabilization of the circulatory function as well as an appropriate anticoagulant therapy are essential. In some cases surgery or a local fibrinolytic intervention is indicated. (orig.) [de

  12. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, L; Thomsen, Simon Francis

    2013-01-01

    In this review we demonstrate that patients with chronic obstructive pulmonary disease (COPD) frequently report sinonasal symptoms. Furthermore, we present evidence that smoking on its own can cause nasal disease, and that in COPD patients, nasal inflammation mimics that of the bronchi. All...... this evidence suggests that COPD related sinonasal disease does exist and that smoking on its own rather than systemic inflammation triggers the condition. However, COPD related sinonasal disease remains to be characterized in terms of symptoms and endoscopic findings. In addition, more studies are needed...... to quantify the negative impact of sinonasal symptoms on the quality of life in COPD patients....

  13. Pulmonary langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Suri Harpreet S

    2012-03-01

    Full Text Available Abstract Pulmonary Langerhans Cell Histiocytosis (PLCH is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

  14. High altitude pulmonary edema: case report

    International Nuclear Information System (INIS)

    Garcia P, Edward; Contreras Zuniga, Eduardo; Zuluaga, Sandra Ximena

    2006-01-01

    Acute pulmonary edema is characterized by the accumulation of liquid in the pulmonary interstice, the alveoli, the bronchi and bronchioles; it is from the excessive circulation from the pulmonary vascular system towards extra vascular and the respiratory spaces. The Liquid filters first at the interstitial space to soon perivascular and peri bronchial and, gradually, towards the alveoli and bronchi

  15. Dual role of neutrophils in inflammation

    NARCIS (Netherlands)

    Pillay, J.

    2011-01-01

    Systemic inflammation is a hallmark of trauma, sepsis and various severe infectious diseases. Severe systemic inflammation can lead to inflammatory complications. The Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MODS) are seen after trauma and in sepsis and are

  16. [Pulmonary reperfusion syndrome after pulmonary stent implants in a patient with vascular tortuosity syndrome].

    Science.gov (United States)

    Berenguer Potenciano, M; Piris Borregas, S; Mendoza Soto, A; Velasco Bayon, J M; Caro Barri, A

    2015-01-01

    Vascular tortuosity syndrome is a rare genetic disorder that causes tortuosity and stenosis of the pulmonary, systemic and / or coronary circulations. As a result of treatment of pulmonary stenosis, symptoms of pulmonary edema, known as lung reperfusion syndrome, may occur. The case is presented of an adolescent patient with vascular tortuosity syndrome who presented with a pulmonary reperfusion syndrome after multiple stent implants in the left pulmonary artery. After the procedure, the patient immediately developed an acute pulmonary edema with severe clinical deterioration, which required assistance with extracorporeal membrane oxygenation for recovery. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  17. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

    2001-01-01

    We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

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

    Science.gov (United States)

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

    2014-09-02

    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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury

    NARCIS (Netherlands)

    Brander, Lukas; Sinderby, Christer; Lecomte, François; Leong-Poi, Howard; Bell, David; Beck, Jennifer; Tsoporis, James N.; Vaschetto, Rosanna; Schultz, Marcus J.; Parker, Thomas G.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

    2009-01-01

    OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (V