Science.gov

Sample records for pulmonary defense mechanisms

  1. Effect of Hypersensitivity Pneumonitis on the Pulmonary Defense Mechanisms of Guinea Pig Lungs

    PubMed Central

    Jakab, George J.; Green, Gareth M.

    1973-01-01

    Many edemagenic and consolidating inflammatory diseases, such as virus pneumonias, of the lung are complicated by bacterial infection. Previous literature has stressed that edema and consolidation may promote bacterial proliferation by interfering with phagocytosis. To test that hypothesis, lung defense mechanisms were studied in guinea pigs with tuberculin-induced hypersensitivity pneumonitis, a noninfectious edemagenic, and consolidating inflammatory disease. Pulmonary bactericidal activity and particle clearance were measured with a mixed aerosol of 32P-labeled Staphylococcus aureus and35S-labeled Proteus mirabilis. Hypersensitivity pneumonitis enhanced the bactericidal activity of the lung but had no effect on particle clearance despite the presence of consolidation and edema. These data indicate that altered host resistance to bacterial infection in acute inflammatory lung diseases can not be attributed to edema, inflammation, consolidation, changes in lung weight, etc., per se and that causes must be sought in functional changes in the bactericidal system of the lung rather than in specific histopathological changes. Images PMID:4632134

  2. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

    PubMed

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2016-03-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. PMID:26735168

  3. Defense Mechanisms: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  4. CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.

    PubMed

    Carevic, M; Öz, H; Fuchs, K; Laval, J; Schroth, C; Frey, N; Hector, A; Bilich, T; Haug, M; Schmidt, A; Autenrieth, S E; Bucher, K; Beer-Hammer, S; Gaggar, A; Kneilling, M; Benarafa, C; Gao, J L; Murphy, P M; Schwarz, S; Moepps, B; Hartl, D

    2016-01-01

    Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

  5. Defense mechanisms of the respiratory membrane.

    PubMed

    Green, G M; Jakab, G J; Low, R B; Davis, G S

    1977-03-01

    The success or failure of pulmonary defense mechanisms largely determines the appearance of clinical lung disease. The lung is protected by interlucking systems of nonspecific and specific defenses. Inhaled substrances can be isolated by mechanical barriers or can be physically removed from the lung either by transport up the bronchial mucociliary escalator or by transport through interstitial and lymphatic channels leading to lymph nodes. Substances can be locally detoxified within the lung by interaction with secretory proteins, such as antibodies, or by neutralization and dissolution within phagocytic cells. The pulmonary alveolar macrophage is the central figure in the protection of the respiratory membrane, operating in all 3 of the nonspecific modes of defense and augmented by specific immunologic mechanisms as well. Alterations in macrophage function and physiology may be crucial in determining the effectiveness of pulmonary defense. Recent advances in the cell biology of the alveolar macrophage have led to a greater understanding of its complex funcition. The multiple origins of macrophages from local and circulating cell pools and the variability in their fate and lifespan reflect the multi-faceted role of this cell type. The importance of the interactions between macrophages, orther lung cells, and other defense mechanisms has become increasingly clear. As well as functioning as resident defender of the alveolus, the macrophage is an important effector of the pulmonary immune response and plays a key role in the pathogenesis of a wide variety of inflammatory, destructive, and fibrotic lung diseases. Humoral and cell-mediated immune responses amplify and direct lung defenses against infection and may also participate in protection against other agents. Immunoglobulin A and G, microbial neutralizing and opsonizing anti-bodies, and macrophage-stimulating T lymphocytes are the major immunospecific forms of lung defense. Infectious agents, cigarette smoke, air

  6. Effects of inhaled acids on respiratory tract defense mechanisms.

    PubMed Central

    Schlesinger, R B

    1985-01-01

    The respiratory tract is endowed with an interlocking array of nonspecific and specific defense mechanisms which protect it from the effects of inhaled microbes and toxicants, and reduce the risk of absorption of materials into the bloodstream, with subsequent systemic translocation. Ambient acids may compromise these defenses, perhaps providing a link between exposure and development of chronic and acute pulmonary disease. This paper reviews the effects of inhaled acids upon the nonspecific clearance system of the lungs. PMID:3908089

  7. Tobacco smoke. Effects on pulmonary host defense.

    PubMed

    Drath, D B; Karnovsky, M L; Huber, G L

    1979-07-01

    Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell. PMID:225267

  8. Protecting the Self: Defense Mechanisms in Action

    ERIC Educational Resources Information Center

    Cramer, Phebe

    2006-01-01

    Integrating theory, research, and practical applications, this book provides a comprehensive examination of defense mechanisms and their role in both normal development and psychopathology. The author describes how children and adults mobilize specific kinds of defenses to maintain their psychological equilibrium and preserve self-esteem,…

  9. Mechanisms of plant defense against insect herbivores

    PubMed Central

    War, Abdul Rashid; Paulraj, Michael Gabriel; Ahmad, Tariq; Buhroo, Abdul Ahad; Hussain, Barkat; Ignacimuthu, Savarimuthu; Sharma, Hari Chand

    2012-01-01

    Plants respond to herbivory through various morphological, biochemicals, and molecular mechanisms to counter/offset the effects of herbivore attack. The biochemical mechanisms of defense against the herbivores are wide-ranging, highly dynamic, and are mediated both by direct and indirect defenses. The defensive compounds are either produced constitutively or in response to plant damage, and affect feeding, growth, and survival of herbivores. In addition, plants also release volatile organic compounds that attract the natural enemies of the herbivores. These strategies either act independently or in conjunction with each other. However, our understanding of these defensive mechanisms is still limited. Induced resistance could be exploited as an important tool for the pest management to minimize the amounts of insecticides used for pest control. Host plant resistance to insects, particularly, induced resistance, can also be manipulated with the use of chemical elicitors of secondary metabolites, which confer resistance to insects. By understanding the mechanisms of induced resistance, we can predict the herbivores that are likely to be affected by induced responses. The elicitors of induced responses can be sprayed on crop plants to build up the natural defense system against damage caused by herbivores. The induced responses can also be engineered genetically, so that the defensive compounds are constitutively produced in plants against are challenged by the herbivory. Induced resistance can be exploited for developing crop cultivars, which readily produce the inducible response upon mild infestation, and can act as one of components of integrated pest management for sustainable crop production. PMID:22895106

  10. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia

    PubMed Central

    Hilliard, Kristie L.; Allen, Eri; Traber, Katrina E.; Kim, Yuri; Wasserman, Gregory A.; Jones, Matthew R.; Mizgerd, Joseph P.

    2015-01-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS; 5 mg/kg of body weight) was followed by intratracheal Escherichia coli (106 CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3−/−). Pneumonia alone (without endotoxemia) was effectively controlled in the absence of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3−/− mice, with significantly reduced levels of circulating and airspace acute-phase proteins, exhibited significantly elevated lung and blood bacterial burdens and mortality. These data suggested that STAT3-dependent liver responses are necessary to promote host defense. While neither recruited airspace neutrophils nor lung injury was altered in endotoxemic hepSTAT3−/− mice, alveolar macrophage reactive oxygen species generation was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3−/− mice allowed greater bacterial growth ex vivo. These results suggest that hepatic STAT3 activation promotes both cellular and humoral lung defenses. Taken together, induction of liver STAT3-dependent gene expression programs is essential to countering the deleterious consequences of sepsis on pneumonia susceptibility. PMID:26216424

  11. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia.

    PubMed

    Hilliard, Kristie L; Allen, Eri; Traber, Katrina E; Kim, Yuri; Wasserman, Gregory A; Jones, Matthew R; Mizgerd, Joseph P; Quinton, Lee J

    2015-10-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS; 5 mg/kg of body weight) was followed by intratracheal Escherichia coli (10(6) CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3(-/-)). Pneumonia alone (without endotoxemia) was effectively controlled in the absence of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3(-/-) mice, with significantly reduced levels of circulating and airspace acute-phase proteins, exhibited significantly elevated lung and blood bacterial burdens and mortality. These data suggested that STAT3-dependent liver responses are necessary to promote host defense. While neither recruited airspace neutrophils nor lung injury was altered in endotoxemic hepSTAT3(-/-) mice, alveolar macrophage reactive oxygen species generation was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3(-/-) mice allowed greater bacterial growth ex vivo. These results suggest that hepatic STAT3 activation promotes both cellular and humoral lung defenses. Taken together, induction of liver STAT3-dependent gene expression programs is essential to countering the deleterious consequences of sepsis on pneumonia susceptibility. PMID:26216424

  12. Antiviral Defense Mechanisms in Honey Bees

    PubMed Central

    Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

    2015-01-01

    Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

  13. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  14. Defense Mechanisms: Discussions and Bibliographies; General or Multiple, and Specific.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    This publication considers some Freudian ego mechanisms. The first discussion and bibliography concerns defense mechanisms, in general or in multiple; after which, the discussions and bibliographies concern specific defense mechanisms: denial; displacement, substitution, sublimation; fixation; identification, introjection, incorporation,…

  15. Immune defense mechanisms of the dental pulp.

    PubMed

    Jontell, M; Okiji, T; Dahlgren, U; Bergenholtz, G

    1998-01-01

    Defense reactions of the dentin/pulp complex involve a variety of biological systems, in which the immune system plays a pivotal role. The knowledge of the organization and function of pulpal immunocompetent cells has been sparse, but in recent years a significant body of information of immune mechanisms in general has provided a footing for substantial new knowledge of the immune mechanisms of the dental pulp. The identification of pulpal dendritic cells (DCs) has generated research activities which have led to a concept of how an antigenic challenge may evoke a pulpal inflammatory response. Although DCs are not able to identify foreign antigens specifically, they provide necessary signals to activate T-lymphocytes which in turn will orchestrate other immunocompetent cells to mount the local immune defense of the dental pulp. The purpose of this review is to accent the organization and function of pulpal DCs and other tissue and cellular components and to provide a basis for how they may interact to instigate pulpal defense mechanisms. PMID:9603235

  16. EFFECTS OF INHALATION OF ETHYLENE DICHLORIDE ON PULMONARY DEFENSES OF MICE AND RATS

    EPA Science Inventory

    The effects of single or multiple 3-hr inhalation exposures to ethylene dichloride (dichloroethane or DCE) on macrophage functions and pulmonary defense were evaluated. Single exposures to the TLV level of DCE (10 ppm) resulted in decreased pulmonary bactericidal activity and inc...

  17. Rock mechanics contributions from defense programs

    SciTech Connect

    Heuze, F.E.

    1992-02-01

    An attempt is made at illustrating the many contributions to rock mechanics from US defense programs, over the past 30-plus years. Large advances have been achieved in the technology-base area covering instrumentation, material properties, physical modeling, constitutive relations and numerical simulations. In the applications field, much progress has been made in understanding and being able to predict rock mass behavior related to underground explosions, cratering, projectile penetration, and defense nuclear waste storage. All these activities stand on their own merit as benefits to national security. But their impact is even broader, because they have found widespread applications in the non-defense sector; to name a few: the prediction of the response of underground structures to major earthquakes, the physics of the earth`s interior at great depths, instrumentation for monitoring mine blasting, thermo-mechanical instrumentation useful for civilian nuclear waste repositories, dynamic properties of earthquake faults, and transient large-strain numerical modeling of geological processes, such as diapirism. There is not pretense that this summary is exhaustive. It is meant to highlight success stories representative of DOE and DOD geotechnical activities, and to point to remaining challenges.

  18. Using Breaking Bad to teach about defense mechanisms.

    PubMed

    Johnson, Justin M; Beresin, Eugene V; Stern, Theodore A

    2014-12-01

    Defense mechanisms represent an important component of medical education that should be taught to all medical students, psychiatry residents, and other mental health trainees. Teaching about defense mechanisms can become more engaging by analyzing popular media. Using Breaking Bad, a well-known television show, we recommend specific scenes and episodes that can be used in teaching about defense mechanisms. PMID:24906848

  19. Macrophage defense mechanisms against intracellular bacteria

    PubMed Central

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  20. An empirical study of defense mechanisms in panic disorder.

    PubMed

    Busch, F N; Shear, M K; Cooper, A M; Shapiro, T; Leon, A C

    1995-05-01

    Psychodynamic factors have rarely been systematically studied in panic disorder, despite indications that these factors may be important in the understanding and treatment of panic. This is a report of a study using the Defense Mechanism Rating Scale to test the hypothesis that patients with panic disorder utilize particular defense mechanisms: reaction formation, undoing, and displacement. The use of defense mechanisms in 22 patients with primary panic disorder was compared with that of 22 patients with primary dysthymic disorder, based on Defense Mechanism Rating Scale ratings of psychodynamic interviews of these patients. Panic subjects scored significantly higher than dysthymics on the defenses of reaction formation and undoing, but not on the defense of displacement. The defense mechanisms found are consistent with a proposed psychodynamic formulation for panic disorder that emphasizes the panic patient's difficulty in tolerating angry feelings toward significant others. Knowledge of these defense mechanisms can be useful for various treatment approaches in panic disorder. PMID:7745383

  1. Early Defensive Mechanisms against Human Papillomavirus Infection.

    PubMed

    Moerman-Herzog, Andrea; Nakagawa, Mayumi

    2015-08-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  2. Early Defensive Mechanisms against Human Papillomavirus Infection

    PubMed Central

    Moerman-Herzog, Andrea

    2015-01-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  3. Prevalence and Mechanisms of Dynamic Chemical Defenses in Tropical Sponges

    PubMed Central

    Rohde, Sven; Nietzer, Samuel; Schupp, Peter J.

    2015-01-01

    Sponges and other sessile invertebrates are lacking behavioural escape or defense mechanisms and rely therefore on morphological or chemical defenses. Studies from terrestrial systems and marine algae demonstrated facultative defenses like induction and activation to be common, suggesting that sessile marine organisms also evolved mechanisms to increase the efficiency of their chemical defense. However, inducible defenses in sponges have not been investigated so far and studies on activated defenses are rare. We investigated whether tropical sponge species induce defenses in response to artificial predation and whether wounding triggers defense activation. Additionally, we tested if these mechanisms are also used to boost antimicrobial activity to avoid bacterial infection. Laboratory experiments with eight pacific sponge species showed that 87% of the tested species were chemically defended. Two species, Stylissa massa and Melophlus sarasinorum, induced defenses in response to simulated predation, which is the first demonstration of induced antipredatory defenses in marine sponges. One species, M. sarasinorum, also showed activated defense in response to wounding. Interestingly, 50% of the tested sponge species demonstrated induced antimicrobial defense. Simulated predation increased the antimicrobial defenses in Aplysinella sp., Cacospongia sp., M. sarasinorum, and S. massa. Our results suggest that wounding selects for induced antimicrobial defenses to protect sponges from pathogens that could otherwise invade the sponge tissue via feeding scars. PMID:26154741

  4. Emotional exhaustion and defense mechanisms in intensive therapy unit nurses.

    PubMed

    Regan, Anna; Howard, Ruth A; Oyebode, Jan R

    2009-05-01

    Contrary to its original conceptualization, research has found that emotional demands do not lead to burnout in nurses. According to psychoanalytic theory, unconscious defense mechanisms may protect nurses from conscious awareness of work-related anxiety. This prevents self-report and may explain research findings. The maturity of defense style influences how anxiety is managed. Immature defenses prevent the conscious processing necessary for resolution of anxiety. Therefore, it is hypothesized that the use of immature defenses will lead to emotional exhaustion. This cross-sectional study used questionnaires to explore the defense mechanisms of 87 Intensive Therapy Unit nurses. Although the sample endorsed a predominantly mature defense style, the use of immature defenses predicted emotional exhaustion. Also, lower levels of reported stress associated with emotional demands predicted emotional exhaustion. Although this strongly implies the mediating role of immature defense mechanisms, the results were not statistically significant. PMID:19440106

  5. CXCL1 Regulates Pulmonary Host Defense to Klebsiella Infection via CXCL2 , CXCL5, NF-κB and MAPKs

    PubMed Central

    Cai, Shanshan; Batra, Sanjay; Lira, Sergio A.; Kolls, Jay K.; Jeyaseelan, Samithamby

    2010-01-01

    Pulmonary bacterial infections are a leading cause of death. Since the introduction of antibiotics, multidrug-resistant Klebsiella pneumoniae (Kp) became an escalating threat. Therefore, development of methods to augment antibacterial defense is warranted. Neutrophil recruitment is critical to clear bacteria and neutrophil migration in the lung requires the production of ELR+ CXC chemokines. Although lung specific CXCL1/KC transgene expression causes neutrophil-mediated clearance of Kp, the mechanisms underlying KC-mediated host defense against Kp have not been explored. Here we delineated the host defense functions of KC during pulmonary Kp infection using KC-/- mice. Our findings demonstrate that KC is important for expression of CXCL2/MIP-2 and CXCL5/LIX and activation of NF-κB, and MAPKs in the lung. Furthermore, KC-derived from both hematopoietic and resident cells contributes to host defense against Kp. Neutrophil depletion in mice prior to Kp infection reveals no differences in the production of MIP-2 and LIX or activation of NF-κB and MAPKs in the lung. Using murine bone marrow-derived (BMMs) and alveolar macrophages, we confirmed KC-mediated upregulation of MIP-2 and activation of NF-κB and MAPKs upon Kp infection. Moreover, neutralizing KC in BMMs prior to Kp challenge decreases bacteria-induced production of KC, MIP-2 and activation of NF-κB and MAPKs. These findings reveal the importance of KC produced by hematopoietic and resident cells in regulating pulmonary host defense against a bacterial pathogen via the activation of transcription factors and MAPKs as well as the expression of cell adhesion molecules and other neutrophil chemoattractants. PMID:20937845

  6. Denial Defense Mechanism in Dialyzed Patients

    PubMed Central

    Nowak, Zbigniew; Wańkowicz, Zofia; Laudanski, Krzysztof

    2015-01-01

    Background It is a struggle to identify the most adaptive coping strategies with disease-mediated stress. Here, we hypothesize that intensity of coping strategies, including denial, in patients with end-stage renal disease (ESRD), varies with type of renal replacement therapy (RRT). Material/Methods We enrolled 60 in-center hemodialyzed patients (HD) and 55 patients treated with continuous ambulatory peritoneal dialysis (CAPD). We administered the Coping Inventory with Stressful Situation, Profile of Mood States, and Stroop Anxiety Inventory to measure patient coping strategies in the context of their ESRD. Denial defense mechanism was measured via the IBS-R/ED. The Nottingham Health Profile was used to evaluate self-perceived quality of life. Serum potassium, urea, creatinine, phosphorus, calcium, albumin, and hematocrit were utilized as the measurements of adequacy of dialysis. Results HD patients had higher self-reported intensity of denial mechanism and avoidance-oriented strategies versus CAPD patients. Because a single strategy is almost never employed, we conducted cluster analysis. We identify 3 patterns of coping strategies using cluster analysis. “Repressors” employed denial and avoidance strategies and were predominant in HD. The second cluster consists of subjects employing predominantly task-oriented strategies with equal distribution among dialyzed patients. The third cluster encompassed a small group of patients who shared higher intensity of both denial and task-oriented strategies. Health-related outcome, anxiety, and mood profile were similar across all patients. Conclusions HD patients predominantly used “repressive” strategies. Patients on RRT utilized denial and avoidance-based strategies to achieve satisfactory outcome in terms of perceived quality of life. We conclude that these coping mechanisms that were previously thought to be inferior are beneficial to patient compliance with RRT. PMID:26094792

  7. EFFECTS OF ARSENIC TRIOXIDE INHALATION EXPOSURE ON PULMONARY ANTIBACTERIAL DEFENSES IN MICE

    EPA Science Inventory

    The effects of single and multiple (5 and 20) 3 hr inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0.4 microme...

  8. Hyperleptinemia is associated with impaired pulmonary host defense

    PubMed Central

    Ubags, Niki D.J.; Stapleton, Renee D.; Vernooy, Juanita H.J.; Burg, Elianne; Bement, Jenna; Hayes, Catherine M.; Ventrone, Sebastian; Zabeau, Lennart; Tavernier, Jan; Poynter, Matthew E.; Parsons, Polly E.; Dixon, Anne E.; Wargo, Matthew J.; Littenberg, Benjamin; Wouters, Emiel F.M.; Suratt, Benjamin T.

    2016-01-01

    We have previously reported that obesity attenuates pulmonary inflammation in both patients with acute respiratory distress syndrome (ARDS) and in mouse models of the disease. We hypothesized that obesity-associated hyperleptinemia, and not body mass per se, drives attenuation of the pulmonary inflammatory response and that this e_ect could also impair the host response to pneumonia. We examined the correlation between circulating leptin levels and risk, severity, and outcome of pneumonia in 2 patient cohorts (NHANES III and ARDSNet-ALVEOLI) and in mouse models of diet-induced obesity and lean hyperleptinemia. Plasma leptin levels in ambulatory subjects (NHANES) correlated positively with annual risk of respiratory infection independent of BMI. In patients with severe pneumonia resulting in ARDS (ARDSNet-ALVEOLI), plasma leptin levels were found to correlate positively with subsequent mortality. In obese mice with pneumonia, plasma leptin levels were associated with pneumonia severity, and in obese mice with sterile lung injury, leptin levels were inversely related to bronchoalveolar lavage neutrophilia, as well as to plasma IL-6 and G-CSF levels. These results were recapitulated in lean mice with experimentally induced hyperleptinemia. Our findings suggest that the association between obesity and elevated risk of pulmonary infection may be driven by hyperleptinemia. PMID:27347561

  9. Molecular and cellular mechanisms of pulmonary fibrosis

    PubMed Central

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  10. Adversity Quotient and Defense Mechanism of Secondary School Students

    ERIC Educational Resources Information Center

    Nikam, Vibhawari B.; Uplane, Megha M.

    2013-01-01

    The present study was conducted to explore the relationship between Adversity Quotient (AQ) and Defense Mechanism (DM) of secondary school students. The aim of the study was to ascertain relationship between Adversity Quotient and Defense mechanism i. e. Turning against object (TAO), Projection (PRO), Turning against self (TAS), Principalisation…

  11. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis.

    PubMed

    Pekovic-Vaughan, Vanja; Gibbs, Julie; Yoshitane, Hikari; Yang, Nan; Pathiranage, Dharshika; Guo, Baoqiang; Sagami, Aya; Taguchi, Keiko; Bechtold, David; Loudon, Andrew; Yamamoto, Masayuki; Chan, Jefferson; van der Horst, Gijsbertus T J; Fukada, Yoshitaka; Meng, Qing-Jun

    2014-03-15

    The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-box-mediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock "gated" pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic Clock(Δ19) mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis. PMID:24637114

  12. The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

    PubMed Central

    Pekovic-Vaughan, Vanja; Gibbs, Julie; Yoshitane, Hikari; Yang, Nan; Pathiranage, Dharshika; Guo, Baoqiang; Sagami, Aya; Taguchi, Keiko; Bechtold, David; Loudon, Andrew; Yamamoto, Masayuki; Chan, Jefferson; van der Horst, Gijsbertus T.J.; Fukada, Yoshitaka; Meng, Qing-Jun

    2014-01-01

    The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-box-mediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock “gated” pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic ClockΔ19 mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis. PMID:24637114

  13. First Line of Defense: Innate Cell-Mediated Control of Pulmonary Aspergillosis

    PubMed Central

    Espinosa, Vanessa; Rivera, Amariliz

    2016-01-01

    Mycotic infections and their effect on the human condition have been widely overlooked and poorly surveilled by many health organizations even though mortality rates have increased in recent years. The increased usage of immunosuppressive and myeloablative therapies for the treatment of malignant as well as non-malignant diseases has contributed significantly to the increased incidence of fungal infections. Invasive fungal infections have been found to be responsible for at least 1.5 million deaths worldwide. About 90% of these deaths can be attributed to Cryptococcus, Candida, Aspergillus, and Pneumocystis. A better understanding of how the host immune system contains fungal infection is likely to facilitate the development of much needed novel antifungal therapies. Innate cells are responsible for the rapid recognition and containment of fungal infections and have been found to play essential roles in defense against multiple fungal pathogens. In this review we summarize our current understanding of host-fungi interactions with a focus on mechanisms of innate cell-mediated recognition and control of pulmonary aspergillosis. PMID:26973640

  14. INHALABLE PARTICLES AND PULMONARY HOST DEFENSE: 'IN VIVO' AND 'IN VITRO' EFFECTS OF AMBIENT AIR AND COMBUSTION PARTICLES

    EPA Science Inventory

    The ability of particulate air pollutants (and possible constituents) to alter pulmonary host defenses was examined using an in vitro alveolar macrophage cytotoxicity assay and an in vivo bacterial infectivity screening test which employed intratracheal injection of the particles...

  15. Pulmonary perfusion during anesthesia and mechanical ventilation.

    PubMed

    Hedenstierna, G

    2005-06-01

    Cardiac output and the pulmonary perfusion can be affected by anesthesia and by mechanical ventilation. The changes contribute to impeded oxygenation of the blood. The major determinant of perfusion distribution in the lung is the relation between alveolar and pulmonary capillary pressures. Perfusion increases down the lung, due to hydrostatic forces. Since atelectasis is located in dependent lung regions, perfusion of non-ventilated lung parenchyma is common, producing shunt of around 8-10% of cardiac output. In addition, non-gravitational inhomogeneity of perfusion, that can be greater than the gravitational inhomogeneity, adds to impeded oxygenation of blood. Essentially all anaesthetics exert some, although mild, cardiodepressant action with one exception, ketamine. Ketamine may also increase pulmonary artery pressure, whereas other agents have little effect on pulmonary vascular tone. Mechanical ventilation impedes venous return and pushes blood flow downwards to dependent lung regions, and the effect may be striking with higher levels of PEEP. During one-lung anesthesia, there is shunt blood flow both in the non-ventilated and the ventilated lung, and shunt can be much larger in the ventilated lung than thought of. Recruitment manoeuvres shall be directed to the ventilated lung and other physical and pharmacological measures can be taken to manipulate blood flow in one lung anesthesia. PMID:15886595

  16. Polyphenol oxidase as a biochemical seed defense mechanism.

    PubMed

    Fuerst, E Patrick; Okubara, Patricia A; Anderson, James V; Morris, Craig F

    2014-01-01

    Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO), when wild oat (Avena fatua L.) caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea), non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems. PMID:25540647

  17. Polyphenol oxidase as a biochemical seed defense mechanism

    PubMed Central

    Fuerst, E. Patrick; Okubara, Patricia A.; Anderson, James V.; Morris, Craig F.

    2014-01-01

    Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO), when wild oat (Avena fatua L.) caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea), non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems. PMID:25540647

  18. Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

    PubMed Central

    2011-01-01

    Background Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse). Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection. PMID:21943386

  19. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium

    PubMed Central

    Pukkila-Worley, Read; Ausubel, Frederick M

    2013-01-01

    Intestinal epithelial cells provide an essential line of defense for Caenorhabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. PMID:22236697

  20. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.

    PubMed

    Han, SeungHye; Mallampalli, Rama K

    2015-05-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications. PMID:25742123

  1. Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

    SciTech Connect

    Aranyi, C.; Bradof, J.N.; O'Shea, W.J.; Graham, J.A.; Miller, F.J.

    1985-01-01

    The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0. 4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to /sup 35/S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

  2. Grooming Behavior as a Mechanism of Insect Disease Defense

    PubMed Central

    Zhukovskaya, Marianna; Yanagawa, Aya; Forschler, Brian T.

    2013-01-01

    Grooming is a well-recognized, multipurpose, behavior in arthropods and vertebrates. In this paper, we review the literature to highlight the physical function, neurophysiological mechanisms, and role that grooming plays in insect defense against pathogenic infection. The intricate relationships between the physical, neurological and immunological mechanisms of grooming are discussed to illustrate the importance of this behavior when examining the ecology of insect-pathogen interactions. PMID:26462526

  3. From Coal Mine Dust To Quartz: Mechanisms of Pulmonary Pathogenicity.

    PubMed

    Castranova, V

    2000-01-01

    Exposure to coal mine dust or crystalline silica can result in the initiation and progression of interstitial lung disease. Pathogenesis is the consequence of damage to lung cells and resulting lung scarring associated with activation of fibrotic processes. This review presents the radiologic and histologic characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathological indices of acute and chronic silicosis. This presentation also reviews the results of in vitro, animal, and human investigations that elucidate mechanisms involved in the development of these pneumoconioses. Results support the involvement of four basic mechanisms in the etiology of CWP and silicosis: 1. Direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring. 2. Activation of oxidant production by pulmonary phagocytes, such as alveolar macrophages. When oxidant production exceeds antioxidant defenses, lipid peroxidation and protein nitrosation occur, resulting in tissue injury and consequent scarring. 3. Activation of mediator release from alveolar macrophages and alveolar epithelial cells. Chemokines recruit polymorphonuclear leukocytes and macrophages from the pulmonary capillaries into the air spaces. Once within the air spaces, these leukocytes are activated by proinflammatory cytokines to produce reactive species, which increase oxidant injury and lung scarring. 4. Secretion of growth factors from alveolar macrophages and alveolar epithelial cells. Release of such mediators stimulates fibroblast proliferation and induces fibrosis. In conclusion, results of in vitro and animal studies have provided the basis for proposing mechanisms that may lead to the initiation and progression of CWP and silicosis. Data obtained from exposed workers has lent support to these proposals. The mechanistic understanding obtained for the development of CWP and silicosis should be useful in

  4. Impaired Pulmonary Defense Against Pseudomonas aeruginosa in VEGF Gene Inactivated Mouse Lung

    PubMed Central

    Breen, Ellen C.; Malloy, Jaret L.; Tang, Kechun; Xia, Feng; Fu, Zhenxing; Hancock, Robert E. W.; Overhage, Joerg; Wagner, Peter D.; Spragg, Roger G.

    2012-01-01

    Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung-targeted VEGF gene inactivation, and alterations in VEGF-dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF-deficient lungs increased PAO1 levels and pro-inflammatory cytokines, TNFα and IL-6, were detected 24 hours after bacterial instillation compared to control lungs. In vivo lung-targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA and SP-D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D. TPA-induced DSPC secretion and apoptosis were elevated in VEGF-deficient type II cells. These results suggest a potential protective role for type II cell-expressed VEGF against bacterial initiated infection. PMID:22718316

  5. Status of pulmonary host defense in the neonatal sheep: cellular and humoral aspects

    SciTech Connect

    Weiss, R.A.; Chanana, A.D.; Joel, D.D.

    1983-01-01

    In consideration of the sheep neonate as a compromised host, we have examined the status of cellular and humoral pulmonary host defense components at selected developmental time points. The dynamic character of the early neonatal lung free cell (LFC) population, reflected in changes in subpopulations and proliferative capacity, most probably contributed to the observed changes in certain cell responses. For example blood and LFC neutrophil chemotaxis appeared intact by day 1. The ability of alveolar macrophages to elaborate a chemotactic factor(s) was first noted at day 21. Bacteria binding and killing presented a biphasic maturation pattern with full competence not present until day 180. Although the in vitro binding and killing activity of day 8 LFCs was comparable to that of the adult, it may be a poor indicator of in vivo host defense capacity, given the relative paucity of endogenous opsonins at that age. In fact, the interdependence of mediators suggests that the sheep neonate may remain a compromised host during the first three months of life. Cellular and humoral parameters begin to approximate those of adult sheep by 180 days.

  6. Induced defense mechanisms in an aquatic angiosperm to insect herbivory.

    PubMed

    Fornoff, Felix; Gross, Elisabeth M

    2014-05-01

    In terrestrial angiosperms, defense and resistance mechanisms against herbivores have been studied extensively; yet this topic is poorly understood in aquatic angiosperms. We investigated induced response mechanisms in Myriophyllum spicatum to the generalist insect herbivore Acentria ephemerella in three independent experiments. Various morphological and chemical response variables were examined in grazed apical shoots and compared to undamaged controls. We further estimated plant palatability of induced and non-induced apices in choice assays, and assessed the growth response of Acentria larvae in no-choice feeding assays. Leaves of induced apices were splayed out horizontally and changed in color from green to red. The dry matter content and thus plant toughness increased by up to 19%, but silica levels stayed constant. Induced apices exhibited a decline in chlorophyll content of up to 34%, reflected also by a 10% decrease in nitrogen levels, while nitrogen increased by 14% in lower parts of grazed shoots. Also, herbivore-deterring total phenolic compounds increased by up to 20% in apices. In choice trials, Acentria larvae strongly avoided grazed tips, and growth was reduced by 25% on induced apices. In total, we observed five different induced resistance and defensive traits in grazed apices: changes in appearance, increased plant toughness, delocalization of N-containing metabolites, increased polyphenols, and reduced nutritional value. The observed changes prevent herbivore damage and loss of apical tissue, which are most valuable for plant fitness. Our study presents the first evidence of multiple, parallel defense strategies including constitutive and induced defense mechanisms in a freshwater angiosperm. PMID:24429525

  7. Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust.

    PubMed

    Gowdy, Kymberly; Krantz, Quentin T; Daniels, Mary; Linak, William P; Jaspers, Ilona; Gilmour, M Ian

    2008-06-15

    Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6, IFN-gamma, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens. PMID:18343473

  8. Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust

    SciTech Connect

    Gowdy, Kymberly; Krantz, Quentin T.; Daniels, Mary; Linak, William P.; Jaspers, Ilona; Gilmour, M. Ian

    2008-06-15

    Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m{sup 3} of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-{alpha}, MIP-2, IL-6, IFN-{gamma}, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens.

  9. Pulmonary mechanics and diffusion after 'shock lung'.

    PubMed Central

    Yernault, J C; Englert, M; Sergysels, R; De Coster, A

    1975-01-01

    Pulmonary function studies performed in seven patients who had recovered from 'shock lung' showed a highly significant decrease of diffusing properties of the lung, a slight loss of lung recoil pressure, and a borderline increase of residual volume with normal vital capacity and total lung capacity. Pulmonary compliance was normal. The interpretation of these findings is discussed. PMID:1145529

  10. The strawberry plant defense mechanism: a molecular review.

    PubMed

    Amil-Ruiz, Francisco; Blanco-Portales, Rosario; Muñoz-Blanco, Juan; Caballero, José L

    2011-11-01

    Strawberry, a small fruit crop of great importance throughout the world, has been considered a model plant system for Rosaceae, and is susceptible to a large variety of phytopathogenic organisms. Most components and mechanisms of the strawberry defense network remain poorly understood. However, from current knowledge, it seems clear that the ability of a strawberry plant to respond efficiently to pathogens relies first on the physiological status of injured tissue (pre-formed mechanisms of defense) and secondly on the general ability to recognize and identify the invaders by surface plant receptors, followed by a broad range of induced mechanisms, which include cell wall reinforcement, production of reactive oxygen species, phytoalexin generation and pathogenesis-related protein accumulation. Dissection of these physiological responses at a molecular level will provide valuable information to improve future breeding strategies for new strawberry varieties and to engineer strawberry plants for durable and broad-spectrum disease resistance. In turn, this will lead to a reduction in use of chemicals and in environmental risks. Advances in the understanding of the molecular interplay between plant (mainly those considered model systems) and various classes of microbial pathogens have been made in the last two decades. However, major progress in the genetics and molecular biology of strawberry is still needed to uncover fully the way in which this elaborate plant innate immune system works. These fundamental insights will provide a conceptual framework for rational human intervention through new strawberry research approaches. In this review, we will provide a comprehensive overview and discuss recent advances in molecular research on strawberry defense mechanisms against pathogens. PMID:21984602

  11. Mechanics of the pulmonary valve in the aortic position.

    PubMed

    Soares, A L F; van Geemen, D; van den Bogaerdt, A J; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2014-01-01

    Mathematical models can provide valuable information to assess and evaluate the mechanical behavior and remodeling of native tissue. A relevant example when studying collagen remodeling is the Ross procedure because it involves placing the pulmonary autograft in the more demanding aortic valve mechanical environment. The objective of this study was therefore to assess and evaluate the mechanical differences between the aortic valve and pulmonary valve and the remodeling that may occur in the pulmonary valve when placed in the aortic position. The results from biaxial tensile tests of pairs of human aortic and pulmonary valves were compared and used to determine the parameters of a structurally based constitutive model. Finite element analyzes were then performed to simulate the mechanical response of both valves to the aortic diastolic load. Additionally, remodeling laws were applied to assess the remodeling of the pulmonary valve leaflet to the new environment. The pulmonary valve showed to be more extensible and less anisotropic than the aortic valve. When exposed to aortic pressure, the pulmonary leaflet appeared to remodel by increasing its thickness and reorganizing its collagen fibers, rotating them toward the circumferential direction. PMID:24035437

  12. Cardiac output estimation using pulmonary mechanics in mechanically ventilated patients

    PubMed Central

    2010-01-01

    The application of positive end expiratory pressure (PEEP) in mechanically ventilated (MV) patients with acute respiratory distress syndrome (ARDS) decreases cardiac output (CO). Accurate measurement of CO is highly invasive and is not ideal for all MV critically ill patients. However, the link between the PEEP used in MV, and CO provides an opportunity to assess CO via MV therapy and other existing measurements, creating a CO measure without further invasiveness. This paper examines combining models of diffusion resistance and lung mechanics, to help predict CO changes due to PEEP. The CO estimator uses an initial measurement of pulmonary shunt, and estimations of shunt changes due to PEEP to predict CO at different levels of PEEP. Inputs to the cardiac model are the PV loops from the ventilator, as well as the oxygen saturation values using known respiratory inspired oxygen content. The outputs are estimates of pulmonary shunt and CO changes due to changes in applied PEEP. Data from two published studies are used to assess and initially validate this model. The model shows the effect on oxygenation due to decreased CO and decreased shunt, resulting from increased PEEP. It concludes that there is a trade off on oxygenation parameters. More clinically importantly, the model also examines how the rate of CO drop with increased PEEP can be used as a method to determine optimal PEEP, which may be used to optimise MV therapy with respect to the gas exchange achieved, as well as accounting for the impact on the cardiovascular system and its management. PMID:21108836

  13. Cardiac output estimation using pulmonary mechanics in mechanically ventilated patients.

    PubMed

    Sundaresan, Ashwath; Chase, J Geoffrey; Hann, Christopher E; Shaw, Geoffrey M

    2010-01-01

    The application of positive end expiratory pressure (PEEP) in mechanically ventilated (MV) patients with acute respiratory distress syndrome (ARDS) decreases cardiac output (CO). Accurate measurement of CO is highly invasive and is not ideal for all MV critically ill patients. However, the link between the PEEP used in MV, and CO provides an opportunity to assess CO via MV therapy and other existing measurements, creating a CO measure without further invasiveness.This paper examines combining models of diffusion resistance and lung mechanics, to help predict CO changes due to PEEP. The CO estimator uses an initial measurement of pulmonary shunt, and estimations of shunt changes due to PEEP to predict CO at different levels of PEEP. Inputs to the cardiac model are the PV loops from the ventilator, as well as the oxygen saturation values using known respiratory inspired oxygen content. The outputs are estimates of pulmonary shunt and CO changes due to changes in applied PEEP. Data from two published studies are used to assess and initially validate this model.The model shows the effect on oxygenation due to decreased CO and decreased shunt, resulting from increased PEEP. It concludes that there is a trade off on oxygenation parameters. More clinically importantly, the model also examines how the rate of CO drop with increased PEEP can be used as a method to determine optimal PEEP, which may be used to optimise MV therapy with respect to the gas exchange achieved, as well as accounting for the impact on the cardiovascular system and its management. PMID:21108836

  14. Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

    PubMed Central

    Friedman, Scott E.; Andrus, Bruce W.

    2012-01-01

    Pulmonary hypertension (PH) is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese. PMID:22988490

  15. Defense High-Level Waste Leaching Mechanisms Program. Final report

    SciTech Connect

    Mendel, J.E.

    1984-08-01

    The Defense High-Level Waste Leaching Mechanisms Program brought six major US laboratories together for three years of cooperative research. The participants reached a consensus that solubility of the leached glass species, particularly solubility in the altered surface layer, is the dominant factor controlling the leaching behavior of defense waste glass in a system in which the flow of leachant is constrained, as it will be in a deep geologic repository. Also, once the surface of waste glass is contacted by ground water, the kinetics of establishing solubility control are relatively rapid. The concentrations of leached species reach saturation, or steady-state concentrations, within a few months to a year at 70 to 90/sup 0/C. Thus, reaction kinetics, which were the main subject of earlier leaching mechanisms studies, are now shown to assume much less importance. The dominance of solubility means that the leach rate is, in fact, directly proportional to ground water flow rate. Doubling the flow rate doubles the effective leach rate. This relationship is expected to obtain in most, if not all, repository situations.

  16. Heavy Metal Stress and Some Mechanisms of Plant Defense Response

    PubMed Central

    Emamverdian, Abolghassem; Ding, Yulong; Mokhberdoran, Farzad; Xie, Yinfeng

    2015-01-01

    Unprecedented bioaccumulation and biomagnification of heavy metals (HMs) in the environment have become a dilemma for all living organisms including plants. HMs at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to excessive augmentation of reactive oxygen species (ROS). This would inflict serious morphological, metabolic, and physiological anomalies in plants ranging from chlorosis of shoot to lipid peroxidation and protein degradation. In response, plants are equipped with a repertoire of mechanisms to counteract heavy metal (HM) toxicity. The key elements of these are chelating metals by forming phytochelatins (PCs) or metallothioneins (MTs) metal complex at the intra- and intercellular level, which is followed by the removal of HM ions from sensitive sites or vacuolar sequestration of ligand-metal complex. Nonenzymatically synthesized compounds such as proline (Pro) are able to strengthen metal-detoxification capacity of intracellular antioxidant enzymes. Another important additive component of plant defense system is symbiotic association with arbuscular mycorrhizal (AM) fungi. AM can effectively immobilize HMs and reduce their uptake by host plants via binding metal ions to hyphal cell wall and excreting several extracellular biomolecules. Additionally, AM fungi can enhance activities of antioxidant defense machinery of plants. PMID:25688377

  17. Heavy metal stress and some mechanisms of plant defense response.

    PubMed

    Emamverdian, Abolghassem; Ding, Yulong; Mokhberdoran, Farzad; Xie, Yinfeng

    2015-01-01

    Unprecedented bioaccumulation and biomagnification of heavy metals (HMs) in the environment have become a dilemma for all living organisms including plants. HMs at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to excessive augmentation of reactive oxygen species (ROS). This would inflict serious morphological, metabolic, and physiological anomalies in plants ranging from chlorosis of shoot to lipid peroxidation and protein degradation. In response, plants are equipped with a repertoire of mechanisms to counteract heavy metal (HM) toxicity. The key elements of these are chelating metals by forming phytochelatins (PCs) or metallothioneins (MTs) metal complex at the intra- and intercellular level, which is followed by the removal of HM ions from sensitive sites or vacuolar sequestration of ligand-metal complex. Nonenzymatically synthesized compounds such as proline (Pro) are able to strengthen metal-detoxification capacity of intracellular antioxidant enzymes. Another important additive component of plant defense system is symbiotic association with arbuscular mycorrhizal (AM) fungi. AM can effectively immobilize HMs and reduce their uptake by host plants via binding metal ions to hyphal cell wall and excreting several extracellular biomolecules. Additionally, AM fungi can enhance activities of antioxidant defense machinery of plants. PMID:25688377

  18. Hope, defense mechanisms, and adjustment: implications for false hope and defensive hopelessness.

    PubMed

    Kwon, Paul

    2002-04-01

    Two studies replicated and expanded an earlier finding that defense style plays a crucial role in the relation between hope and dysphoria (Kwon, 2000). Lower hope and higher defense style immaturity were each associated with greater dysphoria, depression proneness, and maladjustment. Individuals with low hope and low defense immaturity did not have poor outcomes, supporting the existence of a subtype of low hope (defensive hopelessness) that may have adaptive value. The combination of high hope and high defense immaturity was not associated with maladaptive outcomes, arguing against the false hope construct. Additionally, the findings remained after controlling for levels of anxiety. Thus, it appears that the results are not attributable to general distress or negative affectivity. Finally, domain-specific hope was shown to correlate most strongly with matching areas of adjustment, providing evidence for the validity of the construct. PMID:11908846

  19. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense.

    PubMed

    McAleer, Jeremy P; Kolls, Jay K

    2014-07-01

    Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments probably require manipulating the inflammatory response to pathogenic microbes or allergens. Here, we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδ T cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4(+) T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b(+) DCs stimulated with bacteria or fungi secrete IL-1β and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1β and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to antibacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation. PMID:24942687

  20. Molecular mechanisms in progressive idiopathic pulmonary fibrosis.

    PubMed

    Steele, Mark P; Schwartz, David A

    2013-01-01

    There is clear evidence that environmental exposures and genetic predisposition contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cigarette smoking increases the risk of developing IPF several-fold, as do other exposures such as metal-fume and wood-dust exposure. Occupations that increase the risk of IPF are agricultural work, hairdressing, and stone polishing, supporting the role of environmental exposure in disease pathogenesis. Genetic predisposition to IPF is evident from its familial aggregation and the fact that pulmonary fibrosis develops in several rare genetic disorders. Mutations in surfactant proteins lead to pulmonary fibrosis and are associated with endoplasmic reticulum stress in alveolar type II epithelial cells. Mutations in telomerase have been found in several families with IPF, and shortened telomeres are found in sporadic cases of IPF. A common variant in mucin 5B predisposes to both familial and sporadic IPF and is present in the majority of cases, indicating sporadic IPF occurs in those with genetic predisposition. PMID:23020878

  1. Response of pulmonary cellular defenses to the inhalation of high concentrations of diesel exhaust. [Rats

    SciTech Connect

    Strom, K.A.

    1984-01-01

    Rats were exposed to three concentrations of diluted diesel exhaust for 6 mo and 1 yr. Bronchopulmonary lavage was used to obtain the pulmonary phagocytes from the animals in order to study the response of the phagocytic defenses to the inhaled particulate. The cell counts of alveolar macrophages (AM) were proportional to the concentration of diesel exhaust particulate (DP) in the chronic exposures. AM increased in the lungs in response to the rate of DP mass entering the lungs, rather than to the total DP burden in the lung. The geometric mean volumes of AM from the exposed and control animals were approximately 1100 ..mu..m/sup 3/ at both 6 and 12 mo of exposure, although exposed cell-volume distributions skewed towards larger sizes. The AM volume distributions extended to 2000 ..mu..m/sup 3/ in both control and 250 /sup +/g DP/m/sup 3/ exposed animals and up to 5000 ..mu..m/sup 3/ in cells from animals exposed to 750 and 1500 ..mu..g DP/m/sup 3/. Polymorphonuclear leukocytes were present in the lavaged cell populations from the animals exposed to 750 and 1500 ..mu..g/m/sup 3/. In addition, at 1 yr of exposure, lymphocytes were also lavaged from animals exposed to 750 and 1500 ..mu..g DP/m/sup 3/. Protein, ..beta..-glucuronidase activity, and acid phosphatase activity were measured in the lavaged cells, and were elevated in the cells from animals exposed to 750 and 1500 ..mu..g/m/sup 3/. The buoyant density of diesel-laden AM was found to be greater than that of control AM, and overlapped with the buoyant density of the polymorphonuclear leukocytes. 42 references, 9 figures, 7 tables.

  2. Change in Coping and Defense Mechanisms across Adulthood: Longitudinal Findings in a European American Sample

    ERIC Educational Resources Information Center

    Diehl, Manfred; Chui, Helena; Hay, Elizabeth L.; Lumley, Mark A.; Grühn, Daniel; Labouvie-Vief, Gisela

    2014-01-01

    This study examined longitudinal changes in coping and defense mechanisms in an age- and gender-stratified sample of 392 European American adults. Nonlinear age-related changes were found for the coping mechanisms of sublimation and suppression and the defense mechanisms of intellectualization, doubt, displacement, and regression. The change…

  3. Coordination of frontline defense mechanisms under severe oxidative stress.

    PubMed

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays. PMID:20664639

  4. Mechanical properties of porcine intralobar pulmonary arteries.

    PubMed

    Ohtaka, H; Hogg, J C; Moreno, R H; Paré, P D; Schellenberg, R R

    1988-04-01

    The isobaric and isovolumetric properties of intrapulmonary arteries were evaluated by placing a highly compliant balloon inside arterial segments. The passive pressure-volume (P-V) curve was obtained by changing volume (0.004 ml/s) and measuring pressure. The isobaric active volume change (delta V) or isovolumetric active pressure change (delta P) generated by submaximal histamine was measured at four different transmural pressures (Ptm's) reached by balloon inflation. The maximal delta P = 11.2 +/- 0.6 cmH2O (mean +/- SE) was achieved at 30.8 +/- 1.2 cmH2O Ptm and maximal delta V = 0.20 +/- 0.02 ml at 16.7 +/- 1.7 cmH2O Ptm. The P-V relationships were similar when volume was increased after either isobaric or isovolumetric contraction. The calculated length-tension (L-T) relationship showed that the active tension curve was relatively flat and that the passive tension at the optimal length was 149 +/- 11% of maximal active tension. These data show that 1) a large elastic component operates in parallel with the smooth muscle in intralobar pulmonary arteries, and 2) the change in resistance associated with vascular expansion of the proximal arteries is independent of the type of contraction that occurs in the more distal arterial segments. PMID:3378988

  5. Serine/threonine protein phosphatases: multi-purpose enzymes in control of defense mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serine/threonine protein phosphatases are a group of enzymes involved in the regulation of defense mechanisms in plants. This paper describes the effects of an inhibitor of these enzymes on the expression of all of the genes associated with these defense mechanisms. The results suggest that inhibi...

  6. Influence of Defense Mechanisms on Moral Judgment Development: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Hart, Daniel; Chmiel, Susan

    1992-01-01

    At age 13, and for the next 20 years, male subjects were periodically interviewed about their moral judgments. Adolescents with mature use of defense mechanisms reasoned at higher stages of moral judgment 10 to 20 years after the initial interview than did those with immature use of defense mechanisms. (BC)

  7. Hyperphosphorylation as a defense mechanism to reduce TDP-43 aggregation.

    PubMed

    Li, Huei-Ying; Yeh, Po-An; Chiu, Hsiu-Chiang; Tang, Chiou-Yang; Tu, Benjamin Pang-hsien

    2011-01-01

    Several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are characterized by inclusion bodies formed by TDP-43 (TDP). We established cell and transgenic Drosophila models expressing TDP carboxyl terminal fragment (ND251 and ND207), which developed aggregates recapitulating important features of TDP inclusions in ALS/FTLD-U, including hyperphosphorylation at previously reported serine(403,404,409,410) residues, polyubiquitination and colocalization with optineurin. These models were used to address the pathogenic role of hyperphosphorylation in ALS/FTLD-U. We demonstrated that hyperphosphorylation and ubiquitination occurred temporally later than aggregation in cells. Expression of CK2α which phosphorylated TDP decreased the aggregation propensity of ND251 or ND207; this effect could be blocked by CK2 inhibitor DMAT. Mutation of serines(379,403,404,409,410) to alanines (S5A) to eliminate phosphorylation increased the aggregation propensity and number of aggregates of TDP, but mutation to aspartic acids (S5D) or glutamic acids (S5E) to simulate hyperphosphorylation had the opposite effect. Functionally, ND251 or ND207 aggregates decreased the number of neurites of Neuro2a cells induced by retinoic acid or number of cells by MTT assay. S5A mutation aggravated, but S5E mutation alleviated these cytotoxic effects of aggregates. Finally, ND251 or ND251S5A developed aggregates in neurons, and salivary gland of transgenic Drosophila, but ND251S5E did not. Taken together, our data indicate that hyperphosphorylation may represent a compensatory defense mechanism to stop or prevent pathogenic TDP from aggregation. Therefore, enhancement of phosphorylation may serve as an effective therapeutic strategy against ALS/FTLD-U. PMID:21850253

  8. Breakdown of pulmonary host defense in the immunocompromised host: cancer chemotherapy.

    PubMed

    Joos, Ladina; Tamm, Michael

    2005-01-01

    The number of immunocompromised patients is steadily increasing due to HIV infection, solid organ and stem cell transplantation, intensified chemotherapy, immunosuppression for autoimmune diseases, and a marked increase in the use of monoclonal antibodies. Prevention strategies for pulmonary infections and diagnostic methods have evolved and patient outcome has improved. However, therapies affecting the immune system are also given to older patients and patients with comorbidities. While the rate of pulmonary complications in HIV patients has dramatically decreased under antiretroviral therapy, we are seeing more patients with pulmonary problems after chemotherapy. Neutropenia is still the most important risk factor for bacterial and fungal infection. Flexible bronchoscopy with BAL remains an important diagnostic method with a low morbidity and high diagnostic yield in patients with pulmonary infiltrates following cancer chemotherapy. PMID:16322598

  9. Mechanical defenses of plant extrafloral nectaries against herbivory.

    PubMed

    Gish, Moshe; Mescher, Mark C; De Moraes, Consuelo M

    2016-01-01

    Extrafloral nectaries play an important role in plant defense against herbivores by providing nectar rewards that attract ants and other carnivorous insects. However, extrafloral nectaries can themselves be targets of herbivory, in addition to being exploited by nectar-robbing insects that do not provide defensive services. We recently found that the extrafloral nectaries of Vicia faba plants, as well as immediately adjacent tissues, exhibit high concentrations of chemical toxins, apparently as a defense against herbivory. Here we report that the nectary tissues of this plant also exhibit high levels of structural stiffness compared to surrounding tissues, likely due to cell wall lignification and the concentration of calcium oxalate crystals in nectary tissues, which may provide an additional deterrent to herbivore feeding on nectary tissues. PMID:27489584

  10. Mechanical defenses of plant extrafloral nectaries against herbivory

    PubMed Central

    Gish, Moshe; Mescher, Mark C.; De Moraes, Consuelo M.

    2016-01-01

    ABSTRACT Extrafloral nectaries play an important role in plant defense against herbivores by providing nectar rewards that attract ants and other carnivorous insects. However, extrafloral nectaries can themselves be targets of herbivory, in addition to being exploited by nectar-robbing insects that do not provide defensive services. We recently found that the extrafloral nectaries of Vicia faba plants, as well as immediately adjacent tissues, exhibit high concentrations of chemical toxins, apparently as a defense against herbivory. Here we report that the nectary tissues of this plant also exhibit high levels of structural stiffness compared to surrounding tissues, likely due to cell wall lignification and the concentration of calcium oxalate crystals in nectary tissues, which may provide an additional deterrent to herbivore feeding on nectary tissues. PMID:27489584

  11. Change in Coping and Defense Mechanisms across Adulthood: Longitudinal Findings in a European-American Sample

    PubMed Central

    Diehl, Manfred; Chui, Helena; Hay, Elizabeth L.; Lumley, Mark A.; Grühn, Daniel; Labouvie-Vief, Gisela

    2014-01-01

    This study examined longitudinal changes in coping and defense mechanisms in an age- and gender-stratified sample of 392 European-American adults. Nonlinear age-related changes were found for the coping mechanisms of sublimation and suppression and the defense mechanisms of intellectualization, doubt, displacement, and regression. The change trajectories for sublimation and suppression showed that their use increased from adolescence to late middle age and early old age, and remained mostly stable into late old age. The change trajectory for intellectualization showed that the use of this defense mechanism increased from adolescence to middle age, remained stable until late midlife, and started to decline thereafter. The defense mechanisms of doubt, displacement, and regression showed decreases from adolescence until early old age, with increases occurring again after the age of 65. Linear age-related decreases were found for the coping mechanism of ego regression and the defense mechanisms of isolation and rationalization. Gender and socioeconomic status were associated with the mean levels of several coping and defense mechanisms, but did not moderate age-related changes. Increases in ego level were associated with increased use of the defense mechanism intellectualization and decreased use of the defense mechanisms of doubt and displacement. Overall, these findings in a European-American sample suggest that most individuals showed development in the direction of more adaptive and less maladaptive coping and defense strategies from adolescence until late middle age or early old age. However, in late old age this development was reversed, presenting potential challenges to the adaptive capacity of older adults. PMID:23834293

  12. Postoperative Pulmonary Dysfunction and Mechanical Ventilation in Cardiac Surgery

    PubMed Central

    Badenes, Rafael; Lozano, Angels; Belda, F. Javier

    2015-01-01

    Postoperative pulmonary dysfunction (PPD) is a frequent and significant complication after cardiac surgery. It contributes to morbidity and mortality and increases hospitalization stay and its associated costs. Its pathogenesis is not clear but it seems to be related to the development of a systemic inflammatory response with a subsequent pulmonary inflammation. Many factors have been described to contribute to this inflammatory response, including surgical procedure with sternotomy incision, effects of general anesthesia, topical cooling, and extracorporeal circulation (ECC) and mechanical ventilation (VM). Protective ventilation strategies can reduce the incidence of atelectasis (which still remains one of the principal causes of PDD) and pulmonary infections in surgical patients. In this way, the open lung approach (OLA), a protective ventilation strategy, has demonstrated attenuating the inflammatory response and improving gas exchange parameters and postoperative pulmonary functions with a better residual functional capacity (FRC) when compared with a conventional ventilatory strategy. Additionally, maintaining low frequency ventilation during ECC was shown to decrease the incidence of PDD after cardiac surgery, preserving lung function. PMID:25705516

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

    PubMed

    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. PMID:23158869

  14. EFFECTS OF ACUTE EXPOSURE TO PHOSGENE ON PULMONARY HOST DEFENSES AND RESISTANCE TO INFECTION

    EPA Science Inventory

    Phosgene is a toxic gas widely used in industrial processes. he most sensitive endpoint for phosgene toxicity in mice is decreased resistance to challenge with bacterial infection or tumor cells. were attributed to impaired alveolar macrophage (AM) and pulmonary natural killer ce...

  15. Modulation of pulmonary inflammatory responses and anti-microbial defenses in mice exposed to diesel exhaust

    EPA Science Inventory

    Abstract: Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and ...

  16. Calcium Homeostasis and Ionic Mechanisms in Pulmonary Fibroblasts.

    PubMed

    Janssen, Luke J; Mukherjee, Subhendu; Ask, Kjetil

    2015-08-01

    Fibroblasts are key cellular mediators of many chronic interstitial lung diseases, including idiopathic pulmonary fibrosis, scleroderma, sarcoidosis, drug-induced interstitial lung disease, and interstitial lung disease in connective tissue disease. A great deal of effort has been expended to understand the signaling mechanisms underlying the various cellular functions of fibroblasts. Recently, it has been shown that Ca(2+) oscillations play a central role in the regulation of gene expression in human pulmonary fibroblasts. However, the mechanisms whereby cytosolic [Ca(2+)] are regulated and [Ca(2+)] oscillations transduced are both poorly understood. In this review, we present the general concepts of [Ca(2+)] homeostasis, of ionic mechanisms responsible for various Ca(2+) fluxes, and of regulation of gene expression by [Ca(2+)]. In each case, we then also summarize the original findings that pertain specifically to pulmonary fibroblasts. From these data, we propose an overall signaling cascade by which excitation of the fibroblasts triggers pulsatile release of internally sequestered Ca(2+), which, in turn, activates membrane conductances, including voltage-dependent Ca(2+) influx pathways. Collectively, these events produce recurring Ca(2+) oscillations, the frequency of which is transduced by Ca(2+)-dependent transcription factors, which, in turn, orchestrate a variety of cellular events, including proliferation, synthesis/secretion of extracellular matrix proteins, autoactivation (production of transforming growth factor-β), and transformation into myofibroblasts. That unifying hypothesis, in turn, allows us to highlight several specific cellular targets and therapeutic intervention strategies aimed at controlling unwanted pulmonary fibrosis. The relationships between Ca(2+) signaling events and the unfolded protein response and apoptosis are also explored. PMID:25785898

  17. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  18. Inhalable particles and pulmonary host defense: in vivo and in vitro effects of ambient air and combustion particles.

    PubMed

    Hatch, G E; Boykin, E; Graham, J A; Lewtas, J; Pott, F; Loud, K; Mumford, J L

    1985-02-01

    The ability of particulate air pollutants (and possible constituents) to alter pulmonary host defenses was examined using an in vitro alveolar macrophage cytotoxicity assay and an in vivo bacterial infectivity screening test which employed intratracheal injection of the particles. A wide range of response between particles was seen at the 1.0-mg/ml level in vitro and the 0.1-mg/mouse level in vivo. A sample of fluidized-bed coal fly ash, bentonite, asbestos, some ambient air particles, and heavy metal oxides greatly increased susceptibility to pulmonary bacterial infection. Most coal fly ash samples and some air particles caused moderate increases in infectivity, while diesel particulates, volcanic ash, and crystalline silica caused only small increases. Cytotoxic effects on macrophages in vitro were observed with most of the particles. The in vivo and in vitro assays produced a similar ranking of toxicity; however, not all particles that were highly cytotoxic were potent in increasing bacterial infectivity. Increased toxicity measurable by either assay often appeared to be associated with small size or with the presence of metal in the particles. PMID:3967645

  19. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    PubMed

    Sussan, Thomas E; Gajghate, Sachin; Thimmulappa, Rajesh K; Ma, Jinfang; Kim, Jung-Hyun; Sudini, Kuladeep; Consolini, Nicola; Cormier, Stephania A; Lomnicki, Slawo; Hasan, Farhana; Pekosz, Andrew; Biswal, Shyam

    2015-01-01

    Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11) free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections. PMID:25651083

  20. Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model

    PubMed Central

    Sussan, Thomas E.; Gajghate, Sachin; Thimmulappa, Rajesh K.; Ma, Jinfang; Kim, Jung-Hyun; Sudini, Kuladeep; Consolini, Nicola; Cormier, Stephania A.; Lomnicki, Slawo; Hasan, Farhana; Pekosz, Andrew; Biswal, Shyam

    2015-01-01

    Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections. PMID:25651083

  1. Study of Defensive Methods and Mechanisms in Developmental, Emotional (Internalization), and Disruptive Behavior (Externalization) Disorders

    PubMed Central

    Jamilian, H. R.; Zamani, N.; Darvishi, M.; Khansari, M. R.

    2014-01-01

    We need to find a way for adaptation with inherent unpleasantness of being human condition and conflicts that it caused, as we did not fail. Methods that we used for adaptation are named defense. This research have performed with the aim of study and compare defensive mechanisms and methods of Developmental, Emotional (Internalization), and Disruptive behavior (Externalization) disorders. Method, sample of this research included 390 family that are by available sampling method are selected. Tools of research were structured clinical interview of forth cognitive and statistical guide of psychopathic disorders for axis I and the way used for assess defensive mechanisms is defensive method 40 question’s questionnaires of Andrews (1993). The data are compared by statistical methods comparison of averages and one way variance analysis and HSD tests and results show that undeveloped defensive mechanisms in by developmental disorder family(25.2± 3.7) mean and standard deviation, it is most used mechanism and in disruptive behavior disorder family by (11.2 ±1.9) mean and standard deviation is used least mechanism and in developed mechanism of emotional disorder family by (7.8 ± 3.1) mean and standard deviation is most used mechanism and in developmental disorder family by (4.3 ±1.5) mean and standard deviation is least mechanism in neuroticism patient, social phobia affected emotional disorder family (15.6±2.6) and disruptive behavior disorder family have least mean and standard deviation(9.2±1.7) (p< 0.005). Recent research shows significant of study defensive mechanism in psychopathic family of disorder children that affecting on the way of life of persons and interpersonal and intrapersonal relations and method of solving problem in family of them in life, so defensive mechanisms require more attention. PMID:25363187

  2. Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

    PubMed

    Langleben, D; Szarek, J L; Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1988-11-01

    Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model. PMID:3145283

  3. Mechanism of neutrophil recruitment to the lung after pulmonary contusion.

    PubMed

    Hoth, J Jason; Wells, Jonathan D; Hiltbold, Elizabeth M; McCall, Charles E; Yoza, Barbara K

    2011-06-01

    Blunt chest trauma resulting in pulmonary contusion is a common but poorly understood injury. We previously demonstrated that lung contusion activates localized and systemic innate immune mechanisms and recruits neutrophils to the injured lung. We hypothesized that the innate immune and inflammatory activation of neutrophils may figure prominently in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans and evaluated postinjury lung function and pulmonary neutrophil recruitment. Comparisons were made between injured mice with and without neutrophil depletion. We further examined the role of chemokines and adhesion receptors in neutrophil recruitment to the injured lung. We found that lung injury and resultant physiological dysfunction after contusion were dependent on the presence of neutrophils in the alveolar space. We show that CXCL1, CXCL2/3, and CXCR2 are involved in neutrophil recruitment to the lung after injury and that intercellular adhesion molecule 1 is locally expressed and actively participates in this process. Injured gp91-deficient mice showed improved lung function, indicating that oxidant production by neutrophil NADPH oxidase mediates lung dysfunction after contusion. These data suggest that both neutrophil presence and function are required for lung injury after lung contusion. PMID:21330942

  4. Change in children's externalizing and internalizing behavior problems: the role of defense mechanisms.

    PubMed

    Cramer, Phebe

    2015-03-01

    This study investigates the relation of defense mechanism to children's externalizing and internalizing behavior problems, as assessed from mothers' report at age 9 and 12 years, based on archival data. The defense mechanisms of denial, projection, and identification were assessed from Thematic Apperception Test stories told by the children at age 9 years, using the Defense Mechanism Manual (Cramer, The development of defense mechanisms: Theory, research and assessment. New York: Springer-Verlag, 1991a; Protecting the self: Defense mechanisms in action. New York: Guilford Press, 2006). The results showed that the use of identification predicted a decrease in externalizing behaviors between age 9 and 12 years. In contrast, change in internalizing behaviors was not predicted by defense use, but the use of projection was related to fewer internalizing behaviors at both ages. These findings are consistent with the idea that behavioral intervention stressing self-regulation can be effective in reducing externalizing problems, but internalizing problems require an intervention that is sensitive to the underlying behavioral inhibition in these children. PMID:25668653

  5. How does our brain constitute defense mechanisms? First-person neuroscience and psychoanalysis.

    PubMed

    Northoff, Georg; Bermpohl, Felix; Schoeneich, Frank; Boeker, Heinz

    2007-01-01

    Current progress in the cognitive and affective neurosciences is constantly influencing the development of psychoanalytic theory and practice. However, despite the emerging dialogue between neuroscience and psychoanalysis, the neuronal processes underlying psychoanalytic constructs such as defense mechanisms remain unclear. One of the main problems in investigating the psychodynamic-neuronal relationship consists in systematically linking the individual contents of first-person subjective experience to third-person observation of neuronal states. We therefore introduced an appropriate methodological strategy, 'first-person neuroscience', which aims at developing methods for systematically linking first- and third-person data. The utility of first-person neuroscience can be demonstrated by the example of the defense mechanism of sensorimotor regression as paradigmatically observed in catatonia. Combined psychodynamic and imaging studies suggest that sensorimotor regression might be associated with dysfunction in the neural network including the orbitofrontal, the medial prefrontal and the premotor cortices. In general sensorimotor regression and other defense mechanisms are psychoanalytic constructs that are hypothesized to be complex emotional-cognitive constellations. In this paper we suggest that specific functional mechanisms which integrate neuronal activity across several brain regions (i.e. neuronal integration) are the physiological substrates of defense mechanisms. We conclude that first-person neuroscience could be an appropriate methodological strategy for opening the door to a better understanding of the neuronal processes of defense mechanisms and their modulation in psychoanalytic psychotherapy. PMID:17426413

  6. In Defense of a Heuristic Interpretation of Quantum Mechanics

    ERIC Educational Resources Information Center

    Healy, Eamonn F.

    2010-01-01

    Although the presentation of quantum mechanics found in traditional textbooks is intellectually well founded, it suffers from a number of deficiencies. Specifically introducing quantum mechanics as a solution to the arcane dilemma, the ultraviolet catastrophe, does little to impress a nonscientific audience of the tremendous paradigmatic shift…

  7. IFN-γ induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

    PubMed

    Cai, S; Batra, S; Langohr, I; Iwakura, Y; Jeyaseelan, S

    2016-05-01

    The role of interleukin-17A (IL-17A) in host defense against Legionella pneumophila remains elusive. To address this issue, we used Il17a(-/-), Il17f(-/-), and Il17a/Il17f(-/-) mice on a C57Bl/6 (non-permissive) background and IL-17 neutralizing Abs in mice on an A/J (permissive) background. Higher bacterial (L. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in Il17a(-/-), but not Il17f(-/-), mice. We found that neutrophils produce IL-17A homodimer (IL-17A) during L. pneumophila infection, and hematopoietic cell-derived IL-17A is known to be important for bacterial clearance. Thus, intratracheal administration of wild-type neutrophils or recombinant IL-17A restored bacterial clearance and neutrophil recruitment in Il17a(-/-) mice. Furthermore, neutrophil-depleted Rag2(-/-) and Rag2/Il-2rγ(-/-) mice exhibited increased bacterial burden, reduced neutrophil influx and IL-17A production in the lung. Recombinant IFN-γ administration in Il17a(-/-) mice augmented bacterial elimination, whereas IL-17A administration in Ifnγ(-/-) mice did not augment bacterial clearance. IFN-γ is produced by T cells, but not neutrophils or macrophages, suggesting that neutrophil-derived IL-17A induces IFN-γ in a paracrine fashion. Human pneumonic lungs and human neutrophils challenged with L. pneumophila exhibited increased numbers of IL-17A producing cells. These findings display a novel function of neutrophil-derived IL-17A in antibacterial defense via the induction of IFN-γ in a paracrine manner. PMID:26349661

  8. Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents

    PubMed Central

    Dong, Jie; Yu, Xiaoqing; Porter, Dale W.; Battelli, Lori A.; Kashon, Michael L.

    2016-01-01

    Pulmonary fibrosis results from the excessive deposition of collagen fibers and scarring in the lungs with or without an identifiable cause. The mechanism(s) underlying lung fibrosis development is poorly understood, and effective treatment is lacking. Here we compared mouse lung fibrosis induced by pulmonary exposure to prototypical particulate (crystalline silica) or soluble chemical (bleomycin or paraquat) fibrogenic agents to identify the underlying mechanisms. Young male C57BL/6J mice were given silica (2 mg), bleomycin (0.07 mg), or paraquat (0.02 mg) by pharyngeal aspiration. All treatments induced significant inflammatory infiltration and collagen deposition, manifesting fibrotic foci in silica-exposed lungs or diffuse fibrosis in bleomycin or paraquat-exposed lungs on day 7 post-exposure, at which time the lesions reached their peaks and represented a junction of transition from an acute response to chronic fibrosis. Lung genomewide gene expression was analyzed, and differential gene expression was confirmed by quantitative RT-PCR, immunohistochemistry, and immunoblotting for representative genes to demonstrate their induced expression and localization in fibrotic lungs. Canonical signaling pathways, gene ontology, and upstream transcription networks modified by each agent were identified. In particular, these inducers elicited marked proliferative responses; at the same time, silica preferentially activated innate immune functions and the defense against foreign bodies, whereas bleomycin and paraquat boosted responses related to cell adhesion, platelet activation, extracellular matrix remodeling, and wound healing. This study identified, for the first time, the shared and unique genes, signaling pathways, and biological functions regulated by particulate and soluble chemical fibrogenic agents during lung fibrosis, providing insights into the mechanisms underlying human lung fibrotic diseases. PMID:26345256

  9. Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents.

    PubMed

    Dong, Jie; Yu, Xiaoqing; Porter, Dale W; Battelli, Lori A; Kashon, Michael L; Ma, Qiang

    2016-02-01

    Pulmonary fibrosis results from the excessive deposition of collagen fibers and scarring in the lungs with or without an identifiable cause. The mechanism(s) underlying lung fibrosis development is poorly understood, and effective treatment is lacking. Here we compared mouse lung fibrosis induced by pulmonary exposure to prototypical particulate (crystalline silica) or soluble chemical (bleomycin or paraquat) fibrogenic agents to identify the underlying mechanisms. Young male C57BL/6J mice were given silica (2 mg), bleomycin (0.07 mg), or paraquat (0.02 mg) by pharyngeal aspiration. All treatments induced significant inflammatory infiltration and collagen deposition, manifesting fibrotic foci in silica-exposed lungs or diffuse fibrosis in bleomycin or paraquat-exposed lungs on day 7 post-exposure, at which time the lesions reached their peaks and represented a junction of transition from an acute response to chronic fibrosis. Lung genome-wide gene expression was analyzed, and differential gene expression was confirmed by quantitative RT-PCR, immunohistochemistry, and immunoblotting for representative genes to demonstrate their induced expression and localization in fibrotic lungs. Canonical signaling pathways, gene ontology, and upstream transcription networks modified by each agent were identified. In particular, these inducers elicited marked proliferative responses; at the same time, silica preferentially activated innate immune functions and the defense against foreign bodies, whereas bleomycin and paraquat boosted responses related to cell adhesion, platelet activation, extracellular matrix remodeling, and wound healing. This study identified, for the first time, the shared and unique genes, signaling pathways, and biological functions regulated by particulate and soluble chemical fibrogenic agents during lung fibrosis, providing insights into the mechanisms underlying human lung fibrotic diseases. PMID:26345256

  10. Melatonin in relation to cellular antioxidative defense mechanisms.

    PubMed

    Reiter, R J; Carneiro, R C; Oh, C S

    1997-08-01

    macromolecules that occurs during strenuous exercise or ischemia-reperfusion. In experimental models which are used to study neurodegenerative changes associated with Alzheimer's and Parkinson disease, melatonin was found to be effective in reducing neuronal damage. Its lack of toxicity and the ease with which melatonin crosses morphophysiological barriers and enters subcellular compartments are essential features of this antioxidant. Thus far, most frequently pharmacological levels of melatonin have been used to combat oxygen toxicity. The role of physiological levels of melatonin, which are known to decrease with age, is being investigated as to their importance in the total antioxidative defense capacity of the organism. PMID:9288572

  11. Mechanisms of Defense against Intracellular Pathogens Mediated by Human Macrophages.

    PubMed

    Bloom, Barry R; Modlin, Robert L

    2016-06-01

    The key question our work has sought to address has been, "What are the necessary and sufficient conditions that engender protection from intracellular pathogens in the human host?" The origins of this work derive from a long-standing interest in the mechanisms of protection against two such paradigmatic intracellular pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, that have brilliantly adapted to the human host. It was obvious that these pathogens, which cause chronic diseases and persist in macrophages, must have acquired subtle strategies to resist host microbicidal mechanisms, yet since the vast majority of individuals infected with M. tuberculosis do not develop disease, there must be some potent human antimicrobial mechanisms. What follows is not a comprehensive review of the vast literature on the role of human macrophages in protection against infectious disease, but a summary of the research in our two laboratories with collaborators that we hope has contributed to some understanding of mechanisms of resistance and pathogenesis. While mouse models revealed some necessary conditions for protection, e.g., innate immunity, Th1 cells and their cytokines, and major histocompatibility complex class I-restricted T cells, here we emphasize multiple antimicrobial mechanisms that exist in human macrophages that differ from those of most experimental animals. Prominent here is the vitamin D-dependent antimicrobial pathway common to human macrophages activated by innate and acquired immune responses, mediated by antimicrobial peptides, e.g., cathelicidin, through an interleukin-15- and interleukin-32-dependent common pathway that is necessary for macrophage killing of M. tuberculosis in vitro. PMID:27337485

  12. Micropylar pollen tube guidance and burst: adapted from defense mechanisms?

    PubMed

    Dresselhaus, Thomas; Márton, Mihaela L

    2009-12-01

    After the first description of fertilization in flowering plants some 125 years ago (Strasburger E: Neue-Untersuchungen über den Befruchtungsvorgang bei den Phanerogamen als Grundlage für eine Theorie der Zeugung. Gustav Fischer; 1884), we are finally beginning to understand the various molecular mechanisms leading to sperm delivery and discharge inside the hidden micropylar region of the female gametophyte (embryo sac). The last phase of pollen tube guidance culminating in tube burst and explosive release of tube contents requires extensive crosstalk between both male and female gametophytes. The first molecules identified that play key roles in these processes represent highly polymorphic proteins, similar to major components of the plant innate immune system. Here we summarize recent advances and briefly discuss the underlying molecular mechanisms also in respect to prezygotic barriers of reproductive isolation. PMID:19896414

  13. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response

    SciTech Connect

    Zheng, Yi; Tao, Shasha; Lian, Fangru; Chau, Binh T.; Chen, Jie; Sun, Guifan; Fang, Deyu; Lantz, R. Clark; Zhang, Donna D.

    2012-12-15

    Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure. -- Highlights: ► Exposed to arsenic particles and/or SF have elevated Nrf2 and its target genes. ► Sulforaphane prevents pathological alterations, oxidative damage and cell death. ► Sulforaphane alleviates infiltration of inflammatory cells into the lungs. ► Sulforaphane suppresses arsenic-induced proinflammatory cytokine production.

  14. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC1, TH1, and TH17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by TH2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor κB (NF-κB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important. PMID:27373322

  15. Pulmonary Hypertension in the Era of Mechanical Circulatory Support.

    PubMed

    Krishnamurthy, Yamini; Cooper, Lauren B; Parikh, Kishan S; Felker, G Michael; Milano, Carmelo A; Rogers, Joseph G; Hernandez, Adrian F; Patel, Chetan B

    2016-01-01

    Left heart disease (LHD) represents the most common cause of pulmonary hypertension (PH), and is associated with worse prognosis compared with LHD without PH. In addition, PH due to LHD may prevent patients from receiving heart transplantation, because of risk of perioperative right ventricular failure. Current literature lacks comprehensive descriptions and management strategies of PH due to LHD. In this review, we summarize the literature that is available to highlight the definition, pathogenesis, and prognosis of PH due to LHD. Furthermore, we discuss the use of mechanical circulatory support (MCS) in this population. Finally, we provide recommendations regarding the management and reassessment of PH due to LHD in the specific context of MCS. PMID:27442856

  16. 6-Benzylaminopurine inhibits growth of Monilinia fructicola and induces defense-related mechanism in peach fruit.

    PubMed

    Zhang, Yangyang; Zeng, Lizhen; Yang, Jiali; Zheng, Xiaodong; Yu, Ting

    2015-11-15

    This study demonstrated the inhibitory effect of 6-benzylaminopurine (BAP), the first generation synthetic cytokinin, on the invasion of Monilinia fructicola in peach fruit and the possible mechanism involved for the first time. Our results suggested that BAP treatment had a 63% lower disease incidence and approximately 10 times lower lesion diameter compared to the control throughout the incubation period. In vitro BAP showed a direct inhibitory effect on M. fructicola spore germination. BAP could prevent fruit texture deterioration and protect the cell membrane from oxidative stress, while no adverse effects were observed on fruit quality maintenance. Analysis of defense-related enzymes activities indicated that the use of BAP induced higher specific polyphenol oxidase and peroxidase activities which triggered stronger host defensive responses. Thus, our results verified the proposed mechanism of BAP in controlling M. fructicola by direct inhibitory effect, delay peach senescence and activation of defensive enzymes. PMID:25977018

  17. Streptococcus pneumoniae: elusive mechanisms of the body's defense systems.

    PubMed

    Bondi, T; Canessa, C; Lippi, F; Iacopelli, J; Nieddu, F; Azzari, C

    2012-06-01

    Streptococcus pneumoniae is one of the most important human pathogens. It represents the most frequent cause of pneumonia, meningitis, sinusitis and otitis. After the PCV7 vaccine introduction, a serotypic switch was noticed. This phenomenon led to the replacement of the seven serotypes contained in the vaccine with other less common ones, some of which are invasive or characterised by antibiotic-resistance. This replacement is only partially due to the vaccination. Many causes have been suggested to explain this effect: apearance of new serotypes, diffusion of minority serotypes and replacement of common serotypes due to natural secular trend. Pneumococcus has a promiscuous "sex life", characterized by homologous recombinations within the same species and also between different species. This fact can unlock the secret of how these pathogens can develop antibiotic or vaccine-resistance. The serotypic switch involves big loci that are responsible for capsular polysaccharide synthesis. The most important region of the genome involved in this process is near the gene tetM. The same mechanisms are also responsible for antibiotic resistance. In recent years the growth of penicillin, macrolides and clindamycine resistance has been noticed. It is also important to underline that multidrug-resistant bacteria isolation has increased. In conclusion, to obtain more information about bacteria composition and evolution, antibiotic-resistance and vaccine response, it is fundamental to improve the epidemiological surveillance of pneumococcal infections using modern molecular diagnostic techinques. PMID:23240166

  18. FACTORS THAT INFLUENCE THE SUPPRESSION OF PULMONARY ANTIBACTERIAL DEFENSES IN MICE EXPOSED TO OZONE

    EPA Science Inventory

    Exposure to ozone (03) has been shown to increase susceptibility of mice to bacterial infection; however the underlying mechanism has not been well elucidated. his study investigated the effect Of 03 exposure on the ability of mice to combat an infectious challenge of Streptococc...

  19. Psychogenic non-epileptic seizures: so-called psychiatric comorbidity and underlying defense mechanisms.

    PubMed

    Beghi, Massimiliano; Negrini, Paola Beffa; Perin, Cecilia; Peroni, Federica; Magaudda, Adriana; Cerri, Cesare; Cornaggia, Cesare Maria

    2015-01-01

    In Diagnostic and Statistical Manual of Mental Disorders, fifth edition, psychogenic non-epileptic seizures (PNES) do not have a unique classification as they can be found within different categories: conversion, dissociative, and somatization disorders. The ICD-10, instead, considers PNES within dissociative disorders, merging the dissociative disorders and conversion disorders, although the underlying defense mechanisms are different. The literature data show that PNES are associated with cluster B (mainly borderline) personality disorders and/or to people with depressive or anxiety disorders. Defense mechanisms in patients with PNES with a prevalence of anxious/depressive symptoms are of "neurotic" type; their goal is to lead to a "split", either vertical (dissociation) or horizontal (repression). The majority of patients with this type of PNES have alexithymia traits, meaning that they had difficulties in feeling or perceiving emotions. In subjects where PNES are associated with a borderline personality, in which the symbolic function is lost, the defense mechanisms are of a more archaic nature (denial). PNES with different underlying defense mechanisms have different prognoses (despite similar severity of PNES) and need usually a different treatment (pharmacological or psychological). Thus, it appears superfluous to talk about psychiatric comorbidity, since PNES are a different symptomatic expression of specific psychiatric disorders. PMID:26491330

  20. Effects of Sex, Social Desirability, and Birth Order on the Defense Mechanisms Inventory.

    ERIC Educational Resources Information Center

    Dudley, Gary E.

    1978-01-01

    Investigated effects of sex difference, social desirability instructions, and birth order of respondents on defense mechanisms inventory (DMI). Sex difference was found in projection only. Social desirability effects were found in turning-against-others, projection, principalization, and reversal. Thus, an interpretive caution is in order…

  1. Brief Report: The Defense Mechanisms of Homophobic Adolescent Males--A Descriptive Discriminant Analysis

    ERIC Educational Resources Information Center

    Lewis, Andrew J.; White, Jennifer

    2009-01-01

    The study examined the role of defense mechanisms in homophobic attitudes of older male adolescents aged 17-18 years. A cross-sectional survey collected data from final year high school students (N = 86) attending an all male school in a regional centre in Victoria, Australia. The school was identified by teachers as having a problematic culture…

  2. Learning to Recognize Ego Defense Mechanisms: Results of a Structured Teaching Experience for Psychiatric Residents

    ERIC Educational Resources Information Center

    Beresford, Thomas P.

    2005-01-01

    Objective: Ego defense mechanism (EDM) recognition can offer a powerful and practical tool in clinical psychiatry. However, recognition skill learning can be difficult to assess and may account for the lack of formal EDM recognition training in residency courses. Method: This study hypothesized that mean test scores would increase significantly…

  3. Psychogenic non-epileptic seizures: so-called psychiatric comorbidity and underlying defense mechanisms

    PubMed Central

    Beghi, Massimiliano; Negrini, Paola Beffa; Perin, Cecilia; Peroni, Federica; Magaudda, Adriana; Cerri, Cesare; Cornaggia, Cesare Maria

    2015-01-01

    In Diagnostic and Statistical Manual of Mental Disorders, fifth edition, psychogenic non-epileptic seizures (PNES) do not have a unique classification as they can be found within different categories: conversion, dissociative, and somatization disorders. The ICD-10, instead, considers PNES within dissociative disorders, merging the dissociative disorders and conversion disorders, although the underlying defense mechanisms are different. The literature data show that PNES are associated with cluster B (mainly borderline) personality disorders and/or to people with depressive or anxiety disorders. Defense mechanisms in patients with PNES with a prevalence of anxious/depressive symptoms are of “neurotic” type; their goal is to lead to a “split”, either vertical (dissociation) or horizontal (repression). The majority of patients with this type of PNES have alexithymia traits, meaning that they had difficulties in feeling or perceiving emotions. In subjects where PNES are associated with a borderline personality, in which the symbolic function is lost, the defense mechanisms are of a more archaic nature (denial). PNES with different underlying defense mechanisms have different prognoses (despite similar severity of PNES) and need usually a different treatment (pharmacological or psychological). Thus, it appears superfluous to talk about psychiatric comorbidity, since PNES are a different symptomatic expression of specific psychiatric disorders. PMID:26491330

  4. DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A NATURAL BIO-DEFENSE MECHANISM

    EPA Science Inventory

    DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A natural bio-defense mechanism
    Anuradha Mudipalli.

    Maintenance of genetic information, including the correct sequence of nucleotides in DNA, is essential for replication, gene expression, and protein synthesis. DNA lesions onto...

  5. Lung region and racing affect mechanical properties of equine pulmonary microvasculature.

    PubMed

    Stack, Alice; Derksen, Frederik J; Williams, Kurt J; Robinson, N Edward; Jackson, William F

    2014-08-15

    Exercise-induced pulmonary hemorrhage is a performance-limiting condition of racehorses associated with severe pathology, including small pulmonary vein remodeling. Pathology is limited to caudodorsal (CD) lung. Mechanical properties of equine pulmonary microvasculature have not been studied. We hypothesized that regional differences in pulmonary artery and vein mechanical characteristics do not exist in control animals, and that racing and venous remodeling impact pulmonary vein mechanical properties in CD lung. Pulmonary arteries and veins [range of internal diameters 207-386 ± 67 μm (mean ± SD)] were harvested from eight control and seven raced horses. With the use of wire myography, CD and cranioventral (CV) vessels were stretched in 10-μm increments. Peak wall tension was plotted against changes in diameter (length). Length-tension data were compared between vessel type, lung region, and horse status (control and raced). Pulmonary veins are stiffer walled than arteries. CD pulmonary arteries are stiffer than CV arteries, whereas CV veins are stiffer than CD veins. Racing is associated with increased stiffness of CD pulmonary veins and, to a lesser extent, CV arteries. For example, at 305 μm, tension in raced and control CD veins is 27.74 ± 2.91 and 19.67 ± 2.63 mN/mm (means ± SE; P < 0.05, Bonferroni's multiple-comparisons test after two-way ANOVA), and 16.12 ± 2.04 and 15.07 ± 2.47 mN/mm in raced and control CV arteries, respectively. This is the first report of an effect of region and/or exercise on mechanical characteristics of small pulmonary vessels. These findings may implicate pulmonary vein remodeling in exercise-induced pulmonary hemorrhage pathogenesis. PMID:24925981

  6. Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis

    PubMed Central

    Chen, Gwo-Hsiao; Olszewski, Michal A.; McDonald, Roderick A.; Wells, Jason C.; Paine, Robert; Huffnagle, Gary B.; Toews, Galen B.

    2007-01-01

    We investigated the role of granulocyte macrophage colony-stimulating factor (GM-CSF) in host defense in a murine model of pulmonary cryptococcosis induced by intratracheal inoculation of Cryptococcus neoformans. Pulmonary C. neoformans infection of C57BL/6 mice is an established model of an allergic bronchopulmonary mycosis. Our objective was to determine whether GM-CSF regulates the pulmonary Th2 immune response in C. neoformans-infected C57BL/6 mice. Long-term pulmonary fungistasis was lost in GM-CSF knockout (GM−/−) mice, resulting in increased pulmonary burden of fungi between weeks 3 and 5. GM-CSF was required for the early influx of macrophages and CD4 and CD8 T cells into the lungs but was not required later in the infection. Lack of GM-CSF also resulted in reduced eosinophil recruitment and delayed recruitment of mononuclear cells into the airspace. Macrophages from GM+/+ mice showed numerous hallmarks of alternatively activated macrophages: higher numbers of intracellular cryptococci, YM1 crystals, and induction of CCL17. These hallmarks are absent in macrophages from GM−/− mice. Mucus-producing goblet cells were abundantly present within the bronchial epithelial layer in GM+/+ mice but not in GM−/− mice at week 5 after infection. Production of both Th1 and Th2 cytokines was impaired in the absence of GM-CSF, consistent with both reduced C. neoformans clearance and absence of allergic lung pathology. PMID:17322386

  7. Molecular mechanisms of hypoxia-inducible factor-induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension.

    PubMed

    Veith, Christine; Schermuly, Ralph T; Brandes, Ralf P; Weissmann, Norbert

    2016-03-01

    Oxygen (O2) is essential for the viability and function of most metazoan organisms and thus is closely monitored at both the organismal and the cellular levels. However, alveoli often encounter decreased O2 levels (hypoxia), leading to activation of physiological or pathophysiological responses in the pulmonary arteries. Such changes are achieved by activation of transcription factors. The hypoxia-inducible factors (HIFs) are the most prominent hypoxia-regulated transcription factors in this regard. HIFs bind to hypoxia-response elements (HREs) in the promoter region of target genes, whose expression and translation allows the organism, amongst other factors, to cope with decreased environmental O2 partial pressure (pO2). However, prolonged HIF activation can contribute to major structural alterations, especially in the lung, resulting in the development of pulmonary hypertension (PH). PH is characterized by a rise in pulmonary arterial pressure associated with pulmonary arterial remodelling, concomitant with a reduced intravascular lumen area. Patients with PH develop right heart hypertrophy and eventually die from right heart failure. Thus, understanding the molecular mechanisms of HIF regulation in PH is critical for the identification of novel therapeutic strategies. This review addresses the relationship of hypoxia and the HIF system with pulmonary arterial dysfunction in PH. We particularly focus on the cellular and molecular mechanisms underlying the HIF-driven pathophysiological processes. PMID:26228924

  8. Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

    1997-01-01

    BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

  9. Gregarious pupation act as a defensive mechanism against cannibalism and intraguild predation.

    PubMed

    Roberge, Claudia; Fréchette, Bruno; Labrie, Geneviève; Dumont, François; Lucas, Eric

    2016-08-01

    Coccinellid pupae use an array of defensive strategies against their natural enemies. This study aims to assess the efficiency of gregarious pupation as a defensive mechanism against intraguild predators and cannibals in coccinellid. The study was designed specifically (i) to determine the natural occurrence of gregarious pupation in the field for different coccinellid species, and (ii) to evaluate the adaptive value of gregarious pupation as a defensive mechanism against 2 types of predators (i.e., cannibals and intraguild predators). In the field, gregarious pupation consisted of a group of 2-5 pupae. The proportion of gregarious pupation observed varied according to species, the highest rate being observed with Harmonia axyridis Pallas (Coccinellidae; 14.17%). Gregarious pupation had no impact on the probability that intraguild predators and cannibals locate pupae. Intraguild predation occurred more often in site with gregarious pupation, while cannibalism occurred as often in site with gregarious pupation as in site with isolated pupa. However, for a specific pupa, the mortality rate was higher for isolated pupae than for pupae located in a gregarious pupation site both in the presence of intraguild predators and in the presence of cannibals. The spatial location of pupae within the group had no impact on mortality rate. Since it reduces the risk of predation, it is proposed that gregarious pupation act as a defensive mechanism for H. axyridis pupae. PMID:25684624

  10. Pulmonary epithelial barrier function: some new players and mechanisms

    PubMed Central

    Brune, Kieran; Frank, James; Schwingshackl, Andreas; Finigan, James

    2015-01-01

    The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells. In this review, we will discuss a few emerging paradigms of permeability changes through altered ion transport and paracellular regulation by which the epithelium gates its response to potentially detrimental luminal stimuli. This review is a summary of talks presented during a symposium in Experimental Biology geared toward novel and less recognized methods of epithelial barrier regulation. First, we will discuss mechanisms of dynamic regulation of cell-cell contacts in the context of repetitive exposure to inhaled infectious and noninfectious insults. In the second section, we will briefly discuss mechanisms of transcellular ion homeostasis specifically focused on the role of claudins and paracellular ion-channel regulation in chronic barrier dysfunction. In the next section, we will address transcellular ion transport and highlight the role of Trek-1 in epithelial responses to lung injury. In the final section, we will outline the role of epithelial growth receptor in barrier regulation in baseline, acute lung injury, and airway disease. We will then end with a summary of mechanisms of epithelial control as well as discuss emerging paradigms of the epithelium role in shifting between a structural element that maintains tight cell-cell adhesion to a cell that initiates and participates in immune responses. PMID:25637609

  11. Mechanical induction of cough in Idiopathic Pulmonary Fibrosis

    PubMed Central

    2011-01-01

    Background Patients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF. Methods We studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects. Results In patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex. Conclusions This study demonstrates that patients with IPF show

  12. Polydatin Attenuates Hypoxic Pulmonary Hypertension and Reverses Remodeling through Protein Kinase C Mechanisms

    PubMed Central

    Miao, Qing; Shi, Xiao-Peng; Ye, Ming-Xiang; Zhang, Jin; Miao, Shan; Wang, Si-Wang; Li, Bo; Jiang, Xiu-Xiu; Zhang, Song; Hu, Nan; Li, Juan; Zhang, Jian

    2012-01-01

    Hypoxic pulmonary hypertension is a life-threatening emergency if untreated. Consistent pulmonary hypertension also leads to arteries and ventricular remodeling. The clinical therapeutic strategy for pulmonary hypertension and the corresponding remodeling mainly interacts with NO, angiotensin II (Ang II) and elevated endothelin (ET) targets. In the present study, we evaluated the effects of polydatin on hypoxia-induced pulmonary hypertension. It was observed that polydatin attenuated hypoxic pulmonary hypertension, reversed remodeling, and regulated NO, Ang II, ET contents in the serum and lung samples. However, forced activation of PKC signaling by its selective activator thymeleatoxin (THX) could abate the effects of polydatain. These results suggest that polydatin might be a promising candidate for hypoxic pulmonary treatment through interaction with PKC mechanisms. PMID:22837726

  13. Pulmonary edema following scorpion envenomation: mechanisms, clinical manifestations, diagnosis and treatment.

    PubMed

    Bahloul, Mabrouk; Chaari, Anis; Dammak, Hassen; Samet, Mohamed; Chtara, Kamilia; Chelly, Hedi; Ben Hamida, Chokri; Kallel, Hatem; Bouaziz, Mounir

    2013-01-10

    Scorpion envenomation is common in tropical and subtropical regions. Cardio-respiratory manifestations, mainly cardiogenic shock and pulmonary edema, are the leading causes of death after scorpion envenomation. The mechanism of pulmonary edema remains unclear and contradictory conclusions were published. However, most publications confirm that pulmonary edema has been attributed to acute left ventricular failure. Cardiac failure can result from massive release of catecholamines, myocardial damage induced by the venom or myocardial ischemia. Factors usually associated with the diagnosis of pulmonary edema were young age, tachypnea, agitation, sweating, or the presence of high plasma protein concentrations. Treatment of scorpion envenomation has two components: antivenom administration and supportive care. The latter mainly targets hemodynamic impairment and cardiogenic pulmonary edema. In Latin America, and India, the use of Prazosin is recommended for treatment of pulmonary edema because pulmonary edema is associated with arterial hypertension. However, in North Africa, scorpion leads to cardiac failure with systolic dysfunction with normal vascular resistance and dobutamine was recommended. Dobutamine infusion should be used as soon as we have enough evidence suggesting the presence of pulmonary edema, since it has been demonstrated that scorpion envenomation can result in pulmonary edema secondary to acute left ventricular failure. In severe cases, mechanical ventilation can be required. PMID:22075406

  14. Exploring the association of ego defense mechanisms with problematic internet use in a Pakistani medical school.

    PubMed

    Waqas, Ahmed; Rehman, Abdul; Malik, Aamenah; Aftab, Ramsha; Allah Yar, Aroosa; Allah Yar, Arooj; Rai, Aitzaz Bin Sultan

    2016-09-30

    The present study was designed to analyze association between problematic internet use and use of ego defense mechanisms in medical students. This cross-sectional study was undertaken at CMH Lahore Medical College (CMH LMC) in Lahore, Pakistan from 1st March, 2015 to 30th May, 2015. 522 medical and dental students were included in the study. The questionnaire consisted of three sections: a) demographic characteristics of respondent b) the Defense Style Questionnaire-40 (DSQ-40) and c) the Internet Addiction Test (IAT). All data were analyzed in SPSS v20. Chi square, Independent sample t test and One Way ANOVA were run to analyze association of different variables with scores on IAT. Multiple regression analysis was used to delineate ego defenses as predictors of problematic internet use. A total of 32 (6.1%) students reported severe problems with internet usage. Males had higher scores on IAT i.e had more problematic use of internet. Scores on internet addiction test (IAT) were negatively associated with sublimation and positively associated with projection, denial, autistic fantasy, passive aggression and displacement. There was a high prevalence of problematic use of internet among medical and dental students. It had significant associations with several defense mechanisms. PMID:27504797

  15. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem

    PubMed Central

    Ward, Jeremy P.T.; McMurtry, Ivan F.

    2009-01-01

    Hypoxic pulmonary vasoconstriction (HPV) normally optimises ventilation-perfusion matching in the lung, but leads to pulmonary hypertension under conditions of global hypoxia. The past few years have provided some major advances in our understanding of this complex phenomenon, but significant controversy remains concerning many of the key underlying mechanisms. On balance, recent evidence is most consistent with an elevation in mitochondria-derived reactive oxygen species as a key event for initiation of HPV, with consequent Ca2+ release from intracellular ryanodine-sensitive stores, although the activation pathways and molecular identity of the associated Ca2+ entry pathways remain unclear. Recent studies have also raised our perception of the critical role played by Rho kinase in both sustained HPV and the development of pulmonary hypertension, further promoting Rho kinase and the pathways regulating its activity and expression as important therapeutic targets. PMID:19297247

  16. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

    PubMed

    Laveneziana, Pierantonio; Garcia, Gilles; Joureau, Barbara; Nicolas-Jilwan, Fadia; Brahimi, Toufik; Laviolette, Louis; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Similowski, Thomas

    2013-03-01

    Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea. PMID:22790921

  17. [Pathogenesis of pulmonary complications in severe mechanical non-thoracic trauma].

    PubMed

    Deriabin, I I; Novikov, S A

    1979-05-01

    On the grounds of morphologic studies the authors suppose that pulmonary complications of a severe mechanical trauma without injuries to thoracic organs are due to microcirculatory disorders and to microatelectases resulting from the trauma. PMID:452277

  18. Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.

    PubMed

    Adegunsoye, Ayodeji; Balachandran, Jay

    2015-01-01

    Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chronic hypoxemia leading to the release of proinflammatory cytokines that may propagate clinical deterioration and alter the pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1), interleukin- (IL-) 1α, cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β), lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG-1), macrophage inflammatory protein- (MIP-) 1α, MIP-3α, and nuclear factor- (NF-) κB appear to mediate disease progression. Adipocytes may induce hypoxia inducible factor (HIF) 1α production; GERD is associated with increased levels of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and tumor necrosis factor alpha (TNF-α); pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein kinase C (PKC) mediated upregulation of TNF-α and IL-1β also occurs in the pulmonary arteries. Increased understanding of the inflammatory mechanisms driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may potentiate the identification of appropriate therapeutic targets for developing effective therapies. PMID:25944985

  19. Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

    PubMed

    Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

    2016-01-01

    Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered. PMID:26152688

  20. Investigating Aggressive Styles and Defense Mechanisms in Bipolar Patients and in their Parents.

    PubMed

    Bragazzi, Nicola Luigi; Pezzoni, Franca; Del Puente, Giovanni

    2014-11-01

    Bipolar disorder (BD) is a very common mental health disorder, whose etiology concerning aggressive styles and defense mechanisms is still poorly known despite the efforts dedicated to develop psychological and biological theories. After obtaining written signed informed consent, this study will recruit inpatients with a clinical diagnosis of BD, based on Structured Clinical Interview and the Diagnostic and Statistical Manual of Mental Disorders criteria, and their parents. The Bus-Perry Aggression Questionnaire, the Defense Style Questionnaire 40, the Symptom check list SCL-90-R, developed by DeRogatis will be administered to the participants, together with a semi-structured questionnaire concerning demographic data (age, gender, employment, education) and only for the patients clinical information (onset year of the disorder, presence of co-morbidities, alcohol and drug use, suicide tendencies, kind of treatment). All the questionnaires are in the Italian validated version. The successful completion of this study will shed light on the relationship between aggressive styles and defensive mechanisms in bipolar inpatients and in their parents, helping the clinicians to develop ad hoc psychological interventions. PMID:26973942

  1. Molecular Dynamics Simulation and Statistics Analysis Reveals the Defense Response Mechanism in Plants

    NASA Astrophysics Data System (ADS)

    Liu, Zhichao; Zhao, Yunjie; Zeng, Chen; Computational Biophysics Lab Team

    As the main protein of the bacterial flagella, flagellin plays an important role in perception and defense response. The newly discovered locus, FLS2, is ubiquitously expressed. FLS2 encodes a putative receptor kinase and shares many homologies with some plant resistance genes and even with some components of immune system of mammals and insects. In Arabidopsis, FLS2 perception is achieved by the recognition of epitope flg22, which induces FLS2 heteromerization with BAK1 and finally the plant immunity. Here we use both analytical methods such as Direct Coupling Analysis (DCA) and Molecular Dynamics (MD) Simulations to get a better understanding of the defense mechanism of FLS2. This may facilitate a redesign of flg22 or de-novo design for desired specificity and potency to extend the immune properties of FLS2 to other important crops and vegetables.

  2. Mechanism of bystander-blaming: defensive attribution, counterfactual thinking, and gender.

    PubMed

    Levy, Inna; Ben-David, Sarah

    2015-01-01

    Contemporary victimology recognizes that an understanding of the mechanism of blaming requires a comprehensive approach that includes the victim, the offender, and the bystander. However, most of the existing research on blaming focuses on the victim and the offender, ignoring the issue of bystander-blaming. This study highlights the bystander and investigates bystander-blaming by exploring some theoretical explanations, including counterfactual thinking, defensive attribution, and gender differences. The study included 363 young male and female participants, who read vignettes describing the behavior of the victim and the bystander in a rape scenario and answered questions regarding bystander-blaming. The results show that both counterfactual thinking and defensive attribution play a role in bystander-blaming. This article addresses the theoretical and practical implications of these findings. PMID:24052599

  3. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    PubMed Central

    Tsai, I-Chun; Lin, Che; Chuang, Yung-Jen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection. PMID:24757665

  4. Of Amoebae and Men: Extracellular DNA Traps as an Ancient Cell-Intrinsic Defense Mechanism

    PubMed Central

    Zhang, Xuezhi; Soldati, Thierry

    2016-01-01

    Since the discovery of the formation of DNA-based extracellular traps (ETs) by neutrophils as an innate immune defense mechanism (1), hundreds of articles describe the involvement of ETs in physiological and pathological human and animal conditions [reviewed in Ref. (2), and the previous Frontiers Research Topic on NETosis: http://www.frontiersin.org/books/NETosis_At_the_Intersection_of_Cell_Biology_Microbiology_and_Immunology/195]. Interestingly, a few reports reveal that ETs can be formed by immune cells of more ancient organisms, as far back as the common ancestor of vertebrates and invertebrates (3). Recently, we reported that the Sentinel cells of the multicellular slug of the social amoeba Dictyostelium discoideum also produce ETs to trap and kill slug-invading bacteria [see Box 1; and Figure 1 Ref. (4)]. This is a strong evidence that DNA-based cell-intrinsic defense mechanisms emerged much earlier than thought, about 1.3 billion years ago. Amazingly, using extrusion of DNA as a weapon to capture and kill uningestable microbes has its rationale. During the emergence of multicellularity, a primitive innate immune system developed in the form of a dedicated set of specialized phagocytic cells. This professionalization of immunity allowed the evolution of sophisticated defense mechanisms including the sacrifice of a small set of cells by a mechanism related to NETosis. This altruistic behavior likely emerged in steps, starting from the release of “dispensable” mitochondrial DNA by D. discoideum Sentinel cells. Grounded in this realization, one can anticipate that in the near future, many more examples of the invention and fine-tuning of ETs by early metazoan ancestors will be identified. Consequently, it can be expected that this more complete picture of the evolution of ETs will impact our views of the involvement and pathologies linked to ETs in human and animals. PMID:27458458

  5. Of Amoebae and Men: Extracellular DNA Traps as an Ancient Cell-Intrinsic Defense Mechanism.

    PubMed

    Zhang, Xuezhi; Soldati, Thierry

    2016-01-01

    Since the discovery of the formation of DNA-based extracellular traps (ETs) by neutrophils as an innate immune defense mechanism (1), hundreds of articles describe the involvement of ETs in physiological and pathological human and animal conditions [reviewed in Ref. (2), and the previous Frontiers Research Topic on NETosis: http://www.frontiersin.org/books/NETosis_At_the_Intersection_of_Cell_Biology_Microbiology_and_Immunology/195]. Interestingly, a few reports reveal that ETs can be formed by immune cells of more ancient organisms, as far back as the common ancestor of vertebrates and invertebrates (3). Recently, we reported that the Sentinel cells of the multicellular slug of the social amoeba Dictyostelium discoideum also produce ETs to trap and kill slug-invading bacteria [see Box 1; and Figure 1 Ref. (4)]. This is a strong evidence that DNA-based cell-intrinsic defense mechanisms emerged much earlier than thought, about 1.3 billion years ago. Amazingly, using extrusion of DNA as a weapon to capture and kill uningestable microbes has its rationale. During the emergence of multicellularity, a primitive innate immune system developed in the form of a dedicated set of specialized phagocytic cells. This professionalization of immunity allowed the evolution of sophisticated defense mechanisms including the sacrifice of a small set of cells by a mechanism related to NETosis. This altruistic behavior likely emerged in steps, starting from the release of "dispensable" mitochondrial DNA by D. discoideum Sentinel cells. Grounded in this realization, one can anticipate that in the near future, many more examples of the invention and fine-tuning of ETs by early metazoan ancestors will be identified. Consequently, it can be expected that this more complete picture of the evolution of ETs will impact our views of the involvement and pathologies linked to ETs in human and animals. PMID:27458458

  6. Contribution of Patient Defense Mechanisms and Therapist Interventions to the Development of Early Therapeutic Alliance in a Brief Psychodynamic Investigation

    PubMed Central

    Despland, Jean-Nicolas; de Roten, Yves; Despars, Josée; Stigler, Michael; Perry, J. Christopher

    2001-01-01

    This preliminary study examined how patients' defense mechanisms and psychotherapists' techniques influence early alliance formation. The authors assessed the relationships among defense mechanisms, therapist interventions, and the development of alliance in a sample of 12 patients undergoing Brief Psychodynamic Investigation (4 sessions). Alliance development occurred rapidly and was clearly established by the third session. Neither defensive functioning nor supportive or exploratory interventions alone differentiated early alliance development. However, the degree of adjustment of therapists' interventions to patients' level of defensive functioning discriminated a low alliance from both improving and high alliances. The adjustment of therapeutic interventions to patients' level of defensive functioning is a promising predictor of alliance development and should be examined further, alongside other predictors of outcome. PMID:11402078

  7. An Experimental Method for Measuring Mechanical Properties of Rat Pulmonary Arteries Verified With Latex

    PubMed Central

    Drexler, E. S.; Slifka, A. J.; Wright, J. E.; McCowan, C. N.; Finch, D. S.; Quinn, T. P.; McColskey, J. D.; Ivy, D. D.; Shandas, R.

    2003-01-01

    This paper describes a test method for measuring the mechanical properties of small, nonlinear membrane samples from a rat model for pulmonary hypertension. The size and nonlinearity of the pulmonary artery samples poses a challenge for developing a test method that will generate quality, reproducible data in the pressure range experienced by the hypertensive pulmonary artery. The experimental method described here has sufficient precision to yield a combined relative standard uncertainty of 4 %. The method is calibrated against 75 µm thick latex and the data agree well with the neo-Hookian model.

  8. Mechanics and Function of the Pulmonary Vasculature: Implications for Pulmonary Vascular Disease and Right Ventricular Function

    PubMed Central

    Lammers, Steven; Scott, Devon; Hunter, Kendall; Tan, Wei; Shandas, Robin; Stenmark, Kurt R.

    2012-01-01

    The relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship. PMID:23487595

  9. Mechanism of pulmonary conversion of angiotensin I to angiotensin II in the dog.

    NASA Technical Reports Server (NTRS)

    Oparil, S.; Tregear, G. W.; Koerner, T.; Barnes, B. A.; Haber, E.

    1971-01-01

    The conversion mechanism was studied in vivo in the pulmonary circulation of the intact anesthetized dog and in vitro in plasma by using L-Leu-angiotensin I, D-Leu-angiotensin I, and des-Leu-angiotensin I which had been synthesized by the solid-phase technique. The results obtained indicate that pulmonary conversion in vivo and plasma conversion in vitro occur via a dipeptidylcarboxypeptidase and that a D-amino acid at the C-terminus prevents conversion.

  10. Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke.

    PubMed

    Liu, S Q; Fung, Y C

    1993-09-01

    The effect of cigarette smoke on the structure and mechanical properties of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times per day with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The volume fractions of the cells, including smooth muscle cells and fibroblasts, and extracellular matrix components, including collagen, elastin, and remainder (components not specified in this study), of the pulmonary arteries of approximately 450 microns in external diameter (at zero pressure) were determined in smoke-exposed and control rats by using an electron microscopic method. It was found that the volume fractions of the fibroblasts, the collagenous bundles, and the elastic laminae of the pulmonary arteries were increased significantly, whereas those of the smooth muscle cells and the remainder were decreased significantly in both the 2- and 3-month smoke-exposed rats in comparison with those of the corresponding control rats. The mechanical properties of the pulmonary arteries were determined based on the in vitro dimensional measurement of the vessels at various inflation pressures and zero-stress state. An increase in the stiffness of the pulmonary arteries was found in both the 2- and 3-month smoke-exposed rats. We conclude that cigarette smoke can induce structural and mechanical remodeling in the pulmonary arteries of rats. PMID:8368648

  11. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  12. [The structure and mechanical properties of the human pulmonary trunk and its valves].

    PubMed

    Antipas, D B; Milovanova, Z P; Zavalishin, N N

    1993-01-01

    The histological structure and mechanical properties of the pulmonary trunk and its valves were studied in 35 complexes of the pulmonary artery of man. The valvular apparatus of the pulmonary trunk is formed by anatomical elements with different morphological structures. In it there are elements which might be considered from standpoints of biomechanics as membranous (pulmonary trunk, sinuses, cusps) and shaft (fibrous ring, commissural shafts, arcuate crests) elements, the commissural shafts representing a combination of structures forming a closed spatial inter-related construction--a natural elastic framework of the pulmonary trunk root and the sheath elements are morphologically interrelated and fixed on this framework. The mechanical properties of these shaft elements are formed not only at the expense of inclusion of other formations in their structure but also at the expense of changes in the density of distribution and spatial orientation of main carrier structures of sheath elements attached to them. So, the strength and rigidity of the fibrous ring were associated not only with the presence of collagenous fibers and chondroid tissue n it, but also with the regular arrangement of collagenous fibers coming to it from the sinus. Similarly, the strength of arcuate crests was in many respects dependent on dense arrangement of longitudinally oriented smooth muscles. The amount of smooth muscles in the pulmonary trunk was 1.3 and 2 times higher than that of collagenous and elastic structures which allows the pulmonary trunk of man to be referred to arteries of muscular or mixed type. It points to the necessity to take into account the influence of muscle tone on mechanical behavior of the pulmonary trunk under physiological exercise. PMID:7889164

  13. Guardian of the Human Genome: Host Defense Mechanisms against LINE-1 Retrotransposition.

    PubMed

    Ariumi, Yasuo

    2016-01-01

    Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome, encoding a newly identified ORF0 with unknown function, ORF1p with RNA-binding activity and ORF2p with endonuclease and reverse transcriptase activities required for L1 retrotransposition. L1 utilizes an endonuclease (EN) to insert L1 cDNA into target DNA, which induces DNA double-strand breaks (DSBs). The ataxia-telangiectasia mutated (ATM) is activated by DSBs and subsequently the ATM-signaling pathway plays a role in regulating L1 retrotransposition. In addition, the host DNA repair machinery such as non-homologous end-joining (NHEJ) repair pathway is also involved in L1 retrotransposition. On the other hand, L1 is an insertional mutagenic agent, which contributes to genetic change, genomic instability, and tumorigenesis. Indeed, high-throughput sequencing-based approaches identified numerous tumor-specific somatic L1 insertions in variety of cancers, such as colon cancer, breast cancer, and hepatocellular carcinoma (HCC). In fact, L1 retrotransposition seems to be a potential factor to reduce the tumor suppressive property in HCC. Furthermore, recent study demonstrated that a specific viral-human chimeric transcript, HBx-L1, contributes to hepatitis B virus (HBV)-associated HCC. In contrast, host cells have evolved several defense mechanisms protecting cells against retrotransposition including epigenetic regulation through DNA methylation and host defense factors, such as APOBEC3, MOV10, and SAMHD1, which restrict L1 mobility as a guardian of the human genome. In this review, I focus on somatic L1 insertions into the human genome in cancers and host defense mechanisms against deleterious L1 insertions. PMID:27446907

  14. Guardian of the Human Genome: Host Defense Mechanisms against LINE-1 Retrotransposition

    PubMed Central

    Ariumi, Yasuo

    2016-01-01

    Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome, encoding a newly identified ORF0 with unknown function, ORF1p with RNA-binding activity and ORF2p with endonuclease and reverse transcriptase activities required for L1 retrotransposition. L1 utilizes an endonuclease (EN) to insert L1 cDNA into target DNA, which induces DNA double-strand breaks (DSBs). The ataxia-telangiectasia mutated (ATM) is activated by DSBs and subsequently the ATM-signaling pathway plays a role in regulating L1 retrotransposition. In addition, the host DNA repair machinery such as non-homologous end-joining (NHEJ) repair pathway is also involved in L1 retrotransposition. On the other hand, L1 is an insertional mutagenic agent, which contributes to genetic change, genomic instability, and tumorigenesis. Indeed, high-throughput sequencing-based approaches identified numerous tumor-specific somatic L1 insertions in variety of cancers, such as colon cancer, breast cancer, and hepatocellular carcinoma (HCC). In fact, L1 retrotransposition seems to be a potential factor to reduce the tumor suppressive property in HCC. Furthermore, recent study demonstrated that a specific viral-human chimeric transcript, HBx-L1, contributes to hepatitis B virus (HBV)-associated HCC. In contrast, host cells have evolved several defense mechanisms protecting cells against retrotransposition including epigenetic regulation through DNA methylation and host defense factors, such as APOBEC3, MOV10, and SAMHD1, which restrict L1 mobility as a guardian of the human genome. In this review, I focus on somatic L1 insertions into the human genome in cancers and host defense mechanisms against deleterious L1 insertions. PMID:27446907

  15. Contrasting Potato Foliage and Tuber Defense Mechanisms against the Late Blight Pathogen Phytophthora infestans.

    PubMed

    Gao, Liangliang; Bradeen, James M

    2016-01-01

    The late blight pathogen Phytophthora infestans can attack both potato foliage and tubers. When inoculated with P. infestans, foliage of nontransformed 'Russet Burbank' (WT) develops late blight disease while that of transgenic 'Russet Burbank' line SP2211 (+RB) does not. We compared the foliar transcriptome responses of these two lines to P. infestans inoculation using an RNA-seq approach. A total of 515 million paired end RNA-seq reads were generated, representing the transcription of 29,970 genes. We also compared the differences and similarities of defense mechanisms against P. infestans in potato foliage and tubers. Differentially expressed genes, gene groups and ontology bins were identified to show similarities and differences in foliage and tuber defense mechanisms. Our results suggest that R gene dosage and shared biochemical pathways (such as ethylene and stress bins) contribute to RB-mediated incompatible potato-P. infestans interactions in both the foliage and tubers. Certain ontology bins such as cell wall and lipid metabolisms are potentially organ-specific. PMID:27441721

  16. Contrasting Potato Foliage and Tuber Defense Mechanisms against the Late Blight Pathogen Phytophthora infestans

    PubMed Central

    Bradeen, James M.

    2016-01-01

    The late blight pathogen Phytophthora infestans can attack both potato foliage and tubers. When inoculated with P. infestans, foliage of nontransformed ‘Russet Burbank’ (WT) develops late blight disease while that of transgenic ‘Russet Burbank’ line SP2211 (+RB) does not. We compared the foliar transcriptome responses of these two lines to P. infestans inoculation using an RNA-seq approach. A total of 515 million paired end RNA-seq reads were generated, representing the transcription of 29,970 genes. We also compared the differences and similarities of defense mechanisms against P. infestans in potato foliage and tubers. Differentially expressed genes, gene groups and ontology bins were identified to show similarities and differences in foliage and tuber defense mechanisms. Our results suggest that R gene dosage and shared biochemical pathways (such as ethylene and stress bins) contribute to RB-mediated incompatible potato-P. infestans interactions in both the foliage and tubers. Certain ontology bins such as cell wall and lipid metabolisms are potentially organ-specific. PMID:27441721

  17. Trichoderma viride Laccase Plays a Crucial Role in Defense Mechanism against Antagonistic Organisms

    PubMed Central

    Divya, Lakshmanan; Sadasivan, C.

    2016-01-01

    Fungal laccases are involved in a variety of physiological functions such as delignification, morphogenesis, and parasitism. In addition to these functions, we suggest that fungal laccases are involved in defense mechanisms. When the laccase secreting Trichoderma viride was grown in the presence of a range of microorganisms including bacteria and fungi, laccase secretion was enhanced in response to antagonistic organisms alone. In addition, growth of antagonistic microbes was restricted by the secreting fungi. Besides, our study for the first time shows the inability of the secreting fungi (T. viride) to compete with antagonistic organism when laccase activity is inhibited, further emphasizing its involvement in rendering a survival advantage to the secreting organism. When laccase inhibitor was added to the media, the zone of inhibition exerted by the antagonist organism was more pronounced and consequently growth of T. viride was significantly restricted. Based on these observations we accentuate that, laccase plays an important role in defense mechanism and provides endurance to the organism when encountered with an antagonistic organism in its surrounding. PMID:27242756

  18. Association of Ego Defense Mechanisms with Academic Performance, Anxiety and Depression in Medical Students: A Mixed Methods Study

    PubMed Central

    Waqas, Ahmed; Malik, Aamenah; Muhammad, Umer; Khan, Sarah; Mahmood, Nadia

    2015-01-01

    Background: Ego defense mechanisms are unconscious psychological processes that help an individual to prevent anxiety when exposed to a stressful situation. These mechanisms are important in psychiatric practice to assess an individual’s personality dynamics, psychopathologies, and modes of coping with stressful situations, and hence, to design appropriate individualized treatment. Our study delineates the relationship of ego defense mechanisms with anxiety, depression, and academic performance of Pakistani medical students. Methods: This cross-sectional study was done at CMH Lahore Medical College and Fatima Memorial Hospital Medical and Dental College, both in Lahore, Pakistan, from December 1, 2014 to January 15, 2015. Convenience sampling was used and only students who agreed to take part in this study were included. The questionnaire consisted of three sections: 1) Demographics, documenting demographic data and academic scores on participants’ most recent exams; 2) Hospital Anxiety and Depression Scale (HADS); and 3) Defense Style Questionnaire-40 (DSQ-40). The data were analyzed with SPSS v. 20. Mean scores and frequencies were calculated for demographic variables and ego defense mechanisms. Bivariate correlations, one-way ANOVA, and multiple linear regression were used to identify associations between academic scores, demographics, ego defense mechanisms, anxiety, and depression. Results: A total of 409 medical students participated, of whom 286 (70%) were females and 123 (30%) were males. Mean percentage score on the most recent exams was 75.6% in medical students. Bivariate correlation revealed a direct association between mature and neurotic ego defense mechanisms and academic performance, and an indirect association between immature mechanisms and academic performance. One-way ANOVA showed that moderate levels of anxiety (P < .05) and low levels of depression (P < .05) were associated with higher academic performance. Conclusion: There was a

  19. Mechanisms of oxygen sensing: a key to therapy of pulmonary hypertension and patent ductus arteriosus

    PubMed Central

    Weir, E K; Obreztchikova, M; Vargese, A; Cabrera, J A; Peterson, D A; Hong, Z

    2008-01-01

    Specialized tissues that sense acute changes in the local oxygen tension include type 1 cells of the carotid body, neuroepithelial bodies in the lungs, and smooth muscle cells of the resistance pulmonary arteries and the ductus arteriosus (DA). Hypoxia inhibits outward potassium current in carotid body type 1 cells, leading to depolarization and calcium entry through L-type calcium channels. Increased intracellular calcium concentration ([Ca++]i) leads to exocytosis of neurotransmitters, thus stimulating the carotid sinus nerve and respiration. The same K+ channel inhibition occurs with hypoxia in pulmonary artery smooth muscle cells (PASMCs), causing contraction and providing part of the mechanism of hypoxic pulmonary vasoconstriction (HPV). In the SMCs of the DA, the mechanism works in reverse. It is the shift from hypoxia to normoxia that inhibits K+ channels and causes normoxic ductal contraction. In both PA and DA, the contraction is augmented by release of Ca++ from the sarcoplasmic reticulum, entry of Ca++ through store-operated channels (SOC) and by Ca++ sensitization. The same three ‘executive' mechanisms are partly responsible for idiopathic pulmonary arterial hypertension (IPAH). While vasoconstrictor mediators constrict both PA and DA and vasodilators dilate both vessels, only redox changes mimic oxygen by having directly opposite effects on the K+ channels, membrane potential, [Ca++]i and tone in the PA and DA. There are several different hypotheses as to how redox might alter tone, which remain to be resolved. However, understanding the mechanism will facilitate drug development for pulmonary hypertension and patent DA. PMID:18641675

  20. Effects of collagen deposition on passive and active mechanical properties of large pulmonary arteries in hypoxic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Eickhoff, Jens C; Chesler, Naomi C

    2013-11-01

    Proximal pulmonary artery (PA) stiffening is a strong predictor of mortality in pulmonary hypertension. Collagen accumulation is mainly responsible for PA stiffening in hypoxia-induced pulmonary hypertension (HPH) in mouse models. We hypothesized that collagen cross-linking and the type I isoform are the main determinants of large PA mechanical changes during HPH, which we tested by exposing mice that resist type I collagen degradation (Col1a1[Formula: see text] and littermate controls (Col1a1[Formula: see text] to hypoxia for 10 days with or without [Formula: see text]-aminopropionitrile (BAPN) treatment to prevent cross-link formation. Static and dynamic mechanical tests were performed on isolated PAs with smooth muscle cells (SMC) in passive and active states. Percentages of type I and III collagen were quantified by histology; total collagen content and cross-linking were measured biochemically. In the SMC passive state, for both genotypes, hypoxia tended to increase PA stiffness and damping capacity, and BAPN treatment limited these increases. These changes were correlated with collagen cross-linking ([Formula: see text]). In the SMC active state, hypoxia increased PA dynamic stiffness and BAPN had no effect in Col1a1[Formula: see text] mice ([Formula: see text]). PA stiffness did not change in Col1a1[Formula: see text] mice. Similarly, damping capacity did not change for either genotype. Type I collagen accumulated more in Col1a1[Formula: see text] mice, whereas type III collagen increased more in Col1a1[Formula: see text] mice during HPH. In summary, PA passive mechanical properties (both static and dynamic) are related to collagen cross-linking. Type I collagen turnover is critical to large PA remodeling during HPH when collagen metabolism is not mutated and type III collagen may serve as a reserve. PMID:23377784

  1. Systemic Acquired Resistance in Moss: Further Evidence for Conserved Defense Mechanisms in Plants

    PubMed Central

    Winter, Peter S.; Bowman, Collin E.; Villani, Philip J.; Dolan, Thomas E.; Hauck, Nathanael R.

    2014-01-01

    Vascular plants possess multiple mechanisms for defending themselves against pathogens. One well-characterized defense mechanism is systemic acquired resistance (SAR). In SAR, a plant detects the presence of a pathogen and transmits a signal throughout the plant, inducing changes in the expression of various pathogenesis-related (PR) genes. Once SAR is established, the plant is capable of mounting rapid responses to subsequent pathogen attacks. SAR has been characterized in numerous angiosperm and gymnosperm species; however, despite several pieces of evidence suggesting SAR may also exist in non-vascular plants6–8, its presence in non-vascular plants has not been conclusively demonstrated, in part due to the lack of an appropriate culture system. Here, we describe and use a novel culture system to demonstrate that the moss species Amblystegium serpens does initiate a SAR-like reaction upon inoculation with Pythium irregulare, a common soil-borne oomycete. Infection of A. serpens gametophores by P. irregulare is characterized by localized cytoplasmic shrinkage within 34 h and chlorosis and necrosis within 7 d of inoculation. Within 24 h of a primary inoculation (induction), moss gametophores grown in culture became highly resistant to infection following subsequent inoculation (challenge) by the same pathogen. This increased resistance was a response to the pathogen itself and not to physical wounding. Treatment with β-1,3 glucan, a structural component of oomycete cell walls, was equally effective at triggering SAR. Our results demonstrate, for the first time, that this important defense mechanism exists in a non-vascular plant, and, together with previous studies, suggest that SAR arose prior to the divergence of vascular and non-vascular plants. In addition, this novel moss – pathogen culture system will be valuable for future characterization of the mechanism of SAR in moss, which is necessary for a better understanding of the evolutionary history of SAR

  2. Inflammatory mechanisms of pulmonary injury induced by mustards.

    PubMed

    Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Vayas, Kinal N; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-02-26

    Exposure of humans and animals to vesicants, including sulfur mustard (SM) and nitrogen mustard (NM), causes severe and debilitating damage to the respiratory tract. Both acute and long term pathological consequences are observed in the lung following a single exposure to these vesicants. Evidence from our laboratories and others suggest that macrophages and the inflammatory mediators they release play an important role in mustard-induced lung injury. In this paper, the pathogenic effects of SM and NM on the lung are reviewed, along with the potential role of inflammatory macrophages and mediators they release in mustard-induced pulmonary toxicity. PMID:26478570

  3. The nature of antioxidant defense mechanisms: a lesson from transgenic studies.

    PubMed Central

    Ho, Y S; Magnenat, J L; Gargano, M; Cao, J

    1998-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury. Images Figure 1 Figure 3 Figure 4 PMID:9788901

  4. Monuments of memory: defensive mechanisms of the collective psyche and their manifestation in the memorialization process.

    PubMed

    Kalinowska, Malgorzata

    2012-09-01

    The paper searches for insight in the area of collective memory as a part of collective consciousness, a phenomenon understood as a stabilizing factor for a society's self-image and identity. Collective memories are seen as originating from shared communications transmitting and creating the meaning of the past in the form of narrative, symbols and signs. As such, they contain the individual, embodied and lived side of our relations to the past. As well as the identity-building and meaning-making functions of collective memories, their defensive function is discussed with a focus on commemorative practices taking place in a transitional space between psychic and social life. Fears of a lack of collective identity and coherence have contributed to the way Polish commemorative practices have been shaped. This is considered in relation to the Smolensk catastrophe in 2010, viewed in the context of the Jungian concept of the collective psyche and the psychoanalytical understanding of defensive group mechanisms against trauma, especially those relating to loss and mourning. It leads to a consideration of how historical experiences and the experience of history can be accessed, as well as their meaning for individual and group development. PMID:22954041

  5. Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

    PubMed

    Anbaraki, Afrooz; Khoshaman, Kazem; Ghasemi, Younes; Yousefi, Reza

    2016-10-01

    The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. PMID:27316765

  6. PULMONARY PATHOPHYSIOLOGY AND LUNG MECHANICS IN ANESTHESIOLOGY: A CASE-BASED OVERVIEW

    PubMed Central

    Vidal Melo, Marcos F.; Musch, Guido; Kaczka, David W.

    2012-01-01

    The induction and maintenance of anesthesia, surgical requirements, and patients’ unique pathophysiology all combine to create a setting in which our accumulated knowledge of respiratory physiology and lung mechanics take on immediate and central importance in patient management. In this review we will take a case-based approach to illustrate how the complex interactions between anesthesia, surgery, and patient disease impact patient care with respect to pulmonary pathophysiology and clinical decision-making. We will examine two disparate scenarios: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass. In each example we will illustrate how important concepts in pulmonary physiology and respiratory mechanics impact clinical management decisions. PMID:23089508

  7. Pulmonary mechanical function and diffusion capacity after deep saturation dives.

    PubMed Central

    Thorsen, E; Segadal, K; Myrseth, E; Påsche, A; Gulsvik, A

    1990-01-01

    To assess the effects of deep saturation dives on pulmonary function, static and dynamic lung volumes, transfer factor for carbon monoxide (T1CO), delta-N2, and closing volume (CV) were measured before and after eight saturation dives to pressures of 3.1-4.6 MPa. The atmospheres were helium-oxygen mixtures with partial pressures of oxygen of 40-60 kPa. The durations of the dives were 14-30 days. Mean rate of decompression was 10.5-13.5 kPa/hour. A total of 43 divers were examined, six of whom took part in two dives, the others in one only. Dynamic lung volumes did not change significantly but total lung capacity (TLC) increased significantly by 4.3% and residual volume (RV) by 14.8% (p less than 0.05). CV was increased by 16.7% (p less than 0.01). The T1CO was reduced from 13.0 +/- 1.6 to 11.8 +/- 1.7 mmol/min/kPa (p less than 0.01) when corrected to a haemoglobin concentration of 146 g/l. Effective alveolar volume was unchanged. The increase in TLC and decrease in T1CO were correlated (r = -0.574, p less than 0.02). A control examination of 38 of the divers four to six weeks after the dives showed a partial normalisation of the changes. The increase in TLC, RV, and CV, and the decrease in T1CO, could be explained by a loss of pulmonary elastic tissue caused by inflammatory reactions induced by oxygen toxicity or venous gas emboli. PMID:2337532

  8. Close concordance between pulmonary angiography and pathology in a canine model with chronic pulmonary thromboembolism and pathological mechanisms after lung ischemia reperfusion injury.

    PubMed

    Deng, Chaosheng; Wu, Dawen; Zhai, Zhenguo; Lin, Qichang; Zhong, Zhanghua; Yang, Yuanhua; Chen, Qunlin; Lian, Ningfang; Gao, Shaoyong; Yang, Minxia; Liu, Kaixiong; Wang, Chen

    2016-05-01

    To investigate the pulmonary angiography and pathology in a canine model with chronic pulmonary thromboembolism (PTE). The cylindrical blood clots were selectively introduced into the left (n = 10) or right (n = 20) lower pulmonary arteries of dogs. Pulmonary arteriography (PA) was performed before or after embolization. The values after embolization and baseline of mean pulmonary arterial pressure, pulmonary vascular resistance, cardiac output had changed. After 1 or 2 weeks' embolization, local PA demonstrated the abrupt cut-off perfusion defects or webs, bands, and abrupt vascular narrowing. 2 weeks after embolization, the pathology showed that the fibrin networks of the thrombi had multiple recanalization channels, and pulmonary artery had the concentric, lamellar (onion-like) intimal hyperplasia, multilayered, irregular arrangements of endothelial cells, and the infiltration of inflammatory cells. After embolectomy-mediated reperfusion, 2 weeks' subgroup showed destroyed and incomplete alveolar structures, and a large number of exudative cells, primarily neutrophils, and exudate. There close concordance between pulmonary angiography and pathology in a canine model with chronic PTE. The LIRI mechanisms after embolectomy-mediated reperfusion involve the destroyed, incomplete alveolar structures, and infiltration of inflammatory cells, primarily neutrophils. PMID:26286518

  9. The Splitting Index: construction of a scale measuring the defense mechanism of splitting.

    PubMed

    Gould, J R; Prentice, N M; Ainslie, R C

    1996-04-01

    The Splitting Index (SI), a self-report scale based on the writings of Kernberg (e.g., 1976) on self and object representations and the defense mechanism of splitting, was constructed. After development over the course of 6 pilot studies, the SI was validated through 2 further studies. Factor analyses revealed a 24-item scale with three 8-item subscales, measuring the splitting of self, family, and others' images. The SI and its subscales were demonstrated to be internally consistent and stable over a 4-week period. Convergent validity was supported by significant correlations with measures of borderline and narcissistic personality disorders, self-image stability, self-esteem, depression, and negative affectivity. Discriminant validity was demonstrated by near-zero correlations with two measures of cognitive complexity. Contrary to predictions, the SI was significantly correlated with the Dogmatism Scale (Rokeach, 1960), a third measure of cognitive complexity. Research and clinical applications of the SI are discussed. PMID:8869581

  10. Mechanical Properties of Sialic Foamed Ceramic and Applications in Defense Structure

    NASA Astrophysics Data System (ADS)

    Li, Xu-Yang; Li, Yong-Chi; Zhao, Kai; Gao, Guang-Fa

    2014-08-01

    Mechanical properties of a closed-cellular sialic foamed ceramic are investigated by compressive tests. The sialic foamed ceramic under uniaxial stress compression shows brittleness and the flow stress increases with the strain rate. The engineering stress-engineering strain curve under uniaxial strain compression could be divided into three stages: linear elasticity, collapsed plateau and densification. The unloading elastic modulus, Poisson ratio and energy absorption ability are discussed. Shelly cellular material made by sialic foamed ceramic is applied into the stress distribution layer in the defense structure. Field explosion experiments are performed for the sand based stress distribution layer and shelly cellular material based layer. Compared with sand, the shelly cellular material reduces the peak stress of the blast wave.

  11. [The defense and regulatory mechanisms during development of legume-Rhizobium symbiosis].

    PubMed

    Glian'ko, A K; Akimova, G P; Sokolova, M G; Makarova, L E; Vasil'eva, G G

    2007-01-01

    The roles of indolylacetic acid, the peroxidase system, catalase, active oxygen species, and phenolic compounds in the physiological and biochemical mechanisms involved in the autoregulation of nodulation in the developing legume-Rhizobium symbiosis were studied. It was inferred that the concentration of indolylacetic acid in the roots of inoculated plants, controlled by the enzymes of the peroxidase complex, is the signal permitting or limiting nodulation at the initial stages of symbiotic interaction. Presumably, the change in the level of active oxygen species is determined by an antioxidant activity of phenolic compounds. During the development of symbiosis, phytohormones, antioxidant enzymes, and active oxygen species may be involved in the regulation of infection via both a direct antibacterial action and regulation of functional activity of the host plant defense systems. PMID:17619575

  12. Roles of small RNAs in the immune defense mechanisms of crustaceans.

    PubMed

    He, Yaodong; Ju, Chenyu; Zhang, Xiaobo

    2015-12-01

    Small RNAs, 21-24 nucleotides in length, are non-coding RNAs found in most multicellular organisms, as well as in some viruses. There are three main types of small RNAs including microRNA (miRNA), small-interfering RNA (siRNA), and piwi-interacting RNA (piRNA). Small RNAs play key roles in the genetic regulation of eukaryotes; at least 50% of all eukaryote genes are the targets of small RNAs. In recent years, studies have shown that some unique small RNAs are involved in the immune response of crustaceans, leading to lower or higher immune responses to infections and diseases. SiRNAs could be used as therapy for virus infection. In this review, we provide an overview of the diverse roles of small RNAs in the immune defense mechanisms of crustaceans. PMID:26210184

  13. Stress defense mechanisms of NADPH-dependent thioredoxin reductases (NTRs) in plants.

    PubMed

    Cha, Joon-Yung; Barman, Dhirendra Nath; Kim, Min Gab; Kim, Woe-Yeon

    2015-01-01

    Plants establish highly and systemically organized stress defense mechanisms against unfavorable living conditions. To interpret these environmental stimuli, plants possess communication tools, referred as secondary messengers, such as Ca(2+) signature and reactive oxygen species (ROS) wave. Maintenance of ROS is an important event for whole lifespan of plants, however, in special cases, toxic ROS molecules are largely accumulated under excess stresses and diverse enzymes played as ROS scavengers. Arabidopsis and rice contain 3 NADPH-dependent thioredoxin reductases (NTRs) which transfer reducing power to Thioredoxin/Peroxiredoxin (Trx/Prx) system for scavenging ROS. However, due to functional redundancy between cytosolic and mitochondrial NTRs (NTRA and NTRB, respectively), their functional involvements under stress conditions have not been well characterized. Recently, we reported that cytosolic NTRA confers the stress tolerance against oxidative and drought stresses via regulation of ROS amounts using NTRA-overexpressing plants. With these findings, mitochondrial NTRB needs to be further elucidated. PMID:26039478

  14. Defense mechanisms in congenital and acquired facial disfigurement: a clinical-empirical study.

    PubMed

    van den Elzen, Marijke E P; Versnel, Sarah L; Perry, J Christopher; Mathijssen, Irene M J; Duivenvoorden, Hugo J

    2012-04-01

    It is of clinical interest to investigate the degree to which patients with facial disfigurement use defense styles. Therefore, 59 adults born with rare facial clefts, 59 patients with facial deformities acquired at an adult age, and a reference group of 141 adults without facial disfigurements completed standardized questionnaires. There was a significant difference between the group with and the group without disfigurements on immature defense styles, with the disfigured group using the immature style more frequently. There was a trend for the nondisfigured group to use more mature defense styles. No difference between congenital and acquired groups was seen on individual types of defense style. Self-esteem had the strength to differentiate mature and immature defense styles within our disfigured groups. The association of low self-esteem and the utilization of immature defense styles suggests that professional help may tailor treatment on discussing immature defense style and problems triggering or maintaining this style. PMID:22456586

  15. Evaluation of right and left heart mechanics in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy.

    PubMed

    Sunbul, Murat; Kivrak, Tarik; Durmus, Erdal; Yildizeli, Bedrettin; Mutlu, Bulent

    2015-08-01

    The aim of the present study was to evaluate of the right and left heart mechanics by two-dimensional (2D) speckle tracking echocardiography (STE) in chronic thromboembolic pulmonary hypertension (CTEPH) patients before and after pulmonary thromboendarterectomy (PTE). A total of 40 consecutive CTEPH patients (mean age 49.3 ± 13.5 years, 27 female) were included. 2D STE was performed in all patients before, and 3 months, after PTE. 12 months of prognostic data were also recorded via the use of telephone calls. Postoperative 6-minute walk test (6MWT) distances were significantly longer than preoperative values (410.5 ± 61.5 vs. 216.6 ± 131.4 m, p < 0.001). Postoperative left ventricular (LV) and right ventricular (RV) systolic functions (LV EF, TAPSE, RVS) were similar compared to preoperative values. While postoperative RV, right atrial (RA) and systolic pulmonary artery pressure measurements were significantly lower, LV and left atrial (LA) measurements were higher than preoperative values. Postoperative LV and RV global longitudinal strain (GLS) measurements were significantly higher than preoperative values. Postoperative LV global radial and circumferential strain measurements were similar to preoperative values. While postoperative RA reservoir and conduit functions were significantly higher, postoperative LA reservoir and conduit functions were similar to preoperative values. Correlation analysis revealed that baseline 6MWT distances were correlated with LV GLS, RV GLS, and RA reservoir and conduit functions in the preoperative and postoperative periods. 2D STE indices may help the clinician in assessing the effect of PTE on cardiac functions and may also be used for follow-up data in CTEPH patients. PMID:25982176

  16. Structural antioxidant defense mechanisms in the mammalian and nonmammalian kidney: different solutions to the same problem?

    PubMed

    O'Connor, Paul M; Evans, Roger G

    2010-09-01

    Tissue oxygen levels are tightly regulated in all organs. This poses a challenge for the kidney, as its function requires blood flow, and thus, oxygen delivery to greatly exceed its metabolic requirements. Because superoxide production in the kidney is dependent on oxygen availability, tissue hyperoxia could drive oxidative stress. In the mammalian renal cortex, this problem may have been solved, in part, through a structural antioxidant defense mechanism. That is, arteries and veins are closely associated in a countercurrent arrangement, facilitating diffusional arterial-to-venous (AV) oxygen shunting. Because of this mechanism, a proportion of the oxygen delivered in the renal artery never reaches kidney tissue but instead diffuses to the closely associated renal veins, thus limiting oxygen transport to tissue. In the nonmammalian kidney, arteries and veins are not arranged in an intimate countercurrent fashion as in mammals; thus AV oxygen shunting is likely less important in regulation of kidney oxygenation in these species. Instead, the kidney's blood supply is predominately of venous origin. This likely has a similar impact on tissue oxygenation as AV oxygen shunting, of limiting delivery of oxygen to renal tissue. Thus, we hypothesize the evolution of structural antioxidant mechanisms that are anatomically divergent but functionally homologous in the mammalian and nonmammalian kidney. PMID:20660108

  17. In vivo NMR metabolic profiling of Fabrea salina reveals sequential defense mechanisms against ultraviolet radiation.

    PubMed

    Marangoni, Roberto; Paris, Debora; Melck, Dominique; Fulgentini, Lorenzo; Colombetti, Giuliano; Motta, Andrea

    2011-01-01

    Fabrea salina is a hypersaline ciliate that is known to be among the strongest ultraviolet (UV)-resistant microorganisms; however, the molecular mechanisms of this resistance are almost unknown. By means of in vivo NMR spectroscopy, we determined the metabolic profile of living F. salina cells exposed to visible light and to polychromatic UV-B + UV-A + Vis radiation for several different exposure times. We used unsupervised pattern-recognition analysis to compare these profiles and discovered some metabolites whose concentration changed specifically upon UV exposure and in a dose-dependent manner. This variation was interpreted in terms of a two-phase cell reaction involving at least two different pathways: an early response consisting of degradation processes, followed by a late response activating osmoprotection mechanisms. The first step alters the concentration of formate, acetate, and saturated fatty-acid metabolites, whereas the osmoprotection modifies the activity of betaine moieties and other functionally related metabolites. In the latter pathway, alanine, proline, and sugars suggest a possible incipient protein synthesis as defense and/or degeneration mechanisms. We conclude that NMR spectroscopy on in vivo cells is an optimal approach for investigating the effect of UV-induced stress on the whole metabolome of F. salina because it minimizes the invasiveness of the measurement. PMID:21190674

  18. Inflammatory mechanisms in HIV-associated pulmonary arterial hypertension.

    PubMed

    Tcherakian, Colas; Couderc, Louis-Jean; Humbert, Marc; Godot, Véronique; Sitbon, Olivier; Devillier, Philippe

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options. PMID:24037631

  19. Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat

    PubMed Central

    Casey, David B.; Badejo, Adeleke M.; Dhaliwal, Jasdeep S.; Murthy, Subramanyam N.; Hyman, Albert L.; Nossaman, Bobby D.; Kadowitz, Philip J.

    2009-01-01

    Recent studies show that pulmonary vasodilator responses to nitrite are enhanced by hypoxia. However, the mechanism by which nitrite is converted to vasoactive nitric oxide (NO) is uncertain. In the present study, intravenous injections of sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure were enhanced when tone in the pulmonary vascular bed was increased with U-46619. Under elevated tone conditions, decreases in pulmonary and systemic arterial pressures in response to nitrite were attenuated by allopurinol in a dose that did not alter responses to the NO donors, sodium nitroprusside and diethylamine/NO, suggesting that xanthine oxidoreductase is the major enzyme-reducing nitrite to NO. Ventilation with a 10% O2 gas mixture increased pulmonary arterial pressure, and the response to hypoxia was enhanced by NG-nitro-l-arginine methyl ester and not altered by allopurinol. This suggests that NO formed by the endothelium and not from the reduction of plasma nitrite modulates the hypoxic pulmonary vasoconstrictor response. Although intravenous injections of sodium nitrite reversed pulmonary hypertensive responses to U-46619, hypoxia, and NG-nitro-l-arginine methyl ester, the pulmonary vasodilator response to nitrite was not altered by ventilation with 10% O2 when baseline pulmonary arterial pressure was increased to similar values in animals breathing room air or the hypoxic gas. These data provide evidence that xanthine oxidoreductase is the major enzyme-reducing nitrite to vasoactive NO, and that this mechanism is not modified by hypoxia. PMID:19074675

  20. Defense mechanisms of sargassacean species against the epiphytic red alga Neosiphonia harveyi.

    PubMed

    Nakajima, Noboru; Ohki, Kaori; Kamiya, Mitsunobu

    2015-08-01

    Flora diversity and abundance of epiphytes are specific to their basiphyte species and may relate to variations in the defensive abilities of basiphytes. Thus, investigating the interactions between epiphytes and basiphytes is useful for a better understanding of the biological impact of epiphytism and the survival strategies of basiphytes. We examined the epiphyte density on five sargassacean species at six locations between two study sites, which showed that the epiphytic red alga Neosiphonia harveyi was remarkably less abundant on Sargassum siliquastrum at all locations. To assess its defense mechanism against N. harveyi, we performed bioassays of phlorotannins, which are considered effective in deterring fouling, by culturing sargassacean blades with N. harveyi carpospores and observed the process by which sargassacean blades remove epiphytes. When the carpospores were incubated with various concentrations of dissolved phlorotannins, settlement and germination were inhibited only at the highest concentrations (>0.1 g · L(-1) ), and this effect did not significantly differ among the five sargassacean species. When the carpospores were combined with blades from the five species, many of the spores attached and germinated on every blade. Because N. harveyi penetrated rhizoids into basiphyte tissues, cuticle peeling observed in all five sargassacean species could not remove this epiphyte after germination. However, in S. siliquastrum, the blade tissues around the germlings became swollen and disintegrative, and were removed together with the germlings. The spores normally grew on the dead blades, suggesting that the tissue degradation of S. siliquastrum is triggered by the infection of N. harveyi. PMID:26986791

  1. Mechanical properties and structure of isolated pulmonary arteries remodeled by chronic hyperoxia.

    PubMed

    Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1987-08-01

    Normobaric hyperoxia is known to cause pulmonary hypertension with major restructuring of the walls of large and small pulmonary arteries. This study reports the effects of 21 days of exposure to 87% oxygen on the resting and active mechanical properties and structure of pulmonary arterial segments. Segments from the hilar region, extrapulmonary and proximal preacinar, and selected distal preacinar regions were studied. Resting and active (KCl-induced) tension:circumference curves were determined for each vessel. Morphometric measures were made of vessels fixed at a standard circumference using computerized planimetry. The areas of the media and adventitia as well as vessel wall thickness were increased in hyperoxic vessels. The walls of segments from the hypertensive rats demonstrated an increased stiffness based upon analysis of vessel resting tension:circumference relationships while the tangent modulus (a measure of stiffness normalized to tissue dimensions) was unchanged. Paradoxically, despite medial hypertrophy in the pulmonary vessels remodeled by hyperoxia, active tension was reduced. This study reveals that the resulting hypertensive state is not readily explained by an inherent increase in the maximal contractile capabilities of the remodeled vessel. Rather, obliteration of vessels in combination with increased resting stiffness appear to be the basis for pulmonary hypertension induced in hyperoxia. PMID:3619198

  2. Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening.

    PubMed

    Bilek, Anastacia M; Dee, Kay C; Gaver, Donald P

    2003-02-01

    Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage. PMID:12433851

  3. Microbial Signature-Triggered Plant Defense Responses and Early Signaling Mechanisms

    PubMed Central

    Wu, Shujing; Shan, Libo; He, Ping

    2014-01-01

    It has long been observed that microbial elicitors can trigger various cellular responses in plants. Microbial elicitors have recently been referred to as pathogen or microbe-associated molecular patterns (PAMPs or MAMPs) and remarkable progress has been made on research of their corresponding receptors, signaling mechanisms and critical involvement in disease resistance. Plants also generate endogenous signals due to the damage or wounds caused by microbes. These signals were originally called endogenous elicitors and subsequently renamed damage-associated molecular patterns (DAMPs) that serve as warning signals for infections. The cellular responses induced by PAMPs and DAMPs include medium alkalinization, ion fluxes across the membrane, reactive oxygen species (ROS) and ethylene production. They collectively contribute to plant pattern-triggered immunity (PTI) and play an important role in plant basal defense against a broad spectrum of microbial infections. In this review, we provide an update on multiple PTI responses and early signaling mechanisms and discuss its potential applications to improve crop disease resistance. PMID:25438792

  4. Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism Against the Siderophilic Bacterium Vibrio vulnificus

    PubMed Central

    Arezes, João; Jung, Grace; Gabayan, Victoria; Valore, Erika; Ruchala, Piotr; Gulig, Paul A.; Ganz, Tomas; Nemeth, Elizabeta; Bulut, Yonca

    2014-01-01

    SUMMARY Hereditary hemochromatosis, an iron overload disease caused by a deficiency in the iron-regulatory hormone hepcidin, is associated with lethal infections by siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we infected wild-type and hepcidin-deficient mice with the siderophilic bacterium Vibrio vulnificus, and found that hepcidin deficiency results in increased bacteremia and decreased survival of infected mice, which can be partially ameliorated by dietary iron depletion. Additionally, timely administration of hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases bacterial loads and rescues these mice from death, regardless of initial iron levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from hepcidin-deficient mice support extraordinarily rapid bacterial growth, and that this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin-mediated hypoferremia is a host defense mechanism against siderophilic pathogens and suggest that hepcidin agonists may improve infection outcomes in patients with hereditary hemochromatosis or thalassemia. PMID:25590758

  5. Overlapping and complementary oxidative stress defense mechanisms in nontypeable Haemophilus influenzae.

    PubMed

    Harrison, Alistair; Baker, Beth D; Munson, Robert S

    2015-01-01

    The Gram-negative commensal bacterium nontypeable Haemophilus influenzae (NTHI) can cause respiratory tract diseases that include otitis media, sinusitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During colonization and infection, NTHI withstands oxidative stress generated by reactive oxygen species produced endogenously, by the host, and by other copathogens and flora. These reactive oxygen species include superoxide, hydrogen peroxide (H2O2), and hydroxyl radicals, whose killing is amplified by iron via the Fenton reaction. We previously identified genes that encode proteins with putative roles in protection of the NTHI isolate strain 86-028NP against oxidative stress. These include catalase (HktE), peroxiredoxin/glutaredoxin (PgdX), and a ferritin-like protein (Dps). Strains were generated with mutations in hktE, pgdX, and dps. The hktE mutant and a pgdX hktE double mutant were more sensitive than the parent to killing by H2O2. Conversely, the pgdX mutant was more resistant to H2O2 due to increased catalase activity. Supporting the role of killing via the Fenton reaction, binding of iron by Dps significantly mitigated the effect of H2O2-mediated killing. NTHI thus utilizes several effectors to resist oxidative stress, and regulation of free iron is critical to this protection. These mechanisms will be important for successful colonization and infection by this opportunistic human pathogen. PMID:25368297

  6. Chromosome-level genome map provides insights into diverse defense mechanisms in the medicinal fungus Ganoderma sinense

    PubMed Central

    Zhu, Yingjie; Xu, Jiang; Sun, Chao; Zhou, Shiguo; Xu, Haibin; Nelson, David R.; Qian, Jun; Song, Jingyuan; Luo, Hongmei; Xiang, Li; Li, Ying; Xu, Zhichao; Ji, Aijia; Wang, Lizhi; Lu, Shanfa; Hayward, Alice; Sun, Wei; Li, Xiwen; Schwartz, David C.; Wang, Yitao; Chen, Shilin

    2015-01-01

    Fungi have evolved powerful genomic and chemical defense systems to protect themselves against genetic destabilization and other organisms. However, the precise molecular basis involved in fungal defense remain largely unknown in Basidiomycetes. Here the complete genome sequence, as well as DNA methylation patterns and small RNA transcriptomes, was analyzed to provide a holistic overview of secondary metabolism and defense processes in the model medicinal fungus, Ganoderma sinense. We reported the 48.96 Mb genome sequence of G. sinense, consisting of 12 chromosomes and encoding 15,688 genes. More than thirty gene clusters involved in the biosynthesis of secondary metabolites, as well as a large array of genes responsible for their transport and regulation were highlighted. In addition, components of genome defense mechanisms, namely repeat-induced point mutation (RIP), DNA methylation and small RNA-mediated gene silencing, were revealed in G. sinense. Systematic bioinformatic investigation of the genome and methylome suggested that RIP and DNA methylation combinatorially maintain G. sinense genome stability by inactivating invasive genetic material and transposable elements. The elucidation of the G. sinense genome and epigenome provides an unparalleled opportunity to advance our understanding of secondary metabolism and fungal defense mechanisms. PMID:26046933

  7. Respiratory mechanics measured by forced oscillation technique in combined pulmonary fibrosis and emphysema.

    PubMed

    Mori, Kazutaka; Shirai, Toshihiro; Mikamo, Masashi; Shishido, Yuichiro; Akita, Takefumi; Morita, Satoru; Asada, Kazuhiro; Fujii, Masato; Hozumi, Hironao; Suda, Takafumi; Chida, Kingo

    2013-01-15

    The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the lung mechanics measured by multi-frequency forced oscillation technique (FOT) among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41 patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20 Hz was significantly lower in patients with CPFE than in those with IP or COPD, irrespective of the severity of airflow limitation. Within-breath analyses of resistance revealed no difference among the 3 groups; however, the difference between inspiratory and expiratory phases of reactance at 5 Hz, which reflects expiratory flow limitation, in patients with CPFE was significantly higher than in those with IP and lower than in those with COPD. In conclusion, both emphysema and fibrosis affect lung mechanics in CPFE, leading to different findings from IP or COPD alone. PMID:23117106

  8. Numerical investigation of pulmonary drug delivery under mechanical ventilation conditions

    NASA Astrophysics Data System (ADS)

    Banerjee, Arindam; van Rhein, Timothy

    2012-11-01

    The effects of mechanical ventilation waveform on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects of ventilation parameters. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways of patient undergoing mechanical ventilation treatment from the endotracheal tube to generation G7. Waveforms were modeled as those commonly used by commercial mechanical ventilators. Turbulence was modeled with LES. User defined particle force models were used to model the drag force with the Cunningham correction factor, the Saffman lift force, and Brownian motion force. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. Authors acknowledge financial support through University of Missouri Research Board Award.

  9. Evolution and development of gastropod larval shell morphology: experimental evidence for mechanical defense and repair.

    PubMed

    Hickman, C S

    2001-01-01

    The structural diversity of gastropod veliger larvae offers an instructive counterpoint to the view of larval forms as conservative archetypes. Larval structure, function, and development are fine-tuned for survival in the plankton. Accordingly, the study of larval adaptation provides an important perspective for evolutionary-developmental biology as an integrated science. Patterns of breakage and repair in the field, as well as patterns of breakage in arranged encounters with zooplankton under laboratory conditions, are two powerful sources of data on the adaptive significance of morphological and microsculptural features of the gastropod larval shell. Shells of the planktonic veliger larvae of the caenogastropod Nassarius paupertus [GOULD] preserve multiple repaired breaks, attributed to unsuccessful zooplankton predators. In culture, larvae isolated from concentrated zooplankton samples rapidly repaired broken apertural margins and restored the "ideal" apertural form, in which an elaborate projection or "beak" covers the head of the swimming veliger. When individuals with repaired apertures were reintroduced to a concentrated mixture of potential zooplankton predators, the repaired margins were rapidly chipped and broken back. The projecting beak of the larval shell is the first line of mechanical defense, covering the larval head and mouth and potentially the most vulnerable part of the shell to breakage. Patterns of mechanical failure show that spiral ridges do reinforce the beak and retard breakage. The capacity for rapid shell repair and regeneration, and the evolution of features that resist or retard mechanical damage, may play a more prominent role than previously thought in enhancing the ability of larvae to survive in the plankton. PMID:11256430

  10. Apoptosis as a host defense mechanism in Crassostrea virginica and its modulation by Perkinsus marinus.

    PubMed

    Hughes, Francis M; Foster, Brent; Grewal, Snimar; Sokolova, Inna M

    2010-08-01

    Dermo disease caused by the obligatory intracellular protozoan Perkinsus marinus causes extensive oyster mortalities leading to tremendous losses in the oyster industry and damage to estuarine ecosystems. To better understand the mechanisms of the parasite's evasion of the host immune defense system, we have investigated the molecular mechanisms of P.marinus-induced inhibition of apoptosis in oyster cells as a potential parasite's survival strategy. We found that P. marinus modulates apoptosis of oyster immune cells (hemocytes) in a way that may help the parasite to establish infection. We found an increase in apoptosis in the initial stages of infection in vitro and in vivo, consistent with a host response to this intracellular parasite. During infection with highly virulent strains of P. marinus, this was followed by suppression and a return of apoptosis to basal levels 8-24 h post-infection, strongly indicating the parasite-induced inhibition of the immune response. In contrast, during infections with intermediate or low virulence strains of P. marinus, a transient suppression of apoptosis 4-8 h post-infection was followed by sustained elevation of hemocyte apoptosis at later stages, indicating that hemocytes were able to overcome the parasite-induced suppression and successfully combat the infection. Studies of the mechanisms of P. marinus-induced apoptosis indicated that the early post-infection stimulation of apoptosis is caspase-independent. However, this process can be driven (although to a lesser degree) by the killed parasite, suggesting that oyster hemocytes respond to cell surface molecules of P. marinus. Overall, this study provides novel insights into pathogen-induced modulation of apoptosis and its role in parasite virulence and establishment of infections. PMID:20371290

  11. Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation.

    PubMed

    Peták, Ferenc; Fodor, Gergely H; Babik, Barna; Habre, Walid

    2016-07-01

    The contribution of the hematocrit (Hct) of the blood in the pulmonary vasculature to the overall lung mechanics has not been characterized. We therefore set out to establish how changes of the Hct level in the pulmonary circulation affect the airway and lung tissue viscoelastic properties. The Hct level of the blood in an isolated perfused rat lung model was randomly altered. Intermediate (26.5%), followed by low (6.6%) or normal (43.7%), Hct was set in two consecutive sequences. The pulmonary capillary pressure was maintained constant throughout the experiment, and the pulmonary hemodynamic parameters were monitored continuously. The airway resistance (Raw), the viscous (G) and elastic (H) parameters, and the hysteresivity (η = G/H) of the lung tissues were obtained from measurements of forced oscillatory input impedance data. Raw was not affected by the alterations of the Hct levels. As concerns the lung tissues, the decrease of Hct to intermediate or low levels resulted in close to proportional decreases in the viscoelastic parameters G [16.5 ± 7.7% (SD), 12.1 ± 9.5%, P < 0.005] and H (13.2 ± 8.6%, 10.8 ± 4.7%, P < 0.001). No significant changes in η were detected in a wide range of Hct, which indicates that coupled processes cause alterations in the resistive and elastic properties of the lungs following Hct changes in the pulmonary circulation. The diminishment of the viscous and elastic parameters of the pulmonary parenchyma following a reduction of blood Hct demonstrates the significant contribution of the red blood cells to the overall lung viscoelasticity. PMID:27283919

  12. A Proteomics Perspective on Viral DNA Sensors in Host Defense and Viral Immune Evasion Mechanisms

    PubMed Central

    Crow, Marni S.; Javitt, Aaron; Cristea, Ileana M.

    2015-01-01

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular mass spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. PMID:25728651

  13. Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

    PubMed Central

    Shen, Ding-Wu; Pouliot, Lynn M.; Hall, Matthew D.

    2012-01-01

    Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis. PMID:22659329

  14. Triiodothyronine and melatonin influence antioxidant defense mechanism in a teleost Anabas testudineus (Bloch): in vitro study.

    PubMed

    Sreejith, P; Beyo, R S; Divya, L; Vijayasree, A S; Manju, M; Oommen, O V

    2007-06-01

    The effect of the hormones triiodothyronine (T3) and melatonin on antioxidant defense system was studied in 6-propyl thiouracil (6-PTU)-treated or photoperiod-exposed teleost Anabas testudineus. 6-PTU (2 microg/g) treatment or photoperiod exposure (24 h) increased malondialdehyde (MDA) and conjugated dienes (CD) concentrations, indicating increased lipid peroxidation (LPO) in the experimental conditions. T3 or melatonin (10(-6) M) treatment for 15 min in vitro in PTU-treated fish reversed the activity of superoxide dismutase (SOD), catalase and glutathione content. T3-treated group showed no change in glutathione peroxidase (GPx) activity, whereas melatonin treatment decreased its activity. T3 inhibited glutathione reductase (GR) activity. Photoperiod exposure (physiological pinealotomy) induced a stressful situation in this teleost, as evidenced by LPO products and antioxidant enzyme activities. Melatonin and T3 treatment for 15 min in vitro also reversed the effect of photoperiod on peroxidation products and the SOD and catalase activities. GR activity decreased in photoperiod-exposed group and melatonin and T3 treatment reversed the activities. The antioxidant enzymes responded to the stress situation after 6-PTU treatment and photoperiod exposure by altering their activities. The study suggested an independent effect of T3 and melatonin on antioxidant defence mechanism in different physiological situations in fish. PMID:17650585

  15. Defense Mechanisms Reported by Patients with Borderline Personality Disorder and Axis II Comparison Subjects Over 16 Years of Prospective Follow-up: Description and Prediction of Recovery

    PubMed Central

    Zanarini, Mary C.; Frankenburg, Frances R.; Fitzmaurice, Garrett

    2012-01-01

    Objective This study assessed the defensive functioning of 290 borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology over 16 years of prospective follow-up. It also assessed the relationship between time-varying defenses and recovery from borderline personality disorder. Method The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was initially administered at study entry. It was readministered at eight contiguous two-year long follow-up periods. Results Borderline patients had significantly lower scores than axis II comparison subjects on one mature defense mechanism (suppression) and significantly higher scores on seven of the other 18 defenses studied. More specifically, borderline patients had significantly higher scores on one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image-distorting/borderline defenses (projective identification and splitting). In terms of change, borderline patients were found to have had significant improvement on 13 of the 19 defenses studied. More specifically, they had significantly higher scores over time on one mature defense (anticipation) and significantly lower scores on two neurotic defenses (isolation and undoing), all immature defenses, and all image-distorting/borderline defenses except primitive idealization. In addition, four time-varying defense mechanisms were found to predict time-to-recovery: humor, acting out, emotional hypochondriasis, and projection. Conclusions Taken together, the results of this study suggest that the longitudinal defensive functioning of borderline patients is both distinct and improves substantially over time. They also suggest that immature defenses are the best predictors of time-to-recovery. PMID:23223866

  16. Mid-Term Outcome of Mechanical Pulmonary Valve Prostheses: The Importance of Anticoagulation

    PubMed Central

    Sadeghpour, Anita; Kyavar, Majid; Javani, Bahareh; Bakhshandeh, Hooman; Maleki, Majid; Khajali, Zahra; Subrahmanyan, Lakshman

    2014-01-01

    Introduction: Pulmonary valve replacement (PVR) is being performed more commonly late after the correction of tetralogy of Fallot. Most valves are replaced with an allograft or xenograft, although reoperations are a common theme. Mechanical prostheses have a less favorable reputation due to the necessity of lifelong anticoagulation therapy and higher risk of thrombosis, but they are also less likely to require reoperation. There is a paucity of data on the use of prosthetic valves in the pulmonary position. We report the midterm outcomes of 38 cases of PVR with mechanical prostheses. Methods: One hundred twenty two patients who underwent PVR were studied. Thirty-eight patients, mean age 25 ± 8.4 years underwent PVR with mechanical prostheses based on the right ventricular function and the preferences of the patients and physicians. Median age of prosthesis was 1 year (range 3 months to 5 years). Results: Seven (18%) patients had malfunctioning pulmonary prostheses and two patients underwent redo PVR. Mean International Normalized Ratio (INR) in these seven patients was 2.1±0.8. Fibrinolytic therapy was tried and five of them responded to it well. There was no significant association between the severity of right ventricular dysfunction, patient’s age, prostheses valve size and age of the prosthesis in the patients with prosthesis malfunction. Conclusion: PVR with mechanical prostheses can be performed with promising midterm outcomes. Thrombosis on mechanical pulmonary valve prostheses remains a serious complication, but most prosthesis malfunction respond to fibrinolytic therapy, underscoring the need for adequate anticoagulation therapy. PMID:25320663

  17. UVR defense mechanisms in eurytopic and invasive Gracilaria vermiculophylla (Gracilariales, Rhodophyta).

    PubMed

    Roleda, Michael Y; Nyberg, Cecilia D; Wulff, Angela

    2012-10-01

    The invasive success of Gracilaria vermiculophylla has been attributed to its wide tolerance range to different abiotic factors, but its response to ultraviolet radiation (UVR) is yet to be investigated. In the laboratory, carpospores and vegetative thalli of an Atlantic population were exposed to different radiation treatments consisting of high PAR (photosynthetically active radiation) only (P), PAR+UV-A (PA) and PAR+UV-A+UV-B (PAB). Photosynthesis of carpospores was photoinhibited under different radiation treatments but photosystem II (PSII) function was restored after 12 h under dim white light. Growth of vegetative thalli was significantly higher under radiation supplemented with UVR. Decrease in chlorophyll a (Chl a) under daily continuous 16-h exposure to 300 µmol photons m(-2) s(-1) of PAR suggests preventive accumulation of excited chlorophyll molecules within the antennae to minimize the generation of dangerous reactive oxygen species. Moreover, an increase in total carotenoids and xanthophyll cycle pigments (i.e. violaxanthin, antheraxanthin and zeaxanthin) further suggests effective photoprotection under UVR. The presence of the ketocarotenoid β-cryptoxanthin also indicates protection against UVR and oxidative stress. The initial concentration of total mycosporine-like amino acids (MAAs) in freshly-released spores increased approximately four times after 8-h laboratory radiation treatments. On the other hand, initial specific MAAs in vegetative thalli changed in composition after 7-day exposure to laboratory radiation conditions without affecting the total concentration. The above responses suggest that G. vermiculophylla have multiple UVR defense mechanisms to cope with the dynamic variation in light quantity and quality encountered in its habitat. Beside being eurytopic, the UVR photoprotective mechanisms likely contribute to the current invasive success of the species in shallow lagoons and estuaries exposed to high solar radiation. PMID:22420775

  18. Mechanical ventilation in patients with chronic obstructive pulmonary disease and bronchial asthma

    PubMed Central

    Ahmed, Syed Moied; Athar, Manazir

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) and bronchial asthma often complicate the surgical patients, leading to post-operative morbidity and mortality. Many authors have tried to predict post-operative pulmonary complications but not specifically in COPD. The aim of this review is to provide recent evidence-based guidelines regarding predictors and ventilatory strategies for mechanical ventilation in COPD and bronchial asthma patients. Using Google search for indexing databases, a search for articles published was performed using various combinations of the following search terms: ‘Predictors’; ‘mechanical ventilation’; COPD’; ‘COPD’; ‘bronchial asthma’; ‘recent strategies’. Additional sources were also identified by exploring the primary reference list. PMID:26556918

  19. Intrapulmonary haematoma complicating mechanical ventilation in patients with chronic obstructive pulmonary disease.

    PubMed

    Bonmarchand, G; Lefebvre, E; Lerebours-Pigeonnière, G; Genevois, A; Massari, P; Leroy, J

    1988-01-01

    Intrapulmonary haematomas occurred during mechanical ventilation of two patients with advanced chronic obstructive pulmonary disease and bullous dystrophy. In both cases, the haematomas were revealed by blood-stained aspirates, a fall in haemoglobin level, and the appearance of radiological opacities. Haematoma occurrence in the area of a bulla which recently has rapidly increased in size, suggests that the haematoma is due to the rupture of stretched vessels embedded in the wall of the bulla. PMID:3379188

  20. Iron acquisition from Pseudomonas aeruginosa siderophores by human phagocytes: an additional mechanism of host defense through iron sequestration?

    PubMed

    Britigan, B E; Rasmussen, G T; Olakanmi, O; Cox, C D

    2000-03-01

    Chelation of iron to iron-binding proteins is a strategy of host defense. Some pathogens counter this via the secretion of low-molecular-weight iron-chelating agents (siderophores). Human phagocytes possess a high-capacity mechanism for iron acquisition from low-molecular-weight iron chelates. Efficient acquisition and sequestration of iron bound to bacterial siderophores by host phagocytes could provide a secondary mechanism to limit microbial access to iron. In the present work we report that human neutrophils, macrophages, and myeloid cell lines can acquire iron from the two Pseudomonas aeruginosa siderophores. Analogous to iron acquisition from other low-molecular-weight chelates, iron acquisition from the siderophores is ATP independent, induced by multivalent cationic metals, and unaffected by inhibitors of endocytosis and pinocytosis. In vivo, this process could serve as an additional mechanism of host defense to limit iron availability to invading siderophore-producing microbes. PMID:10678937

  1. Iron Acquisition from Pseudomonas aeruginosa Siderophores by Human Phagocytes: an Additional Mechanism of Host Defense through Iron Sequestration?

    PubMed Central

    Britigan, Bradley E.; Rasmussen, George T.; Olakanmi, Oyebode; Cox, Charles D.

    2000-01-01

    Chelation of iron to iron-binding proteins is a strategy of host defense. Some pathogens counter this via the secretion of low-molecular-weight iron-chelating agents (siderophores). Human phagocytes possess a high-capacity mechanism for iron acquisition from low-molecular-weight iron chelates. Efficient acquisition and sequestration of iron bound to bacterial siderophores by host phagocytes could provide a secondary mechanism to limit microbial access to iron. In the present work we report that human neutrophils, macrophages, and myeloid cell lines can acquire iron from the two Pseudomonas aeruginosa siderophores. Analogous to iron acquisition from other low-molecular-weight chelates, iron acquisition from the siderophores is ATP independent, induced by multivalent cationic metals, and unaffected by inhibitors of endocytosis and pinocytosis. In vivo, this process could serve as an additional mechanism of host defense to limit iron availability to invading siderophore-producing microbes. PMID:10678937

  2. Histopathologic pulmonary changes from mechanical ventilation at high peak airway pressures.

    PubMed

    Tsuno, K; Miura, K; Takeya, M; Kolobow, T; Morioka, T

    1991-05-01

    We investigated the histopathologic pulmonary changes induced by mechanical pulmonary ventilation (MV) with a high peak airway pressure and a large tidal volume in healthy baby pigs. Eleven animals were mechanically ventilated at a peak inspiratory pressure (PIP) of 40 cm H2O, a respiratory rate (RR) of 20 min-1, a positive end-expiratory pressure (PEEP) of 3 to 5 cm H2O, and an FIO2 of 0.4. High airway pressure MV was terminated in 22 +/- 11 h because of severe hypoxemia in the animals. Five of the baby pigs were killed for gross and light microscope studies. The pulmonary changes consisted of alveolar hemorrhage, alveolar neutrophil infiltration, alveolar macrophage and type II pneumocyte proliferation, interstitial congestion and thickening, interstitial lymphocyte infiltration, emphysematous change, and hyaline membrane formation. Those lesions were similar to that seen in the early stage of the adult respiratory distress syndrome (ARDS). The remaining six animals were treated for 3 to 6 days with conventional respiratory care with appropriate ventilator settings. Prominent organized alveolar exudate in addition to lesions was also found in the five animals. These findings were indistinguishable from the clinical late stage of ARDS. Six control animals were mechanically ventilated at a PIP of less than 18 cm H2O, a RR of 20 min-1, a PEEP of 3 to 5 cm H2O, and an FIO2 of 0.4 for 48 h. They showed no notable changes in lung functions and histopathologic findings. Aggressive MV with a high PIP is often applied to patients with respiratory distress to attain adequate pulmonary gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2024823

  3. Indications for manual lung hyperinflation (MHI) in the mechanically ventilated patient with chronic obstructive pulmonary disease.

    PubMed

    Ntoumenopoulos, G

    2005-01-01

    Manual lung hyperinflation (MHI) can enhance secretion clearance, improve total lung/thorax compliance and assist in the resolution of acute atelectasis. To enhance secretion clearance in the intubated patient, the evidence highlights the need to maximize expiratory flow. Chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have often been cited as potential precautions and/or contra-indications to the use of manual lung hyperinflation (MHI). There is an absence of evidence on the effects of MHI in the patient with COPD. Research on the effects of mechanical ventilation in the patient with COPD provides a useful clinical examination of the effect of positive pressure on cardiac and pulmonary function. The potential effects of MHI in the COPD patient group were extrapolated on the basis of the MHI and mechanical ventilation literature. There is the potential for MHI to have both detrimental and beneficial effects on cardiac and pulmonary function in patients with COPD. The potential detrimental effects of MHI may include either, increased intrinsic peep through inadequate time for expiration by the breath delivery rate, tidal volume delivered or through the removal of applied external PEEP thereby causing more dynamic airway compression compromising downward expiratory flow, which may also retard bronchial mucus transport. MHI may also increase right ventricular after load through raised intrathoracic pressures with lung hyperinflation, and may therefore impair right ventricular function in patients with evidence of cor pulmonale. There is the potential for beneficial effects from MHI in the intubated COPD patient group (i.e., secretion clearance), but further research is required, especially on the effect of MHI on inspiratory and expiratory flow rate profiles in this patient group. The more controlled delivery of lung hyperinflation through the use of the mechanical ventilator may be a more optimal means of providing lung hyperinflation

  4. Pulmonary mechanics by spectral analysis of forced random noise.

    PubMed Central

    Michaelson, E D; Grassman, E D; Peters, W R

    1975-01-01

    The magnitude (Zrs) and phase angle (thetars) of the total respiratory impedance (Zrs), from 3 to 45 Hz, were rapidly obtained by a modification of the forced oscillation method, in which a random noise pressure wave is imposed on the respiratory system at the mouth and compared to the induced random flow using Fourier and spectral analysis. No significant amplitude or phase errors were introduced by the instrumentation. 10 normals, 5 smokers, and 5 patients with chronic obstructive lung disease (COPD) were studied. Measurements of Zrs were corrected for the parallel shunt impedance of the mouth, which was independently measured during a Valsalva maneuver, and from which the mechanical properties of the mouth were derived. There were small differences in Zrs between normals and smokers but both behaved approximately like a second-order system with thetars = 0 degree in the range of 5--9 Hz, and thetars in the range of +40 degrees at 20 Hz and +60 degrees at 40 Hz. In COPD, thetars remained more negative (compared to normals and smokers) at all frequencies and crossed 0 between 15 and 29 Hz. Changes in Zrs, similar in those in COPD, were also observed at low lung volumes in normals. These changes, the effects of a bronchodilator in COPD, and deviations of Zrs from second-order behavior in normals, can best be explained by a two-compartment parallel model, in which time-constant discrepancies between the lung parenchyma and compliant airway keep compliant greater than inertial reactance, resulting in a more negative phase angle as frequency is increased. PMID:1184746

  5. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films.

    PubMed

    Parra, Elisa; Pérez-Gil, Jesús

    2015-01-01

    The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension of the unique mechanical and rheological properties of surfactant layers is crucial for the diagnostics and treatment of lung diseases, either by analyzing the contribution of surfactant impairment to the pathophysiology or by improving the formulations in surfactant replacement therapies. Finally, a short review is also included on the most relevant experimental techniques currently employed to evaluate lung surfactant mechanics, rheology, and inhibition and reactivation processes. PMID:25260665

  6. Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat.

    PubMed

    Casey, David B; Badejo, Adeleke M; Dhaliwal, Jasdeep S; Murthy, Subramanyam N; Hyman, Albert L; Nossaman, Bobby D; Kadowitz, Philip J

    2009-02-01

    Recent studies show that pulmonary vasodilator responses to nitrite are enhanced by hypoxia. However, the mechanism by which nitrite is converted to vasoactive nitric oxide (NO) is uncertain. In the present study, intravenous injections of sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure were enhanced when tone in the pulmonary vascular bed was increased with U-46619. Under elevated tone conditions, decreases in pulmonary and systemic arterial pressures in response to nitrite were attenuated by allopurinol in a dose that did not alter responses to the NO donors, sodium nitroprusside and diethylamine/NO, suggesting that xanthine oxidoreductase is the major enzyme-reducing nitrite to NO. Ventilation with a 10% O(2) gas mixture increased pulmonary arterial pressure, and the response to hypoxia was enhanced by N(G)-nitro-l-arginine methyl ester and not altered by allopurinol. This suggests that NO formed by the endothelium and not from the reduction of plasma nitrite modulates the hypoxic pulmonary vasoconstrictor response. Although intravenous injections of sodium nitrite reversed pulmonary hypertensive responses to U-46619, hypoxia, and N(G)-nitro-l-arginine methyl ester, the pulmonary vasodilator response to nitrite was not altered by ventilation with 10% O(2) when baseline pulmonary arterial pressure was increased to similar values in animals breathing room air or the hypoxic gas. These data provide evidence that xanthine oxidoreductase is the major enzyme-reducing nitrite to vasoactive NO, and that this mechanism is not modified by hypoxia. PMID:19074675

  7. Growth, photosynthesis, and defense mechanism of antimony (Sb)-contaminated Boehmeria nivea L.

    PubMed

    Chai, Li-Yuan; Mubarak, Hussani; Yang, Zhi-Hui; Yong, Wang; Tang, Chong-Jian; Mirza, Nosheen

    2016-04-01

    Ramie (Boehmeria nivea L.) is the oldest cash fiber crop in China and is widely grown in antimony (Sb) mining areas. To evaluate the extent of Sb resistance and tolerance, the growth, tolerance index (TI), Sb content in plant parts and in Hoagland solution, bioaccumulation factor (BF), photosynthesis, and physiological changes in Sb-contaminated B. nivea (20, 40, 80, and 200 mg L(-1) Sb) grown hydroponically were investigated. The Sb tolerance and resistance of ramie were clearly revealed by growth inhibition, a TI between 13 and 99 %, non-significant changes in the maximum quantum efficiency of photosystem (F v /F m ), energy-harvesting efficiency (photosystem II (PSII)) and single-photon avalanche diode (SPAD) value, a significant increase in Sb in plant parts, BF >1, and an increase in catalase (CAT) and malondialdehyde (MDA) at 200 mg L(-1) Sb. Under increasing Sb stress, nearly the same non-significant decline in the maximum quantum efficiency of photosystem (F v /F m ), energy-harvesting efficiency (PSII), relative quantum yield of photosystem II (φPSII), and photochemical quenching (qP), except for F v /F m at 20 mg L(-1) Sb, were recorded. SPAD values for chlorophyll under Sb stress showed an increasing trend, except for a slight decrease, i.e., <2 %, than the control SPAD value at 200 mg L(-1) Sb. With a continuous increase in MDA, superoxide dismutase (SOD), peroxidase (POD), and CAT activities were suppressed under Sb addition up to 40 mg L(-1) Sb and the addition of Sb enhanced enzyme production at 80 and 200 mg L(-1) Sb. A continuous decrease in SOD, POD, and CAT up to 40 mg L(-1) Sb and enhancements at ≥80 mg L(-1), along with the continuous enhancement of MDA activity and inhibited biomass production, clearly reveal the roles of these enzymes in detoxifying Sb stress and the defense mechanism of ramie at 80 mg L(-1) Sb. Thus, B. nivea constitutes a promising candidate for Sb phytoremediation at mining sites. PMID:26711292

  8. Zinc triggers signaling mechanisms and defense responses promoting resistance to Alternaria brassicicola in Arabidopsis thaliana.

    PubMed

    Martos, Soledad; Gallego, Berta; Cabot, Catalina; Llugany, Mercè; Barceló, Juan; Poschenrieder, Charlotte

    2016-08-01

    According to the elemental defense hypothesis the accumulation of trace elements by plants may substitute for organic defenses, while the joint effects hypothesis proposes that trace elements and organic defenses can have additive or synergistic effects against pathogens or herbivores. To evaluate these hypotheses the response of the pathosystem Alternaria brassicicola-Arabidopsis thaliana to control (2μM) and surplus (12μM) Zn was evaluated using the camalexin deficient mutant pad3-1 and mtp1-1, a mutant with impaired Zn vacuolar storage, along with the corresponding wildtypes. In vitro, a 50% inhibition of fungal growth was achieved by 440μM Zn. A. thaliana leaves could accumulate equivalent concentrations without harm. In fact, surplus Zn enhanced the resistance of A. thaliana to fungal attack in Columbia (Col-0), Wassilewskija (WS), and mtp1-1. However, surplus Zn was unable to protect pad3-1 demonstrating that Zn cannot substitute for camalexin, the main organic defense in A. thaliana. High, non phytotoxic leaf Zn concentrations enhanced the resistance to A. brassicicola of A. thaliana genotypes able to produce camalexin. This was mainly due to Zn-induced enhancement of the JA/ETH signaling pathway leading to enhanced PAD3 expression. These results support the joint effects hypothesis and highlight the importance of adequate Zn supply for reinforced pathogen resistance. PMID:27297986

  9. Mechanical exsufflation, noninvasive ventilation, and new strategies for pulmonary rehabilitation and sleep disordered breathing.

    PubMed Central

    Bach, J. R.

    1992-01-01

    Manual and mechanical exsufflation are important but underutilized ways to clear airway secretions. These methods are especially useful when used in concert with noninvasive intermittent positive airway pressure ventilatory assistance to facilitate extubation and ventilator weaning. This can be used as much as 24 hours a day as an alternative to tracheostomy ventilation or body ventilator use for patients with paralytic restrictive ventilatory insufficiency. These techniques expedite community management of ventilator assisted individuals by avoiding tracheostomy and need for invasive suctioning and ongoing wound care. For these techniques to be effective and to prevent further suppression of ventilatory drive, supplemental oxygen administration must be avoided unless pO2 is less than 60 mm Hg despite normalization of pCO2. Custom molded interfaces for the delivery of noninvasive intermittent positive airway pressure ventilatory assistance can also be used to facilitate the delivery of variable inspiratory expiratory positive airway pressure for patients with obstructive sleep apnea. Noninvasive intermittent positive airway pressure ventilatory assistance or body ventilator use can rest the respiratory muscles of patients with advanced chronic obstructive pulmonary disease. This and pulmonary rehabilitation programs geared to exercise reconditioning are therapeutic options that significantly improve the quality of life of these patients. For both paralytic restrictive and obstructive pulmonary patients, these techniques decrease cost and frequency of hospitalizations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1586868

  10. Brief Report: Self-Harm Is Associated with Immature Defense Mechanisms but Not Substance Use in a Nonclinical Scottish Adolescent Sample

    ERIC Educational Resources Information Center

    Brody, Stuart; Carson, Carron Maryjane

    2012-01-01

    It has been unclear whether adolescent deliberate self-harm (DSH) is more associated with substance use or with characterological impairments. Multivariate determination of (N = 114 Scottish adolescents) ever engaging in DSH (Youth Risk Behavior Survey) from alcohol use, other substance use, and immature defense mechanism use (Defense Style…

  11. A shared mechanism of defense against predators and parasites: chitin regulation and its implications for life-history theory

    PubMed Central

    Beckerman, Andrew P; de Roij, Job; Dennis, Stuart R; Little, Tom J

    2013-01-01

    Defenses against predators and parasites offer excellent illustrations of adaptive phenotypic plasticity. Despite vast knowledge about such induced defenses, they have been studied largely in isolation, which is surprising, given that predation and parasitism are ubiquitous and act simultaneously in the wild. This raises the possibility that victims must trade-off responses to predation versus parasitism. Here, we propose that arthropod responses to predators and parasites will commonly be based on the endocrine regulation of chitin synthesis and degradation. The proposal is compelling because many inducible defenses are centered on temporal or spatial modifications of chitin-rich structures. Moreover, we show how the chitin synthesis pathway ends in a split to carapace or gut chitin, and how this form of molecular regulation can be incorporated into theory on life-history trade-offs, specifically the Y-model. Our hypothesis thus spans several biological scales to address advice from Stearns that “Endocrine mechanisms may prove to be only the tip of an iceberg of physiological mechanisms that modulate the expression of genetic covariance”. PMID:24455141

  12. Glucose and Stress Independently Regulate Source and Sink Metabolism and Defense Mechanisms via Signal Transduction Pathways Involving Protein Phosphorylation.

    PubMed Central

    Ehness, R.; Ecker, M.; Godt, D. E.; Roitsch, T.

    1997-01-01

    In higher plants, sugars are required not only to sustain heterotrophic growth but also to regulate the expression of a variety of genes. Environmental stresses, such as pathogen infection and wounding, activate a cascade of defense responses and may also affect carbohydrate metabolism. In this study, the relationship between sugar- and stress-activated signal transduction pathways and the underlying regulatory mechanism was analyzed. Photoautotrophically growing suspension culture cells of Chenopodium rubrum were used as a model system to study the effects of the metabolic regulator D-glucose and of different stress-related stimuli on photosynthesis, sink metabolism, and defense response by analyzing the regulation of mRNAs for representative enzymes of these pathways. Glucose as well as the fungal elicitor chitosan, the phosphatase inhibitor endothall, and benzoic acid were shown to result in a coordinated regulatory mechanism. The mRNAs for phenylalanine ammonia-lyase, a key enzyme of defense response, and for the sink-specific extracellular invertase were induced. In contrast, the mRNA for the Calvin cycle enzyme ribulose bisphosphate carboxylase was repressed. This inverse regulatory pattern was also observed in experiments with wounded leaves of C. rubrum plants. The differential effect of the protein kinase inhibitor staurosporine on mRNA regulation demonstrates that the carbohydrate signal and the stress-related stimuli independently activate different intracellular signaling pathways that ultimately are integrated to coordinately regulate source and sink metabolism and activate defense responses. The various stimuli triggered the transient and rapid activation of protein kinases that phosphorylate the myelin basic protein. The involvement of phosphorylation in signal transduction is further supported by the effect of the protein kinase inhibitor staurosporine on mRNA levels. PMID:12237349

  13. Anatomy and function of the ptychoid defensive mechanism in the mite Euphthiracarus cooki (Acari: Oribatida).

    PubMed

    Sanders, Francis H; Norton, Roy A

    2004-02-01

    Ptychoidy is a defensive adaptation of several groups of oribatid mites in which legs and coxisternum can be fully retracted into the opisthosoma and protected by a ventrally deflected prodorsum, resulting in a seed-like appearance. Using Euphthiracarus cooki as a model, we examined details of exoskeletal and muscular anatomy in combination with studies of live individuals to provide the first functional analysis of ptychoidy. There are two main functional components: the first is a set of exoskeletal and muscular adaptations, mostly of the podosoma and prodorsum, that combine to effect leg withdrawal and prodorsal deflection; the second comprises adaptations of the opisthosoma that allow control of hydrostatic pressure during the large hemocoel volume adjustments associated with ptychoidy. Adaptations important in the closing process (enptychosis) are found in four body regions. Much of the podosomal exoskeleton (especially pleural) is unsclerotized, which facilitates leg retraction and prodorsal deflection during enptychosis. The coxisternum has several flexible furrows along which it folds in order to bring legs into a tightly parallel arrangement. The prodorsum has specialized attachment surfaces (manubrium and inferior retractor process) for retractor muscles and a paired bothridial scale that participates in prodorsal alignment during enptychosis. The subcapitulum has a prominent capitular apodeme on which important retractor muscles insert. The mineralized notogaster has an anterior "collar" that accommodates the retracted prodorsum; it includes paired notches and receptacles that accommodate the bothridial scales, thereby creating a temporary fixed axis for rotation of the prodorsum in a "lazy hinge" mechanism. Specialized muscles form the retractor system; most conspicuous are the large coxisternal retractors and prodorsal retractors, both of which originate on the notogaster. Other components have adjustor roles; among them are muscles of the endosternal

  14. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  15. Mechanical ventilation causes pulmonary mitochondrial dysfunction and delayed alveolarization in neonatal mice.

    PubMed

    Ratner, Veniamin; Sosunov, Sergey A; Niatsetskaya, Zoya V; Utkina-Sosunova, Irina V; Ten, Vadim S

    2013-12-01

    Hyperoxia inhibits pulmonary bioenergetics, causing delayed alveolarization in mice. We hypothesized that mechanical ventilation (MV) also causes a failure of bioenergetics to support alveolarization. To test this hypothesis, neonatal mice were ventilated with room air for 8 hours (prolonged) or for 2 hours (brief) with 15 μl/g (aggressive) tidal volume (Tv), or for 8 hours with 8 μl/g (gentle) Tv. After 24 hours or 10 days of recovery, lung mitochondria were examined for adenosine diphosphate (ADP)-phosphorylating respiration, using complex I (C-I)-dependent, complex II (C-II)-dependent, or cytochrome C oxidase (C-IV)-dependent substrates, ATP production rate, and the activity of C-I and C-II. A separate cohort of mice was exposed to 2,4-dinitrophenol (DNP), a known uncoupler of oxidative phosphorylation. At 10 days of recovery, pulmonary alveolarization and the expression of vascular endothelial growth factor (VEGF) were assessed. Sham-operated littermates were used as control mice. At 24 hours after aggressive MV, mitochondrial ATP production rates and the activity of C-I and C-II were significantly decreased compared with control mice. However, at 10 days of recovery, only mice exposed to prolonged-aggressive MV continued to exhibit significantly depressed mitochondrial respiration. This was associated with significantly poorer alveolarization and VEGF expression. In contrast, mice exposed to brief-aggressive or prolonged-gentle MV exhibited restored mitochondrial ADP-phosphorylation, normal alveolarization and pulmonary VEGF content. Exposure to DNP fully replicated the phenotype consistent with alveolar developmental arrest. Our data suggest that the failure of bioenergetics to support normal lung development caused by aggressive and prolonged ventilation should be considered a fundamental mechanism for the development of bronchopulmonary dysplasia in premature neonates. PMID:23980609

  16. Update on molecular mechanisms of corticosteroid resistance in chronic obstructive pulmonary disease.

    PubMed

    Jiang, Zhilong; Zhu, Lei

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory and irreversible pulmonary disorder that is characterized by inflammation and airway destruction. In recent years, COPD has become a global epidemic due to increased air pollution and exposure to cigarette smoke. Current therapeutics using bronchiodialator and anti-inflammatory corticosteroids are most widely used for all patients with persistent COPD, but these approaches are disappointing due to limited improvement in symptom control and survival rate. More importantly, a certain number of COPD patients are resistant to the corticosteroid treatment and their symptoms worsen. Therefore, more effective anti-inflammatory drugs and combinational treatment are required. Understanding of the underlying molecular and immunological mechanisms is critical to developing new therapeutics. Lung inflammation and the released pro-inflammatory cytokines affect glucocorticoid receptor (GR), histone deacetylase 2 (HDAC2) and surfactant protein D (SP-D) activities in many cell types. Macrophages, neutrophils, airway epithelial cells and lymphocytes are involved in the induction of corticosteroid resistance. This review updated the recent advances in molecular and immunological mechanisms of steroid resistance among patients and animal models with COPD. Meanwhile we discussed novel therapeutic approaches in controlling lung inflammation and improving corticosteroid sensitivity among the steroid resistant patients with COPD. PMID:26805715

  17. Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives.

    PubMed

    Chelladurai, Prakash; Seeger, Werner; Pullamsetti, Soni Savai

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date. PMID:27246590

  18. Plant Defense Mechanisms Are Activated during Biotrophic and Necrotrophic Development of Colletotricum graminicola in Maize1[W][OA

    PubMed Central

    Vargas, Walter A.; Martín, José M. Sanz; Rech, Gabriel E.; Rivera, Lina P.; Benito, Ernesto P.; Díaz-Mínguez, José M.; Thon, Michael R.; Sukno, Serenella A.

    2012-01-01

    Hemibiotrophic plant pathogens first establish a biotrophic interaction with the host plant and later switch to a destructive necrotrophic lifestyle. Studies of biotrophic pathogens have shown that they actively suppress plant defenses after an initial microbe-associated molecular pattern-triggered activation. In contrast, studies of the hemibiotrophs suggest that they do not suppress plant defenses during the biotrophic phase, indicating that while there are similarities between the biotrophic phase of hemibiotrophs and biotrophic pathogens, the two lifestyles are not analogous. We performed transcriptomic, histological, and biochemical studies of the early events during the infection of maize (Zea mays) with Colletotrichum graminicola, a model pathosystem for the study of hemibiotrophy. Time-course experiments revealed that mRNAs of several defense-related genes, reactive oxygen species, and antimicrobial compounds all begin to accumulate early in the infection process and continue to accumulate during the biotrophic stage. We also discovered the production of maize-derived vesicular bodies containing hydrogen peroxide targeting the fungal hyphae. We describe the fungal respiratory burst during host infection, paralleled by superoxide ion production in specific fungal cells during the transition from biotrophy to a necrotrophic lifestyle. We also identified several novel putative fungal effectors and studied their expression during anthracnose development in maize. Our results demonstrate a strong induction of defense mechanisms occurring in maize cells during C. graminicola infection, even during the biotrophic development of the pathogen. We hypothesize that the switch to necrotrophic growth enables the fungus to evade the effects of the plant immune system and allows for full fungal pathogenicity. PMID:22247271

  19. Caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against Trypanosoma cruzi infection.

    PubMed

    Carrillo, Ileana; Droguett, Daniel; Castillo, Christian; Liempi, Ana; Muñoz, Lorena; Maya, Juan Diego; Galanti, Norbel; Kemmerling, Ulrike

    2016-09-01

    Congenital Chagas disease is caused by the protozoan parasite Trypanosoma cruzi that must cross the placental barrier during transmission. The trophoblast constitutes the first tissue in contact with the maternal-blood circulating parasite. Importantly, the congenital transmission rates are low, suggesting the presence of local placental defense mechanisms. Cellular proliferation and differentiation as well as apoptotic cell death are induced by the parasite and constitute part of the epithelial turnover of the trophoblast, which has been suggested to be part of those placental defenses. On the other hand, caspase-8 is an essential molecule in the modulation of trophoblast turnover by apoptosis and by epithelial differentiation. As an approach to study whether T. cruzi induced trophoblast turnover and infection is mediated by caspase-8, we infected BeWo cells (a trophoblastic cell line) with the parasite and determined in the infected cells the expression and enzymatic activity of caspase-8, DNA synthesis (as proliferation marker), β-human chorionic gonadotropin (β-hCG) (as differentiation marker) and activity of Caspase-3 (as apoptotic death marker). Parasite load in BeWo cells was measured by DNA quantification using qPCR and cell counting. Our results show that T. cruzi induces caspase-8 activity and that its inhibition increases trophoblast cells infection while decreases parasite induced cellular differentiation and apoptotic cell death, but not cellular proliferation. Thus, caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against T. cruzi infection. Together with our previous results, we suggest that the trophoblast turnover is part of local placental anti-parasite mechanisms. PMID:27328973

  20. A comparison of the pulmonary defenses against streptococcal infection in rats and mice following O3 exposure: Differences in disease susceptibility and neutrophil recruitment

    SciTech Connect

    Gilmour, M.I.; Selgrade, M.K. )

    1993-12-01

    Ozone (O3) exposure reduces alveolar macrophage (AM) phagocytosis in mice and increases their susceptibility to Streptococcus zooepidemicus. O3 exposure also decreases AM phagocytosis in rats but does not result in mortality to infection. To investigate the mechanism of disease protection in rats, antibacterial defenses of two strains of mice and F344 rats were compared. O3 exposure (3 hr, 0.4 or 0.8 ppm) and infection with S. zooepidemicus resulted in a dose-dependent proliferation of bacteria in the lungs of mice and high mortality. Polymorphonuclear leukocytes (PMNs) were observed in severely affected individuals 2 or more days postinfection and did not alter the fatal infection. In contrast, microbial inactivation was only impaired in O3-exposed rat lungs during the first 48 hr after infection. In these animals PMNs could be isolated from bronchoalveolar lavage fluid between 6 and 48 hr postinfection with the peak response occurring at 24 hr. Pretreatment with anti-PMN serum eliminated the neutrophil influx and impaired further the bactericidal activity in ozone-exposed rats. The results suggest that inhaled streptococci are cleared normally from the mouse lung by AMs. Following exposure to O3, AM phagocytosis is reduced and the mice develop a fatal infection. The persistence of bacteria in the lungs of O3-exposed rats triggers a transient influx of PMNs whose appearance corresponds with elimination of the bacteria. Differences in antimicrobial defenses between various experimental species and humans need to be better understood in order to predict effects of air pollutants on susceptibility to infection in man.

  1. Postnatal overnutrition in mice leads to impaired pulmonary mechanics in response to salbutamol.

    PubMed

    Teixeira, Vanessa P; Cervilha, Daniela A B; Cabral, Layla D M; Oliveira, Luiz M; Incerpi, Erika K; Novaes, Rômulo D; Ionta, Marisa; Soncini, Roseli

    2016-05-01

    Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and could potentially explain compromised lung functions. In the present study, the obesity was induced by postnatal overnutrition in Swiss mice and we investigated the pulmonary mechanics after aerosolization of saline, methacholine, and salbutamol. The lungs were prepared for morphometric analysis. Obese animals showed bronchoconstriction in response to methacholine, as evidenced by airway and tissue resistance, tissue elastance, and hysteresivity. Salbutamol was effective at recovering the response only for airway resistance but not for tissue mechanics. We suggest that this impaired response in obese mice is related to collapsed alveolar, to inflammatory cells, and to elevated deposition collagen fibers in parenchymal tissue. PMID:26497334

  2. Pathogenic mechanisms in chronic obstructive pulmonary disease due to biomass smoke exposure.

    PubMed

    Silva, Rafael; Oyarzún, Manuel; Olloquequi, Jordi

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) mortality and morbidity have increased significantly worldwide in recent decades. Although cigarette smoke is still considered the main risk factor for the development of the disease, estimates suggest that between 25% and 33% of COPD patients are non-smokers. Among the factors that may increase the risk of developing COPD, biomass smoke has been proposed as one of the most important, affecting especially women and children in developing countries. Despite the epidemiological evidence linking exposure to biomass smoke with adverse health effects, the specific cellular and molecular mechanisms by which this pollutant can be harmful for the respiratory and cardiovascular systems remain unclear. In this article we review the main pathogenic mechanisms proposed to date that make biomass smoke one of the major risk factors for COPD. PMID:25614376

  3. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

    PubMed Central

    Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

    2015-01-01

    Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

  4. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  5. Proteome and Phosphoproteome Characterization Reveals New Response and Defense Mechanisms of Brachypodium distachyon Leaves under Salt Stress*

    PubMed Central

    Lv, Dong-Wen; Subburaj, Saminathan; Cao, Min; Yan, Xing; Li, Xiaohui; Appels, Rudi; Sun, Dong-Fa; Ma, Wujun; Yan, Yue-Ming

    2014-01-01

    Salinity is a major abiotic stress affecting plant growth and development. Understanding the molecular mechanisms of salt response and defense in plants will help in efforts to improve the salt tolerance of crops. Brachypodium distachyon is a new model plant for wheat, barley, and several potential biofuel grasses. In the current study, proteome and phosphoproteome changes induced by salt stress were the focus. The Bd21 leaves were initially treated with salt in concentrations ranging from 80 to 320 mm and then underwent a recovery process prior to proteome analysis. A total of 80 differentially expressed protein spots corresponding to 60 unique proteins were identified. The sample treated with a median salt level of 240 mm and the control were selected for phosphopeptide purification using TiO2 microcolumns and LC-MS/MS for phosphoproteome analysis to identify the phosphorylation sites and phosphoproteins. A total of 1509 phosphoproteins and 2839 phosphorylation sites were identified. Among them, 468 phosphoproteins containing 496 phosphorylation sites demonstrated significant changes at the phosphorylation level. Nine phosphorylation motifs were extracted from the 496 phosphorylation sites. Of the 60 unique differentially expressed proteins, 14 were also identified as phosphoproteins. Many proteins and phosphoproteins, as well as potential signal pathways associated with salt response and defense, were found, including three 14-3-3s (GF14A, GF14B, and 14-3-3A) for signal transduction and several ABA signal-associated proteins such as ABF2, TRAB1, and SAPK8. Finally, a schematic salt response and defense mechanism in B. distachyon was proposed. PMID:24335353

  6. Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism

    PubMed Central

    Benlloch, María; Obrador, Elena; Valles, Soraya L.; Rodriguez, María L.; Sirerol, J. Antoni; Alcácer, Javier; Pellicer, José A.; Salvador, Rosario; Cerdá, Concha; Sáez, Guillermo T.

    2016-01-01

    Abstract Aims: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). Results: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, at levels measured within the tumors, did not affect melanoma growth in vitro. Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone, and thereby downregulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing melanomas. Exogenous corticosterone or genetically induced Nrf2 overexpression in melanoma cells prevented the inhibition of tumor growth and decreased antioxidant defenses in these malignant cells. These effects and mechanisms were also found in mice bearing different human pancreatic cancers. Glutathione depletion (selected as an antimelanoma strategy) facilitated the complete elimination by chemotherapy of melanoma cells isolated from mice treated with Pter. Innovation: Although bioavailability-related limitations may preclude direct anticancer effects in vivo, natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis. Conclusions: Pter downregulates glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling/transcription and the antioxidant protection of melanoma and pancreatic cancer cells

  7. A novel preterm respiratory mechanics active simulator to test the performances of neonatal pulmonary ventilators

    NASA Astrophysics Data System (ADS)

    Cappa, Paolo; Sciuto, Salvatore Andrea; Silvestri, Sergio

    2002-06-01

    A patient active simulator is proposed which is capable of reproducing values of the parameters of pulmonary mechanics of healthy newborns and preterm pathological infants. The implemented prototype is able to: (a) let the operator choose the respiratory pattern, times of apnea, episodes of cough, sobs, etc., (b) continuously regulate and control the parameters characterizing the pulmonary system; and, finally, (c) reproduce the attempt of breathing of a preterm infant. Taking into account both the limitation due to the chosen application field and the preliminary autocalibration phase automatically carried out by the proposed device, accuracy and reliability on the order of 1% is estimated. The previously indicated value has to be considered satisfactory in light of the field of application and the small values of the simulated parameters. Finally, the achieved metrological characteristics allow the described neonatal simulator to be adopted as a reference device to test performances of neonatal ventilators and, more specifically, to measure the time elapsed between the occurrence of a potentially dangerous condition to the patient and the activation of the corresponding alarm of the tested ventilator.

  8. Molecular Mechanisms of Nanosized Titanium Dioxide–Induced Pulmonary Injury in Mice

    PubMed Central

    Sang, Xuezi; Cui, Yaling; Wang, Xiaochun; Gui, Suxin; Tan, Danlin; Zhu, Min; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling; Hong, Fashui; Tang, Meng

    2013-01-01

    The pulmonary damage induced by nanosized titanium dioxide (nano-TiO2) is of great concern, but the mechanism of how this damage may be incurred has yet to be elucidated. Here, we examined how multiple genes may be affected by nano-TiO2 exposure to contribute to the observed damage. The results suggest that long-term exposure to nano-TiO2 led to significant increases in inflammatory cells, and levels of lactate dehydrogenase, alkaline phosphate, and total protein, and promoted production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse lung tissue. We also observed nano-TiO2 deposition in lung tissue via light and confocal Raman microscopy, which in turn led to severe pulmonary inflammation and pneumonocytic apoptosis in mice. Specifically, microarray analysis showed significant alterations in the expression of 847 genes in the nano-TiO2-exposed lung tissues. Of 521 genes with known functions, 361 were up-regulated and 160 down-regulated, which were associated with the immune/inflammatory responses, apoptosis, oxidative stress, the cell cycle, stress responses, cell proliferation, the cytoskeleton, signal transduction, and metabolic processes. Therefore, the application of nano-TiO2 should be carried out cautiously, especially in humans. PMID:23409001

  9. Antimicrobial terpenes from oleoresin of ponderosa pine tree Pinus ponderosa: A defense mechanism against microbial invasion

    SciTech Connect

    Himejima, Masaki; Hobson, K.R.; Otsuka, Toshikazu; Wood, D.L.; Kubo, Isao )

    1992-10-01

    The oleoresin of the ponderosa pine, Pinus ponderosa (Pinaceae) exhibited broad antimicrobial activity. In order to identify the active compounds, the oleoresin was steam distilled to give a distillate and residue. The distillate contained mainly monoterpenes and some sesquiterpenes, while the residue consisted chiefly of four structurally related diterpene acids. An antimicrobial assay with the pure compounds indicated that the monoterpenes were active primarily against fungi, but there was also some activity against gram-positive bacteria. The diterpene acids, in contrast, only exhibited activity against gram-positive bacteria. Although not all of the identified sesquiterpenes could be tested, longifolene showed activity only against gram-positive bacteria. Therefore, it appears that the oleoresin of P. ponderosa functions as a biochemical defense against microbial invasion.

  10. A method to measure mechanical properties of pulmonary epithelial cell layers.

    PubMed

    Dassow, Constanze; Armbruster, Caroline; Friedrich, Christian; Smudde, Eva; Guttmann, Josef; Schumann, Stefan

    2013-10-01

    The lung has a huge inner alveolar surface composed of epithelial cell layers. The knowledge about mechanical properties of lung epithelia is helpful to understand the complex lung mechanics and biomechanical interactions. Methods have been developed to determine mechanical indices (e.g., tissue elasticity) which are both very complex and in need of costly equipment. Therefore, in this study, a mechanostimulator is presented to dynamically stimulate lung epithelial cell monolayers in order to determine their mechanical properties based on a simple mathematical model. First, the method was evaluated by comparison to classical tensile testing using silicone membranes as substitute for biological tissue. Second, human pulmonary epithelial cells (A549 cell line) were grown on flexible silicone membranes and stretched at a defined magnitude. Equal secant moduli were determined in the mechanostimulator and in a conventional tension testing machine (0.49 ± 0.05 MPa and 0.51 ± 0.03 MPa, respectively). The elasticity of the cell monolayer could be calculated by the volume-pressure relationship resulting from inflation of the membrane-cell construct. The secant modulus of the A549 cell layer was calculated as 0.04 ± 0.008 MPa. These findings suggest that the mechanostimulator may represent an adequate device to determine mechanical properties of cell layers. PMID:23564730

  11. Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma.

    PubMed

    Kazimierová, I; Jošková, M; Pecháňová, O; Šutovská, M; Fraňová, S

    2015-01-01

    Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline. PMID:25315622

  12. The Transcriptome and Terpene Profile of Eucalyptus grandis Reveals Mechanisms of Defense Against the Insect Pest, Leptocybe invasa.

    PubMed

    Oates, Caryn N; Külheim, Carsten; Myburg, Alexander A; Slippers, Bernard; Naidoo, Sanushka

    2015-07-01

    Plants have evolved complex defenses that allow them to protect themselves against pests and pathogens. However, there is relatively little information regarding the Eucalyptus defensome. Leptocybe invasa is one of the most damaging pests in global Eucalyptus forestry, and essentially nothing is known regarding the molecular mechanisms governing the interaction between the pest and host. The aim of the study was to investigate changes in the transcriptional landscape and terpene profile of a resistant and susceptible Eucalyptus genotype in an effort to improve our understanding of this interaction. We used RNA-seqencing to investigate transcriptional changes following L. invasa oviposition. Expression levels were validated using real-time quantitative PCR. Terpene profiles were investigated using gas chromatography coupled to mass spectometry on uninfested and oviposited leaves. We found 698 and 1,115 significantly differentially expressed genes from the resistant and susceptible interactions, respectively. Gene Ontology enrichment and Mapman analyses identified putative defense mechanisms including cell wall reinforcement, protease inhibitors, cell cycle suppression and regulatory hormone signaling pathways. There were significant differences in the mono- and sesquiterpene profiles between genotypes and between control and infested material. A model of the interaction between Eucalyptus and L. invasa was proposed from the transcriptomic and chemical data. PMID:25948810

  13. Defense mechanisms against herbivory in Picea: sequence evolution and expression regulation of gene family members in the phenylpropanoid pathway

    PubMed Central

    2011-01-01

    the evolution of plant defense mechanisms against insect pests and provide substantial potential for the functional characterization of several not yet resolved alternative pathways in plant defenses. PMID:22177423

  14. Microstructure and Mechanical Property of Glutaraldehyde-Treated Porcine Pulmonary Ligament.

    PubMed

    Chen, Huan; Zhao, Xuefeng; Berwick, Zachary C; Krieger, Joshua F; Chambers, Sean; Kassab, Ghassan S

    2016-06-01

    There is a significant need for fixed biological tissues with desired structural and material constituents for tissue engineering applications. Here, we introduce the lung ligament as a fixed biological material that may have clinical utility for tissue engineering. To characterize the lung tissue for potential clinical applications, we studied glutaraldehyde-treated porcine pulmonary ligament (n = 11) with multiphoton microscopy (MPM) and conducted biaxial planar experiments to characterize the mechanical property of the tissue. The MPM imaging revealed that there are generally two families of collagen fibers distributed in two distinct layers: The first family largely aligns along the longitudinal direction with a mean angle of θ = 10.7 ± 9.3 deg, while the second one exhibits a random distribution with a mean θ = 36.6 ± 27.4. Elastin fibers appear in some intermediate sublayers with a random orientation distribution with a mean θ = 39.6 ± 23 deg. Based on the microstructural observation, a microstructure-based constitutive law was proposed to model the elastic property of the tissue. The material parameters were identified by fitting the model to the biaxial stress-strain data of specimens, and good fitting quality was achieved. The parameter e0 (which denotes the strain beyond which the collagen can withstand tension) of glutaraldehyde-treated tissues demonstrated low variability implying a relatively consistent collagen undulation in different samples, while the stiffness parameters for elastin and collagen fibers showed relatively greater variability. The fixed tissues presented a smaller e0 than that of fresh specimen, confirming that glutaraldehyde crosslinking increases the mechanical strength of collagen-based biomaterials. The present study sheds light on the biomechanics of glutaraldehyde-treated porcine pulmonary ligament that may be a candidate for tissue engineering. PMID:27040732

  15. A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.

    PubMed

    Mohanty, Tirthankar; Sjögren, Jonathan; Kahn, Fredrik; Abu-Humaidan, Anas H A; Fisker, Niels; Assing, Kristian; Mörgelin, Matthias; Bengtsson, Anders A; Borregaard, Niels; Sørensen, Ole E

    2015-10-29

    Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis. PMID:26243777

  16. Do pathogen-specific defense mechanisms contribute to wound-induced resistance in tomato?

    PubMed Central

    Francia, Doriana; Demaria, Daniele; Calderini, Ornella; Ferraris, Lucia; Valentino, Danila; Arcioni, Sergio; Tamietti, Giacomo

    2008-01-01

    A network of shared intermediates/components and/or common molecular outputs in biotic and abiotic stress signaling has long been known, but the possibility of effective influence between differently triggered stresses (co-protection) is less studied. Recent observations show that wounding induces transient protection in tomato (Solanum lycopersicum L.) to four pathogens with a range of lifestyles, locally and systemically. The contribution of ethylene (ET) in basal but also in wound-induced resistance to each pathogen, although dispensable, is demonstrated to be positive (Botrytis cinerea, Phytophthora capsici) or negative (Fusarium oxysporum, Pseudomonas syringae pv. tomato). Furthermore, the expression of several defense markers is influenced locally and/or systemically by wounding and ET, and might be part of that core of conserved molecular responses whereby an abiotic stress such as wounding imparts co-resistance to biotic stress. In this addendum, we speculate on some of the physiological responses to wounding that might contribute to the modulation of resistance in a more pathogen-specific manner. PMID:19841665

  17. Identification of a key role for permeability glycoprotein in enhancing the cellular defense mechanisms of fertilized oocytes.

    PubMed

    Martin, Jacinta H; Nixon, Brett; Lord, Tessa; Bromfield, Elizabeth G; Aitken, R John

    2016-09-01

    Double strand breaks (DSBs) are highly damaging DNA lesions that can destabilize the genome and generate a suite of adverse physiological outcomes in the oocyte and early embryo. While it is therefore likely that these cells possess a sophisticated suite of protective mechanisms to ameliorate such damage, the precise nature of these defense systems are yet to be fully elucidated. This study characterizes the sensitivity of the oocyte to etoposide, a chemotherapeutic agent with the ability to elicit DSBs. We demonstrate significant developmental changes in etoposide vulnerability, with fertilization of the oocyte leading to an enhancement of its cellular defense machinery. Using a parthenogenic model we show that this response is mediated, at least in part, by permeability glycoprotein (PGP), an endogenous multidrug efflux transporter that is up-regulated, translocated to the oolemma and phosphorylated upon oocyte activation. Moreover, evidence from dye exclusion assays in the presence of a specific PGP pharmacological inhibitor (PSC833), illustrates that these events effectively increase oocyte efflux activity, thereby enhancing the ability of these cells to exclude genotoxicants capable of eliciting DSB formation. PMID:27397031

  18. De novo Transcriptome Analysis Reveals Distinct Defense Mechanisms by Young and Mature Leaves of Hevea brasiliensis (Para Rubber Tree).

    PubMed

    Fang, Yongjun; Mei, Hailiang; Zhou, Binhui; Xiao, Xiaohu; Yang, Meng; Huang, Yacheng; Long, Xiangyu; Hu, Songnian; Tang, Chaorong

    2016-01-01

    Along with changes in morphology in the course of maturation, leaves of Hevea brasiliensis become more resistant to leaf diseases, including the South American Leaf Blight (SALB), a devastating fungal disease of this economically important tree species. To understand the underlying mechanisms of this defense, and to identify the candidate genes involved, we sequenced the Hevea leaf transcriptome at four developmental stages (I to IV) by Illumina sequencing. A total of 62.6 million high-quality reads were generated, and assembled into 98,796 unique transcripts. We identified 3,905 differentially expressed genes implicated in leaf development, 67.8% (2,651) of which were during the transition to leaf maturation. The genes involved in cyanogenic metabolism, lignin and anthocyanin biosynthesis were noteworthy for their distinct patterns of expression between developing leaves (stages I to III) and mature leaves (stage IV), and the correlation with the change in resistance to SALB and the Oidium/Colletotrichum leaf fall. The results provide a first profile of the molecular events that relate to the dynamics of leaf morphology and defense strategies during Hevea leaf development. This dataset is beneficial to devising strategies to engineer resistance to leaf diseases as well as other in-depth studies in Hevea tree. PMID:27619402

  19. Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

    PubMed

    Wang, Bin; Caluch, Adam; Fodil, Redouane; Féréol, Sophie; Zadigue, Patricia; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2012-01-01

    Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h. We used RGD-coated ferromagnetic beads and measured permeability before and after stress application. We find that endothelial permeability increases in the stressed endothelium, hence reflecting a loss of integrity. Structural and mechanical results suggest that this endothelial barrier alteration would be due to physically-founded discrepancies in latero-basal reinforcement of adhesion sites in response to the global increase in CSK stiffness or centripetal intracellular forces. Basal reinforcement of adhesion is presently evidenced by the marked redistribution of αvβ3 integrin with cluster formation in the stressed endothelium. PMID:22766716

  20. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

    PubMed

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications. PMID:26881892

  1. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host–Pathogen Interaction Networks

    PubMed Central

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892

  2. Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism.

    PubMed

    Ferreira, J H T; Terzi, R G G; Paschoal, I A; Silva, W A; Moraes, A C; Moreira, M M

    2006-09-01

    The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 +/- 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 +/- 8.64 to 39.14 +/- 6.77 mmHg) and alveolar air (from 92.97 +/- 2.14 to 63.91 +/- 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 +/- 42.01 to 84.34 +/- 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 +/- 0.34 to 0.33 +/- 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 +/- 1.71 to 60.76 +/- 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 +/- 1.22 to 23.15 +/- 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 +/- 1.36 to 37.61 +/- 12.79 mmHg), as also did the calculated alveolar (from 56.38 +/- 22.47 to 178.09 +/- 37.46 mL) and physiological (from 0.37 +/- 0.05 to 0.75 +/- 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation

  3. Chemical and Mechanical Defenses Vary among Maternal Lines and Leaf Ages in Verbascum thapsus L. (Scrophulariaceae) and Reduce Palatability to a Generalist Insect

    PubMed Central

    Alba, Christina; Bowers, M. Deane; Blumenthal, Dana; Hufbauer, Ruth A.

    2014-01-01

    Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores. PMID:25127229

  4. Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

    NASA Astrophysics Data System (ADS)

    Waters, Kendall R.; Mukdadi, Osama M.

    2005-04-01

    Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

  5. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats.

    PubMed

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing; Xue, Ping

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  6. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats

    PubMed Central

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  7. Pulmonary arterioplasty using video-assisted thoracic surgery mechanical suture technique

    PubMed Central

    Xu, Xin; Huang, Jun; Yin, Weiqiang; Zhang, Xin; Chen, Hanzhang; Mo, Lili

    2016-01-01

    Lung cancer invading pulmonary trunk is a locally advanced condition, which may indicate poor prognosis. Surgical resection of the lesion can significantly improve survival for some patients. Lobectomy/Pneumonectomy with pulmonary arterioplasty via thoracotomy were generally accepted and used in the past. As the rapid development of minimally invasive techniques and devices, pulmonary arterioplasty is feasible via video-assisted thoracic surgery (VATS). However, few studies have reported the VATS surgical techniques. In this study, we reported the techniques of pulmonary arterioplasty via VATS. PMID:27076961

  8. Chronic obstructive pulmonary disease and ischemic heart disease comorbidity: overview of mechanisms and clinical management.

    PubMed

    Campo, Gianluca; Pavasini, Rita; Malagù, Michele; Mascetti, Susanna; Biscaglia, Simone; Ceconi, Claudio; Papi, Alberto; Contoli, Marco

    2015-04-01

    In the last few years, many studies focused their attention on the relationship between chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD), showing that these diseases are mutually influenced. Many different biological processes such as hypoxia, systemic inflammation, endothelial dysfunction, heightened platelet reactivity, arterial stiffness and right ventricle modification interact in the development of the COPD-IHD comorbidity, which therefore deserves special attention in early diagnosis and treatment. Patients with COPD-IHD comorbidity have a worst outcome, when compared to patients with only COPD or only IHD. These patients showed a significant increase on risk of adverse events and of hospital readmissions for recurrent myocardial infarction, heart failure, coronary revascularization, and acute exacerbation of COPD. Taken together, these complications determine a significant increase in mortality. In most cases death occurs for cardiovascular cause, soon after an acute exacerbation of COPD or a cardiovascular adverse event. Recent data regarding incidence, mechanisms and prognosis of this comorbidity, along with the development of new drugs and interventional approaches may improve the management and long-term outcome of COPD-IHD patients. The aim of this review is to describe the current knowledge on COPD-IHD comorbidity. Particularly, we focused our attention on underlying pathological mechanisms and on all treatment and strategies that may improve and optimize the clinical management of COPD-IHD patients. PMID:25645653

  9. Pulmonary Drug Delivery System for inhalation therapy in mechanically ventilated patients.

    PubMed

    Dhand, Rajiv; Sohal, Harjyot

    2008-01-01

    The Pulmonary Drug Delivery System (PDDS) Clinical represents a newer generation of electronic nebulizers that employ a vibrating mesh or aperture plate to generate an aerosol. The PDDS Clinical is designed for aerosol therapy in patients receiving mechanical ventilation. The components of the device include a control module that is connected to the nebulizer/reservoir unit by a cable. The nebulizer contains Aerogen's OnQ aerosol generator. A pressure sensor monitors the pressure in the inspiratory limb of the ventilator circuit and provides feedback to the control module. Based on the feedback from the pressure sensor, aerosol generation occurs only during a specific part of the respiratory cycle. In bench models, the PDDS Clinical has high efficiency for aerosol delivery both on and off the ventilator, with a lower respiratory tract delivery of 50-70% of the nominal dose. Currently, the PDDS Clinical is being evaluated for the treatment of ventilator-associated pneumonia with aerosolized amikacin, an aminoglycoside antibiotic. Preliminary studies in patients with ventilator-associated pneumonia found that the administration of amikacin via PDDS reduced the need for concomitant intravenous antibiotics; however, more definitive clinical studies are needed. The PDDS Clinical delivers a high percentage of the nominal dose to the lower respiratory tract, and is well suited for inhalation therapy in mechanically ventilated patients. PMID:18095891

  10. Study the mechanical pulmonary changes in patients with congestive heart failure (CHF) by impulse oscillometry

    PubMed Central

    Nourizadeh, Mohammad; Ghelich, Yunose; Amin, Ahmad; Eidani, Esmaeel; Gholampoor, Yousef; Asadmoghadam, Mahsa; Asadinia, Najme

    2013-01-01

    Background Heart failure is one of the most leading cause of death worldwide, but the mechanical characteristics of the pulmonary system in these patients have not been studied enough. The aim of this study was to measure mechanical pulmonary changes in patients with congestive heart failure (CHF) by using impulse oscillometry (IOS), which can obtain data by simpler means and independently from respiratory muscle strength. Materials and methods We assessed 24 CHF patients and 24 controls by spirometry and IOS using the Jaeger IOS system. IOS measures central and peripheral airway resistances (R20, R5) and central and peripheral reactances (X20, X5) using sound waves with different frequencies, which superimposed on the patients respiratory tidal volume and then records reflects. P value < 0.05 was taken to be significant. Results The mean age of patients and controls was 61 ± 10 and 57 ± 7 years, respectively. The mean ejection fraction (EF) was 37 ± 17% for patients and 55 ± 7% for controls. Patients had a lower X5 (−0.20 ± 0.13 vs −0.13 ± 0.07; P < 0.05), forced expiratory volume in 1 second (FEV1; 2.26 ± 0.68 vs 3.09 ± 0.82: P < 0.01 L/min), and forced vital capacity (FVC; 2.55 ± 0.86 vs 3.32 ± 0.87; P < 0.05) compared to the controls. They also had elevated R5: 0.37 ± 0.21 vs 0.27 ± 0.09; P < 0.06). X5 was correlated with spirometric abnormalities (P < 0.05) and was lower in patients than in controls. Conclusion X5 was lower and R5 was higher in patients than in controls. CHF patients can be assessed by IOS more comfortable than by spirometry. IOS can reliably measure peripheral airway resistance in this group of patients. PMID:24027371

  11. Crosstalk of Signaling Mechanisms Involved in Host Defense and Symbiosis Against Microorganisms in Rice.

    PubMed

    Akamatsu, Akira; Shimamoto, Ko; Kawano, Yoji

    2016-08-01

    Rice is one of the most important food crops, feeding about half population in the world. Rice pathogens cause enormous damage to rice production worldwide. In plant immunity research, considerable progress has recently been made in our understanding of the molecular mechanisms underlying microbe-associated molecular pattern (MAMP)-triggered immunity. Using genome sequencing and molecular techniques, a number of new MAMPs and their receptors have been identified in the past two decades. Notably, the mechanisms for chitin perception via the lysine motif (LysM) domain-containing receptor OsCERK1, as well as the mechanisms for bacterial MAMP (e.g. flg22, elf18) perception via the leucine-rich repeat (LRR) domain-containing receptors FLS2 and EFR, have been clarified in rice and Arabidopsis, respectively. In chitin signaling in rice, two direct substrates of OsCERK1, Rac/ROP GTPase guanine nucleotide exchange factor OsRacGEF1 and receptor-like cytoplasmic kinase OsRLCK185, have been identified as components of the OsCERK1 complex and are rapidly phosphorylated by OsCERK1 in response to chitin. Interestingly, OsCERK1 also participates in symbiosis with arbuscular mycorrhizal fungi (AMF) in rice and plays a role in the recognition of short-chitin molecules (CO4/5), which are symbiotic signatures included in AMF germinated spore exudates and induced by synthetic strigolactone. Thus, OsCERK1 contributes to both immunity and symbiotic responses. In this review, we describe recent studies on pathways involved in rice immunity and symbiotic signaling triggered by interactions with microorganisms. In addition, we describe recent advances in genetic engineering by using plant immune receptors and symbiotic microorganisms to enhance disease resistance of rice. PMID:27499679

  12. Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

    PubMed

    Walters, Edgar T

    2014-08-01

    Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. PMID:25017887

  13. Roles for redox mechanisms controlling protein kinase G in pulmonary and coronary artery responses to hypoxia.

    PubMed

    Neo, Boon Hwa; Kandhi, Sharath; Wolin, Michael S

    2011-12-01

    We previously reported that isolated endothelium-removed bovine pulmonary arteries (BPAs) contract to hypoxia associated with removal of peroxide- and cGMP-mediated relaxation. In contrast, bovine coronary arteries (BCAs) relax to hypoxia associated with cytosolic NADPH oxidation coordinating multiple relaxing mechanisms. Since we recently found that H(2)O(2) relaxes BPAs through PKG activation by both soluble guanylate cyclase (sGC)/cGMP-dependent and cGMP-independent thiol oxidation/subunit dimerization mechanisms, we investigated if these mechanisms participate in BPA contraction and BCA relaxation to hypoxia. The contraction of BPA (precontracted with 20 mM KCl) to hypoxia was associated with decreased PKG dimerization and PKG-mediated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. In contrast, exposure of 20 mM KCl-precontracted endothelium-removed BCAs to hypoxia caused relaxation and increased dimerization and VASP phosphorylation. Depletion of sGC by organoid culture of BPAs with an oxidant of the sGC heme (10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) increased aerobic force generation, decreased VASP phosphorylation, and inhibited further contraction to hypoxia and changes in VASP phosphorylation. Thiol reduction with dithiothreitol increased aerobic force in BPAs and decreased PKG dimerization, VASP phosphorylation, and the contraction to hypoxia. Furthermore, PKG-1α and sGC β(1)-subunit small interfering RNA-transfected BPAs demonstrated increased aerobic K(+) force and inhibition of further contraction to hypoxia, associated with an attenuation of H(2)O(2)-elicited relaxation and VASP phosphorylation. Thus, decreases in both a sGC/cGMP-dependent and a dimerization-dependent activation of PKG by H(2)O(2) appear to contribute to the contraction of BPAs elicited by hypoxia. In addition, stimulation of PKG activation by dimerization may be important in the relaxation of coronary arteries to hypoxia. PMID:21926339

  14. Study design for a randomised controlled trial to explore the modality and mechanism of Tai Chi in the pulmonary rehabilitation of chronic obstructive pulmonary disease

    PubMed Central

    Fu, Juan-Juan; Min, Jie; Yu, Peng-Ming; McDonald, Vanessa M; Mao, Bing

    2016-01-01

    Introduction Although pulmonary rehabilitation (PR) is associated with significant clinical benefits in chronic obstructive pulmonary disease (COPD) and has been recommended by guidelines, PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations. Alternative exercise such as Tai Chi has been investigated and the results are promising. However, the strengths and weaknesses of the exercise modality of Tai Chi, conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear. This study aims to address the above research gaps in a well-designed clinical trial. Methods and analysis This study is a single-blind, randomised controlled trial. Participants with stable COPD will be recruited and randomly assigned to one of four groups receiving Tai Chi exercise, conventional PR using a total body recumbent stepper (TBRS), combined Tai Chi and TBRS, or usual care (control) in a 1:1:1:1 ratio. Participants will perform 30 min of supervised exercise three times a week for 8 weeks; they will receive sequential follow-ups until 12 months after recruitment. The primary outcome will be health-related quality of life as measured by the St George's Respiratory Questionnaire. Secondary outcomes will include 6 min walking distance, pulmonary function, the modified Medical Research Council Dyspnoea Scale, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, the Berg Balance Scale, exacerbation frequency during the study period, and systemic inflammatory and immune markers. Ethics and dissemination Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No TCM-2015-82). Written informed consent will be obtained from each participant before any procedures are performed. The study findings will be published in peer-reviewed journals and presented at national

  15. Application of an improved proteomics method for abundant protein cleanup: molecular and genomic mechanisms study in plant defense.

    PubMed

    Zhang, Yixiang; Gao, Peng; Xing, Zhuo; Jin, Shumei; Chen, Zhide; Liu, Lantao; Constantino, Nasie; Wang, Xinwang; Shi, Weibing; Yuan, Joshua S; Dai, Susie Y

    2013-11-01

    High abundance proteins like ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) impose a consistent challenge for the whole proteome characterization using shot-gun proteomics. To address this challenge, we developed and evaluated Polyethyleneimine Assisted Rubisco Cleanup (PARC) as a new method by combining both abundant protein removal and fractionation. The new approach was applied to a plant insect interaction study to validate the platform and investigate mechanisms for plant defense against herbivorous insects. Our results indicated that PARC can effectively remove Rubisco, improve the protein identification, and discover almost three times more differentially regulated proteins. The significantly enhanced shot-gun proteomics performance was translated into in-depth proteomic and molecular mechanisms for plant insect interaction, where carbon re-distribution was used to play an essential role. Moreover, the transcriptomic validation also confirmed the reliability of PARC analysis. Finally, functional studies were carried out for two differentially regulated genes as revealed by PARC analysis. Insect resistance was induced by over-expressing either jacalin-like or cupin-like genes in rice. The results further highlighted that PARC can serve as an effective strategy for proteomics analysis and gene discovery. PMID:23943779

  16. Application of an Improved Proteomics Method for Abundant Protein Cleanup: Molecular and Genomic Mechanisms Study in Plant Defense*

    PubMed Central

    Zhang, Yixiang; Gao, Peng; Xing, Zhuo; Jin, Shumei; Chen, Zhide; Liu, Lantao; Constantino, Nasie; Wang, Xinwang; Shi, Weibing; Yuan, Joshua S.; Dai, Susie Y.

    2013-01-01

    High abundance proteins like ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) impose a consistent challenge for the whole proteome characterization using shot-gun proteomics. To address this challenge, we developed and evaluated Polyethyleneimine Assisted Rubisco Cleanup (PARC) as a new method by combining both abundant protein removal and fractionation. The new approach was applied to a plant insect interaction study to validate the platform and investigate mechanisms for plant defense against herbivorous insects. Our results indicated that PARC can effectively remove Rubisco, improve the protein identification, and discover almost three times more differentially regulated proteins. The significantly enhanced shot-gun proteomics performance was translated into in-depth proteomic and molecular mechanisms for plant insect interaction, where carbon re-distribution was used to play an essential role. Moreover, the transcriptomic validation also confirmed the reliability of PARC analysis. Finally, functional studies were carried out for two differentially regulated genes as revealed by PARC analysis. Insect resistance was induced by over-expressing either jacalin-like or cupin-like genes in rice. The results further highlighted that PARC can serve as an effective strategy for proteomics analysis and gene discovery. PMID:23943779

  17. An investigation of the influence of cell topography on epithelial mechanical stresses during pulmonary airway reopening

    NASA Astrophysics Data System (ADS)

    Jacob, A. M.; Gaver, D. P.

    2005-03-01

    The goal of this study is to assess the local mechanical environment of the pulmonary epithelium in a computational model of airway reopening. To this end, the boundary element method (BEM) in conjunction with lubrication theory is implemented to assess the stationary-state behavior of a semi-infinite bubble traveling through a liquid-occluded parallel plate flow chamber lined with epithelial cells. The fluid occlusion is assumed to be Newtonian and inertia is neglected. The interactions between the microgeometry of the model airway's walls and the interfacial kinematics surrounding the bubble's tip result in a complex, spatially and temporally dependent stress distribution. The walls' nonplanar topography magnifies the normal and shear stresses and stress gradients. We find that decreasing the bubble's speed serves to increase the maximum normal stress and stress gradient but decrease the maximum shear stress and stress gradient. Our results give credence to the pressure-gradient-induced epithelial damage theory recently proposed by Bilek et al. [J. Appl. Physiol. 94, 770 (2003)] and Kay et al. [J. Appl. Physiol. 97, 269 (2004)]. We conclude that the amplified pressure gradients found in this study may be even more detrimental to the airway's cellular epithelium during airway reopening.

  18. An investigation of the influence of cell topography on epithelial mechanical stresses during pulmonary airway reopening.

    PubMed

    Jacob, A M; Gaver, D P

    2005-01-01

    The goal of this study is to assess the local mechanical environment of the pulmonary epithelium in a computational model of airway reopening. To this end, the boundary element method (BEM) in conjunction with lubrication theory is implemented to assess the stationary-state behavior of a semi-infinite bubble traveling through a liquid-occluded parallel plate flow chamber lined with epithelial cells. The fluid occlusion is assumed to be Newtonian and inertia is neglected. The interactions between the microgeometry of the model airway's walls and the interfacial kinematics surrounding the bubble's tip result in a complex, spatially and temporally dependent stress distribution. The walls' nonplanar topography magnifies the normal and shear stresses and stress gradients. We find that decreasing the bubble's speed serves to increase the maximum normal stress and stress gradient but decrease the maximum shear stress and stress gradient. Our results give credence to the pressure-gradient-induced epithelial damage theory recently proposed by Bilek et al. [J. Appl. Physiol. 94, 770 (2003)] and Kay et al. [J. Appl. Physiol. 97, 269 (2004)]. We conclude that the amplified pressure gradients found in this study may be even more detrimental to the airway's cellular epithelium during airway reopening. PMID:23745044

  19. An investigation of the influence of cell topography on epithelial mechanical stresses during pulmonary airway reopening

    PubMed Central

    Jacob, A. M.; Gaver, D. P.

    2013-01-01

    The goal of this study is to assess the local mechanical environment of the pulmonary epithelium in a computational model of airway reopening. To this end, the boundary element method (BEM) in conjunction with lubrication theory is implemented to assess the stationary-state behavior of a semi-infinite bubble traveling through a liquid-occluded parallel plate flow chamber lined with epithelial cells. The fluid occlusion is assumed to be Newtonian and inertia is neglected. The interactions between the microgeometry of the model airway’s walls and the interfacial kinematics surrounding the bubble’s tip result in a complex, spatially and temporally dependent stress distribution. The walls’ nonplanar topography magnifies the normal and shear stresses and stress gradients. We find that decreasing the bubble’s speed serves to increase the maximum normal stress and stress gradient but decrease the maximum shear stress and stress gradient. Our results give credence to the pressure-gradient-induced epithelial damage theory recently proposed by Bilek et al. [J. Appl. Physiol. 94, 770 (2003)] and Kay et al. [J. Appl. Physiol. 97, 269 (2004)]. We conclude that the amplified pressure gradients found in this study may be even more detrimental to the airway’s cellular epithelium during airway reopening. PMID:23745044

  20. High Level Resistance against Rhizomania Disease by Simultaneously Integrating Two Distinct Defense Mechanisms

    PubMed Central

    Pavli, Ourania I.; Tampakaki, Anastasia P.; Skaracis, George N.

    2012-01-01

    With the aim of achieving durable resistance against rhizomania disease of sugar beet, the employment of different sources of resistance to Beet necrotic yellow vein virus was pursued. To this purpose, Nicotiana benthamiana transgenic plants that simultaneously produce dsRNA originating from a conserved region of the BNYVV replicase gene and the HrpZPsph protein in a secreted form (SP/HrpZPsph) were produced. The integration and expression of both transgenes as well as proper production of the harpin protein were verified in all primary transformants and selfed progeny (T1, T2). Transgenic resistance was assessed by BNYVV-challenge inoculation on T2 progeny by scoring disease symptoms and DAS-ELISA at 20 and 30 dpi. Transgenic lines possessing single transformation events for both transgenes as well as wild type plants were included in inoculation experiments. Transgenic plants were highly resistant to virus infection, whereas in some cases immunity was achieved. In all cases, the resistant phenotype of transgenic plants carrying both transgenes was superior in comparison with the ones carrying a single transgene. Collectively, our findings demonstrate, for a first time, that the combination of two entirely different resistance mechanisms provide high level resistance or even immunity against the virus. Such a novel approach is anticipated to prevent a rapid virus adaptation that could potentially lead to the emergence of isolates with resistance breaking properties. PMID:23284692

  1. Acute respiratory failure induced by mechanical pulmonary ventilation at a peak inspiratory pressure of 40 cmH2O.

    PubMed

    Tsuno, K; Sakanashi, Y; Kishi, Y; Urata, K; Tanoue, T; Higashi, K; Yano, T; Terasaki, H; Morioka, T

    1988-09-01

    The effects of high pressure mechanical pulmonary ventilation at a peak inspiratory pressure of 40 cmH(2)O were studied on the lungs of healthy newborn pigs (14-21 days after birth). Forty percent oxygen in nitrogen was used for ventilation to prevent oxygen intoxication. The control group (6 pigs) was ventilated for 48 hours at a peak inspiratory pressure less than 18 cmH(2)O and a PEEP of 3-5 cmH(2)O with a normal tidal volume, and a respiratory rate of 20 times/min. The control group showed few deleterious changes in the lungs for 48 hours. Eleven newborn pigs were ventilated at a peak inspiratory pressure of 40 cmH(2)O with a PEEP of 3-5 cmH(2)O and a respiratory rate of 20 times/min. To avoid respiratory alkalosis, a dead space was placed in the respiratory circuit, and normocarbia was maintained by adjusting dead space volume. In all cases in the latter group, severe pulmonary impairments, such as abnormal chest roentgenograms, hypoxemia, decreased total static lung compliance, high incidence of pneumothorax, congestive atelectasis, and increased lung weight were found within 48 hours of ventilation. When the pulmonary impairments became manifest, 6 of the 11 newborn pigs were switched to the conventional medical and ventilatory therapies for 3-6 days. However, all of them became ventilator dependent, and severe lung pathology was found at autopsy. These pulmonary insults by high pressure mechanical pulmonary ventilation could be occurring not infrequently in the respiratory management of patients with respiratory failure. PMID:15236077

  2. [Four cases of pulmonary tuberculosis resembling pulmonary abscess with a so-called niveau-like shadow in a medical school hospital: discussion concerning the formation mechanism of niveau-like shadows].

    PubMed

    Kobashi, Y; Niki, Y; Kawane, H; Matsushima, T

    1996-04-01

    Four cases of pulmonary tuberculosis resembling pulmonary abscess radiographically were reviewed from their clinical features, chest X-ray and chest CT, and the mechanism of formation of so-called niveau-like shadows was discussed. Only one case showed a newly formed tuberculous cavity with air fluid level on chest X-ray, however, even in this case, the possibility of the infection with tubercle bacilli of an emphysematous bulla of the lung could not be completely excluded as several bulla were found on chest CT. The remaining three cases showed a slightly different mechanism of the formation of niveau-like shadows. Namely, mycobacterium tuberculosis spread into an existed bulla and a tubercle bacilli infected bulla was formed. Regarding the clinical features, no remarkable findings were detected and we could find no differences with common tuberculosis. Based on these experiences, the presence of pulmonary tuberculosis resembling the shadow of pulmonary abscess should be emphasized. PMID:8683908

  3. Francisella tularensis subsp. tularensis Induces a Unique Pulmonary Inflammatory Response: Role of Bacterial Gene Expression in Temporal Regulation of Host Defense Responses

    PubMed Central

    Walters, Kathie-Anne; Olsufka, Rachael; Kuestner, Rolf E.; Cho, Ji Hoon; Li, Hong; Zornetzer, Gregory A.; Wang, Kai; Skerrett, Shawn J.; Ozinsky, Adrian

    2013-01-01

    Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4). Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis) and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa) pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways. PMID:23690939

  4. Immune-Related Transcriptome of Coptotermes formosanus Shiraki Workers: The Defense Mechanism

    PubMed Central

    Hussain, Abid; Li, Yi-Feng; Cheng, Yu; Liu, Yang; Chen, Chuan-Cheng; Wen, Shuo-Yang

    2013-01-01

    Formosan subterranean termites, Coptotermes formosanus Shiraki, live socially in microbial-rich habitats. To understand the molecular mechanism by which termites combat pathogenic microbes, a full-length normalized cDNA library and four Suppression Subtractive Hybridization (SSH) libraries were constructed from termite workers infected with entomopathogenic fungi (Metarhizium anisopliae and Beauveria bassiana), Gram-positive Bacillus thuringiensis and Gram-negative Escherichia coli, and the libraries were analyzed. From the high quality normalized cDNA library, 439 immune-related sequences were identified. These sequences were categorized as pattern recognition receptors (47 sequences), signal modulators (52 sequences), signal transducers (137 sequences), effectors (39 sequences) and others (164 sequences). From the SSH libraries, 27, 17, 22 and 15 immune-related genes were identified from each SSH library treated with M. anisopliae, B. bassiana, B. thuringiensis and E. coli, respectively. When the normalized cDNA library was compared with the SSH libraries, 37 immune-related clusters were found in common; 56 clusters were identified in the SSH libraries, and 259 were identified in the normalized cDNA library. The immune-related gene expression pattern was further investigated using quantitative real time PCR (qPCR). Important immune-related genes were characterized, and their potential functions were discussed based on the integrated analysis of the results. We suggest that normalized cDNA and SSH libraries enable us to discover functional genes transcriptome. The results remarkably expand our knowledge about immune-inducible genes in C. formosanus Shiraki and enable the future development of novel control strategies for the management of Formosan subterranean termites. PMID:23874972

  5. Lead tolerance mechanism in Conyza canadensis: subcellular distribution, ultrastructure, antioxidative defense system, and phytochelatins.

    PubMed

    Li, Ying; Zhou, Chuifan; Huang, Meiying; Luo, Jiewen; Hou, Xiaolong; Wu, Pengfei; Ma, Xiangqing

    2016-03-01

    We used hydroponic experiments to examine the effects of different concentrations of lead (Pb) on the performance of the Pb-tolerable plant Conyza canadensis. In these experiments, most of the Pb was accumulated in the roots; there was very little Pb accumulated in stems and leaves. C. canadensis is able to take up significant amounts of Pb whilst greatly restricting its transportation to specific parts of the aboveground biomass. High Pb concentrations inhibited plant growth, increased membrane permeability, elevated antioxidant enzyme activity in roots, and caused a significant increase in root H2O2 and malondialdehyde content. Analysis of Pb content at the subcellular level showed that most Pb was associated with the cell wall fraction, followed by the nucleus-rich fraction, and with a minority present in the mitochondrial and soluble fractions. Furthermore, transmission electron microscopy and energy dispersive X-ray analysis of root cells revealed that the cell wall and intercellular space in C. canadensis roots are the main locations of Pb accumulation. Additionally, high Pb concentrations adversely affected the cellular structure of C. canadensis roots. The increased enzyme activity suggests that the antioxidant system may play an important role in eliminating or alleviating Pb toxicity in C. canadensis roots. However, the levels of non-protein sulfhydryl compounds, glutathione, and phytochelatin did not significantly change in either the roots or leaves under Pb-contaminated treatments. Our results provide strong evidence that cell walls restrict Pb uptake into the root and act as an important barrier protecting root cells, while demonstrating that antioxidant enzyme levels are correlated with Pb exposure. These findings demonstrate the roles played by these detoxification mechanisms in supporting Pb tolerance in C. canadensis. PMID:26733305

  6. Functional residual capacity tool: A practical method to assess lung volume changes during pulmonary complications in mechanically ventilated patients.

    PubMed

    Veena, S; Palepu, Sudeep; Umamaheswara Rao, G S; Ramesh, V J

    2010-07-01

    In this report, we describe a patient in whom we used a functional residual capacity (FRC) tool available on a critical care ventilator to identify the loss of lung volume associated with pulmonary complications and increase in FRC with the application of a recruitment maneuver. The case report underlines the utility of the FRC tool in rapid visualization of the lung volume changes and the effects of application of corrective strategies in patients receiving mechanical ventilation. PMID:21253350

  7. Identification of several inducible defense-related genes in mechanically damaged soybean (glycine max l. merr) stems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple defense-related genes have been identified in soybean (Glycine max L. Merr), however, research has primarily focused on the plant leaves, and despite the numerous insects and pathogens that feed on soybean stem tissues, relatively little is known about the stem defense response. In the curr...

  8. Sex-dependent liver colonization of human melanoma in SCID mice--role of host defense mechanisms.

    PubMed

    Dobos, Judit; Mohos, Anita; Tóvári, József; Rásó, Erzsébet; Lőrincz, Tamás; Zádori, Gergely; Tímár, József; Ladányi, Andrea

    2013-04-01

    The possibility that endocrine factors may influence the clinical course of malignant melanoma is suggested by the superior survival data of women. In preclinical models we observed a higher rate of colony formation by human melanoma cells in male compared to female SCID mice, but only in the case of the liver and not in other organs. The gender difference could be seen at an early phase of colony formation. On the other hand, in our human melanoma cell lines we failed to detect steroid receptor protein expression, and treatment with sex hormones did not considerably influence their in vitro behavior. Investigating the possible contribution of host cells to the observed gender difference, we performed in vivo blocking experiments applying pretreatment of the animals with Kupffer cell inhibitor gadolinium chloride and the NK cell inhibitor anti-asialo GM1 antibody. While Kupffer cell blockade enhanced melanoma liver colonization equally in the two sexes, a more prominent increase was observed in female than in male mice in the case of NK cell inhibition. Further supporting the importance of NK cells in the lower liver colonization efficiency of melanoma cells in females, gender difference in colony formation was lost in NSG mice lacking NK activity. Although in humans no organ selectivity of gender difference in melanoma progression has been observed according to data in the literature, our results possibly indicate a contribution of natural host defense mechanisms to gender difference in survival of patients with melanoma or other tumor types as well. PMID:23203681

  9. Characterization of Hg-phytochelatins complexes in vines (Vitis vinifera cv Malbec) as defense mechanism against metal stress.

    PubMed

    Spisso, Adrian A; Cerutti, Soledad; Silva, Fernanda; Pacheco, Pablo H; Martinez, Luis D

    2014-06-01

    An approach to understand vines (Vitis vinifera) defense mechanism against heavy metal stress by isolation and determination of Hg-phytochelatins (PCs) complexes was performed. PCs are important molecules involved in the control of metal concentration in plants. PCs complex toxic metals through -SH groups and stores them inside cells vacuole avoiding any toxic effect of free metals in the cytosol. The Hg-PCs identification was achieved by determination of Hg and S as hetero-tagged atoms. A method involving two-dimensional chromatographic analysis coupled to atomic spectrometry and confirmation by tandem mass spectrometry is proposed. An approach involving size exclusion chromatography coupled to inductively coupled plasma mass spectrometry on roots, stems, and leaves extracts describing Hg distribution according to molecular weight and sulfur associations is proposed for the first time. Medium-low molecular weight Hg-S associations of 29-100 kDa were found, suggesting PCs presence. A second approach employing reversed-phase chromatography coupled to atomic fluorescence spectrometry analysis allowed the determination of Hg-PCs complexes within the mentioned fractions. Chromatograms showed Hg-PC2, Hg-PC3 and Hg-PC4 presence only in roots. Hg-PCs presence in roots was confirmed by ESI-MS/MS analysis. PMID:24715273

  10. A mechanical plant defense defines the opening of a phenological window for gall induction by Asphondylia aucubae (Cecidomyiidae: Diptera).

    PubMed

    Imai, Kensuke; Ohsaki, Naota

    2009-04-01

    Many insect herbivores can only use hosts during a specific phenological stage, i.e., a phenological window. Previous studies have primarily examined the effects of these windows on insect herbivores, but relatively little is known about the mechanisms controlling the phenological windows. In most gall insect systems, phenological windows have been attributed to the short duration of physiologically active plant tissues that induce gall formation (reactive plant tissue). In the fruit gall midge, Asphondylia aucubae Yukawa and Ohsaki, and the host plant (i.e., Aucuba japonica) system, the disappearance of reactive plant tissue closes the phenological window, but its presence does not define the opening of the window. The hard endocarp of the fruit covers most potential oviposition sites just before the midge emergence season, but decreases in proportional cover during the emergence season. We experimentally manipulated the timing of oviposition relative to fruit development. Midges that emerged earliest and attacked fruits during their earliest developmental stages were unable to oviposit because of intact, hard endocarps, whereas their counterparts that emerged later could oviposit more readily through cracks in the endocarp. We noted possible oviposition avoidance behavior and the necessity of more frequent (repeated) ovipositor insertions to intensively stimulate the decreased reactive tissues during the latter half of the emergence season. Overall, our results indicated that the fragmentation of the defensive, hard endocarp of the host plant defines the opening of the phenological window in this plant-herbivore system. PMID:19389289

  11. Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

    PubMed

    Güldner, Andreas; Kiss, Thomas; Serpa Neto, Ary; Hemmes, Sabrine N T; Canet, Jaume; Spieth, Peter M; Rocco, Patricia R M; Schultz, Marcus J; Pelosi, Paolo; Gama de Abreu, Marcelo

    2015-09-01

    Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials. PMID:26120769

  12. The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease

    PubMed Central

    Wang, Qing; Guo, Yi-Zhan; Zhang, Yi-Tao; Xue, Jiao-Jie; Chen, Zhi-Chong; Cheng, Shi-Yao; Ou, Mao-De; Cheng, Kang-Lin; Zeng, Wei-Jie

    2016-01-01

    Background Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. Methods Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group. Results Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group. Conclusions Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the

  13. Aspiration-related pulmonary syndromes.

    PubMed

    Hu, Xiaowen; Lee, Joyce S; Pianosi, Paolo T; Ryu, Jay H

    2015-03-01

    Aspiration of foreign matter into the airways and lungs can cause a wide spectrum of pulmonary disorders with various presentations. The type of syndrome resulting from aspiration depends on the quantity and nature of the aspirated material, the chronicity, and the host responses. Aspiration is most likely to occur in subjects with a decreased level of consciousness, compromised airway defense mechanisms, dysphagia, gastroesophageal reflux, and recurrent vomiting. These aspiration-related syndromes can be categorized into airway disorders, including vocal cord dysfunction, large airway obstruction with a foreign body, bronchiectasis, bronchoconstriction, and diffuse aspiration bronchiolitis, or parenchymal disorders, including aspiration pneumonitis, aspiration pneumonia, and exogenous lipoid pneumonia. In idiopathic pulmonary fibrosis, aspiration has been implicated in disease progression and acute exacerbation. Aspiration may increase the risk of bronchiolitis obliterans syndrome in patients who have undergone a lung transplant. Accumulating evidence suggests that a causative role for aspiration is often unsuspected in patients presenting with aspiration-related pulmonary diseases; thus, many cases go undiagnosed. Herein, we discuss the broadening spectrum of these pulmonary syndromes with a focus on presenting features and diagnostic aspects. PMID:25732447

  14. Defense styles of pedophilic offenders.

    PubMed

    Drapeau, Martin; Beretta, Véronique; de Roten, Yves; Koerner, Annett; Despland, Jean-Nicolas

    2008-04-01

    This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization. PMID:17875603

  15. Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery.

    PubMed

    Baranowska-Kuczko, Marta; MacLean, Margaret R; Kozłowska, Hanna; Malinowska, Barbara

    2012-09-01

    Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)-nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve K(Ca) or the NO pathway. PMID:22627170

  16. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    PubMed

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study. PMID:26780263

  17. Mechanical characteristics of the pulmonary artery in beagle dogs with hepatopulmonary syndrome and portopulmonary hypertension

    PubMed Central

    YAN, GUOZHEN; HE, JUNFENG; YU, YUELI; LIU, YANG; YUAN, YANFEN; GUO, ZHIYONG

    2016-01-01

    The continuous changes in pulmonary hemodynamic properties in hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) have not been fully characterized in large animal models of HPS and PoPH. Beagle dog models of HPS and PoPH were induced by chronic common bile duct ligation and Sephadex microspheres, respectively. The model was validated by catheter examination and pathological analyses, and the hemodynamic characteristics of the models were observed. The results revealed that the cross-sectional area of the blood vessel was significantly increased in HPS models, but it was significantly decreased in the PoPH models. Furthermore, the resistance of pulmonary circulation was elevated in models of HPS, but it was decreased in models of PoPH. The present findings renew the traditional view that pulmonary hypertension is due to the enhanced peripheral resistance. PMID:26870333

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

    PubMed Central

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

    2014-01-01

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

  19. Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

    PubMed Central

    Groeneveld, AB Johan; Jansen, Evert K; Verheij, Joanne

    2007-01-01

    Background Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs. Methods To test this hypothesis, we studied the postoperative pulmonary leak index (PLI) for 67Ga-transferrin and (transpulmonary) extravascular lung water (EVLW) in consecutive patients undergoing on-pump (n = 31) and off-pump (n = 8) cardiac surgery. We also studied transfusion history, radiographs, ventilatory and gas exchange variables. Results The postoperative PLI and EVLW were elevated above normal in 42 and 29% after on-pump surgery and 63 and 37% after off-pump surgery, respectively (ns). Transfusion of red blood cell (RBC) concentrates, PLI, EVLW, occurrence of atelectasis, ventilatory variables and duration of mechanical ventilation did not differ between groups, whereas patients with atelectasis had higher venous admixture and airway pressures than patients without atelectasis (P = 0.037 and 0.049). The PLI related to number of RBC concentrates infused (P = 0.025). Conclusion The lung vascular injury in about half of patients after cardiac surgery is not caused by CPB perfusion but by trauma necessitating RBC transfusion, so that off-pump surgery may not afford a benefit in this respect. However, atelectasis rather than lung vascular injury is a major determinant of postoperative pulmonary dysfunction, irrespective of CPB perfusion. PMID:17300720

  20. Effects of Relaxation Training on Pulmonary Mechanics in Children with Asthma.

    ERIC Educational Resources Information Center

    Alexander, A. Barney; And Others

    1979-01-01

    Heart rate and to some extent muscle tension results tended to confirm the attainment of relaxed states. However, the lung function results failed to substantiate the previous, preliminary findings of a clinically meaningful change in pulmonary function following relaxation. (Author/DLS)

  1. Mechanisms of pulmonary cyst pathogenesis in Birt-Hogg-Dube syndrome: The stretch hypothesis.

    PubMed

    Kennedy, John C; Khabibullin, Damir; Henske, Elizabeth P

    2016-04-01

    Loss-of-function mutations in the folliculin gene (FLCN) on chromosome 17p cause Birt-Hogg-Dube syndrome (BHD), which is associated with cystic lung disease. The risk of lung collapse (pneumothorax) in BHD patients is 50-fold higher than in the general population. The cystic lung disease in BHD is distinctive because the cysts tend to be basilar, subpleural and lentiform, differentiating BHD from most other cystic lung diseases. Recently, major advances in elucidating the primary functions of the folliculin protein have been made, including roles in mTOR and AMPK signaling via the interaction of FLCN with FNIP1/2, and cell-cell adhesion via the physical interaction of FLCN with plakophilin 4 (PKP4), an armadillo-repeat containing protein that interacts with E-cadherin and is a component of the adherens junctions. In addition, in just the last three years, the pulmonary impact of FLCN deficiency has been examined for the first time. In mouse models, evidence has emerged that AMPK signaling and cell-cell adhesion are involved in alveolar enlargement. In addition, the pathologic features of human BHD cysts have been recently comprehensively characterized. The "stretch hypothesis" proposes that cysts in BHD arise because of fundamental defects in cell-cell adhesion, leading to repeated respiration-induced physical stretch-induced stress and, over time, expansion of alveolar spaces particularly in regions of the lung with larger changes in alveolar volume and at weaker "anchor points" to the pleura. This hypothesis ties together many of the new data from cellular and mouse models of BHD and from the human pathologic studies. Critical questions remain. These include whether the consequences of stretch-induced cyst formation arise through a destructive/inflammatory program or a proliferative program (or both), whether cyst initiation involves a "second hit" genetic event inactivating the remaining wild-type copy of FLCN (as is known to occur in BHD-associated renal cell

  2. Assessment of right ventricular geometry and mechanics in chronic obstructive pulmonary disease patients living at high altitude.

    PubMed

    Güvenç, Tolga Sinan; Kul, Seref; Doğan, Coşkun; Yıldırım, Binnaz Zeynep; Karabağ, Yavuz; Cetin, Rengin; Kaya, Yüksel; Karadağ, Pelin; Değirmencioğlu, Aleks; Balcı, Bahattin

    2014-10-01

    Degree of increase in pulmonary artery pressure (PAP) and adaptive responses in right ventricular morphology and mechanics play an important role in the prognosis of chronic obstructive pulmonary disease (COPD) patients. Three dimensional echocardiography and deformation imaging are recent advancements in echocardiography that allow more through assessment of right ventricle. We aimed to investigate right ventricular geometry and mechanics in a stable COPD population living at moderately high altitude. A total of 26 stable COPD patients with variable disease severity were included to this study. Pulmonary function tests, six minutes walking test (6MWT) and two- and three-dimensional echocardiography were performed for evaluation and data collection. Both systolic (43.06 ± 11.79 mmHg) and mean (33.38 ± 9.75 mmHg) PAPs were significantly higher in COPD patients compared to controls (p < 0.05, p < 0.001; respectively). Right ventricular volumes were similar between groups, although right ventricular free wall thickness was significantly increased in COPD group. The number of subjects with a sub-normal (<40 %) right ventricular ejection fraction was significantly higher in COPD group (45.8 vs. 17.4 %, p < 0.05), and the mean right ventricular strain was significantly lower (-21.05 ± 3.80 vs. -24.14 ± 5.37; p < 0.05). Only mean PAP and body surface area were found as independent predictors for 6MWT distance. Increased PAP and reduced right ventricular contractility were found in COPD patients living at moderately high altitude, although right ventricular volumes were normal. Similar findings can be expected in other COPD patients with high PAP, since these findings probably represents the effect of increased PAP on right ventricular mechanics. PMID:24950729

  3. Inhibition of Nitro-Oxidative Stress Attenuates Pulmonary and Systemic Injury Induced by High-Tidal Volume Mechanical Ventilation.

    PubMed

    Martínez-Caro, Leticia; Nin, Nicolás; Sánchez-Rodríguez, Carolina; Ferruelo, Antonio; El Assar, Mariam; de Paula, Marta; Fernández-Segoviano, Pilar; Esteban, Andrés; Lorente, José A

    2015-07-01

    Mechanisms contributing to pulmonary and systemic injury induced by high tidal volume (VT) mechanical ventilation are not well known. We tested the hypothesis that increased peroxynitrite formation is involved in organ injury and dysfunction induced by mechanical ventilation. Male Sprague-Dawley rats were subject to low- (VT, 9 mL/kg; positive end-expiratory pressure, 5 cmH2O) or high- (VT, 25 mL/kg; positive end-expiratory pressure, 0 cmH2O) VT mechanical ventilation for 120 min, and received 1 of 3 treatments: 3-aminobenzamide (3-AB, 10 mg/kg, intravenous, a poly adenosine diphosphate ribose polymerase [PARP] inhibitor), or the metalloporphyrin manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, 5 mg/kg intravenous, a peroxynitrite scavenger), or no treatment (control group), 30 min before starting the mechanical ventilation protocol (n = 8 per group, 6 treatment groups). We measured mean arterial pressure, peak inspiratory airway pressure, blood chemistry, and gas exchange. Oxidation (fluorescence for oxidized dihydroethidium), protein nitration (immunofluorescence and Western blot for 3-nitrotyrosine), PARP protein (Western blot) and gene expression of the nitric oxide (NO) synthase (NOS) isoforms (quantitative real-time reverse transcription polymerase chain reaction) were measured in lung and vascular tissue. Lung injury was quantified by light microscopy. High-VT mechanical ventilation was associated with hypotension, increased peak inspiratory airway pressure, worsened oxygenation; oxidation and protein nitration in lung and aortic tissue; increased PARP protein in lung; up-regulation of NOS isoforms in lung tissue; signs of diffuse alveolar damage at histological examination. Treatment with 3AB or MnTMPyP attenuated the high-VT mechanical ventilation-induced changes in pulmonary and cardiovascular function; down-regulated the expression of NOS1, NOS2, and NOS3; decreased oxidation and nitration in lung and aortic tissue; and attenuated

  4. Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity

    PubMed Central

    Oppenheimer, Beno W.; Berger, Kenneth I.; Ali, Saleem; Segal, Leopoldo N.; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M.

    2016-01-01

    Rationale Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. Objectives We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. Methods 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Measurements and Main Results Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. Conclusions Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the

  5. Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism.

    PubMed

    Shin, Eun-Joo; Nam, Yunsung; Tu, Thu-Hien Thi; Lim, Yong Kwang; Wie, Myung-Bok; Kim, Dae-Joong; Jeong, Ji Hoon; Kim, Hyoung-Chun

    2016-04-01

    We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ς) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity. PMID:25895139

  6. Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment.

    PubMed

    Langer, Daniel; Ciavaglia, Casey E; Neder, J Alberto; Webb, Katherine A; O'Donnell, Denis E

    2014-12-01

    Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the contribution of lung hyperinflation to exercise limitation and discuss its impact on symptoms and physical activity. Finally, we will examine the physiological rationale and efficacy of selected pharmacological and non-pharmacological 'lung deflating' interventions aimed at improving symptoms and physical functioning. PMID:25159007

  7. [Pulmonary circulation in embolic pulmonary edema].

    PubMed

    Sanotskaia, N V; Polikarpov, V V; Matsievskiĭ, D D

    1989-02-01

    The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism. PMID:2923969

  8. Hypothesis: Neuroendocrine Mechanisms (Hypothalamus–Growth Hormone–STAT5 Axis) Contribute to Sex Bias in Pulmonary Hypertension

    PubMed Central

    Sehgal, Pravin B; Yang, Yang-Ming; Miller, Edmund J

    2015-01-01

    Pulmonary hypertension (PH) is a disease with high morbidity and mortality. The prevalence of idiopathic pulmonary arterial hypertension (IPAH) and hereditary pulmonary arterial hypertension (HPAH) is approximately two- to four-fold higher in women than in men. Paradoxically, there is an opposite male bias in typical rodent models of PH (chronic hypoxia or monocrotaline); in these models, administration of estrogenic compounds (for example, estradiol-17β [E2]) is protective. Further complexities are observed in humans ingesting anorexigens (female bias) and in rodent models, such as after hypoxia plus SU5416/Sugen (little sex bias) or involving serotonin transporter overexpression or dexfenfluramine administration (female bias). These complexities in sex bias in PH remain incompletely understood. We recently discovered that conditional deletion of signal transducer and activator of transcription 5a/b (STAT5a/b) in vascular smooth muscle cells abrogated the male bias in PH in hypoxic mice and that late-stage obliterative lesions in patients of both sexes with IPAH and HPAH showed reduced STAT5a/b, reduced Tyr-P-STAT5 and reduced B-cell lymphoma 6 protein (BCL6). In trying to understand the significance of these observations, we realized that there existed a well-characterized E2-sensitive central neuroendocrine mechanism of sex bias, studied over the last 40 years, that, at its peripheral end, culminated in species-specific male (“pulsatile”) versus female (“more continuous”) temporal patterns of circulating growth hormone (GH) levels leading to male versus female patterned activation of STAT5a/b in peripheral tissues and thus sex-biased expression of hundreds of genes. In this report, we consider the contribution of this neuroendocrine mechanism (hypothalamus-GH-STAT5) in the generation of sex bias in different PH situations. PMID:26252185

  9. Mechanical analysis of ovine and pediatric pulmonary artery for heart valve stent design.

    PubMed

    Cabrera, M S; Oomens, C W J; Bouten, C V C; Bogers, A J J C; Hoerstrup, S P; Baaijens, F P T

    2013-08-01

    Transcatheter heart valve replacement is an attractive and promising technique for congenital as well as acquired heart valve disease. In this procedure, the replacement valve is mounted in a stent that is expanded at the aimed valve position and fixated by clamping. However, for this technique to be appropriate for pediatric patients, the material properties of the host tissue need to be determined to design stents that can be optimized for this particular application. In this study we performed equibiaxial tensile tests on four adult ovine pulmonary artery walls and compared the outcomes with one pediatric pulmonary artery. Results show that the pediatric pulmonary artery was significantly thinner (1.06 ± 0.36 mm (mean ± SD)) than ovine tissue (2.85 ± 0.40 mm), considerably stiffer for strain values that exceed the physiological conditions (beyond 50% strain in the circumferential and 60% in the longitudinal direction), more anisotropic (with a significant difference in stiffness between the longitudinal and circumferential directions beyond 60% strain) and presented stronger non-linear stress-strain behavior at equivalent strains (beyond 26% strain) compared to ovine tissue. These discrepancies suggest that stents validated and optimized using the ovine pre-clinical model might not perform satisfactorily in pediatric patients. The material parameters derived from this study may be used to develop stent designs for both applications using computational models. PMID:23849135

  10. Inhalation of particulate lead oxide disrupts pulmonary macrophage-mediated functions important for host defense and tumor surveillance in the lung

    SciTech Connect

    Zelikoff, J.T.; Parsons, E.; Schlesinger, R.B. )

    1993-08-01

    Lead, an immunomodulator and potential human carcinogen, is a major airborne pollutant in industrial environments which poses a serious threat to human health. Despite the wide-spread occurrence of respirable lead particles in the air, and the potential human health risks, effects associated with inhalation of particulate lead on the the lung have been poorly studied. This study was performed to determine whether inhalation of particulate lead oxide (PbO), at a concentration below the currently acceptable air lead standard for occupational exposure, disrupts macrophage (M phi) functions important for maintaining pulmonary immunocompetence. These functions include phagocytosis, production of reactive oxygen intermediates, and the biological activity of tumor necrosis factor-alpha (TNF-alpha). Rabbits exposed to PbO at 30 micrograms/m3 for 4 days (3 hr/day) were sacrificed and their lungs lavaged immediately, 24 hr, and 72 hr after the final exposure. Lactate dehydrogenase (a marker of lung cell damage) and lysozyme activity (a marker of lysosome permeability), measured in the lavage fluid, were significantly increased 24 and 72 hr after exposure. PbO produced neutrophil infiltration nor effects on M phi viability or total numbers. Effects on M phi functions were as follows. Phagocytic uptake of latex particles was reduced with increasing post-exposure time reaching a maximum inhibition at 72 hr. Inhalation of PbO enhanced hydrogen peroxide (H2O2) and superoxide anion radical (O2-) production in a time-dependent manner; effects on H2O2 began at 24 hr and were persistent up to 72 hr. Effects on TNF-alpha release/activity appeared earliest and were persistent up to 72 hr. Immediately and 24 hr after exposure, lipopolysaccharide-stimulated activity of TNF-alpha was depressed by 62 and 50%, respectively; after 72 hr, TNF-alpha release was significantly enhanced compared to control levels.

  11. Pulmonary edema

    MedlinePlus

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

  12. Effect of hypophosphatemia on the withdrawal of mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    ZHAO, YULIANG; LI, ZHIHAI; SHI, YINJUN; CAO, GUNGKE; MENG, FANYING; ZHU, WANG; YANG, GE

    2016-01-01

    Mechanical ventilation (MV) is a life-supporting modality frequently performed in critically ill patients to mechanically assist or replace spontaneous breathing. The aim of this study was to investigate the effect of hypophosphatemia on the withdrawal of MV in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The medical records of 67 AECOPD cases, treated with MV between 2011 and 2013, were analyzed retrospectively. The patients were assigned to the hypophosphatemic and the normophosphatemic groups according to their serum phosphate levels (with the threshold of 0.87 mmol/l). The results showed that the morbidity rate of hypophosphatemia in these AECOPD patients was 56.72%. A significantly higher percentage of failure-to-wean from MV was observed in the hypophosphatemia group vs. the normophosphatemic group (34.21 vs. 10.34%, P<0.05). Furthermore, hypophosphatemia was associated with respiratory muscular weakness, as reflected by a decrease in the tidal volume of spontaneous respiration, reduced static lung compliance and impaired pulmonary function, leading to weaning failure. The findings suggested that hypophosphatemia significantly affected the weaning from MV in AECOPD patients. Serum phosphorus levels may therefore serve as a reference index to determine the success of weaning. PMID:27073623

  13. Auxin promotes susceptibility to Pseudomonas syringae via a mechanism independent of suppression of salicylic acid-mediated defenses.

    PubMed

    Mutka, Andrew M; Fawley, Stephen; Tsao, Tiffany; Kunkel, Barbara N

    2013-06-01

    Auxin is a key plant growth regulator that also impacts plant-pathogen interactions. Several lines of evidence suggest that the bacterial plant pathogen Pseudomonas syringae manipulates auxin physiology in Arabidopsis thaliana to promote pathogenesis. Pseudomonas syringae strategies to alter host auxin biology include synthesis of the auxin indole-3-acetic acid (IAA) and production of virulence factors that alter auxin responses in host cells. The application of exogenous auxin enhances disease caused by P. syringae strain DC3000. This is hypothesized to result from antagonism between auxin and salicylic acid (SA), a major regulator of plant defenses, but this hypothesis has not been tested in the context of infected plants. We further investigated the role of auxin during pathogenesis by examining the interaction of auxin and SA in the context of infection in plants with elevated endogenous levels of auxin. We demonstrated that elevated IAA biosynthesis in transgenic plants overexpressing the YUCCA 1 (YUC1) auxin biosynthesis gene led to enhanced susceptibility to DC3000. Elevated IAA levels did not interfere significantly with host defenses, as effector-triggered immunity was active in YUC1-overexpressing plants, and we observed only minor effects on SA levels and SA-mediated responses. Furthermore, a plant line carrying both the YUC1-overexpression transgene and the salicylic acid induction deficient 2 (sid2) mutation, which impairs SA synthesis, exhibited additive effects of enhanced susceptibility from both elevated auxin levels and impaired SA-mediated defenses. Thus, in IAA overproducing plants, the promotion of pathogen growth occurs independently of suppression of SA-mediated defenses. PMID:23521356

  14. Pulmonary embolus

    MedlinePlus

    ... blood clot; Blood clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... x-ray CT angiogram of the chest Pulmonary ventilation/perfusion scan, also called a V/Q scan ...

  15. Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism

    PubMed Central

    Yang, Ying; Nie, Wei; Yuan, Jianmin; Zhang, Bingkun; Wang, Zhong

    2010-01-01

    Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser1179 which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models. PMID:20926919

  16. The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells.

    PubMed

    Angelini, Daniel J; Moyer, Robert A; Cole, Stephanie; Willis, Kristen L; Oyler, Jonathan; Dorsey, Russell M; Salem, Harry

    2015-01-01

    Organophosphorus (OP) pesticides are known to induce pulmonary toxicity in both humans and experimental animals. To elucidate the mechanism of OP-induced cytotoxicity, we examined the effects of parathion and malathion and their respective metabolites, paraoxon and malaoxon, on primary cultured human large and small airway cells. Exposure to paraoxon and malaoxon produced a dose-dependent increase in cytotoxicity following a 24-hour exposure, while treatment with parathion or malathion produced no effects at clinically relevant concentrations. Exposure to paraoxon-induced caspase activation, but malaoxon failed to induce this response. Since caspases have a major role in the regulation of apoptosis and cell death, we evaluated OP-induced cell death in the presence of a caspase inhibitor. Pharmacological caspase inhibition protected against paraoxon-induced cell death but not malaoxon-induced cell death. These data suggest that caspase activation is a key signaling element in paraoxon-induced cell death, but not malaoxon-induced cellular death in the pulmonary epithelium. PMID:26173615

  17. Analysis of the Molecular Dialogue Between Gray Mold (Botrytis cinerea) and Grapevine (Vitis vinifera) Reveals a Clear Shift in Defense Mechanisms During Berry Ripening.

    PubMed

    Kelloniemi, Jani; Trouvelot, Sophie; Héloir, Marie-Claire; Simon, Adeline; Dalmais, Bérengère; Frettinger, Patrick; Cimerman, Agnès; Fermaud, Marc; Roudet, Jean; Baulande, Sylvain; Bruel, Christophe; Choquer, Mathias; Couvelard, Linhdavanh; Duthieuw, Mathilde; Ferrarini, Alberto; Flors, Victor; Le Pêcheur, Pascal; Loisel, Elise; Morgant, Guillaume; Poussereau, Nathalie; Pradier, Jean-Marc; Rascle, Christine; Trdá, Lucie; Poinssot, Benoit; Viaud, Muriel

    2015-11-01

    Mature grapevine berries at the harvesting stage (MB) are very susceptible to the gray mold fungus Botrytis cinerea, while veraison berries (VB) are not. We conducted simultaneous microscopic and transcriptomic analyses of the pathogen and the host to investigate the infection process developed by B. cinerea on MB versus VB, and the plant defense mechanisms deployed to stop the fungus spreading. On the pathogen side, our genome-wide transcriptomic data revealed that B. cinerea genes upregulated during infection of MB are enriched in functional categories related to necrotrophy, such as degradation of the plant cell wall, proteolysis, membrane transport, reactive oxygen species (ROS) generation, and detoxification. Quantitative-polymerase chain reaction on a set of representative genes related to virulence and microscopic observations further demonstrated that the infection is also initiated on VB but is stopped at the penetration stage. On the plant side, genome-wide transcriptomic analysis and metabolic data revealed a defense pathway switch during berry ripening. In response to B. cinerea inoculation, VB activated a burst of ROS, the salicylate-dependent defense pathway, the synthesis of the resveratrol phytoalexin, and cell-wall strengthening. On the contrary, in infected MB, the jasmonate-dependent pathway was activated, which did not stop the fungal necrotrophic process. PMID:26267356

  18. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation.

    PubMed

    Campos, Renata; Shimizu, Maria Heloísa Massola; Volpini, Rildo Aparecido; de Bragança, Ana Carolina; Andrade, Lucia; Lopes, Fernanda Degobbi Tenório Quirino Dos Santos; Olivo, Clarice; Canale, Daniele; Seguro, Antonio Carlos

    2012-04-01

    Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the α-subunit of the epithelial sodium channel (α-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, α-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis. PMID:22268121

  19. Selection on defensive traits in a sterile caste - caste evolution: a mechanism to overcome life-history trade-offs?

    PubMed

    Roux, Estelle A; Roux, Maurice; Korb, Judith

    2009-01-01

    During development and evolution individuals generally face a trade-off between the development of weapons and gonads. In termites, characterized by reproductive division of labor, a caste evolved-the soldiers-which is completely sterile and which might be released from developmental trade-offs between weapons and testes. These soldiers are exclusively dedicated to defense. First, we investigated whether defensive traits are under selection in sterile termite soldiers using allometric analyses. In soldiers of the genus Cryptotermes phragmotic traits such as a sculptured and foreshortened head evolve rapidly but were also lost twice. Second, we compared the scaling relationships of these weapons with those in solitary insects facing a trade-off between weapons and gonads. Defensive traits consistently had lower slopes than nondefensive traits which supports the existence of stabilizing selection on soldier phragmotic traits in order to plug galleries. Moreover, soldier head widths were colony specific and correlated with the minimum gallery diameter of a colony. This can proximately be explained by soldiers developing from different instars. The scaling relationships of these termite soldiers contrast strikingly with those of weapons of solitary insects, which are generally exaggerated (i.e., overscaling) male traits. These differences may provide important insights into trait evolution. Trade-offs constraining the development of individuals may have been uncoupled in termites by evolving different castes, each specialized for one function. When individuals in social insect are "released" from developmental constraints through the evolution of castes, this certainly contributed to the ecological and evolutionary success of social insects. PMID:19196335

  20. Human induced pluripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cells.

    PubMed

    Armstrong, Lyle; Tilgner, Katarzyna; Saretzki, Gabriele; Atkinson, Stuart P; Stojkovic, Miodrag; Moreno, Ruben; Przyborski, Stefan; Lako, Majlinda

    2010-04-01

    The generation of induced pluripotent stem cells (iPSC) has enormous potential for the development of patient-specific regenerative medicine. Human embryonic stem cells (hESC) are able to defend their genomic integrity by maintaining low levels of reactive oxygen species (ROS) through a combination of enhanced removal capacity and limited production of these molecules. Such limited ROS production stems partly from the small number of mitochondria present in hESC; thus, it was important to determine that human iPSC (hiPSC) generation is able to eliminate the extra mitochondria present in the parental fibroblasts (reminiscent of "bottleneck" situation after fertilization) and to show that hiPSC have antioxidant defenses similar to hESC. We were able to generate seven hiPSC lines from adult human dermal fibroblasts and have fully characterized two of those clones. Both hiPSC clones express pluripotency markers and are able to differentiate in vitro into cells belonging to all three germ layers. One of these clones is able to produce fully differentiated teratoma, whereas the other hiPSC clone is unable to silence the viral expression of OCT4 and c-MYC, produce fully differentiated teratoma, and unable to downregulate the expression of some of the pluripotency genes during the differentiation process. In spite of these differences, both clones show ROS stress defense mechanisms and mitochondrial biogenesis similar to hESC. Together our data suggest that, during the reprogramming process, certain cellular mechanisms are in place to ensure that hiPSC are provided with the same defense mechanisms against accumulation of ROS as the hESC. PMID:20073085

  1. Light regulation of plant defense.

    PubMed

    Ballaré, Carlos L

    2014-01-01

    Precise allocation of limited resources between growth and defense is critical for plant survival. In shade-intolerant species, perception of competition signals by informational photoreceptors activates shade-avoidance responses and reduces the expression of defenses against pathogens and insects. The main mechanism underlying defense suppression is the simultaneous downregulation of jasmonate and salicylic acid signaling by low ratios of red:far-red radiation. Inactivation of phytochrome B by low red:far-red ratios appears to suppress jasmonate responses by altering the balance between DELLA and JASMONATE ZIM DOMAIN (JAZ) proteins in favor of the latter. Solar UVB radiation is a positive modulator of plant defense, signaling through jasmonate-dependent and jasmonate-independent pathways. Light, perceived by phytochrome B and presumably other photoreceptors, helps plants concentrate their defensive arsenals in photosynthetically valuable leaves. The discovery of connections between photoreceptors and defense signaling is revealing novel mechanisms that control key resource allocation decisions in plant canopies. PMID:24471835

  2. Animal Models of Pulmonary Hypertension: Matching Disease Mechanisms to Etiology of the Human Disease

    PubMed Central

    Colvin, Kelley L.; Yeager, Michael E.

    2015-01-01

    Recently a great deal of progress has been made in our understanding of pulmonary hypertension (PH). Research from the past 30 years has resulted in newer treatments that provide symptomatic improvements and delayed disease progression. Unfortunately, the cure for patients with this lethal syndrome remains stubbornly elusive. With the relative explosion of scientific literature regarding PH, confusion has arisen regarding animal models of the disease and their correlation to the human condition. This short review uniquely focuses on the clear and present need to better correlate mechanistic insights from existing and emerging animal models of PH to specific etiologies and histopathologies of human PH. A better understanding of the pathologic processes in various animal models and how they relate to the human disease should accelerate the development of newer and more efficacious therapies. PMID:25705569

  3. Permanent alveolar collapse is the predominant mechanism in idiopathic pulmonary fibrosis.

    PubMed

    Todd, Nevins W; Atamas, Sergei P; Luzina, Irina G; Galvin, Jeffrey R

    2015-08-01

    Alveolar epithelial cell loss and impaired epithelial cell regeneration are currently accepted as central initiating events in idiopathic pulmonary fibrosis (IPF), but subsequent downstream effects remain uncertain. The most accepted downstream effect is aberrant and dysregulated mesenchymal cell proliferation and excess extracellular matrix (ECM) accumulation. However, biochemical and imaging studies have perhaps somewhat surprisingly indicated little increase in total lung collagen and lung tissue, and have rather shown a substantial decrease in lung aeration and lung air volume. Loss of tissue aeration is a consequence of alveolar collapse, which occurs in IPF as a result of apposition and septal incorporation of denuded basal lamina. Permanent alveolar collapse is well-documented following epithelial injury, has the ability to mimic interstitial fibrosis radiologically and histologically, and is a better supported explanation than dysregulated fibroblast proliferation and excess ECM accumulation for the constellation of findings in patients with IPF. PMID:26165208

  4. Mechanism of action of ATP on canine pulmonary vagal C fibre nerve terminals.

    PubMed Central

    Pelleg, A; Hurt, C M

    1996-01-01

    1. The effects of extracellular adenosine 5'-triphosphate (ATP) on pulmonary vagal afferent fibres (n = 46) was studied in a canine model in vivo (n = 38). 2. ATP (3-6 mumol kg-1), administered as a rapid bolus into the right atrium, elicited a transient burst of action potentials in cervical vagal fibres, which was not affected by either blockade of ganglionic transmission (hexamethonium) or a drop in arterial blood pressure (nitroglycerine). 3. The fibres with ATP-sensitive terminals were otherwise quiescent with no activity related to either cardiac or respiratory cycles and their conduction velocity was 0.85 +/- 0.13 m s-1 (n = 7). 4. Inflation of the lungs to 2-3 times the tidal volume triggered brief bursts of action potentials in these fibres. 5. Capsaicin (10 micrograms kg-1), given as a rapid bolus into the right atrium, elicited a burst of action potentials in these ATP-sensitive fibres. 6. Smaller amounts of ATP and capsaicin (0.5-3 mumol kg-1 and 1-5 micrograms kg-1, respectively) had similar effects when the two compounds were given into the right pulmonary artery. 7. Adenosine, adenosine 5'-monophosphate, or adenosine 5'-diphosphate did not excite these fibres (n = 30). 8. The non-degradable analogue of ATP alpha,beta-methylene ATP (alpha,beta-mATP) was tenfold more potent than ATP while beta,gamma-methylene ATP (beta,gamma-mATP) was in active. 9. The selective P2x-purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid markedly attenuated the effect of ATP but not of capsaicin. The P2Y-purinoceptor antagonist Reactive Blue 2 was without effect. 10. Pretreatment with pertussis toxin (PTX) did not affect this action of ATP. 11. In the canine lungs ATP activates vagal C fibre nerve terminals. This action is mediated by P2X-purinoceptors and is independent of a PTX-sensitive guanine nucleotide binding protein (G protein). PMID:8745294

  5. Amniotic fluid embolism: moving diagnosis through the time. From the mechanical pulmonary vascular occlusion until an immuno - inflammatory pathogenesis?

    PubMed

    Turillazzi, Emanuela; Neri, Maria; Bello, Stefania; Riezzo, Irene; Fineschi, Vittorio

    2014-01-01

    Amniotic fluid embolism (AFE) is a rare, catastrophic syndrome that presents during labor and delivery or immediately postpartum. Efforts to develop a clinical diagnostic test are ongoing; however the diagnosis still relies on rapid bedside evaluation and depends on the exclusion of other diseases. Classically, the diagnosis was made at autopsy, with the demonstration of squamous cells or debris in the maternal pulmonary vasculature. Clinico-pathological correlations have strengthened the evidence for a role of the immune system in the pathogenesis of AFE and have lead to the development of new laboratory tests, such as the serum tryptase and complement measurements, which should provide scientific support for the presumed immunological mechanism of AFE. Recently, studies on the effects of amniotic fluid (AF) on platelet - neutrophil aggregation and neutrophil/platelet activation have opened new insight in the comprehension of the mechanisms underlying AFE, suggesting that a severe inflammatory response might have a paramount causative role, so opening new diagnostic and therapeutic perspectives. Considering the complex interplay between the different mechanisms involved in the pathogenesis of AFE, the diagnosis still arises from a complex diagnostic puzzle in which clinical, macroscopic, laboratory, histological and immunohistochemical data converge toward AFE. PMID:24804724

  6. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

    PubMed

    Wedzicha, Jadwiga A; Brill, Simon E; Allinson, James P; Donaldson, Gavin C

    2013-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities. PMID:23945277

  7. New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

    PubMed Central

    Blanco, Isabel; Izquierdo-García, José Luis; Dudzik, Danuta; Markuszewski, Michał J.; Peinado, Victor Ivo; Laclaustra, Martín; Barberá, Joan Albert; Barbas, Coral

    2016-01-01

    Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups’ classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease. PMID:27486806

  8. Lights and shadows of non-invasive mechanical ventilation for chronic obstructive pulmonary disease (COPD) exacerbations

    PubMed Central

    Lopez-Campos, Jose Luis; Jara-Palomares, Luis; Muñoz, Xavier; Bustamante, Víctor; Barreiro, Esther

    2015-01-01

    Despite the overwhelming evidence justifying the use of non-invasive ventilation (NIV) for providing ventilatory support in chronic obstructive pulmonary disease (COPD) exacerbations, recent studies demonstrated that its application in real-life settings remains suboptimal. European clinical audits have shown that 1) NIV is not invariably available, 2) its availability depends on countries and hospital sizes, and 3) numerous centers declare their inability to provide NIV to all of the eligible patients presenting throughout the year. Even with an established indication, the use of NIV in acute respiratory failure due to COPD exacerbations faces important challenges. First, the location and personnel using NIV should be carefully selected. Second, the use of NIV is not straightforward despite the availability of technologically advanced ventilators. Third, NIV therapy of critically ill patients requires a thorough knowledge of both respiratory physiology and existing ventilatory devices. Accordingly, an optimal team-training experience, the careful selection of patients, and special attention to the selection of devices are critical for optimizing NIV outcomes. Additionally, when applied, NIV should be closely monitored, and endotracheal intubation should be promptly available in the case of failure. Another topic that merits careful consideration is the use of NIV in the elderly. This patient population is particularly fragile, with several physiological and social characteristics requiring specific attention in relation to NIV. Several other novel indications should also be critically examined, including the use of NIV during fiberoptic bronchoscopy or transesophageal echocardiography, as well as in interventional cardiology and pulmonology. The present narrative review aims to provide updated information on the use of NIV in acute settings to improve the clinical outcomes of patients hospitalized for COPD exacerbations. PMID:25829958

  9. Disentangling Detoxification: Gene Expression Analysis of Feeding Mountain Pine Beetle Illuminates Molecular-Level Host Chemical Defense Detoxification Mechanisms

    PubMed Central

    Robert, Jeanne A.; Pitt, Caitlin; Bonnett, Tiffany R.; Yuen, Macaire M. S.; Keeling, Christopher I.; Bohlmann, Jörg; Huber, Dezene P. W.

    2013-01-01

    The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle. PMID:24223726

  10. Current understanding of grapevine defense mechanisms against the biotrophic fungus (Erysiphe necator), the causal agent of powdery mildew disease

    PubMed Central

    Qiu, Wenping; Feechan, Angela; Dry, Ian

    2015-01-01

    The most economically important disease of cultivated grapevines worldwide is powdery mildew (PM) caused by the ascomycete fungus Erysiphe necator. The majority of grapevine cultivars used for wine, table grape, and dried fruit production are derived from the Eurasian grape species Vitis vinifera because of its superior aroma and flavor characteristics. However, this species has little genetic resistance against E. necator meaning that grape production is highly dependent on the frequent use of fungicides. The integration of effective genetic resistance into cultivated grapevines would lead to significant financial and environmental benefits and represents a major challenge for viticultural industries and researchers worldwide. This review will outline the strategies being used to increase our understanding of the molecular basis of V. vinifera susceptibility to this fungal pathogen. It will summarize our current knowledge of different resistance loci/genes that have evolved in wild grapevine species to restrict PM infection and assess the potential application of these defense genes in the generation of PM-resistant grapevine germplasm. Finally, it addresses future research priorities which will be important in the rapid identification, evaluation, and deployment of new PM resistance genes which are capable of conferring effective and durable resistance in the vineyard. PMID:26504571

  11. Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO2 with small muscle mass exercise.

    PubMed

    Richardson, Russell S; Leek, Bryan T; Gavin, Timothy P; Haseler, Luke J; Mudaliar, Sundar R D; Henry, Robert; Mathieu-Costello, Odile; Wagner, Peter D

    2004-01-01

    We studied six patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 1.1 +/- 0.2 L, 32% of predicted) and six age- and activity level-matched control subjects while performing both maximal bicycle exercise and single leg knee-extensor exercise. Arterial and femoral venous blood sampling, thermodilution blood flow measurements, and needle biopsies allowed the assessment of muscle oxygen supply, utilization, and structure. Maximal work rates and single leg VO2max (control subjects = 0.63 +/- 0.1; patients with COPD = 0.37 +/- 0.1 L/minute) were significantly greater in the control group during bicycle exercise. During knee-extensor exercise this difference in VO2max disappeared, whereas maximal work capacity was reduced (flywheel resistance: control subjects = 923 +/- 198; patients with COPD = 612 +/- 81 g) revealing a significantly reduced mechanical efficiency (work per unit oxygen consumed) with COPD. The patients had an elevated number of less efficient type II muscle fibers, whereas muscle fiber cross-sectional areas, capillarity, and mitochondrial volume density were not different between the groups. Therefore, although metabolic capacity per se is unchanged, fiber type differences associated with COPD may account for the reduced muscular mechanical efficiency that becomes clearly apparent during knee-extensor exercise, when muscle function is no longer overshadowed by the decrement in lung function. PMID:14500263

  12. The effect of manual lung hyperinflation and postural drainage on pulmonary complications in mechanically ventilated trauma patients.

    PubMed

    Ntoumenopoulos, G; Gild, A; Cooper, D J

    1998-10-01

    This study questioned whether manual lung hyperinflation (MHI) and postural drainage reduced the incidence of nosocomial pneumonia or improved other outcome variables in mechanically ventilated trauma patients. Patients were withdrawn from the study if they developed nosocomial pneumonia according to a predetermined definition or on the clinical suspicion of nosocomial pneumonia by the attending intensivist. Of the 46 patients who fulfilled all the inclusion criteria and were enrolled into the study, 22 patients were randomized to group A (physiotherapy) and 24 patients to group B (control group). Twice as many patients were withdrawn in group B (8/24) compared with group A (4/22), although the differences were not statistically significant, [X2(1, 1) = 1.36, P = 0.24]. The length of time receiving mechanical ventilation and in the ICU was similar between the two groups and there were no differences in pulmonary dysfunction ("worst" daily PaO2/FiO2 ratio) between the two groups. There were no ICU deaths in either group. Physiotherapy as used in this study was not associated with a reduced incidence of nosocomial pneumonia based on standard clinical criteria. Nevertheless the trend to more frequent nosocomial pneumonia in the control patients suggests that a larger study in more severely injured patients with stricter clinical criteria for the definition of nosocomial pneumonia is indicated. PMID:9807602

  13. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  14. Pulmonary embolus

    MedlinePlus

    ... Blood clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... area). This type of clot is called a deep vein thrombosis (DVT) . The blood clot breaks off and travels ...

  15. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease. PMID:27161368

  16. Sildenafil to facilitate weaning from inhaled nitric oxide and mechanical ventilation in a patient with severe secondary pulmonary hypertension and a patent foramen ovale.

    PubMed

    Elias, Shlomo; Sviri, Sigal; Orenbuch-Harroch, Efrat; Fellig, Yakov; Ben-Yehuda, Arie; Fridlender, Zvi G; Gilon, Dan; Bayya, Abed

    2011-10-01

    We describe the case of a woman who presented to the intensive care unit with acute respiratory failure that required mechanical ventilation. She had severe pulmonary hypertension secondary to interstitial lung disease, and her history included sarcoidosis and tuberculosis. She was dependent on inhaled nitric oxide (INO) to maintain safe arterial oxygen saturation and could not be weaned from mechanical ventilation. Echocardiography revealed a patent foramen ovale with substantial right-to-left shunt, which probably contributed to her hypoxemia. Sildenafil enabled weaning from INO and substantially reduced the flow through the patent foramen ovale. She was successfully extubated and discharged home. To our knowledge, this is the first report of weaning from INO and mechanical ventilation in a patient with both severe secondary pulmonary hypertension and a right-to-left shunt through a patent foramen ovale. PMID:21513610

  17. The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension

    PubMed Central

    2013-01-01

    Background Recent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism. Methods A rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and −9 were detected by the western blot. Results Compared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9. Conclusions Our animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and

  18. Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery

    PubMed Central

    Lee, Su Hyun; Kim, Namo; Lee, Chang Yeong; Ban, Min Gi; Oh, Young Jun

    2016-01-01

    BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with moderate COPD during lung cancer surgery. DESIGN A randomised, double-blinded, placebo-controlled study. SETTING Single university hospital. PARTICIPANTS Fifty patients scheduled for video-assisted thoracoscopic surgery who had moderate COPD. Patients were randomly allocated to a control group or a Dex group (n = 25 each). INTERVENTIONS In the Dex group, dexmedetomidine was given as an initial loading dose of 1.0 μg kg−1 over 10 min followed by a maintenance dose of 0.5 μg kg−1 h−1 during OLV while the control group was administered a comparable volume of 0.9% saline. Data were measured at 30 min (DEX-30) and 60 min (DEX-60) after dexmedetomidine or saline administration during OLV. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on oxygenation. The secondary outcome was the effect of dexmedetomidine administration on postoperative pulmonary complications. RESULTS Patients in the Dex group had a significantly higher PaO2/FiO2 ratio (27.9 ± 5.8 vs. 22.5 ± 8.4 and 28.6 ± 5.9 vs. 21.0 ± 9.9 kPa, P < 0.05), significantly lower dead space ventilation (19.2 ± 8.5 vs. 24.1 ± 8.1 and 19.6 ± 6.7 vs. 25.3 ± 7.8%, P < 0.05) and higher dynamic compliance at DEX-30 and DEX-60 (P = 0.0001 and P = 0.0184) compared with the control group. In the Dex group, the PaO2/FiO2 ratio in the postoperative period was significantly higher (P = 0.022) and the incidence of ICU admission was

  19. Electro-Mechanical Manipulator for Use in the Remote Equipment Decontamination Cell at the Defense Waste Processing Facility, Savannah River Site - 12454

    SciTech Connect

    Lambrecht, Bill; Dixon, Joe; Neuville, John R.

    2012-07-01

    One of the legacies of the cold war is millions of liters of radioactive waste. One of the locations where this waste is stored is at the Savannah River Site (SRS) in South Carolina. A major effort to clean up this waste is on-going at the defense waste processing facility (DWPF) at SRS. A piece of this effort is decontamination of the equipment used in the DWPF to process the waste. The remote equipment decontamination cell (REDC) in the DWPF uses electro-mechanical manipulators (EMM) arms manufactured and supplied by PaR Systems to decontaminate DWPF process equipment. The decontamination fluid creates a highly corrosive environment. After 25 years of operational use the original EMM arms are aging and need replacement. To support continued operation of the DWPF, two direct replacement EMM arms were delivered to the REDC in the summer of 2011. (authors)

  20. Dual 5-HT mechanisms in basolateral and central nuclei of amygdala in the regulation of the defensive behavior induced by electrical stimulation of the inferior colliculus.

    PubMed

    Macedo, Carlos Eduardo; Castilho, Vanessa Moreno; de Souza e Silva, Maria Angélica; Brandão, Marcus L

    2002-11-30

    Regulatory mechanisms in the basolateral nucleus of the amygdala (BLA) serves as a filter for unconditioned and conditioned aversive information that ascend to higher structures from the brainstem whereas the central nucleus (CeA) is the main output for the resultant defense reaction. We have shown that neural substrates in the inferior colliculus are activated by threatening stimuli of acoustic nature and have important functional links with the amygdala. In this work, we examined the influence of lesions with 5,7-dihydroxytryptamine (5,7-DHT) of these nuclei of amygdala on the aversive responses induced by electrical stimulation of the inferior colliculus. Thus, rats were implanted with an electrode in the CeA of the inferior colliculus for the determination of the thresholds of alertness, freezing and escape responses. Each rat also bore a cannula implanted in the BLA or CeA for injection of 5,7-DHT (8.0 microg/0.8 microl) or its vehicle. The data obtained show that CeA lesions increase the thresholds of aversive responses whereas BLA lesions decrease the thresholds of these responses. From this evidence it is suggested that defensive behavior induced by activation of the neural substrates of aversion in the inferior colliculus seems to depend on the integrity of the amygdala. BLA regulates the input and CeA functions as the output for these aversive states generated at brainstem level. It is likely that aversive information ascending from the inferior colliculus may receive either inhibitory or excitatory influences of 5-HT mechanisms in the BLA or CeA, respectively. PMID:12431748

  1. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver.

    PubMed

    Cavin, C; Marin-Kuan, M; Langouët, S; Bezençon, C; Guignard, G; Verguet, C; Piguet, D; Holzhäuser, D; Cornaz, R; Schilter, B

    2008-04-01

    Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses. PMID:17976884

  2. Korean red ginseng extract rejuvenates testicular ineffectiveness and sperm maturation process in aged rats by regulating redox proteins and oxidative defense mechanisms.

    PubMed

    Kopalli, Spandana Rajendra; Hwang, Seock-Yeon; Won, Yu-Jin; Kim, Sung-Won; Cha, Kyu-Min; Han, Chang-Kyun; Hong, Jae-Yup; Kim, Si-Kwan

    2015-09-01

    Distortion of intracellular oxidant and antioxidant balances appears to be a common feature that underlies in age-related male sexual impairment. Therefore regulating oxidative defense mechanisms might be an ideal approach in improving male sexual dysfunctions. In the present study, the effect of Korean red ginseng aqueous extract (KRG) on age-induced testicular dysfunction in rats was investigated. KRG (200mg/kg) mixed with regular pellet diet was administered orally for six months and the morphological, spermatogenic and antioxidant enzyme status in testis of aged rats (18months) were evaluated. Data indicated a significant change in morphology and decrease in spermatogenesis-related parameters in aged rats (AC) compared with young rats (YC). Sperm number, germ cell count, Sertoli cell count and Sertoli cell index were significantly (p<0.05) restored in KRG-treated aged rat groups (G-AC). Further the increased lipid peroxidation as measured by malondialdehyde (p<0.05), and altered enzymatic (superoxide dismutase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and catalase) and non-enzymatic (reduced glutathione, ascorbic acid and α-tocopherol) antioxidants (p<0.05) were attenuated by KRG treatment in aged rats to near normal levels as in YC groups. Furthermore, proteomic analysis demonstrated differential expression of selected proteins such as phosphatidylinositol transfer protein, fatty acid binding protein-9, triosephosphate isomerase-1 and aldehyde (aldose) reductase-1in aged rats was significantly (p<0.05) protected by KRG treatment. In conclusion, long-term administration of KRG restored aging-induced testicular ineffectiveness in rats by modulating redox proteins and oxidative defense mechanisms. PMID:25980653

  3. Effect of Alterations in Mechanical Ventilator Settings on Pulmonary Gas Exchange in Hyaline Membrane Disease

    PubMed Central

    Reynolds, E. O. R.

    1971-01-01

    The effect of altering peak airway pressure, respiratory frequency, and inspiration: expiration ratio on arterial blood gas tensions, blood pressure, and calculated right-to-left shunt was investigated in 6 infants undergoing mechanical ventilation for hyaline membrane disease with a Bennet ventilator. The use of a very long inspiratory phase resulted in a large increase in Pao2 and fall in right-to-left shunt without affecting mean arterial blood pressure. ImagesFIG. 1FIG. 4 PMID:5576023

  4. Pulmonary valve stenosis

    MedlinePlus

    ... valve pulmonary stenosis; Pulmonary stenosis; Stenosis - pulmonary valve; Balloon valvuloplasty - pulmonary ... water pills) Treat abnormal heartbeats and rhythms Percutaneous balloon pulmonary dilation (valvuloplasty) may be performed when no ...

  5. Cytotoxic activity of dendritic cells as a possible mechanism of negative regulation of T lymphocytes in pulmonary tuberculosis.

    PubMed

    Sakhno, Ludmila V; Tikhonova, Marina A; Tyrinova, Tamara V; Leplina, Olga Yu; Shevela, Ekaterina Ya; Nikonov, Sergey D; Zhdanov, Oleg A; Ostanin, Alexander A; Chernykh, Elena R

    2012-01-01

    The PD-1/B7-H1-mediated induction of T cell apoptosis/anergy as a possible mechanism of immune response failure was studied in 76 patients with pulmonary tuberculosis (TB) with normal and low-proliferative response to antigens of M. tuberculosis (purified protein derivative (PPD)). It was revealed that dendritic cells (DCs), generated in vitro from patient blood monocytes with GM-CSF + IFN-α, were characterized by increased B7-H1 expression, upproduction of IL-10, and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). Moreover, DCs of patients with TB were able to enhance T cell apoptosis and to block T-cell division in MLC. It was shown that neutralizing anti-PD1 antibodies significantly decreased the proapoptogenic/tolerogenic effect of DCs. Correlation analysis revealed a direct relationship between IL-10 production and level of B7-H1 expression in the general group of investigated patients. It was demonstrated that generation of healthy donor DCs in the presence of IL-10 led to an increase in the number of DCs-expressed B7-H1 molecule, DC proapoptogenic activity, and a decrease in their allostimulatory activity. Obviously, the revealed phenomenon of the PD-1/B7-H1-mediated pro-apoptogenic activity of DCs is clinically significant since the cytotoxic/tolerogenic potential of DCs is more pronounced in patients with PPD anergy. PMID:23056139

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

    PubMed

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

    2016-01-01

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

  7. The Effect of Pressure-Controlled Ventilation and Volume-Controlled Ventilation in Prone Position on Pulmonary Mechanics and Inflammatory Markers.

    PubMed

    Şenay, Hasan; Sıvacı, Remziye; Kokulu, Serdar; Koca, Buğra; Bakı, Elif Doğan; Ela, Yüksel

    2016-08-01

    The aim of this present study is to compare the effect of pressure-controlled ventilation and volume-controlled ventilation on pulmonary mechanics and inflammatory markers in prone position. The study included 41 patients undergoing to vertebrae surgery. The patients were randomized into two groups: Group 1 received volume-controlled ventilation, while group 2 received pressure-controlled ventilation. The demographic data, pulmonary mechanics, the inflammatory marker levels just after the induction of anesthetics, at the 6th and 12th hours, and gas analysis from arterial blood samples taken at the beginning and the 30th minute were recorded. The inflammatory marker levels increased in both groups, without any significant difference among groups. Peak inspiratory pressure level was higher in the volume-controlled ventilation group. This study revealed that there is no difference regarding inflammatory marker levels between volume- and pressure-controlled ventilation. PMID:27221140

  8. Cardiovascular modeling in pulmonary arterial hypertension: focus on mechanisms and treatment of right heart failure using the CircAdapt model.

    PubMed

    Lumens, Joost; Delhaas, Tammo

    2012-09-15

    In recent years, increased understanding of cardiovascular system dynamics has led to the development of mathematical models of the heart and circulation. Models that enable realistic simulation of ventricular mechanics and interactions under a range of conditions have the potential to provide an ideal method with which to investigate the effects of pulmonary arterial hypertension and its treatment on cardiac mechanics and hemodynamics. Such mathematical models have the potential to contribute to a personalized, patient-specific treatment approach and allow more objective diagnostic decision-making, patient monitoring, and assessment of treatment outcome. This review discusses the development of mathematical models of the heart and circulation, with particular reference to the closed-loop CircAdapt model, and how the model performs under both normal and pathophysiological (pulmonary hypertensive) conditions. PMID:22921031

  9. Engineering tissue constructs to mimic native aortic and pulmonary valve leaflets' structures and mechanics

    NASA Astrophysics Data System (ADS)

    Masoumi, Nafiseh

    There are several disadvantages correlated with current heart valve replacement, including anticoagulation therapy for patients with mechanical valves and the low durability of bioprosthetic valves. The non-viable nature of such devices is a critical drawback especially for pediatric cases due to the inability of the graft to grow in vivo with the patients. A tissue engineered heart valve (TEHV) with remodeling and growth ability, is conceptually appealing to use in the surgical repair and could serve as a permanent replacements when operating for pediatric valvular lesions. It is critical that scaffolds for functional heart valve tissue engineering, be capable of mimicking the native leaflet's structure and mechanical properties at the time of implantation. Meanwhile, the scaffolds should be able to support cellular proliferation and native-like tissue formation as the TEHV remodels toward a scaffold-free state. Our overall hypothesis is that an "ideal" engineered construct, designed based on native leaflet's structure and mechanics, will complement a native heart valve leaflet in providing benchmarks for use in the design of clinically-applicable TEHV. This hypothesis was addressed through several experiments conducted in the present study. To establish a functional biomimetic TEHV, we developed scaffolds capable of matching the anisotropic stiffness of native leaflet while promoting native-like cell and collagen content and supporting the ECM generation. Scaffolds with various polymer contents (e.g., poly (glycerol sebacate) (PGS) and poly (epsilon-caprolactone) (PCL)) and structural designs (e.g., microfabricated and microfibrous scaffolds), were fabricated based on native leaflet's structure and mechanics. It was found that the tri-layered scaffold, designed with assembly of microfabricated PGS and microfibrous PGS/PCL was a functional leaflet capable of promoting tissue formation. Furthermore, to investigate the effect of cyclic stress and flexure

  10. Chronic hypoxia upregulates pulmonary arterial ASIC1: a novel mechanism of enhanced store-operated Ca2+ entry and receptor-dependent vasoconstriction.

    PubMed

    Jernigan, Nikki L; Herbert, Lindsay M; Walker, Benjimen R; Resta, Thomas C

    2012-03-15

    Acid-sensing ion channel 1 (ASIC1) is a newly characterized contributor to store-operated Ca(2+) entry (SOCE) in pulmonary vascular smooth muscle (VSM). Since SOCE is implicated in elevated basal VSM intracellular Ca(2+) concentration ([Ca(2+)](i)) and augmented vasoconstriction in chronic hypoxia (CH)-induced pulmonary hypertension, we hypothesized that ASIC1 contributes to these responses. To test this hypothesis, we examined effects of the specific pharmacologic ASIC1a inhibitor, psalmotoxin 1 (PcTX1), on vasoconstrictor and vessel wall [Ca(2+)](i) responses to UTP and KCl (depolarizing stimulus) in fura-2-loaded, pressurized small pulmonary arteries from control and CH (4 wk at 0.5 atm) Wistar rats. PcTX1 had no effect on basal vessel wall [Ca(2+)](i), but attenuated vasoconstriction and increases in vessel wall [Ca(2+)](i) to UTP in arteries from control and CH rats; normalizing responses between groups. In contrast, responses to the depolarizing stimulus, KCl, were unaffected by CH exposure or PcTX1. Upon examining potential Ca(2+) influx mechanisms, we found that PcTX1 prevented augmented SOCE following CH. Exposure to CH resulted in a significant increase in pulmonary arterial ASIC1 protein. This study supports a novel role of ASIC1 in elevated receptor-stimulated vasoconstriction following CH which is likely mediated through increased ASIC1 expression and SOCE. PMID:22205392

  11. Kluyveromyces lactis: A Suitable Yeast Model to Study Cellular Defense Mechanisms against Hypoxia-Induced Oxidative Stress

    PubMed Central

    González Siso, M. Isabel; Cerdán, M. Esperanza

    2012-01-01

    Studies about hypoxia-induced oxidative stress in human health disorders take advantage from the use of unicellular eukaryote models. A widely extended model is the fermentative yeast Saccharomyces cerevisiae. In this paper, we describe an overview of the molecular mechanisms induced by a decrease in oxygen availability and their interrelationship with the oxidative stress response in yeast. We focus on the differential characteristics between S. cerevisiae and the respiratory yeast Kluyveromyces lactis, a complementary emerging model, in reference to multicellular eukaryotes. PMID:22928082

  12. Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive ana...

  13. [Postural therapy during mechanical pulmonary ventilation with PEEP in patients with unilateral lung damage].

    PubMed

    Neverin, V K; Vlasenko, A V; Mitrokhin, A A; Galushka, S V; Ostapchenko, D V; Shishkina, E V

    2000-01-01

    Mechanical ventilation of the lungs (MVL) with positive end expiratory pressure (PEEP) is difficult in patients with unilateral lung damage because of uneven distribution of volumes and pressures in the involved and intact lungs. Harmful effects are easier manifested under such conditions. Selective MVL with selective PEEP is widely used abroad for optimizing MVL, but this method is rather expensive and is not devoid of shortcomings. Our study carried out in 32 patients with unilateral lung involvement showed that traditional MVL with general PEEP can effectively (in 75% cases) regulate gaseous exchange and decrease its untoward effects if MVL is performed with the patient lying on the healthy side and not supine. MVL in patients with unilateral lung injury lying on the healthy side can be a simpler and cheaper alternative to selective MVL with selective PEEP. PMID:10833838

  14. Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity.

    PubMed Central

    MacLean, J. A.; Xia, W.; Pinto, C. E.; Zhao, L.; Liu, H. W.; Kradin, R. L.

    1996-01-01

    Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells (APCs) of the lung, playing a vital role in the induction of cell-mediated immunity to inhaled antigens. We have previously demonstrated that an airway challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of specific antigen-presenting cell activity by purified pulmonary DCs and a cell-mediated immune response in the lung upon secondary challenge. To examine how a particulate antigen leads to a cell-mediated response in vivo, graded concentrations of heat-killed Listeria (HKL) were injected intratracheally into Lewis rats. The bacteria were rapidly ingested by lung macrophages and polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in vivo by an airway challenge with HKL to subsequently stimulate HKL-specific responses ex vivo showed a threshold response, requiring a dose in excess of 10(9) organisms/rat. By contrast, all dosages of HKL yielded specific sensitization of lymphocytes in the draining bilar nodes. Pulmonary DCs purified from rats after a secondary in vivo airway challenge with HKL at day 14 were ineffective antigen-presenting cells except at high dosages of antigen. The generation of cell-mediated pulmonary inflammation paralleled the antigen-presenting cell activity of pulmonary DCs and was observed only at high antigen dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected intratracheally yielded comparable results to those observed with HKL. We suggest that a pulmonary cellular immune response is generated to an inhaled particulate antigen when the protective phagocytic capacities of the lung are exceeded and antigen is able to interact directly with interstitial DCs. The diversion of particulate antigens by pulmonary phagocytes may help to limit undesirable pulmonary inflammation while allowing the generation of antigen-specific immune lymphocytes in vivo. Images Figure 2 Figure 4 Figure 5 Figure 7 Figure 9

  15. Evidence for Negative Effects of Elevated Intra-Abdominal Pressure on Pulmonary Mechanics and Oxidative Stress

    PubMed Central

    Davarcı, I.; Karcıoğlu, M.; Tuzcu, K.; İnanoğlu, K.; Yetim, T. D.; Motor, S.; Ulutaş, K. T.; Yüksel, R.

    2015-01-01

    Objective. To compare the effects of pneumoperitoneum on lung mechanics, end-tidal CO2 (ETCO2), arterial blood gases (ABG), and oxidative stress markers in blood and bronchoalveolar lavage fluid (BALF) during laparoscopic cholecystectomy (LC) by using lung-protective ventilation strategy. Materials and Methods. Forty-six patients undergoing LC and abdominal wall hernia (AWH) surgery were assigned into 2 groups. Measurements and blood samples were obtained before, during pneumoperitoneum, and at the end of surgery. BALF samples were obtained after anesthesia induction and at the end of surgery. Results. Peak inspiratory pressure, ETCO2, and pCO2 values at the 30th minute were significantly increased, while there was a significant decrease in dynamic lung compliance, pH, and pO2 values in LC group. In BALF samples, total oxidant status (TOS), arylesterase, paraoxonase, and malondialdehyde levels were significantly increased; the glutathione peroxidase levels were significantly decreased in LC group. The serum levels of TOS and paraoxonase were significantly higher at the end of surgery in LC group. In addition, arylesterase level in the 30th minute was increased compared to baseline. Serum paraoxonase level at the end of surgery was significantly increased when compared to AWH group. Conclusions. Our study showed negative effects of pneumoperitoneum in both lung and systemic levels despite lung-protective ventilation strategy. PMID:25685845

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

    PubMed Central

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

    2016-01-01

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

  17. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves.

    PubMed

    Lammers, Steven R; Kao, Phil H; Qi, H Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R; Shandas, Robin

    2008-10-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

  18. (1)H NMR and GC-MS Based Metabolomics Reveal Defense and Detoxification Mechanism of Cucumber Plant under Nano-Cu Stress.

    PubMed

    Zhao, Lijuan; Huang, Yuxiong; Hu, Jerry; Zhou, Hongjun; Adeleye, Adeyemi S; Keller, Arturo A

    2016-02-16

    Because copper nanoparticles are being increasingly used in agriculture as pesticides, it is important to assess their potential implications for agriculture. Concerns have been raised about the bioaccumulation of nano-Cu and their toxicity to crop plants. Here, the response of cucumber plants in hydroponic culture at early development stages to two concentrations of nano-Cu (10 and 20 mg/L) was evaluated by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and gas chromatography-mass spectrometry (GC-MS) based metabolomics. Changes in mineral nutrient metabolism induced by nano-Cu were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Results showed that nano-Cu at both concentrations interferes with the uptake of a number of micro- and macro-nutrients, such as Na, P, S, Mo, Zn, and Fe. Metabolomics data revealed that nano-Cu at both levels triggered significant metabolic changes in cucumber leaves and root exudates. The root exudate metabolic changes revealed an active defense mechanism against nano-Cu stress: up-regulation of amino acids to sequester/exclude Cu/nano-Cu; down-regulation of citric acid to reduce the mobilization of Cu ions; ascorbic acid up-regulation to combat reactive oxygen species; and up-regulation of phenolic compounds to improve antioxidant system. Thus, we demonstrate that nontargeted (1)H NMR and GC-MS based metabolomics can successfully identify physiological responses induced by nanoparticles. Root exudates metabolomics revealed important detoxification mechanisms. PMID:26751164

  19. Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

    PubMed

    Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

    2016-06-01

    Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response. PMID:27039215

  20. A Role for the Anti-Viral Host Defense Mechanism in the Phylogenetic Divergence in Baculovirus Evolution.

    PubMed

    Nagamine, Toshihiro; Sako, Yasushi

    2016-01-01

    Although phylogenic analysis often suggests co-evolutionary relationships between viruses and host organisms, few examples have been reported at the microevolutionary level. Here, we show a possible example in which a species-specific anti-viral response may drive phylogenic divergence in insect virus evolution. Two baculoviruses, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), have a high degree of DNA sequence similarity, but exhibit non-overlapping host specificity. In our study of their host-range determination, we found that BmNPV replication in B. mori cells was prevented by AcMNPV-P143 (AcP143), but not BmNPV-P143 (BmP143) or a hybrid P143 protein from a host-range expanded phenotype. This suggests that AcMNPV resistance in B. mori cells depends on AcP143 recognition and that BmNPV uses BmP143 to escapes this recognition. Based on these data, we propose an insect-baculovirus co-evolution scenario in which an ancestor of silkworms exploited an AcMNPV-resistant mechanism; AcMNPV counteracted this resistance via P143 mutations, resulting in the birth of BmNPV. PMID:27244571

  1. A Role for the Anti-Viral Host Defense Mechanism in the Phylogenetic Divergence in Baculovirus Evolution

    PubMed Central

    Nagamine, Toshihiro; Sako, Yasushi

    2016-01-01

    Although phylogenic analysis often suggests co-evolutionary relationships between viruses and host organisms, few examples have been reported at the microevolutionary level. Here, we show a possible example in which a species-specific anti-viral response may drive phylogenic divergence in insect virus evolution. Two baculoviruses, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV), have a high degree of DNA sequence similarity, but exhibit non-overlapping host specificity. In our study of their host-range determination, we found that BmNPV replication in B. mori cells was prevented by AcMNPV-P143 (AcP143), but not BmNPV-P143 (BmP143) or a hybrid P143 protein from a host-range expanded phenotype. This suggests that AcMNPV resistance in B. mori cells depends on AcP143 recognition and that BmNPV uses BmP143 to escapes this recognition. Based on these data, we propose an insect-baculovirus co-evolution scenario in which an ancestor of silkworms exploited an AcMNPV-resistant mechanism; AcMNPV counteracted this resistance via P143 mutations, resulting in the birth of BmNPV. PMID:27244571

  2. Single Exposure to near Roadway Particulate Matter Leads to Confined Inflammatory and Defense Responses: Possible Role of Metals.

    PubMed

    Pardo, Michal; Shafer, Martin M; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2015-07-21

    Inhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single ("subclinical response") exposure to water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-α), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage. PMID:26121492

  3. Autonomic mechanism for initiation of rapid firing from atria and pulmonary veins: evidence by ablation of ganglionated plexi

    PubMed Central

    Lu, Zhibing; Scherlag, Benjamin J.; Lin, Jiaxiong; Yu, Lilei; Guo, Ji-Hong; Niu, Guodong; Jackman, Warren M.; Lazzara, Ralph; Jiang, Hong; Po, Sunny S.

    2009-01-01

    Aims Previous studies showed that autonomic activation by high-frequency electrical stimulation (HFS) during myocardial refractoriness evokes rapid firing from pulmonary vein (PV) and atria, both in vitro and in vivo. This study sought to investigate the autonomic mechanism underlying the rapid firings at various sites by systematic ablation of multiple ganglionated plexi (GP). Methods and results In 43 mongrel dogs, rapid firing-mediated atrial fibrillation (AF) was induced by local HFS (200 Hz, impulse duration 0.1 ms, train duration 40 ms) to the PVs and atria during myocardial refractoriness. The main GP in the atrial fat pads or the ganglia along the ligament of Marshall (LOM) were then ablated. Ablation of the anterior right GP and inferior right GP significantly increased the AF threshold by HFS at the right atrium and PVs. The AF threshold at left atrium and PVs was significantly increased by ablation of the superior left GP and inferior left GP, and was further increased by ablation of the LOM. Ablation of left- or right-sided GP on the atria had a significant effect on contralateral PVs and atrium. Administration of esmolol (1 mg/kg) or atropine (1 mg) significantly increased AF threshold at all sites. Conclusion HFS applied to local atrial and PV sites initiated rapid firing via activation of the interactive autonomic network in the heart. GP in either left side or right side contributes to the rapid firings and AF originating from ipsolateral and contralateral PVs and atrium. Autonomic denervation suppresses or eliminates those rapid firings. PMID:19520703

  4. PULMONARY CIRCULATION AT EXERCISE

    PubMed Central

    NAEIJE, R; CHESLER, N

    2012-01-01

    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40–50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease. PMID:23105961

  5. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

    PubMed

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha

    2015-09-01

    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. PMID:24615921

  6. Pulmonary hypertension caused by pulmonary venous hypertension

    PubMed Central

    2014-01-01

    Abstract The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility. PMID:25610595

  7. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  8. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  9. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  10. Pulmonary Embolism.

    PubMed

    Rali, Parth; Gandhi, Viral; Malik, Khalid

    2016-01-01

    Pulmonary embolism covers a wide spectrum of presentation from an asymptomatic individual to a life-threatening medical emergency. It is of paramount importance to appropriately risk stratify patients with pulmonary embolism, particularly with those who present without hypotension. Right ventricular dysfunction can evolve after a patient has received a diagnosis of pulmonary embolism, necessitating aggressive measures rather than simple anticoagulation. In this review, we discuss definition, risk stratification, pathogenesis, diagnostic approach, and management, with particular focus on massive pulmonary embolism. PMID:26919674

  11. Secured network sensor-based defense system

    NASA Astrophysics Data System (ADS)

    Wei, Sixiao; Shen, Dan; Ge, Linqiang; Yu, Wei; Blasch, Erik P.; Pham, Khanh D.; Chen, Genshe

    2015-05-01

    Network sensor-based defense (NSD) systems have been widely used to defend against cyber threats. Nonetheless, if the adversary finds ways to identify the location of monitor sensors, the effectiveness of NSD systems can be reduced. In this paper, we propose both temporal and spatial perturbation based defense mechanisms to secure NSD systems and make the monitor sensor invisible to the adversary. The temporal-perturbation based defense manipulates the timing information of published data so that the probability of successfully recognizing monitor sensors can be reduced. The spatial-perturbation based defense dynamically redeploys monitor sensors in the network so that the adversary cannot obtain the complete information to recognize all of the monitor sensors. We carried out experiments using real-world traffic traces to evaluate the effectiveness of our proposed defense mechanisms. Our data shows that our proposed defense mechanisms can reduce the attack accuracy of recognizing detection sensors.

  12. Defense Mechanisms of Conifers 1

    PubMed Central

    Lewinsohn, Efraim; Gijzen, Mark; Savage, Thomas J.; Croteau, Rodney

    1991-01-01

    Cell-free extracts from Pinus ponderosa Lawson (ponderosa pine) and Pinus sylvestris L. (Scotch pine) wood exhibited high levels of monoterpene synthase (cyclase) activity, whereas bark extracts of these species contained no detectable activity, and they inhibited cyclase activity when added to extracts from wood, unless polyvinylpyrrolidone was included in the preparation. The molecular mass of the polyvinylpyrrolidone added was of little consequence; however, polyvinylpolypyrrolidone (a cross-linked insoluble form of the polymer) was ineffective in protecting enzyme activity. Based on these observations, methods were developed for the efficient extraction and assay of monoterpene cyclase activity from conifer stem (wood and bark) tissue. The level of monoterpene cyclase activity for a given conifer species was shown to correlate closely with the monoterpene content of the oleoresin and with the degree of anatomical complexity of the specialized resin-secreting structures. Cyclase activity and monoterpene content were lowest in the stems of species containing only isolated resin cells, such as western red cedar (Thuja plicata D. Don). Increasing levels of cyclase activity and oleoresin monoterpenes were observed in advancing from species with multicellular resin blisters (true firs [Abies]) to those with organized resin passages, such as western larch (Larix occidentalis Nutt.), Colorado blue spruce (Picea pungens Engelm.) and Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco). The highest levels of cyclase activity and oleoresin monoterpenes were noted in Pinus species that contain the most highly developed resin duct systems. The relationship between biosynthetic capacity, as measured by cyclase activity, monoterpene content, and the degree of organization of the secretory structures for a given species, may reflect the total number of specialized resin-producing cells per unit mass of stem tissue. PMID:16668182

  13. Post splenectomy related pulmonary hypertension

    PubMed Central

    Palkar, Atul V; Agrawal, Abhinav; Verma, Sameer; Iftikhar, Asma; Miller, Edmund J; Talwar, Arunabh

    2015-01-01

    Splenectomy predisposes patients to a slew of infectious and non-infectious complications including pulmonary vascular disease. Patients are at increased risk for venous thromboembolic events due to various mechanisms that may lead to chronic thromboembolic pulmonary hypertension (CTEPH). The development of CTEPH and pulmonary vasculopathy after splenectomy involves complex pathophysiologic mechanisms, some of which remain unclear. This review attempts congregate the current evidence behind our understanding about the etio-pathogenesis of pulmonary vascular disease related to splenectomy and highlight the controversies that surround its management. PMID:26949600

  14. [Pulmonary vasoconstrictor responses].

    PubMed

    Onodera, S

    1992-12-01

    Alterations in the physiological balance to maintain the pulmonary circulation at a normal low pressure level result in an elevation in pulmonary vascular tone. Pulmonary vasoconstrictor responses were analyzed under some experimental conditions, which included microembolism, administration of vasoactive agents, hypoxia, and monocrotaline-induced pulmonary hypertension. It is widely accepted that these responses are highly localized and complex. In the present study, excised canine lung lobes, rat lungs, and pulmonary arterial rings from the rat were employed according to the particular experimental design. The mechanism of the initial rapid elevation followed by a gradual decline in perfusion pressure in microembolism was considered to be related not only to the size of the emboli, but to the degree of mechanical injury of the endothelium. The main sites of constriction of the pulmonary vasculature by several drugs were determined in the pulsatile perfused canine lung lobes, according to the degree of decrease in inflow wave amplitude during antegrade or retrograde perfusion. Further, by applying the same method it was confirmed that the site of hypoxic vasoconstriction is located in the peripheral pulmonary vascular bed between the muscular arteries and veins, which are constricted mainly by serotonin and histamine, respectively. A cross perfusion system was set up, employing two lobes from the same dog, in which normoxic blood was perfused into the hypoxic ventilated lobe and vice versa. As a result, the pulmonary vessels showed a response to ventilation hypoxia that was far more sensitive than that to perfusion hypoxia. The effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol, pindolol) on hypoxic vasoconstriction were observed. Although pindolol (a vasodilatory beta-blocker) abolished hypoxic pulmonary vasoconstriction, which was similar to the effect of isoproterenol, the mechanism of action of pindolol was suggested to be different

  15. Values as Defenses

    ERIC Educational Resources Information Center

    Hultman, Kenneth E.

    1976-01-01

    The author outlines a cognitive approach for explaining how and why people use values as defenses. He examines the relationship between defensive values and irrational beliefs, suggests a number of criteria for diagnosing the presence of defensive values, and proposes some strategies for dealing with defensive values in counseling. (Author)

  16. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  17. The reproductive toxicity on the rotifer Brachionus plicatilis induced by BDE-47 and studies on the effective mechanism based on antioxidant defense system changes.

    PubMed

    Wang, Hong; Tang, Xuexi; Sha, Jingjing; Chen, Hongmei; Sun, Tianli; Wang, You

    2015-09-01

    2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a low-brominated Tetra-BDE that is widely distributed in the marine ecosystem, was selected to investigate the reproductive toxicity on the rotifer, Brachionus plicatilis, and the possible mechanism based on antioxidant defense system changes were studied. The results showed the following: (1) A low concentration of BDE-47 had a slight effect on the egg production of individual females and the egg production rate (EPR) of the population. In fact, BDE-47 exerted reproductive inhibition effects in a time- and concentration-dependent manner. The obtained life tables indicated that BDE-47 at a high concentration prolonged the generation time, whereas low and moderate concentrations of BDE-47 had the opposite effects. BDE-47 at a medium concentration significantly decreased the life expectancy and net reproductive rate (P<0.05). Additionally, a high concentration of BDE-47 markedly decreased the net reproductive rate and intrinsic increase rate (P<0.05). The ultra-structure of the ovary showed that BDE-47 severely damaged the ovary. (2) BDE-47 stress elevated the ROS level in B. plicatilis. The GST activity was induced significantly by the low concentration of BDE-47 and inhibited by the highest concentration tested. The GPx activity and GSH content were significant decreased in all the tested groups, and GR activity was induced. GST and GSH appeared to be sensitive to oxidative stress, and all of the glutathione-related enzymes were found to play an important role in maintaining the antioxidant/pro-oxidant balance based on Pearson's correlation analysis. The results indicated that BDE-47 causes reproductive toxicity in B. plicatilis and that the ROS-mediated pathway is responsible for the observed toxicity. PMID:25950406

  18. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    PubMed Central

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells. PMID:25060396

  19. Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense

    PubMed Central

    2013-01-01

    Background Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. Methods The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 μg/ml) and GA (up to 10 μg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. Results AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. Conclusions AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula. PMID:23826868

  20. Pulmonary Hypertension in Cardiac Surgery

    PubMed Central

    Denault, André; Deschamps, Alain; Tardif, Jean-Claude; Lambert, Jean; Perrault, Louis

    2010-01-01

    Pulmonary hypertension is an important prognostic factor in cardiac surgery associated with increased morbidity and mortality. With the aging population and the associated increase severity of illness, the prevalence of pulmonary hypertension in cardiac surgical patients will increase. In this review, the definition of pulmonary hypertension, the mechanisms and its relationship to right ventricular dysfunction will be presented. Finally, pharmacological and non-pharmacological therapeutic and preventive approaches will be presented. PMID:21286273

  1. [Transsexual defense].

    PubMed

    Pfäfflin, F

    1994-01-01

    The prevalent approach to the treatment of patients displaying transsexual symptoms is one that favours somatic intervention of either a hormonal or surgical nature. Normally these patients refuse to avail themselves of the possibility of psychotherapy and are indeed regarded by many therapists as largely inaccessible to therapy of this kind. Pfäfflin looks into the factors involved in the disinclination displayed by both patients and therapists to embark upon such a process. He discusses the unconscious defence mechanisms operative in this disinclination with particular reference to the incipient stages of a course of treatment extending over a number of years and involving a patient initially determined to undergo a surgical "sex change". The patient's insistence on being acknowledged as a woman is regarded here as a creative defence against a major diffusion of identity from a genetically earlier phase, connected with incomplete separation and individuation. In the author's opinion the patient's ability to relinquish this defence will depend largely on the therapist's ability to acknowledge its creativity. PMID:7972887

  2. Strategic defense initiative: critical issues

    SciTech Connect

    Nuckolls, J.H.

    1985-06-01

    The objectives of the Strategic Defense Initiative (SDI) as outlined by President Reagan are discussed. The principal objective for SDI is as a defense against ballistic missiles. Soviet objections and a summary of US-USSR dialogue on the subject are reviewed. Most US studies have been critical of SDI. Four critical issues are addressed in depth: are defense weapons technologically feasible which have high economic leverage relative to offensive ballistic missiles; would the defense feasibility and leverage be degraded or enhanced in the technological race between weapons innovation and countermeasures; could stability be achieved during and after the transition to the defense dominated world envisioned by SDI proponents; would the deployment of high leverage defensive weapons increase or decrease the security of NATO Europe, and the probability of major conventional or nuclear wars. The issue of SDI may lead to a paradox that contains the seeds of catastrophe. The author concludes by warning that nuclear disarmament may eliminate the highly successful deterrent mechanism for avoiding another major world war. In a world made safe for major conventional wars by the apparent ''elimination'' of nuclear weapons, the leaders in a conventional World War III - involving unimaginable suffering, hatred, terror, and death - would be strongly motivated to introduce nuclear weapons in the crucial decisive battles. Even if diplomacy could ''eliminate'' nuclear weapons, man's knowledge of nuclear weapons can never be eliminated. The paradox is the attempt to eliminate nuclear weapons may maximize the probability of their use. (DMC)

  3. High-frequency oscillatory ventilation compared with conventional mechanical ventilation in the treatment of respiratory failure in preterm infants: assessment of pulmonary function at 9 months of corrected age. HiFi Study Group.

    PubMed

    1990-06-01

    In a comparison of the outcome of high-frequency oscillatory ventilation (HFO) and conventional mechanical ventilation (intermittent mandatory ventilation (IMV] in newborn infants, the degree of late pulmonary damage in these infants was assessed in a multicenter trial by examining their pulmonary status, including pulmonary function test results at 9 months of corrected age. A total of 432 infants were followed, 222 in the IMV group and 210 in the HFO group. Two-hundred twenty-three infants had their pulmonary mechanics measured, 118 in the IMV group and 105 in the HFO group. There were no significant differences between the two groups in conditions known to predispose infants to chronic lung disease. At 9 months of age, both groups has similar growth and a similar incidence of respiratory tract infections and hospital readmissions, and of retractions and episodes of wheezing. None of the pulmonary mechanics measurements differed. Forced expiratory flow at functional residual capacity was decreased (132 +/- 86 vs 135 +/- 92 ml/sec in the IMV and HFO groups, respectively), peak-to-peak esophageal pressure change was elevated (14.4 +/- 5.7 vs 13.5 +/- 5.7 cm H2O), dynamic compliance was in the low normal range (1.2 +/- 0.5 vs 1.3 +/- 0.6 ml/cm H2O/kg), and total pulmonary resistance was elevated (63 +/- 43 vs 57 +/- 34 cm H2O/L/sec) when the measurements were compared with normal values. The results indicate that in both groups, 30% to 40% of infants survived with chronic pulmonary changes similar to those described in infants with bronchopulmonary dysplasia. The use of high-frequency ventilation, in comparison with IMV, did not improve long-term pulmonary outcome. PMID:2112188

  4. Respiratory mechanics measured by forced oscillation technique in rheumatoid arthritis-related pulmonary abnormalities: frequency-dependence, heterogeneity and effects of smoking.

    PubMed

    Sokai, Risa; Ito, Satoru; Iwano, Shingo; Uchida, Akemi; Aso, Hiromichi; Kondo, Masashi; Ishiguro, Naoki; Kojima, Toshihisa; Hasegawa, Yoshinori

    2016-01-01

    Rheumatoid arthritis (RA)-related pulmonary disorders specifically airway abnormalities and interstitial pneumonia (IP) are important extra-articular manifestations. The forced oscillation technique (FOT) is a useful method to assess respiratory impedance, respiratory resistance (Rrs) and reactance (Xrs), at different oscillatory frequencies during tidal breathing. The aim of this study was to characterize the respiratory mechanics of patients with RA and to relate them to parameters of the pulmonary function test and findings of chest CT images. Respiratory impedance of RA patients (n = 69) was measured as a function of frequency from 4 to 36 Hz using the FOT device and compared with that of healthy subjects (n = 10). Data were retrospectively reviewed. Patients were female-dominant (60.9 %) and 95.7 % had abnormal CT findings including airway and parenchymal abnormalities. Thirty-seven of 69 patients (53.6 %) were smokers. Rrs was significantly frequency-dependent in RA patients but not in the healthy subjects. Xrs were significantly frequency-dependent in both RA and healthy groups. Rrs was significantly higher during an expiratory phase in both RA and healthy groups. Xrs was significantly lower (more negative) during an expiratory phase than that during an inspiratory phase in RA patients but not in healthy subjects. Xrs of the RA group was significantly more negative than that of the normal control. There was no difference in impedance parameters between the airway lesion dominant (n = 27) and IP dominant groups (n = 23) in the RA group. The impedance parameters of the RA group significantly correlated with most parameters of the pulmonary function test. In pulmonary function test results, % of the predicted value for forced expiratory flow from 25 to 75 % of forced vital capacity was significantly lower and % of the predicted value for diffusing capacity of the lung for carbon monoxide was higher in the airway lesion dominant group than those in

  5. The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery.

    PubMed

    Trichet, B; Falke, K; Togut, A; Laver, M B

    1975-01-01

    The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2 = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous

  6. Pulmonary hypertension complicating pulmonary sarcoidosis.

    PubMed

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    2016-06-01

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis. PMID:27194118

  7. Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary endothelial cell dysfunction☆

    PubMed Central

    Panwar, Hariom; Jain, Deepika; Khan, Saba; Pathak, Neelam; Raghuram, Gorantla V.; Bhargava, Arpit; Banerjee, Smita; Mishra, Pradyumna K.

    2013-01-01

    Mechanistic investigations coupled with epidemiology, case-control, cohort and observational studies have increasingly linked isocyanate exposure (both chronic and acute) with pulmonary morbidity and mortality. Though ascribed for impairment in endothelial cell function, molecular mechanisms of these significant adverse pulmonary outcomes remains poorly understood. As preliminary studies conducted in past have failed to demonstrate a cause-effect relationship between isocyanate toxicity and compromised pulmonary endothelial cell function, we hypothesized that direct exposure to isocyanate may disrupt endothelial structural lining, resulting in cellular damage. Based on this premise, we comprehensively evaluated the molecular repercussions of methyl isocyanate (MIC) exposure on human pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA damage response and apoptotic index. Our results demonstrate that exposure to MIC, augment mitochondrial reactive oxygen species production, depletion in antioxidant defense enzymes, elevated pro-inflammatory cytokine response and induced endothelial cell apoptosis via affecting the balance of mitochondrial-nuclear cross talk. We herein delineate the first and direct molecular cascade of isocyanate-induced pulmonary endothelial cell dysfunction. The results of our study might portray a connective link between associated respiratory morbidities with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype relationship in observed deficits of pulmonary endothelial cell function. Further, understanding of inter- and intra-cellular signaling pathways involved in isocyanate-induced endothelial damage would not only aid in biomarker identification but also provide potential new avenues to target specific therapeutic interventions. PMID:24024149

  8. Incidences of Deep Vein Thrombosis and Pulmonary Embolism after Total Knee Arthroplasty Using a Mechanical Compression Device with and without Low-Molecular-Weight Heparin

    PubMed Central

    Park, Sin Hyung; Ahn, Joong Hyeon; Park, Yong Bok; Lee, Sun Geun

    2016-01-01

    Purpose To investigate the incidence of thromboembolic events and complications related to bleeding after total knee arthroplasty (TKA) with a mechanical compression device alone or in combination with low-molecular-weight heparin (LMWH). Materials and Methods A total of 489 TKA patients (776 knees) were retrospectively reviewed for the incidence of thromboembolic events and complications related to bleeding. While 233 patients (354 knees) were treated with a mechanical compressive device without LMWH, 256 patients (422 knees) were treated with the mechanical compressive device along with LMWH. Results The incidences of deep vein thrombosis (DVT) and pulmonary embolism (PE) were 15 of 375 knees (4.0%) and 5 of 375 knees (1.3%), respectively, in the group that used only a mechanical compressive device, and 14 of 401 knees (3.4%) and 5 of 401 knees (1.2%), respectively, in the group that used the mechanical compressive device with LMWH. There was no significant difference between the two groups (p=0.125 and p=0.146, respectively). The postoperative hemovac drainage amount was 635±57 mL in the group with a mechanical compressive device only and 813±84 mL in the group with the device and LMWH; therefore, the amount of drainage was significantly greater in the latter group (p=0.013). Conclusions Mechanical compression alone for prophylaxis against DVT and PE after TKA can be an attractive option in Korean patients. PMID:27595075

  9. Pulmonary rehabilitation.

    PubMed

    Troosters, Thierry; Demeyer, Heleen; Hornikx, Miek; Camillo, Carlos Augusto; Janssens, Wim

    2014-03-01

    Pulmonary rehabilitation is a therapy that offers benefits to patients with chronic obstructive pulmonary disease that are complementary to those obtained by pharmacotherapy. The main objective of pulmonary rehabilitation is to restore muscle function and exercise tolerance, reverse other nonrespiratory consequences of the disease, and help patients to self-manage chronic obstructive pulmonary disease and its exacerbations and symptoms. To do so, a multidisciplinary program tailored to the patient in terms of program content, exercise prescription, and setting must be offered. Several settings and programs have shown to spin off in significant immediate results. The challenge lies in maintaining the benefits outside the program. PMID:24507849

  10. RNase 7 in Cutaneous Defense

    PubMed Central

    Rademacher, Franziska; Simanski, Maren; Harder, Jürgen

    2016-01-01

    RNase 7 belongs to the RNase A superfamily and exhibits a broad spectrum of antimicrobial activity against various microorganisms. RNase 7 is expressed in human skin, and expression in keratinocytes can be induced by cytokines and microbes. These properties suggest that RNase 7 participates in innate cutaneous defense. In this review, we provide an overview about the role of RNase 7 in cutaneous defense with focus on the molecular mechanism of the antimicrobial activity of RNase 7, the regulation of RNase 7 expression, and the role of RNase 7 in skin diseases. PMID:27089327

  11. Chemical and mechanical defenses vary among maternal lines and leaf ages in Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist insect

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intra-specific variation in host-plant quality affects herbivore foraging decisions and, because of this, can feed back to shape plant fitness. In particular, among- and within plant variation in defense shapes herbivore behavior, and if genetically based, may respond to natural selection by herbivo...

  12. Defense styles in Intermittent Explosive Disorder.

    PubMed

    Puhalla, Alexander A; McCloskey, Michael S; Brickman, Lauren J; Fauber, Robert; Coccaro, Emil F

    2016-04-30

    The overreliance on immature and/or neurotic defense mechanisms, as opposed to more mature defensive functioning has been linked to several psychiatric disorders. However, to date, the role of defense styles among individuals with Intermittent Explosive Disorder (IED) has not been examined. Given that individuals with IED display difficulties controlling their anger and aggression, one might expect these individuals to exhibit more immature and less mature defense styles. The current study compared participants with IED to a personality disorder (PD) comparison group, as well as to healthy volunteers (HV) on the Defense Style Questionnaire, a self-report measure that assesses the extent to which individuals endorse using mature, immature, and neurotic defense styles. Subjects with IED had significantly higher scores than both comparison groups on immature defense styles and exhibited lower scores on mature defense mechanisms. Hierarchical regression of significant defense style subscales showed that higher levels of acting out and lower levels of sublimation uniquely discriminated participants with IED from the PD and HV comparison groups. PMID:27086223

  13. Radiological Defense. Textbook.

    ERIC Educational Resources Information Center

    Defense Civil Preparedness Agency (DOD), Washington, DC.

    This textbook has been prepared under the direction of the Defense Civil Preparedness Agency (DCPA) Staff College for use as a student reference manual in radiological defense (RADEF) courses. It provides much of the basic technical information necessary for a proper understanding of radiological defense and summarizes RADEF planning and expected…

  14. CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis

    PubMed Central

    Juffermans, Nicole P.; Leemans, Jaklien C.; Florquin, Sandrine; Verbon, Annelies; Kolk, Arend H.; Speelman, Peter; van Deventer, Sander J. H.; van der Poll, Tom

    2002-01-01

    Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs activate immune cells to produce cytokines. CpG ODNs protect mice against infections with intracellular bacteria by the induction of a T helper 1 (Th1) response. To determine the effect of CpG ODNs in pulmonary tuberculosis, mice were treated with CpG ODNs or control ODNs at the time of intranasal infection. CpG ODNs reduced mycobacterial outgrowth for up to 5 weeks after Mycobacterium tuberculosis infection and were associated with a decrease in inflammation in lung tissue. CpG treatment was also associated with elevated levels of gamma interferon (IFN-γ) and decreased levels of interleukin 4 in the lungs and an increased capacity of splenocytes to secrete Th1-type cytokines. CpG ODNs given 2 weeks after infection were still able to reduce mycobacterial outgrowth and to enhance a Th1 response 5 weeks postinfection. Administration of CpG ODNs to IFN-γ-gene-deficient mice failed to reduce mycobacterial outgrowth. These data suggest that CpG ODNs improve host defense during pulmonary tuberculosis by an IFN-γ-dependent mechanism. PMID:11748176

  15. [Effect of methylphenidatum on inspiratory muscles function in patients with chronic obstructive pulmonary disease and its mechanism].

    PubMed

    Wang, Y; Luo, Y; Chen, W; Yuan, Y; He, T; Zeng, J

    1997-03-01

    To have a better understanding of the effect of methylphenidatum on inspiratory muscles function, we studied the respiratory force parameters of 70 patients with chronic obstructive pulmonary disease by intravenous infusion methylphenidatum in a randomized controlled clinical trial. The indices of respiratory force parameter included maximal inspiratory mouth pressure (MIP), maximal midinspiratory flow (MMIF), forced inspiratory capacity (FIC), maximal works of inspiration (Wimax) and airway occlusion pressure (P0.1), etc. Aminophylline and Nikethamidi were chosen as controls. The results showed that MIP, MMIF, FIC, Wimax, P0.1 and minute ventilation (Vr) were significantly increased after administration of methylphenidatum and aminophylline. There were no significant differences in MIP, MMIF, FIC and Wimax after administration of Nikethamidi, but P0.1 was significantly increased and the increase was higher than that after administration of methylphenidatum and aminophylline groups. We conclude that methylphenidatum can significantly improve the function of inspiratory muscles as aminophylline can do. PMID:10684069

  16. Pulmonary cachexia.

    PubMed

    Schols, Annemie M W J

    2002-09-01

    Weight loss is a frequent complication in patients with chronic obstructive pulmonary disease (COPD) and is a determining factor of functional capacity, health status, and mortality. Weight loss in COPD is a consequence of increased energy requirements unbalanced by dietary intake. Both metabolic and mechanical inefficiency contribute to the elevated energy expenditure during physical activity, while systemic inflammation is a determinant of hypermetabolism at rest. A disbalance between protein synthesis and protein breakdown may cause a disproportionate depletion of fat-free mass in some patients. Nutritional support is indicated for depleted patients with COPD because it provides not only supportive care, but direct intervention through improvement in respiratory and peripheral skeletal muscle function and in exercise performance. A combination of oral nutritional supplements and exercise or anabolic stimulus appears to be the best treatment approach to obtaining significant functional improvement. Patients responding to this treatment even demonstrated a decreased mortality. Poor response was related to the effects of systemic inflammation on dietary intake and catabolism. The effectiveness of anticatabolic modulation requires further investigation. PMID:12163214

  17. Role of NADPH Oxidase versus Neutrophil Proteases in Antimicrobial Host Defense

    PubMed Central

    Grimm, Melissa J.; Lewandowski, David C.; Pham, Christine T. N.; Blackwell, Timothy S.; Petraitiene, Ruta; Petraitis, Vidmantas; Walsh, Thomas J.; Urban, Constantin F.; Segal, Brahm H.

    2011-01-01

    NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the release of sequestered proteases that are posited to be critical effectors of host defense. To definitively determine the contribution of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility to fungal and bacterial infection in mice with engineered disruptions of these pathways. NADPH oxidase-deficient mice (p47phox−/−) were highly susceptible to pulmonary infection with Aspergillus fumigatus. In contrast, double knockout neutrophil elastase (NE)−/−×cathepsin G (CG)−/− mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no impairment in antifungal host defense. In separate studies of systemic Burkholderia cepacia infection, uniform fatality occurred in p47phox−/− mice, whereas NE−/−×CG−/− mice cleared infection. Together, these results show a critical role for NADPH oxidase in antimicrobial host defense against A. fumigatus and B. cepacia, whereas the proteases we evaluated were dispensable. Our results indicate that NADPH oxidase dependent pathways separate from neutrophil serine protease activation are required for host defense against specific pathogens. PMID:22163282

  18. Severe Pulmonary Arteriopathy Is Associated with Persistent Hypoxemia after Pulmonary Endarterectomy in Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Tanabe, Nobuhiro; Sakao, Seiichiro; Ishibashi-Ueda, Hatsue; Ishida, Keiichi; Naito, Akira; Kato, Fumiaki; Takeuchi, Takao; Sekine, Ayumi; Nishimura, Rintaro; Sugiura, Toshihiko; Shigeta, Ayako; Masuda, Masahisa; Tatsumi, Koichiro

    2016-01-01

    Background Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by occlusion of pulmonary arteries by organized chronic thrombi. Persistent hypoxemia and residual pulmonary hypertension (PH) following successful pulmonary endarterectomy (PEA) are clinically important problems; however, the underlying mechanisms remain unclear. We have previously reported that residual PH is closely related to severe pulmonary vascular remodeling and hypothesize that this arteriopathy might also be involved in impaired gas exchange. The purpose of this study was to evaluate the association between hypoxemia and pulmonary arteriopathy after PEA. Methods and Results Between December 2011 and November 2014, 23 CTEPH patients underwent PEA and lung biopsy. The extent of pulmonary arteriopathy was quantified pathologically in lung biopsy specimens. We then analyzed the relationship between the severity of pulmonary arteriopathy and gas exchange after PEA. We observed that the severity of pulmonary arteriopathy was negatively correlated with postoperative and follow-up PaO2 (postoperative PaO2: r = -0.73, p = 0.0004; follow-up PaO2: r = -0.66, p = 0.001), but not with preoperative PaO2 (r = -0.373, p = 0.08). Multivariate analysis revealed that the obstruction ratio and patient age were determinants of PaO2 one month after PEA (R2 = 0.651, p = 0.00009). Furthermore, the obstruction ratio and improvement of pulmonary vascular resistance were determinants of PaO2 at follow-up (R2 = 0.545, p = 0.0002). Severe pulmonary arteriopathy might increase the alveolar-arterial oxygen difference and impair diffusion capacity, resulting in hypoxemia following PEA. Conclusion The severity of pulmonary arteriopathy was closely associated with postoperative and follow-up hypoxemia. PMID:27571267

  19. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  20. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis See also: Aspergillosis Symptoms You may not have ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Update Date 8/31/2014 Updated by: Jatin ...

  1. Pulmonary Atresia

    MedlinePlus

    ... to repair the defect. Return to main topic: Congenital Heart Disease See on other sites: MedlinePlus https://medlineplus.gov/ency/article/001091.htm Pulmonary atresia American Heart Association www. ...

  2. Pulmonary atresia

    MedlinePlus

    ... blood flow from the right ventricle (right side pumping chamber) to the lungs. In pulmonary atresia, a ... Reconstructing the heart as a single ventricle (1 pumping chamber instead of 2) Heart transplant

  3. Pulmonary atresia

    MedlinePlus

    ... form of heart disease that occurs from birth (congenital heart disease), in which the pulmonary valve does not form ... As with most congenital heart diseases, there is no known cause of ... is associated with another type of congenital heart defect ...

  4. [Pulmonary rehabilitation].

    PubMed

    Senjyu, Hideaki

    2016-05-01

    Pulmonary rehabilitation commenced in Japan in 1957. However, the development of pulmonary rehabilitation took a long time due to the lack of the necessary health and medical services. Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. The benefits of pulmonary rehabilitation include a decrease in breathlessness and an improvement in exercise tolerance. It is important that the gains in exercise tolerance lead to an increase in daily physical activity. PMID:27254948

  5. Pulmonary Embolism

    MedlinePlus

    ... is a sudden blockage in a lung artery. The cause is usually a blood clot in the leg called a deep vein thrombosis that breaks loose and travels through the bloodstream to the lung. Pulmonary embolism is a ...

  6. The Child as Psychologist: Attributions and Evaluations of Defensive Strategies.

    ERIC Educational Resources Information Center

    Dollinger, Stephen J.; And Others

    1981-01-01

    Studied children's attributions and evaluations concerning defense mechanisms used by other children. Children negatively evaluated the blame-externalizing defense of projection and viewed it as a masculine characteristic. The internalizing defense of self-blame was evaluated more positively and viewed as a feminine characteristic. (Author/DB)

  7. Pulmonary Edema

    PubMed Central

    Tanser, Paul H.

    1980-01-01

    The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients. PMID:21293700

  8. [Use of BiPAP during weaning from mechanical ventilation in a patient with chronic obstructive pulmonary disease and acute respiratory failure].

    PubMed

    Sakai, T; Shimada, M; Ishizaki, T; Nakai, T

    1997-08-01

    In a 65-year-old man with chronic obstructive pulmonary disease and acute respiratory failure, bi-level positive airway pressure device (BiPAP) was used as part of weaning from mechanical ventilation. As an outpatient, he had had dyspnea of grade V (Hugh-Jones) and was hypercapnic (PaCO2 of 70 torr) and hypoxemic (PaO2 of 60 torr), while he was receiving oxygen at 2 L/min via nasal cannula. Acute respiratory failure developed due to pneumonia, and mechanical ventilation was begun. However, he could not be weaned with a standard weaning technique (T-piece). On the fifth day of mechanical ventilation, he was extubated and treatment with BiPAP was begun. He did not complain of dyspnea even though PaCO2 did not decrease, which indicates that BiPAP reduced the work of breathing. Use of BiPAP might make reintubation unnecessary when acute ventilatory failure develops soon after extubation in patients with COPD. PMID:9366166

  9. Genome defense against exogenous nucleic acids in eukaryotes by non-coding DNA occurs through CRISPR-like mechanisms in the cytosol and the bodyguard protection in the nucleus.

    PubMed

    Qiu, Guo-Hua

    2016-01-01

    In this review, the protective function of the abundant non-coding DNA in the eukaryotic genome is discussed from the perspective of genome defense against exogenous nucleic acids. Peripheral non-coding DNA has been proposed to act as a bodyguard that protects the genome and the central protein-coding sequences from ionizing radiation-induced DNA damage. In the proposed mechanism of protection, the radicals generated by water radiolysis in the cytosol and IR energy are absorbed, blocked and/or reduced by peripheral heterochromatin; then, the DNA damage sites in the heterochromatin are removed and expelled from the nucleus to the cytoplasm through nuclear pore complexes, most likely through the formation of extrachromosomal circular DNA. To strengthen this hypothesis, this review summarizes the experimental evidence supporting the protective function of non-coding DNA against exogenous nucleic acids. Based on these data, I hypothesize herein about the presence of an additional line of defense formed by small RNAs in the cytosol in addition to their bodyguard protection mechanism in the nucleus. Therefore, exogenous nucleic acids may be initially inactivated in the cytosol by small RNAs generated from non-coding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. Exogenous nucleic acids may enter the nucleus, where some are absorbed and/or blocked by heterochromatin and others integrate into chromosomes. The integrated fragments and the sites of DNA damage are removed by repetitive non-coding DNA elements in the heterochromatin and excluded from the nucleus. Therefore, the normal eukaryotic genome and the central protein-coding sequences are triply protected by non-coding DNA against invasion by exogenous nucleic acids. This review provides evidence supporting the protective role of non-coding DNA in genome defense. PMID:27036064

  10. Diseases of Pulmonary Surfactant Homeostasis

    PubMed Central

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

  11. Diseases of pulmonary surfactant homeostasis.

    PubMed

    Whitsett, Jeffrey A; Wert, Susan E; Weaver, Timothy E

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

  12. Technologies for Distributed Defense

    SciTech Connect

    Seiders, Barbara AB; Rybka, Anthony J.

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of "citizen soldiers," with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  13. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

    PubMed

    Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

    2015-09-01

    Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway. PMID:26966681

  14. A Novel p38 Mitogen-activated Protein Kinase/Elk-1 Transcription Factor-dependent Molecular Mechanism Underlying Abnormal Endothelial Cell Proliferation in Plexogenic Pulmonary Arterial Hypertension*

    PubMed Central

    Patel, Monal; Predescu, Dan; Tandon, Rajive; Bardita, Cristina; Pogoriler, Jennifer; Bhorade, Sangeeta; Wang, Minhua; Comhair, Suzy; Ryan-Hemnes, Anna; Chen, Jiwang; Machado, Roberto; Husain, Aliya; Erzurum, Serpil; Predescu, Sanda

    2013-01-01

    Plexiform lesions (PLs), the hallmark of plexogenic pulmonary arterial hypertension (PAH), contain phenotypically altered, proliferative endothelial cells (ECs). The molecular mechanism that contributes to EC proliferation and formation of PLs is poorly understood. We now show that a decrease in intersectin-1s (ITSN-1s) expression due to granzyme B (GrB) cleavage during inflammation associated with PAH and the high p38/Erk1/2MAPK activity ratio caused by the GrB/ITSN cleavage products lead to EC proliferation and selection of a proliferative/plexiform EC phenotype. We used human pulmonary artery ECs of PAH subjects (ECPAH), paraffin-embedded and frozen human lung tissue, and animal models of PAH in conjunction with microscopy imaging, biochemical, and molecular biology approaches to demonstrate that GrB cleaves ITSN-1s, a prosurvival protein of lung ECs, and generates two biologically active fragments, an N-terminal fragment (GrB-EHITSN) with EC proliferative potential and a C-terminal product with dominant negative effects on Ras/Erk1/2. The proliferative potential of GrB-EHITSN is mediated via sustained phosphorylation of p38MAPK and Elk-1 transcription factor and abolished by chemical inhibition of p38MAPK. Moreover, lung tissue of PAH animal models and human specimens and ECPAH express lower levels of ITSN-1s compared with controls and the GrB-EHITSN cleavage product. Moreover, GrB immunoreactivity is associated with PLs in PAH lungs. The concurrent expression of the two cleavage products results in a high p38/Erk1/2MAPK activity ratio, which is critical for EC proliferation. Our findings identify a novel GrB-EHITSN-dependent pathogenic p38MAPK/Elk-1 signaling pathway involved in the poorly understood process of PL formation in severe PAH. PMID:23893408

  15. A novel p38 mitogen-activated protein kinase/Elk-1 transcription factor-dependent molecular mechanism underlying abnormal endothelial cell proliferation in plexogenic pulmonary arterial hypertension.

    PubMed

    Patel, Monal; Predescu, Dan; Tandon, Rajive; Bardita, Cristina; Pogoriler, Jennifer; Bhorade, Sangeeta; Wang, Minhua; Comhair, Suzy; Hemnes, Anna Ryan; Ryan-Hemnes, Anna; Chen, Jiwang; Machado, Roberto; Husain, Aliya; Erzurum, Serpil; Predescu, Sanda

    2013-09-01

    Plexiform lesions (PLs), the hallmark of plexogenic pulmonary arterial hypertension (PAH), contain phenotypically altered, proliferative endothelial cells (ECs). The molecular mechanism that contributes to EC proliferation and formation of PLs is poorly understood. We now show that a decrease in intersectin-1s (ITSN-1s) expression due to granzyme B (GrB) cleavage during inflammation associated with PAH and the high p38/Erk1/2(MAPK) activity ratio caused by the GrB/ITSN cleavage products lead to EC proliferation and selection of a proliferative/plexiform EC phenotype. We used human pulmonary artery ECs of PAH subjects (EC(PAH)), paraffin-embedded and frozen human lung tissue, and animal models of PAH in conjunction with microscopy imaging, biochemical, and molecular biology approaches to demonstrate that GrB cleaves ITSN-1s, a prosurvival protein of lung ECs, and generates two biologically active fragments, an N-terminal fragment (GrB-EH(ITSN)) with EC proliferative potential and a C-terminal product with dominant negative effects on Ras/Erk1/2. The proliferative potential of GrB-EH(ITSN) is mediated via sustained phosphorylation of p38(MAPK) and Elk-1 transcription factor and abolished by chemical inhibition of p38(MAPK). Moreover, lung tissue of PAH animal models and human specimens and EC(PAH) express lower levels of ITSN-1s compared with controls and the GrB-EH(ITSN) cleavage product. Moreover, GrB immunoreactivity is associated with PLs in PAH lungs. The concurrent expression of the two cleavage products results in a high p38/Erk1/2(MAPK) activity ratio, which is critical for EC proliferation. Our findings identify a novel GrB-EH(ITSN)-dependent pathogenic p38(MAPK)/Elk-1 signaling pathway involved in the poorly understood process of PL formation in severe PAH. PMID:23893408

  16. Effects of indacaterol versus tiotropium on respiratory mechanics assessed by the forced oscillation technique in patients with chronic obstructive pulmonary disease

    PubMed Central

    Inui, Naoki; Matsushima, Sayomi; Kato, Shinpei; Yasui, Hideki; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Toyoshima, Mikio; Suda, Takafumi

    2015-01-01

    The forced oscillation technique (FOT) can measure respiratory mechanics and has attracted attention in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of only indacaterol and tiotropium monotherapies on airflow limitation and respiratory impedance. Pulmonary function tests, COPD assessment test (CAT), and multifrequency FOT with MostGraph-01 were performed at the beginning and after 8 weeks of treatment with indacaterol or tiotropium. The resistance index, resistance at 5 Hz (R5), resistance at 20 Hz (R20), reactance index, reactance at 5 Hz (X5), resonant frequency (Fres), and low-frequency reactance area (ALX) were determined at whole-breath, inspiratory, and expiratory phases. Eighty-two patients (mean age: 73 years; mean forced expiratory volume in 1 second (FEV1): 61.6%±19.0% predicted) were randomized to indacaterol or tiotropium treatment. Both bronchodilators improved airflow limitation, with mean trough improvements in FEV1 of 165 mL and 80 mL in the indacaterol and tiotropium groups, respectively. The CAT score decreased in the indacaterol group (P<0.001; 11.2±6.6 to 7.5±5.6). Compared with tiotropium, indacaterol significantly improved FEV1, percent predicted FEV1, and CAT score (P=0.042, P=0.008, and P=0.027, respectively). For respiratory impedance, indacaterol and tiotropium changed R5, X5, Fres, and ALX at whole-breath, inspiratory, and expiratory phases. In the indacaterol group, the changes in R5, R5–R20, X5, Fres, and ALX were significantly correlated with the changes in FEV1. The use of the FOT may enable the evaluation of the effects of bronchodilators in addition to FEV1-indicated therapeutic effects in COPD. PMID:26124653

  17. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation

    PubMed Central

    Ogbozor, Uchenna D.; Opene, Michael; Renteria, Lissette S.; McBride, Shaemion; Ibe, Basil O.

    2015-01-01

    Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway. PMID:26966681

  18. Primitive defenses: cognitive aspects and therapeutic handling.

    PubMed

    Groh, L S

    In this paper the primitive defenses first described by Melanie Klein under the label of "schizoid mechanisms" are examined. The defenses considered are splitting the pathological uses of identification and projective identification, and the psychotic forms of denial. This examination is twofold: (1) the cognitive aspects of these defenses as described in terms of concepts developed by Jean Piaget; (2) concrete examples of the operation of these defenses during the treatment of schizophrenic patients are given and the effects of interventions based on the cognitive analysis are described. It is stressed that at times interventions, such as interpretation and confrontation, based on cognitive analysis, can temporarily and in some instances even permanently stop the operation of these defenses, allowing emotionally meaningful material to emerge which expedites the therapeutic process. PMID:7429737

  19. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  20. Lung epithelial MyD88 drives early pulmonary clearance of Pseudomonas aeruginosa by a flagellin dependent mechanism.

    PubMed

    Anas, Adam A; van Lieshout, Miriam H P; Claushuis, Theodora A M; de Vos, Alex F; Florquin, Sandrine; de Boer, Onno J; Hou, Baidong; Van't Veer, Cornelis; van der Poll, Tom

    2016-08-01

    Pseudomonas aeruginosa is a flagellated pathogen frequently causing pneumonia in hospitalized patients and sufferers of chronic lung disease. Here we investigated the role of the common Toll-like receptor (TLR) adaptor myeloid differentiation factor (MyD)88 in myeloid vs. lung epithelial cells in clearance of P. aeruginosa from the airways. Mice deficient for MyD88 in lung epithelial cells (Sftpccre-MyD88-lox mice) or myeloid cells (LysMcre-MyD88-lox mice) and bone marrow chimeric mice deficient for TLR5 (the receptor recognizing Pseudomonas flagellin) in either parenchymal or hematopoietic cells were infected with P. aeruginosa via the airways. Sftpccre-MyD88-lox mice demonstrated a reduced influx of neutrophils into the bronchoalveolar space and an impaired early antibacterial defense after infection with P. aeruginosa, whereas the response of LysMcre-MyD88-lox mice did not differ from control mice. The immune-enhancing role of epithelial MyD88 was dependent on recognition of pathogen-derived flagellin by epithelial TLR5, as demonstrated by an unaltered clearance of mutant P. aeruginosa lacking flagellin from the lungs of Sftpccre-MyD88-lox mice and an impaired bacterial clearance in bone marrow chimeric mice lacking TLR5 in parenchymal cells. These data indicate that early clearance of P. aeruginosa from the airways is dependent on flagellin-TLR5-MyD88-dependent signaling in respiratory epithelial cells. PMID:27288486

  1. Pulmonary embolism

    SciTech Connect

    Dunnick, N.R.; Newman, G.E.; Perlmutt, L.M.; Braun, S.D.

    1988-11-01

    Pulmonary embolism is a common medical problem whose incidence is likely to increase in our aging population. Although it is life-threatening, effective therapy exists. The treatment is not, however, without significant complications. Thus, accurate diagnosis is important. Unfortunately, the clinical manifestations of pulmonary embolism are nonspecific. Furthermore, in many patients the symptoms of an acute embolism are superimposed on underlying chronic heart or lung disease. Thus, a high index of suspicion is needed to identify pulmonary emboli. Laboratory parameters, including arterial oxygen tensions and electrocardiography, are as nonspecific as the clinical signs. They may be more useful in excluding another process than in diagnosing pulmonary embolism. The first radiologic examination is the chest radiograph, but the clinical symptoms are frequently out of proportion to the findings on the chest films. Classic manifestations of pulmonary embolism on the chest radiograph include a wedge-shaped peripheral opacity and a segmental or lobar diminution in vascularity with prominent central arteries. However, these findings are not commonly seen and, even when present, are not specific. Even less specific findings include cardiomegaly, pulmonary infiltrate, elevation of a hemidiaphragm, and pleural effusion. Many patients with pulmonary embolism may have a normal chest radiograph. The chest radiograph is essential, however, for two purposes. First, it may identify another cause of the patient's symptoms, such as a rib fracture, dissecting aortic aneurysm, or pneumothorax. Second, a chest radiograph is essential to interpretation of the radionuclide V/Q scan. The perfusion scan accurately reflects the perfusion of the lung. However, a perfusion defect may result from a variety of etiologies. Any process such as vascular stenosis or compression by tumor may restrict blood flow. 84 references.

  2. Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study

    PubMed Central

    Xin, Xiaofeng; Dai, Wei; Wu, Jie; Fang, Liping; Zhao, Ming; Zhang, Pengpeng; Chen, Min

    2016-01-01

    The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens-1 (ZO-1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO-1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF-α, IFN-γ and IL-8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses. PMID:27588054

  3. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  4. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  5. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  6. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  7. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  8. Schools and Civil Defense.

    ERIC Educational Resources Information Center

    Office of Civil Defense (DOD), Washington, DC.

    Civil defense is a planned, coordinated action to protect the population during any emergency whether arising from thermonuclear attack or natural disaster. The Federal Government has assumed four responsibilities--(1) to keep track of the nature of the threat which the civil defense program must meet, (2) to prepare and disseminate information…

  9. Forgiveness and Defense Style

    ERIC Educational Resources Information Center

    Maltby, John; Day, Liz

    2004-01-01

    Within the literature on the psychology of forgiveness, researchers have hypothesized that the 1st stage in the process of being able to forgive is the role of psychological defense. To examine such a hypothesis, the authors explored the relationship between forgiveness and defense style. The 304 respondents (151 men, 153 women) completed measures…

  10. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease

    PubMed Central

    Li, Jiansheng; Zhao, Peng; Li, Ya; Tian, Yange; Wang, Yonghua

    2015-01-01

    The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo. Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF. PMID:26469778

  11. The Mechanism of the Osteoprotective Action of a Polyphenol-Rich Aronia melanocarpa Extract during Chronic Exposure to Cadmium is Mediated by the Oxidative Defense System.

    PubMed

    Brzóska, Malgorzata M; Rogalska, Joanna; Roszczenko, Alicja; Galazyn-Sidorczuk, Malgorzata; Tomczyk, Michal

    2016-05-01

    Recently, we demonstrated in a rat model that consumption of a polyphenol-rich extract obtained from the berries of Aronia melanocarpa could protect from cadmium-induced disorders in bone turnover and changes in bone mineral status. The aim of this study was to investigate whether the osteoprotective effect of this extract is mediated by the oxidative defense system. Enzymatic and nonenzymatic antioxidants, total antioxidative and oxidative status, hydrogen peroxide, and markers of oxidative protein, lipid, and DNA damage were determined in bone tissue at the distal femoral epiphysis of female Wistar rats receiving 0.1 % aqueous A. melanocarpa extract (prepared from the lyophilized commercial extract containing 65.74 % of polyphenols) as the only drinking fluid and/or cadmium in the diet (1 and 5 mg/kg) for 3, 10, 17, and 24 months. The total oxidative and antioxidative status of the serum was also evaluated. The administration of A. melanocarpa extract provided significant protection from cadmium-induced oxidative stress in the bone and serum, and from lipid peroxidation and oxidative damage to the protein and DNA in the bone tissue. Numerous correlations were noted between indices of the oxidative/antioxidative bone status and markers of bone metabolism previously assayed in the animals receiving A. melanocarpa extract. The results allow the conclusion that the ability of A. melanocarpa extract to mediate the oxidative defense system and prevent oxidative modifications of protein, lipid, and DNA in the bone tissue plays an important role in its osteoprotective action under exposure to cadmium. The findings provide further evidence supporting our suggestion that chokeberry may be a promising natural agent for protection against the toxic action of cadmium in women chronically exposed to this metal. PMID:27096624

  12. Mechanisms of Attenuation of Pulmonary V’O2 Slow Component in Humans after Prolonged Endurance Training

    PubMed Central

    Zoladz, Jerzy A.; Majerczak, Joanna; Grassi, Bruno; Szkutnik, Zbigniew; Korostyński, Michał; Gołda, Sławomir; Grandys, Marcin; Jarmuszkiewicz, Wiesława; Kilarski, Wincenty; Karasinski, Janusz; Korzeniewski, Bernard

    2016-01-01

    In this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V’O2) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean±SD: age 22.33±1.44 years, V’O2peak 3198±458 mL ∙ min-1) performed an endurance training composed mainly of moderate-intensity cycling, lasting 20 weeks. Training resulted in a decrease (by ~5%, P = 0.027) in V’O2 during prior low-intensity exercise (20 W) and in shortening of τp of the V’O2 on-kinetics (30.1±5.9 s vs. 25.4±1.5 s, P = 0.007) during subsequent heavy-intensity cycling. This was accompanied by a decrease of the slow component of V’O2 on-kinetics by 49% (P = 0.001) and a decrease in the end-exercise V’O2 by ~5% (P = 0.005). An increase (P = 0.02) in the vascular endothelial growth factor receptor 2 mRNA level and a tendency (P = 0.06) to higher capillary-to-fiber ratio in the vastus lateralis muscle were found after training (n = 11). No significant effect of training on the V’O2peak was found (P = 0.12). However, the power output reached at the lactate threshold increased by 19% (P = 0.01). The power output obtained at the V’O2peak increased by 14% (P = 0.003) and the time of 1,500-m performance decreased by 5% (P = 0.001). Computer modeling of the skeletal muscle bioenergetic system suggests that the training-induced decrease in the slow component of V’O2 on-kinetics found in the present study is mainly caused by two factors: an intensification of the each-step activation (ESA) of oxidative phosphorylation (OXPHOS) complexes after training and decrease in the ‘‘additional” ATP usage rising gradually during heavy-intensity exercise. PMID:27104346

  13. Mechanisms of Attenuation of Pulmonary V'O2 Slow Component in Humans after Prolonged Endurance Training.

    PubMed

    Zoladz, Jerzy A; Majerczak, Joanna; Grassi, Bruno; Szkutnik, Zbigniew; Korostyński, Michał; Gołda, Sławomir; Grandys, Marcin; Jarmuszkiewicz, Wiesława; Kilarski, Wincenty; Karasinski, Janusz; Korzeniewski, Bernard

    2016-01-01

    In this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V'O2) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean±SD: age 22.33±1.44 years, V'O2peak 3198±458 mL ∙ min-1) performed an endurance training composed mainly of moderate-intensity cycling, lasting 20 weeks. Training resulted in a decrease (by ~5%, P = 0.027) in V'O2 during prior low-intensity exercise (20 W) and in shortening of τp of the V'O2 on-kinetics (30.1±5.9 s vs. 25.4±1.5 s, P = 0.007) during subsequent heavy-intensity cycling. This was accompanied by a decrease of the slow component of V'O2 on-kinetics by 49% (P = 0.001) and a decrease in the end-exercise V'O2 by ~5% (P = 0.005). An increase (P = 0.02) in the vascular endothelial growth factor receptor 2 mRNA level and a tendency (P = 0.06) to higher capillary-to-fiber ratio in the vastus lateralis muscle were found after training (n = 11). No significant effect of training on the V'O2peak was found (P = 0.12). However, the power output reached at the lactate threshold increased by 19% (P = 0.01). The power output obtained at the V'O2peak increased by 14% (P = 0.003) and the time of 1,500-m performance decreased by 5% (P = 0.001). Computer modeling of the skeletal muscle bioenergetic system suggests that the training-induced decrease in the slow component of V'O2 on-kinetics found in the present study is mainly caused by two factors: an intensification of the each-step activation (ESA) of oxidative phosphorylation (OXPHOS) complexes after training and decrease in the ''additional" ATP usage rising gradually during heavy-intensity exercise. PMID:27104346

  14. Managing comorbidities in idiopathic pulmonary fibrosis

    PubMed Central

    Fulton, Blair G; Ryerson, Christopher J

    2015-01-01

    Major risk factors for idiopathic pulmonary fibrosis (IPF) include older age and a history of smoking, which predispose to several pulmonary and extra-pulmonary diseases. IPF can be associated with additional comorbidities through other mechanisms as either a cause or a consequence of these diseases. We review the literature regarding the management of common pulmonary and extra-pulmonary comorbidities, including chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, venous thromboembolism, sleep-disordered breathing, gastroesophageal reflux disease, coronary artery disease, depression and anxiety, and deconditioning. Recent studies have provided some guidance on the management of these diseases in IPF; however, most treatment recommendations are extrapolated from studies of non-IPF patients. Additional studies are required to more accurately determine the clinical features of these comorbidities in patients with IPF and to evaluate conventional treatments and management strategies that are beneficial in non-IPF populations. PMID:26451121

  15. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    PubMed Central

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  16. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens.

    PubMed

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4(+) or CD8(+) T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b(+) myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b(+) myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  17. Two systems and defenses.

    PubMed

    Novick, Jack; Novick, Kerry Kelly

    2013-02-01

    The authors suggest that Freud's concept of defense differentiated psychoanalysis from other medical and psychological theories of personality development and functioning then and now. Reclaiming the concept's centrality and linking it with interdisciplinary research findings, they illustrate their extension of defense into a two-system model of self-protection and self-regulation with a clinical example. The authors suggest that the two-system model allows for the reintegration of defense into a multidimensional psychoanalytic theory and multimodal therapeutic technique. PMID:23421665

  18. Genetic transformation of cotton with a harpin-encoding gene hpaXoo confers an enhanced defense response against different pathogens through a priming mechanism

    PubMed Central

    2010-01-01

    Background The soil-borne fungal pathogen Verticillium dahliae Kleb causes Verticillium wilt in a wide range of crops including cotton (Gossypium hirsutum). To date, most upland cotton varieties are susceptible to V. dahliae and the breeding for cotton varieties with the resistance to Verticillium wilt has not been successful. Results Hpa1Xoo is a harpin protein from Xanthomonas oryzae pv. oryzae which induces the hypersensitive cell death in plants. When hpa1Xoo was transformed into the susceptible cotton line Z35 through Agrobacterium-mediated transformation, the transgenic cotton line (T-34) with an improved resistance to Verticillium dahliae was obtained. Cells of the transgenic T-34, when mixed with the conidia suspension of V. dahliae, had a higher tolerance to V. dahliae compared to cells of untransformed Z35. Cells of T-34 were more viable 12 h after mixing with V. dahliae conidia suspension. Immunocytological analysis showed that Hpa1Xoo, expressed in T-34, accumulated as clustered particles along the cell walls of T-34. In response to the infection caused by V. dahliae, the microscopic cell death and the generation of reactive oxygen intermediates were observed in leaves of T-34 and these responses were absent in leaves of Z35 inoculated with V. dahliae. Quantitative RT-PCR analysis indicated that five defense-related genes, ghAOX1, hin1, npr1, ghdhg-OMT, and hsr203J, were up-regulated in T-34 inoculated with V. dahliae. The up-regulations of these defense-relate genes were not observed or in a less extent in leaves of Z-35 after the inoculation. Conclusions Hpa1Xoo accumulates along the cell walls of the transgenic T-34, where it triggers the generation of H2O2 as an endogenous elicitor. T-34 is thus in a primed state, ready to protect the host from the pathogen. The results of this study suggest that the transformation of cotton with hpa1Xoo could be an effective approach for the development of cotton varieties with the improved resistance against soil

  19. Intrinsic cellular defenses against human immunodeficiency viruses.

    PubMed

    Blanco-Melo, Daniel; Venkatesh, Siddarth; Bieniasz, Paul D

    2012-09-21

    Viral infections are often detrimental to host survival and reproduction. Consequently, hosts have evolved a variety of mechanisms to defend themselves against viruses. A component of this arsenal is a set of proteins, termed restriction factors, which exhibit direct antiviral activity. Among these are several classes of proteins (APOBEC3, TRIM5, Tetherin, and SAMHD1) that inhibit the replication of human and simian immunodeficiency viruses. Here, we outline the features, mechanisms, and evolution of these defense mechanisms. We also speculate on how restriction factors arose, how they might interact with the conventional innate and adaptive immune systems, and how an understanding of these intrinsic cellular defenses might be usefully exploited. PMID:22999946

  20. Pulmonary alveolar proteinosis.

    PubMed

    Khan, Ajmal; Agarwal, Ritesh

    2011-07-01

    Pulmonary alveolar proteinosis is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component. Novel insights from an animal model aided the discovery of granulocyte macrophage colony stimulating factor (GM-CSF) antibodies as a pathogenetic mechanism in human pulmonary alveolar proteinosis. The vast majority of pulmonary alveolar proteinosis occurs as an autoimmune disease; less commonly, it is congenital or secondary to an underlying disorder such as infection, hematological malignancy, or immunodeficiency. The subacute indolent course of this disease often delays the diagnosis by months to years. Crazy-paving appearance in a geographic distribution is a characteristic feature of this disease visible on high-resolution computed tomography (CT). A definitive diagnosis, however, requires lung biopsy, which typically shows partial or complete filling of alveoli with periodic-acid-Schiff-positive granular and eosinophilic material in preserved alveolar architecture. Patients with minimal symptoms are managed conservatively, whereas patients with hypoxemia require a more aggressive approach. Whole-lung lavage is the most widely accepted therapy for symptomatic pulmonary alveolar proteinosis. Correction of GM-CSF deficiency with exogenous GM-CSF is an alternative therapy. The combination of a systemic treatment (GM-CSF) and a local treatment (whole-lung lavage) augmenting the action of one another is a promising new approach. As the knowledge about this rare disease increases, the role of novel therapies is likely to be better defined and optimized. PMID:21496372

  1. Pulmonary langerhans cell histiocytosis

    PubMed Central

    2012-01-01

    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. PMID:22429393

  2. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have it, the blood ... heart has to work harder to pump the blood through. Over time, your heart weakens and ... of PH include Shortness of breath during routine activity, such ...

  3. PULMONARY TOXICOLOGY

    EPA Science Inventory

    Pulmonary disease and dysfunction exact a tremendous health burden on society. In a recent survey of lung disease published by the American Lung Association in 2012, upwards of 10 million Americans were diagnosed with chronic bronchitis while over 4 million Americans had emphysem...

  4. Pulmonary ascariasis.

    PubMed

    Mukerjee, C M; Thompson, J E

    1979-07-28

    A case of pulmonary ascariasis is reported for the first time in Australia. Because of increasing immigration from countries which have a high incidence of ascariasis (especially those of South-East Asia), and increasing travel to Asian countries, the awareness of this infestation as a cause of respiratory disease may be of great importance. PMID:40103

  5. Pulmonary nocardiosis

    MedlinePlus

    ... infection from returning. Alternative Names Nocardiosis - pulmonary Images Respiratory system References Limper AH. Overview of pneumonia. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier Saunders; 2010: ...

  6. Pulmonary Hypertension

    MedlinePlus

    ... Anticoagulants (blood-thinning medicine) Calcium channel blockers Diuretics (water pills) Digoxin Your doctor will decide what type of medicine is right for you. In some cases, people who have pulmonary hypertension need surgical treatment. Surgical treatment options include a lung transplant and ...

  7. [Chronic dependence on mechanical pulmonary ventilation in pediatric care: a necessary debate for Brazil's Unified Health System].

    PubMed

    Costa, Maria Tereza Fonseca da; Gomes, Maria Auxiliadora; Pinto, Márcia

    2011-10-01

    People with prolonged dependence on mechanical ventilation require permanent care and the use of equipment that can result in longer term hospital internment. This can lead to difficulty of access for patients with acute injuries, as well as personal difficulties and stress with reduced quality of life for their families or caregivers due to such longer hospital internment. This critical review of publications dealing with dependence on mechanical ventilation among children and adolescents aimed at making information organized in a systematic manner available in order to support discussion on the subject. It should be borne in mind that changes in epidemiological profile and growing technological access determine needs such as intensive therapy hospital beds and complex home care for chronic patients, which still have limits of supply and regulatory restrictions in the Brazilian public health system. PMID:22031144

  8. Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM)

    PubMed Central

    Burrowes, K. S.; De Backer, J.; Smallwood, R.; Sterk, P. J.; Gut, I.; Wirix-Speetjens, R.; Siddiqui, S.; Owers-Bradley, J.; Wild, J.; Maier, D.; Brightling, C.

    2013-01-01

    The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium (Airway disease Predicting Outcomes through patient-specific computational Modelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD. PMID:24427517

  9. Combined and Independent Action of Proteins SP-B and SP-C in the Surface Behavior and Mechanical Stability of Pulmonary Surfactant Films

    PubMed Central

    Schürch, David; Ospina, Olga L.; Cruz, Antonio; Pérez-Gil, Jesús

    2010-01-01

    The hydrophobic proteins SP-B and SP-C are essential for pulmonary surfactant function, even though they are a relatively minor component (<2% of surfactant dry mass). Despite countless studies, their specific differential action and their possible concerted role to optimize the surface properties of surfactant films have not been completely elucidated. Under conditions kept as physiologically relevant as possible, we tested the surface activity and mechanical stability of several surfactant films of varying protein composition in vitro using a captive bubble surfactometer and a novel (to our knowledge) stability test. We found that in the naturally derived surfactant lipid mixtures, surfactant protein SP-B promoted film formation and reextension to lower surface tensions than SP-C, and in particular played a vital role in sustaining film stability at the most compressed states, whereas SP-C produced no stabilization. Preparations containing both proteins together revealed a slight combined effect in enhancing film formation. These results provide a qualitative and quantitative framework for the development of future synthetic therapeutic surfactants, and illustrate the crucial need to include SP-B or an efficient SP-B analog for optimal function. PMID:21081077

  10. Relaxation to bradykinin in bovine pulmonary supernumerary arteries can be mediated by both a nitric oxide-dependent and -independent mechanism

    PubMed Central

    Tracey, A; Bunton, D; Irvine, J; MacDonald, A; Shaw, A M

    2002-01-01

    The aim of the present study was to determine the relative contribution of prostanoids, nitric oxide and K+ channels in the bradykinin-induced relaxation of bovine pulmonary supernumerary arteries. In endothelium-intact, but not denuded rings, bradykinin produced a concentration-dependent relaxation (pEC50, 9.6±0.1), which was unaffected by the cyclo-oxygenase inhibitor indomethacin. The nitric oxide scavenger hydroxocobalamin (200 μM, pEC50, 8.5±0.2) and the nitric oxide synthase inhibitor L-NAME (100 μM, pEC50, 8.9±0.1) and the combination of L-NAME and hydroxocobalamin (pEC50, 8.1±0.2) produced rightward shifts in the bradykinin concentration response curve. The guanylyl cyclase inhibitor ODQ (10 μM, pEC50, 9.6±0.4) did not affect the response to bradykinin. Elevating the extracellular [K+] to 30 mM did not affect the response to bradykinin but abolished the response when ODQ or L-NAME was present. The K+ channel blocker apamin (100 nM), combined with charybdotoxin (100 nM), produced a small reduction in the maximum response to bradykinin but they abolished the response to bradykinin when ODQ, L-NAME or hydroxocobalamin were present. Apamin (100 nM) combined with iberiotoxin (100 nM) also reduced the response to bradykinin in the presence of hydroxocobalamin or L-NAME. The concentration response curve for sodium nitroprusside-induced relaxation was abolished by ODQ (10 μM) and shifted to the right by apamin and charybdotoxin. These studies suggest that in bovine pulmonary supernumerary arteries bradykinin can stimulate the formation of nitric oxide and activate an EDHF-like mechanism and that either of these pathways alone can mediate the bradykinin-induced relaxation. In addition nitric oxide, acting through guanylyl cyclase, can activate an apamin/charbydotoxin-sensitive K+ channel in this tissue. PMID:12359636

  11. Deacylated Pulmonary Surfactant Protein SP-C Transforms From α-Helical to Amyloid Fibril Structure via a pH-Dependent Mechanism: An Infrared Structural Investigation

    PubMed Central

    Dluhy, Richard A.; Shanmukh, Saratchandra; Leapard, J. Brian; Krüger, Peter; Baatz, John E.

    2003-01-01

    Bovine pulmonary surfactant protein C (SP-C) is a hydrophobic, α-helical membrane-associated lipoprotein in which cysteines C4 and C5 are acylated with palmitoyl chains. Recently, it has been found that the α-helix form of SP-C is metastable, and under certain circumstances may transform from an α-helix to a β-strand conformation that resembles amyloid fibrils. This transformation is accelerated when the protein is in its deacylated form (dSP-C). We have used infrared spectroscopy to study the structure of dSP-C in solution and at membrane interfaces. Our results show that dSP-C transforms from an α-helical to a β-type amyloid fibril structure via a pH-dependent mechanism. In solution at low pH, dSP-C is α-helical in nature, but converts to an amyloid fibril structure composed of short β-strands or β-hairpins at neutral pH. The α-helix structure of dSP-C is fully recoverable from the amyloid β-structure when the pH is once again lowered. Attenuated total reflectance infrared spectroscopy of lipid-protein monomolecular films showed that the fibril β-form of dSP-C is not surface-associated at the air-water interface. In addition, the lipid-associated α-helix form of dSP-C is only retained at the surface at low surface pressures and dissociates from the membrane at higher surface pressures. In situ polarization modulation infrared spectroscopy of protein and lipid-protein monolayers at the air-water interface confirmed that the residual dSP-C helix conformation observed in the attenuated total reflectance infrared spectra of transferred films is randomly or isotropically oriented before exclusion from the membrane interface. This work identifies pH as one of the mechanistic causes of amyloid fibril formation for dSP-C, and a possible contributor to the pathogenesis of pulmonary alveolar proteinosis. PMID:14507705

  12. Pharmacodynamic activity of a cephalosporin, Ro 40-6890, in human skin blister fluid: antibiotic activity in concert with host defense mechanisms.

    PubMed Central

    Hoogkamer, J F; Hesse, W H; Sansano, S; Zimmerli, W

    1993-01-01

    The pharmacokinetics of an antimicrobial drug in human plasma and in vitro susceptibility testing of an antimicrobial drug do not necessarily predict its efficacy in vivo. Therefore, the combined activity of an antimicrobial drug and blood-derived polymorphonuclear leukocytes (PMN) against Staphylococcus aureus were investigated in vitro. In addition, a pharmacological model allowing analysis of the bactericidal activity of a drug-containing exudate against S. aureus ex vivo was developed. For this purpose, a phagocytic-bactericidal assay was miniaturized to a volume of 100 microliters in order to test the bactericidal activities of an antimicrobial drug with blood PMN in vitro and with skin blister fluid (CBF) ex vivo. Ro 40-6890, the active metabolite of the ester prodrug Ro 41-3399, was used as the test drug. Killing of S. aureus was clearly enhanced when Ro 41-6890 was combined in vitro with a suboptimal number of blood-derived PMN. In eight healthy volunteers, skin blisters were provoked by plasters containing cantharidin. Following a single oral dose of Ro 41-3399, CBF containing PMN was sampled at regular intervals and incubated ex vivo with S. aureus (5 x 10(5) CFU/ml) for 2, 4, 6, and 24 h at 37 degrees C. Concentrations of Ro 40-6890 were measured in CBF (CCBF) and plasma. Ro 40-6890 distributed well from plasma into CBF. When CCBF was below the MIC, an enhanced effect of Ro 40-6890 and host defense factors present in CBF against S. aureus was observed. In conclusion, the present model can provide additional information on human plasma drug concentrations and MICs established in vitro. PMID:8109926

  13. Pulmonary Hypertension: Types and Treatments

    PubMed Central

    Rose-Jones, Lisa J; Mclaughlin, Vallerie V

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmo-nary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario. PMID:24251459

  14. Schistosomiasis-associated pulmonary hypertension

    PubMed Central

    Mocumbi, Ana Olga H.; Kim, Nick H.; Mandel, Jess

    2014-01-01

    Abstract Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension–like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy. PMID:25610596

  15. Central and peripheral pulmonary vascular resistance: Implications for who should undergo pulmonary thromboendarterectomy.

    PubMed

    Poullis, Mike

    2015-08-01

    Pulmonary thromboendarterectomy remains a technically challenging procedure with variable outcomes with regard to improvement in pulmonary function. Reducing the resistance to flow between the pulmonary valve and the pulmonary capillary bed is the key aim of surgery. The resistance to flow is due to the combination of resistance due to the central clot and distal capillary resistance. We hypothesise that the use of fluid mechanics in combination with modern radiology and electronic circuit theory can potentially predict who should or should not undergo a thromboendarterectomy. Electronic circuit theory of two resistors in series was utilised to demonstrate the concept of a model of a central clot and the peripheral pulmonary capillary bed. A simplified 2D model of the lungs utilising finite element analysis and Poiseuille's law was constructed for proof of principle. Modelling predicts that cardiac output and anatomical obstruction interplay and can have profound effects on the outcomes after thromboendarterectomy. Identical pulmonary artery pressures, due to differing cardiac outputs and identical anatomical obstructions due to thrombus can have very different physiological outcomes with regard to changes in pulmonary artery pressure. Modelling the pulmonary vasculature to determine central and peripheral pulmonary vascular resistance may help in predicting who should undergo pulmonary thromboendarterectomy. Mathematical modelling can potentially predict which patients have haemodynamically significant clots in their pulmonary arteries that thromboendarterectomy may potentially help in the setting of pulmonary capillary disease. PMID:25997984

  16. Deception used for Cyber Defense of Control Systems

    SciTech Connect

    Wayne F. Boyer; Miles A. McQueen

    2009-05-01

    Control system cyber security defense mechanisms may employ deception to make it more difficult for attackers to plan and execute successful attacks. These deceptive defense mechanisms are organized and initially explored according to a specific deception taxonomy and the seven abstract dimensions of security previously proposed as a framework for the cyber security of control systems.

  17. Nitrogen modulation on plant direct and indirect defenses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Instead of being passively attacked by insect pests, plants possess a myriad of defense mechanisms to protect themselves. These mechanisms function broadly either by directly reducing herbivore fitness (direct plant defense), or by indirectly attracting natural enemies of the herbivores (indirect p...

  18. Hepcidin and Host Defense against Infectious Diseases

    PubMed Central

    Michels, Kathryn; Nemeth, Elizabeta; Ganz, Tomas; Mehrad, Borna

    2015-01-01

    Hepcidin is the master regulator of iron homeostasis in vertebrates. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. While the role of hepcidin in iron regulation is well established, its contribution to host defense is emerging as complex and multifaceted. In this review, we summarize the literature on the role of hepcidin as a mediator of antimicrobial immunity. Hepcidin induction during infection causes depletion of extracellular iron, which is thought to be a general defense mechanism against many infections by withholding iron from invading pathogens. Conversely, by promoting iron sequestration in macrophages, hepcidin may be detrimental to cellular defense against certain intracellular infections, although critical in vivo studies are needed to confirm this concept. It is not yet clear whether hepcidin exerts any iron-independent effects on host defenses. PMID:26291319

  19. Hepcidin and Host Defense against Infectious Diseases.

    PubMed

    Michels, Kathryn; Nemeth, Elizabeta; Ganz, Tomas; Mehrad, Borna

    2015-08-01

    Hepcidin is the master regulator of iron homeostasis in vertebrates. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. While the role of hepcidin in iron regulation is well established, its contribution to host defense is emerging as complex and multifaceted. In this review, we summarize the literature on the role of hepcidin as a mediator of antimicrobial immunity. Hepcidin induction during infection causes depletion of extracellular iron, which is thought to be a general defense mechanism against many infections by withholding iron from invading pathogens. Conversely, by promoting iron sequestration in macrophages, hepcidin may be detrimental to cellular defense against certain intracellular infections, although critical in vivo studies are needed to confirm this concept. It is not yet clear whether hepcidin exerts any iron-independent effects on host defenses. PMID:26291319

  20. Pulmonary function in space.

    PubMed

    West, J B; Elliott, A R; Guy, H J; Prisk, G K

    1997-06-25

    The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth. PMID:9200637

  1. Pulmonary function in space

    NASA Technical Reports Server (NTRS)

    West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

    1997-01-01

    The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

  2. PULMONARY ANTIOXIDANTS

    EPA Science Inventory

    One of the most vital of the cellular defenses against pollution is an 'antioxidant armanentarium' which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate re...

  3. Effects of buthionine sulfoximine on the development of ozone-induced pulmonary fibrosis.

    PubMed

    Sun, J D; Pickrell, J A; Harkema, J R; McLaughlin, S I; Hahn, F F; Henderson, R F

    1988-10-01

    The capacity of reduced glutathione (GSH) to protect lung tissue against ozone-induced pulmonary fibrosis was investigated. Male B6C3F1 mice were exposed to 0, 0.2, 0.5, and 1.0 ppm ozone for 23 hr/day for 14 days. During exposures and/or for a period of 90 days after exposures, subgroups of mice at each exposure level were given drinking water containing 30 mM L-buthionine-S,R-sulfoximine (BSO) to lower in vivo levels of GSH. These BSO treatments reduced blood glutamylcysteine synthetase (GCS) activity (regulatory enzyme for GSH biosynthesis) and lung nonprotein sulfhydryl (NPSH) levels in nonexposed animals by approximately half. In contrast, ozone exposures increased blood GCS activity and lung NPSH levels in a concentration-dependent manner, with smaller increases in the BSO-treated mice. Immediately after exposures, an ozone-related inflammatory response was seen in lungs, but no histopathological signs of developing fibrosis were evident. Ninety days later, mice exposed to 1 ppm ozone and not treated with BSO had modest evidence of pulmonary fibrosis. Mice exposed to 1 ppm ozone and treated with BSO during this post-exposure period (regardless of BSO treatment during exposures) showed histopathological evidence of exacerbated pulmonary fibrosis, compared to similarly exposed mice not treated with BSO postexposure. These results indicated that interference with the body's normal defense mechanisms against oxidant damage, including suppression of GSH biosynthesis, exacerbates the subsequent development of pulmonary fibrosis. PMID:2901982

  4. [Pulmonary melioidosis].

    PubMed

    Perret, J L; Vidal, D; Thibault, F

    1998-12-01

    Melioidosis is most frequently encountered in pulmonary localization. Melioidosis is an infectious disease caused by Burkholderia pseudomallei first described by Whitmore in 1912 in Burma. B. pseudomallei is a Gram negative rod belonging to the Pseudomonadaceae family. Soil and water are the natural reservoirs for the germ which is a specific pathogen for several mammal species. Long endemic in Southeast Asia and several tropical zones, B. pseudomallei has recently been found in temperate zones, including France. Human contamination occurs via the transcutaneous route and often leads to dormant inapparent infection. Many conditions, such as diabetes, renal lithiasis, various circumstances of immunodepression or stress, facilitate clinical manifestations which vary greatly. Pulmonary manifestations may be acute and extensive, producing a torpid pseudo-tuberculous condition or a variety of clinical and radiological features mimicking other diseases. Bacteriological and serological tests may be negative. Exposure in an endemic zone, the notion of a favorable context, weight loss, cavitary images on successive chest x-rays and the presence of extra-pulmonary localizations may be suggestive. Ceftazidime or the amoxicillin-clavulanic acid combination are indicated, but mortality in acute forms still reaches 40%. Relapse can be expected if the treatment duration is too short. PMID:10100350

  5. Moscow's defense intellectuals

    SciTech Connect

    Lambeth, B.S.

    1990-01-01

    This essay was originally written two decades ago as a seminar paper. A substantial portion of it addresses what were then only the first steps toward the establishment of a community of professional civilian defense analysts in the Soviet Union. Throughout most of the intervening period, that community found itself mired in immobilism as jurisdiction over such key Soviet national security inputs as military doctrine, force requirements, resource needs, and to a considerable degree, arms negotiating positions remained an exclusive prerogative of the Defense Ministry and the General Staff. Today, this former military monopoly has come to be challenged with increasing success by a host of newcomers to the Soviet defense scene, including the Foreign Ministry, the Supreme Soviet, and an ambitious cadre of civilian analysts attached to the social science research institutes of the Academy of Sciences. These individuals are making a determined bid for greater influence over Soviet defense policy, with the express encouragement of President Gorbachev and his supporters. The result has been an unprecedented infusion of pluralism into Soviet defense politics and a significant change in the content and goals of Soviet military policy.

  6. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  7. What Causes Pulmonary Hypertension?

    MedlinePlus

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

  8. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology.

    PubMed

    Humbert, M

    2010-03-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy. PMID:20956167

  9. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  10. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  11. Presurgical Pulmonary Evaluation in Renal Transplant Patients

    PubMed Central

    Sahni, Sonu; Molmenti, Ernesto; Bhaskaran, Madhu C.; Ali, Nicole; Basu, Amit; Talwar, Arunabh

    2014-01-01

    Patients with chronic renal failure (CRF) due to various mechanisms are prone to significant pulmonary comorbidities. With the improvements in renal replacement therapy (RRT), patients with CRF are now expected to live longer, and thus may develop complications in the lung from these processes. The preferred treatment of CRF is kidney transplantation and patients who are selected to undergo transplant must have a thorough preoperative pulmonary evaluation to assess pulmonary status and to determine risk of postoperative pulmonary complications. A MEDLINE®/PubMed® search was performed to identify all articles outlining the course of pre-surgical pulmonary evaluation with an emphasis on patients with CRF who have been selected for renal transplant. Literature review concluded that in addition to generic pre-surgical evaluation, renal transplant patients must also undergo a full cardiopulmonary and sleep evaluation to investigate possible existing pulmonary pathologies. Presence of any risk factor should then be aggressively managed or treated prior to surgery. PMID:25599047

  12. Non-infectious Pulmonary Diseases and HIV.

    PubMed

    Triplette, M; Crothers, K; Attia, E F

    2016-06-01

    Pulmonary complications remain among the most frequent causes of morbidity and mortality for individuals with HIV despite the advent of antiretroviral therapy (ART) and improvement in its efficacy and availability. The prevalence of non-infectious pulmonary diseases is rising in this population, reflecting both an increase in smoking and the independent risk associated with HIV. The unique mechanisms of pulmonary disease in these patients remain poorly understood, and direct effects of HIV, genetic predisposition, inflammatory pathways, and co-infections have all been implicated. Lung cancer, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension are the most prevalent non-infectious pulmonary diseases in persons with HIV, and the risk of each of these diseases is higher among HIV-infected (HIV+) persons than in the general population. This review discusses the latest advances in the literature on these important complications of HIV infection. PMID:27121734

  13. A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node.

    PubMed

    Ye, Wenduo; Wang, Jun; Song, Yingnan; Yu, Diankun; Sun, Cheng; Liu, Chao; Chen, Fading; Zhang, Yanding; Wang, Fen; Harvey, Richard P; Schrader, Laura; Martin, James F; Chen, YiPing

    2015-07-15

    In humans, atrial fibrillation is often triggered by ectopic pacemaking activity in the myocardium sleeves of the pulmonary vein (PV) and systemic venous return. The genetic programs that abnormally reinforce pacemaker properties at these sites and how this relates to normal sinoatrial node (SAN) development remain uncharacterized. It was noted previously that Nkx2-5, which is expressed in the PV myocardium and reinforces a chamber-like myocardial identity in the PV, is lacking in the SAN. Here we present evidence that in mice Shox2 antagonizes the transcriptional output of Nkx2-5 in the PV myocardium and in a functional Nkx2-5(+) domain within the SAN to determine cell fate. Shox2 deletion in the Nkx2-5(+) domain of the SAN caused sick sinus syndrome, associated with the loss of the pacemaker program. Explanted Shox2(+) cells from the embryonic PV myocardium exhibited pacemaker characteristics including node-like electrophysiological properties and the capability to pace surrounding Shox2(-) cells. Shox2 deletion led to Hcn4 ablation in the developing PV myocardium. Nkx2-5 hypomorphism rescued the requirement for Shox2 for the expression of genes essential for SAN development in Shox2 mutants. Similarly, the pacemaker-like phenotype induced in the PV myocardium in Nkx2-5 hypomorphs reverted back to a working myocardial phenotype when Shox2 was simultaneously deleted. A similar mechanism is also adopted in differentiated embryoid bodies. We found that Shox2 interacts with Nkx2-5 directly, and discovered a substantial genome-wide co-occupancy of Shox2, Nkx2-5 and Tbx5, further supporting a pivotal role for Shox2 in the core myogenic program orchestrating venous pole and pacemaker development. PMID:26138475

  14. PKC δ and βII regulate angiotensin II-mediated fibrosis through p38: a mechanism of RV fibrosis in pulmonary hypertension

    PubMed Central

    Chichger, Havovi; Vang, Alexander; O'Connell, Kelly A.; Zhang, Peng; Mende, Ulrike; Harrington, Elizabeth O.

    2015-01-01

    Pulmonary hypertension (PH) eventually leads to right ventricular (RV) fibrosis and dysfunction that is associated with increased morbidity and mortality. Although angiotensin II plays an important role in RV remodeling associated with hypoxic PH, the molecular mechanisms underlying RV fibrosis in PH largely remain unresolved. We hypothesized that PKC-p38 signaling is involved in RV collagen accumulation in PH and in response to angiotensin II stimulation. Adult male Sprague-Dawley rats were exposed to 3 wk of normoxia or hypoxia (10% FiO2) as a model of PH. Hypoxic rats developed RV hypertrophy and fibrosis associated with an increase in PKC βII and δ protein expression and p38 dephosphorylation in freshly isolated RV cardiac fibroblasts. Further mechanistic studies were performed in cultured primary cardiac fibroblasts stimulated with angiotensin II, a key activator of ventricular fibrosis in PH. Angiotensin II induced a reduction in p38 phosphorylation that was attenuated following chemical inhibition of PKC βII and δ. Molecular and chemical inhibition of PKC βII and δ abrogated angiotensin II-induced cardiac fibroblast proliferation and collagen deposition in vitro. The effects of PKC inhibition on proliferation and fibrosis were reversed by chemical inhibition of p38. Conversely, constitutive activation of p38 attenuated angiotensin II-induced increase of cardiac fibroblast proliferation and collagen accumulation. PKC βII- and δ-dependent inactivation of p38 regulates cardiac fibroblast proliferation and collagen deposition in response to angiotensin II, which suggests that the PKC-p38 signaling in cardiac fibroblasts may be involved and important in the pathophysiology of RV fibrosis in PH. PMID:25659900

  15. Value of space defenses

    SciTech Connect

    Canavan, G.H.

    1992-10-29

    This report discusses the economic value of defenses against Near-Earth Object (NEO) impacts is bounded by calculating expected losses in their absence, which illustrates the contributions from NEOs of different sizes and the sensitivity of total expected losses to impact frequencies. For typical size distributions and damage of only a few decades duration, losses are most sensitive to small NEOs, and lead to defenses worth a few $M/yr. When the persistence of damage with NEO size is taken into account, that shifts the loss to the largest NEOs and greatly increases expected loss and values.

  16. Respiratory epithelial cells orchestrate pulmonary innate immunity.

    PubMed

    Whitsett, Jeffrey A; Alenghat, Theresa

    2015-01-01

    The epithelial surfaces of the lungs are in direct contact with the environment and are subjected to dynamic physical forces as airway tubes and alveoli are stretched and compressed during ventilation. Mucociliary clearance in conducting airways, reduction of surface tension in the alveoli, and maintenance of near sterility have been accommodated by the evolution of a multi-tiered innate host-defense system. The biophysical nature of pulmonary host defenses are integrated with the ability of respiratory epithelial cells to respond to and 'instruct' the professional immune system to protect the lungs from infection and injury. PMID:25521682

  17. Simple pulmonary eosinophilia

    MedlinePlus

    Pulmonary infiltrates with eosinophilia; Loffler syndrome; Eosinophilic pneumonia; Pneumonia - eosinophilic ... simple pulmonary eosinophilia is a severe type of pneumonia called acute idiopathic eosinophilic pneumonia.

  18. Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.

    PubMed

    Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos

    2016-03-01

    Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis. PMID:26494773

  19. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen

    SciTech Connect

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-03

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, F{sub v}/F{sub m}, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H{sub 2}O{sub 2} production and greater increases in H{sub 2}O{sub 2}-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. - Highlights: • We employ two different types of photodynamic stress, white and brown necrosis. • We examine molecular mechanisms of antioxidative and detoxification systems. • ALA and OF develop differential actions of antioxidant and detoxification systems. • Coordinated mechanism of antioxidants and detoxification works against toxic ROS. • Detoxification system plays critical roles in protection against photodynamic stress.

  20. [Commemorative lecture of receiving Imamura Memorial Prize. NK cell in pulmonary tuberculosis from basic and clinical point of view].

    PubMed

    Yoneda, T

    1996-11-01

    Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis. NK cell activity in patients with active pulmonary tuberculosis was significantly augmented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel surface marker of mice NK cells, which inhibited activation of NK cells by interferon. Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immune-spectrum classification was associated with clinical manifestations. Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5 g/dl. More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer

  1. Severe Pulmonary Valve Regurgitation 40 Years After Blunt Chest Trauma.

    PubMed

    Fuglsang, Simon; Heiberg, Johan; Hjortdal, Vibeke Elisabeth

    2015-10-01

    Severe pulmonary valve regurgitation caused by a pulmonary valve tear is a rare complication to a blunt chest trauma. In this case report, we present a patient with pulmonary regurgitation originating from a chest trauma 40 years ago. Possible mechanisms are osseous pinch of the pulmonary valve between the anterior chest wall and the vertebral column, and retrograde blowout from severe compression of the lungs. PMID:26434447

  2. Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

    PubMed

    Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

    2015-11-01

    Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations. PMID:26471823

  3. Pulmonary vascular stiffness: measurement, modeling, and implications in normal and hypertensive pulmonary circulations.

    PubMed

    Hunter, Kendall S; Lammers, Steven R; Shandas, Robin

    2011-07-01

    This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hypertension. It then progresses from the systems-level to the local level, discusses proposed methods by which upstream pulmonary vessels increase in stiffness, introduces concepts around vascular mechanics, and concludes by describing recent work incorporating advanced numerical methods to more thoroughly evaluate changes in local mechanical properties of pulmonary arteries. PMID:23733649

  4. Pulmonary Vascular Stiffness: Measurement, Modeling, and Implications in Normal and Hypertensive Pulmonary Circulations

    PubMed Central

    Hunter, Kendall S.; Lammers, Steven R.; Shandas, Robin

    2014-01-01

    This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hypertension. It then progresses from the systems-level to the local level, discusses proposed methods by which upstream pulmonary vessels increase in stiffness, introduces concepts around vascular mechanics, and concludes by describing recent work incorporating advanced numerical methods to more thoroughly evaluate changes in local mechanical properties of pulmonary arteries. PMID:23733649

  5. 75 FR 76423 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of... a closed meeting of the Defense Intelligence Agency National Defense Intelligence College Board...

  6. 76 FR 28960 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of... a closed meeting of the Defense Intelligence Agency National Defense Intelligence College Board...

  7. 76 FR 28757 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... of the Secretary Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Notice of Availability (NOA) of Revised Defense Logistics Agency Regulation. SUMMARY: The Defense...

  8. Radiological Defense Manual.

    ERIC Educational Resources Information Center

    Defense Civil Preparedness Agency (DOD), Washington, DC.

    Originally prepared for use as a student textbook in Radiological Defense (RADEF) courses, this manual provides the basic technical information necessary for an understanding of RADEF. It also briefly discusses the need for RADEF planning and expected postattack emergency operations. There are 14 chapters covering these major topics: introduction…

  9. Censorship: Tactics for Defense.

    ERIC Educational Resources Information Center

    Lowery, Skip

    1998-01-01

    Book banners are generally successful because they have a wide network of support, including national coalitions with sophisticated organizational methods--such as electing certain people to school boards. School officials should get organized and devise defensive strategies, such as inviting critics to class, asking what they would like to…

  10. Defense Language Institute.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    Discussed in this Defense Language Institute (DLI) brochure are its intensive language programs' history, and its four schools, which are located in Monterey, California, Washington, D.C., Lackland Air Force Base, and Fort Bliss, Texas. Proficiency levels determined by the DLI and utilization of the audiolingual method are also described.…

  11. [Pulmonary embolism].

    PubMed

    Söffker, Gerold; Kluge, Stefan

    2015-01-01

    Acute pulmonary embolism is an important differential diagnosis of acute chest pain. The clinical signs are often non-specific. However, diagnosis and therapy must be done quickly in order to reduce morbidity and mortality. The new (2014) European guidelines for acute pulmonary embolism (PE) focus on risk-adapted diagnostic algorithms and prognosis adapted therapy concepts. According to the hemodynamic presentation the division in a high-risk group (unstable patient with persistent hypotension or shock) or in non-high-risk groups (hemodynamically stable) was proposed. In the high-risk group the immediate diagnosis is usually done by multidetector spiral computed tomography (MDCT) and primarily the medical therapy of right ventricular dysfunction and thrombolysis is recommended.In the non-high-risk group, this is subdivided into an intermediate-risk group and low-risk group, the diagnosis algorithm based on the PE-pretest probability--determined by validated scores. Moreover, the diagnosis is usually secured by MDCT--the new gold standard in the PE-diagnosis, scores, or it can be primarily ruled out due to the high negative predictive value of D-dimer determination. To improve the prognostic risk stratification in non-high-risk group patients the additional detection of right ventricular dysfunction (MDCT, echocardiography), cardiac biomarkers (troponin, NT proBNP) and validated scores (e.g. Pulmonary Embolism Severity Index) is recommended. Therefore, the intermediate-risk group can be further subdivided. For treatment of non-high-risk group patients, the initial anticoagulation (except those with severe renal insufficiency) using low molecular weight heparin/fondaparinux and conversion to vitamin-K antagonists or alternatively with direct oral anticoagulants (DOAK) is recommended. Hemodynamically stable patients with right ventricular dysfunction and myocardial ischemia (Intermediate-high-risk group patients) but with clinically progressive hemodynamic

  12. INCREASED PULMONARY DISEASE MEDIATED THROUGH ALTERED BACTERIAL DEFENSES

    EPA Science Inventory

    The process of infection has been defined as an interaction of a host, a microbe, and the environment. In the natural environment, healthy individuals exist in equilibrium with potentially pathogenic microorganisms. Using this concept, an animal-model system was developed to stud...

  13. 9. BASRELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. BAS-RELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT DEARBORN - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  14. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen.

    PubMed

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-01

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, Fv/Fm, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H2O2 production and greater increases in H2O2-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. PMID:25735982

  15. Pulmonary antioxidants

    SciTech Connect

    Massaro, E.J.; Grose, E.C.; Hatch, G.E.; Slade, R.

    1987-05-01

    One of the most vital of the cellular defenses against pollution is an antioxidant armanentarium which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate reductase, catalase, GSH synthetase, GSH peroxidase, GSH reductase, and GSH transferase) and appears to function in keeping oxidant forces under control. Pollutants can upset the oxidant/antioxidant balance of cells by inhibiting vital enzymes, by reacting with oxidant scavengers, or by forming free radical intermediates which initiate uncontrolled tissue reactions with molecular oxygen. The book chapter reviews possible interactions between pollutants and the oxidant/antioxidant balance.

  16. Immune dysregulation in the pathogenesis of pulmonary alveolar proteinosis.

    PubMed

    Martinez-Moczygemba, Margarita; Huston, David P

    2010-09-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense. PMID:20623372

  17. SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms.

    PubMed

    Wang, Xiao-Xiao; Wang, Xu-Lei; Tong, Ming-ming; Gan, Lu; Chen, Huali; Wu, Si-si; Chen, Jia-Xiang; Li, Ru-Li; Wu, Yao; Zhang, Heng-yu; Zhu, Ye; Li, Yan-xin; He, Jin-han; Wang, Meijing; Jiang, Wei

    2016-03-01

    SIRT6, a member of the NAD(+)-dependent class III deacetylase sirtuin family, has been revealed to play important roles in promoting cellular resistance against oxidative stress. The formation of reactive oxygen species (ROS) and oxidative stress are the crucial mechanisms underlying cellular damage and dysfunction in cardiac ischemia/reperfusion (I/R) injury, but the role of SIRT6 in I/R-induced ROS and oxidative stress is poorly understood. In this study, by using heterozygous SIRT6 knockout (SIRT6(+/-)) mice and cultured neonatal cardiomyocyte models, we investigated how SIRT6 mediates oxidative stress and myocardial injury during I/R. Partial knockout (KO) of SIRT6 aggravated myocardial damage, ventricular remodeling, and oxidative stress in mice subjected to myocardial I/R, whereas restoration of SIRT6 expression by direct cardiac injection of adenoviral constructs encoding SIRT6 reversed these deleterious effects of SIRT6 KO in the ischemic heart. In addition, partial deletion of the SIRT6 gene decreased myocardial functional recovery following I/R in a Langendorff perfusion model. Similarly, the protective effects of SIRT6 were also observed in cultured cardiomyocytes following hypoxia/reoxygenation. Intriguingly, SIRT6 was noticed to up-regulate AMP/ATP and then activate the adenosine 5'-monophosphate-activated protein kinase (AMPK)-forkhead box O3α (FoxO3α) axis and further initiated the downstream antioxidant-encoding gene expression (manganese superoxide dismutase and catalase), thereby decreasing cellular levels of oxidative stress and mediating cardioprotection in the ischemic heart. These results suggest that SIRT6 protects the heart from I/R injury through FoxO3α activation in the ischemic heart in an AMP/ATP-induced AMPK-dependent way, thus upregulating antioxidants and suppressing oxidative stress. PMID:26786260

  18. Pulmonary Surfactant: An Immunological Perspective

    PubMed Central

    Chroneos, Zissis C.; Sever-Chroneos, Zvjezdana; Shepherd, Virginia L.

    2009-01-01

    Pulmonary surfactant has two crucial roles in respiratory function; first, as a biophysical entity it reduces surface tension at the air water interface, facilitating gas exchange and alveolar stability during breathing, and, second, as an innate component of the lung's immune system it helps maintain sterility and balance immune reactions in the distal airways. Pulmonary surfactant consists of 90% lipids and 10% protein. There are four surfactant proteins named SP-A, SP-B, SP-C, and SP-D; their distinct interactions with surfactant phospholipids are necessary for the ultra-structural organization, stability, metabolism, and lowering of surface tension. In addition, SP-A and SP-D bind pathogens, inflict damage to microbial membranes, and regulate microbial phagocytosis and activation or deactivation of inflammatory responses by alveolar macrophages. SP-A and SP-D, also known as pulmonary collectins, mediate microbial phagocytosis via SP-A and SP-D receptors and the coordinated induction of other innate receptors. Several receptors (SP-R210, CD91/calreticulin, SIRPα, and toll-like receptors) mediate the immunological functions of SP-A and SP-D. However, accumulating evidence indicate that SP-B and SP-C and one or more lipid constituents of surfactant share similar immuno-regulatory properties as SP-A and SP-D. The present review discusses current knowledge on the interaction of surfactant with lung innate host defense. PMID:20054141

  19. INFLUENCE OF ROOT COLONIZING BACTERIA ON THE DEFENSE RESPONSES OF BEAN

    EPA Science Inventory

    Colonization of plant roots by fluorescent pseudomonads has been correlated with disease suppression. ne mechanism may involve altered defense responses in the plant upon colonization. ltered defense responses were observed in bean (Phaseolus vulgaris) inoculated with fluorescent...

  20. Changed profile of microRNAs in acute lung injury induced by cardio-pulmonary bypass and its mechanism involved with SIRT1

    PubMed Central

    Yang, Kun; Gao, Bingren; Wei, Wansheng; Li, Zhenzhen; Pan, Li; Zhang, Jing; Zhao, Qiming; Chen, Wensheng; Xu, Zhiyi

    2015-01-01

    Objective: Acute lung injury (ALI) is a severe complication for patients undergoing cardiac surgery necessitating cardio-pulmonary bypass (CPB), however, the possible relationship between microRNAs change and ALI induced by CPB is still not completely understood. Objective: the aim of this study is to determine the microRNAs level changes in patients with ALI induced by CPB and its involved mechanism. Methods: We collected blood samples from 45 patients and performed microRNA microarray experiments to determine the microRNAs level changes in patients with ALI induced by CPB then the result was verified by quantitative real-time PCR (qRT-PCR). Plasma TNF-α level and respiration parameters including respiration index (RI) and oxygenation index (OI) were measured at five different time points before or after CPB. Meanwhile the correlationship between significantly changed microRNAs and TNF-α level and respiration parameters was analyzed. Further more, we transfected miR-320 mimic and inhibitor into A549 cells and observed the proliferation inhibition and apoptosis change caused by oxygen-glucose deprivation/reperfusion. Finally we using dual-luciferase reporter assay, qRT-PCR and western blot investigated the potential target of miR-320. Results: The level of miR-320 was higher in CPB caused ALI with the most significance. Correlation analysis found that the level of miR-320 was positively associated with TNF-α and RI (r = 0.649 and 0.564, P < 0.05), but negative correlated with OI (r = -0.638, P < 0.05). In A549 cells, up-regulated miR-320 induced proliferation inhibition and more apoptosis. SIRT1 may be a target of miR-320 and higher miR-320 resulted in lower expression of SIRT both in mRNA and protein level. Conclusion: miR-320 may mediate the ALI after CPB in which alveolar epithelial cells are injured via down-regulating SIRT1. PMID:25972997

  1. Denervation as a Common Mechanism Underlying Different Pulmonary Vein Isolation Strategies for Paroxysmal Atrial Fibrillation: Evidenced by Heart Rate Variability after Ablation

    PubMed Central

    Wang, Kejing; Chang, Dong; Chu, Zhenliang; Yang, Yanzong; Gao, Lianjun; Zhang, Shulong; Xia, Yunlong; Dong, Yingxue; Yin, Xiaomeng; Cong, Peixin; Jia, Jingjing

    2013-01-01

    Backgrounds. Segmental and circumferential pulmonary vein isolations (SPVI and CPVI) have been demonstrated to be effective therapies for paroxysmal atrial fibrillation (PAF). PVI is well established as the endpoint of different ablation techniques, whereas it may not completely account for the long-term success. Methods. 181 drug-refractory symptomatic PAF patients were referred for segmental or circumferential PVI (SPVI = 67; CPVI = 114). Heart rate variability (HRV) was assessed before and after the final ablation. Results. After following up for 62.23 ± 12.75 months, patients underwent 1.41 ± 0.68 procedures in average, and the success rates in SPVI and CPVI groups were comparable. 119 patients were free from AF recurrence (SPVI-S, n = 43; CPVI-S, n = 76). 56 patients had recurrent episodes (SPVI-R, n = 21; CPVI-R, n = 35). Either ablation technique decreased HRV significantly. Postablation SDNN and rMSSD were significantly lower in SPVI-S and CPVI-S subgroups than in SPVI-R and CPVI-R subgroups (SPVI-S versus SPVI-R: SDNN 91.8 ± 32.6 versus 111.5 ± 36.2 ms, rMSSD 47.4 ± 32.3 versus 55.2 ± 35.2 ms; CPVI-S versus CPVI-R: SDNN 83.0 ± 35.6 versus 101.0 ± 40.7 ms, rMSSD 41.1 ± 22.9 versus 59.2 ± 44.8 ms; all P < 0.05). Attenuation of SDNN and rMSSD remained for 12 months in SPVI-S and CPVI-S subgroups, whereas it recovered earlier in SPVI-R and CPVI-R subgroups. Multivariate logistic regression analysis identified SDNN as the only predictor of long-term success. Conclusions. Beyond PVI, denervation may be a common mechanism underlying different ablation strategies for PAF. PMID:24058286

  2. Pythium infection activates conserved plant defense responses in mosses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The moss Physcomitrella patens (P. patens) is a useful model to study abiotic stress responses since it is highly tolerant to drought, salt and osmotic stress. However, little is known about the defense mechanisms activated in this moss after pathogen assault. Here the induction of defense responses...

  3. Genomics applications to plant defense research and crop pest management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-insect interaction is a complex and dynamic process, leading to a variety of beneficial and deleterious outcome. Mechanisms of plant defense against insect attack, including constitutive and induced defenses, have been evolving for millions of years and are therefore shared across many plant ...

  4. Chronic hypoxia-induced upregulation of Ca2+-activated Cl- channel in pulmonary arterial myocytes: a mechanism contributing to enhanced vasoreactivity.

    PubMed

    Sun, Hui; Xia, Yang; Paudel, Omkar; Yang, Xiao-Ru; Sham, James S K

    2012-08-01

    Chronic hypoxic pulmonary hypertension (CHPH) is associated with altered expression and function of cation channels in pulmonary arterial smooth muscle cells (PASMCs), but little is known for anion channels. The Ca(2+)-activated Cl(-) channel (CaCC), recently identified as TMEM16A, plays important roles in pulmonary vascular function. The present study sought to determine the effects of chronic hypoxia (CH) on the expression and function of CaCCs in PASMCs, and their contributions to the vascular hyperreactivity in CHPH. Male Wistar rats were exposed to room air or 10% O(2) for 3–4 weeks to generate CHPH. CaCC current (I(CI.Ca)) elicited by caffeine-induced Ca(2+) release or by depolarization at a constant high [Ca(2+)](i) (500 or 750 nm) was significantly larger in PASMCs of CH rats compared to controls. The enhanced I(CI.Ca)) density in CH PASMCs was unrelated to changes in amplitude of Ca(2+) release, Ca(2+)-dependent activation, voltage-dependent properties or calcineurin-dependent modulation of CaCCs, but was associated with increased TMEM16A mRNA and protein expression. Maximal contraction induced by serotonin, an important mediator of CHPH, was potentiated in endothelium-denuded pulmonary arteries of CH rats. The enhanced contractile response was prevented by the CaCC blockers niflumic acid and T16A(inh)-A01, or by the L-type Ca(2+) channel antagonist nifedipine. The effects of niflumic acid and nifedipine were non-additive. Our results demonstrate for the first time that CH increases I(CI.Ca) density, which is attributable to an upregulation of TMEM16A expression in PASMCs. The augmented CaCC activity in PASMCs may potentiate membrane depolarization and L-type channel activation in response to vasoconstrictors and enhance pulmonary vasoreactivity in CHPH. PMID:22674716

  5. Pulmonary fibrosis: pathogenesis, etiology and regulation

    PubMed Central

    Wilson, MS; Wynn, TA

    2009-01-01

    Pulmonary fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The etiology of pulmonary fibrotic diseases is varied, with an array of triggers including allergens, chemicals, radiation and environmental particles. However, the cause of one of the most common pulmonary fibrotic conditions, idiopathic pulmonary fibrosis (IPF), is still unclear. This review examines common mechanisms of pulmonary wound-healing responses following lung injury, and highlights the pathogenesis of some of the most widespread pulmonary fibrotic diseases. A three phase model of wound repair is reviewed that includes; (1) injury; (2) inflammation; and (3) repair. In most pulmonary fibrotic conditions dysregulation at one or more of these phases has been reported. Chronic inflammation can lead to an imbalance in the production of chemokines, cytokines, growth factors, and disrupt cellular recruitment. These changes coupled with excessive pro-fibrotic IL-13 and/or TGFβ1 production can turn a well-controlled healing response into a pathogenic fibrotic response. Endogenous regulatory mechanisms are discussed including novel areas of therapeutic intervention. Restoring homeostasis to these dysregulated healing responses, or simply neutralizing the key pro-fibrotic mediators may prevent or slow the progression of pulmonary fibrosis. PMID:19129758

  6. [Thoughts on "defensive" medicine].

    PubMed

    Csiba, László

    2007-03-25

    "Defensive" medicine is called medical behaviour characterized by deformation of diagnostic and therapeutic activities due to fears endangering existence and work, thus some interventions are omitted or, on the contrary, superfluous examinations are proposed on account of internal uncertainty, the patient's distrust or hostile social environment. Trust relation between patient and physician is the most gravely damaged because of aggravation and distortion of some conscienceless physicians' abuses by the media; patient-physician relations may not be degraded to contractual legal relations. Young physicians must get acquainted with the joy of success in diagnostics that enriches the personality. They shall have healthy self-esteem and be ready to take diagnostic and therapeutic challenges on themselves. All of us have to fight against social atmosphere hostile to physicians, against causes inducing and augmenting practice of defensive medicine. PMID:17444017

  7. Iron chelation inhibits the development of pulmonary vascular remodeling.

    PubMed

    Wong, Chi-Ming; Preston, Ioana R; Hill, Nicholas S; Suzuki, Yuichiro J

    2012-11-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. Because iron is an important regulator of ROS biology, this study examined the effects of iron chelation on the development of pulmonary vascular remodeling. The administration of an iron chelator, deferoxamine, to rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Various iron chelators inhibited the growth of cultured pulmonary artery smooth muscle cells. Protein carbonylation, an important iron-dependent biological event, was promoted in association with pulmonary vascular remodeling and cell growth. A proteomic approach identified that Rho GDP-dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human plasma, the protein carbonyl content was significantly higher in patients with idiopathic pulmonary arterial hypertension than in healthy controls. These results suggest that iron plays an important role in the ROS-dependent mechanism underlying the development of pulmonary hypertension. PMID:22974762

  8. Defense Waste Processing Facility

    SciTech Connect

    Haselow, J.S.; Wilhite, E.L.; Stieve, A.L.

    1990-05-01

    The information contained in this report is intended to supplement the original Environmental Impact Statement (EIS) for the Defense Waste Processing Facility (DWPF). Since the original EIS in 1982, alterations have been made to he conceptual process that reduce the impact to the groundwater. This reduced impact is documented in this report along with an update of the understanding of seismology and geology of the Savannah River Site. 6 refs., 2 figs., 2 tabs.

  9. Convergent and discriminant validity of overall defensive functioning.

    PubMed

    Perry, J C; Høglend, P

    1998-09-01

    We examined the validity of the construct of overall defensive functioning and its discrimination from standard diagnostic assessments. Within a multisite field trial, patients received intake diagnostic interviews by clinicians who made standard axis I through V diagnoses, then rated defense mechanisms using the Defense Mechanism Rating Scales (DMRS). Patients filled out self-report measures of distress and defenses, the SCL-90-R, and Defense Style Questionnaire (DSQ). Overall defensive functioning (ODF) scales were derived from both the DMRS and the DSQ. Overlap between clinical and self-report ratings of defenses was modest. By two different methods of factor analysis, followed by confirmatory factor analysis, clinical ratings of ODF were clearly discriminable from axis I, axis II personality disorders, current and usual global functioning, and subjective distress. ODF measured by the DSQ was not clearly discriminated from subjective distress ratings, consistent with the hypothesis that subjective distress may distort conscious derivatives of actual defensive processes. The DSQ alone probably should not be considered as a substitute for observer-rated assessment of defensive functioning, although further study of the issue is warranted. PMID:9741558

  10. Pulmonary actinomycosis.

    PubMed

    Celebi, Solmaz; Sevinir, Betul; Saraydaroglu, Ozlem; Gurpinar, Arif; Hacimustafaoglu, Mustafa

    2009-02-01

    Pulmonary actinomycosis is rarely reported in pediatric age. An 11-year-old girl with history of two-month back pain was admitted to our hospital. On physical examination respiratory sounds were diminished on the left upper lung. Chest radiograph revealed a mass in the left upper lobe. Computed tomography showed solitary lesion (5.6 x 4.5 cm in size) in the left upper lobe. We could not rule out the possibility of malignant thoracic tumor. The patient underwent surgery. Histological examination of the resected tissue revealed, numerous sulfur granules, characteristic of Actinomyces, surrounded by purulent exudates, which are consistent with actinomycosis. She was treated with penicillin G. The patient responded well to penicillin therapy and the lesions regressed completely. She remained well throughout the three-year follow-up. PMID:19129990

  11. Pulmonary embolism

    PubMed Central

    Tarbox, Abigail K.; Swaroop, Mamta

    2013-01-01

    Pulmonary embolism (PE) is responsible for approximately 100,000 to 200,000 deaths in the United States each year. With a diverse range of clinical presentations from asymptomatic to death, diagnosing PE can be challenging. Various resources are available, such as clinical scoring systems, laboratory data, and imaging studies which help guide clinicians in their work-up of PE. Prompt recognition and treatment are essential for minimizing the mortality and morbidity associated with PE. Advances in recognition and treatment have also enabled treatment of some patients in the home setting and limited the amount of time spent in the hospital. This article will review the risk factors, pathophysiology, clinical presentation, evaluation, and treatment of PE. PMID:23724389

  12. Immunosuppression of pulmonary natural killer activity by exposure to ozone

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.; Stutzman, J.D. )

    1989-01-01

    Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless involves several cell types and/or products of these cells. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, following 23.5 hours of exposure. NK activity is important for defense against viral, bacterial, and neoplastic disease. The depressed NK activity resulting from continuous ozone exposure could therefore result in a compromised ability to defend against pulmonary diseases.

  13. Diffuse interstitial pulmonary fibrosis: pulmonary fibrosis in mice induced by treatment with butylated hydroxytoluene and oxygen

    SciTech Connect

    Haschek, W.M.; Brody, A.R.; Klein-Szanto, A.J.P.; Witschi, H.

    1981-12-01

    It is proposed that the pulmonary fibrosis induced in mice by treatment with BHT and oxygen is a good experimental model for human pulmonary fibrosis. The mechanism of synergistic and additive effects of various agents on pulmonary injury and the epithelial mesenchymal interactions occurring during the early and late phases of lung repair could be studied. This model could be used for study of the effects of various concentrations of oxygen on diffusely damaged lung and assessment of the efficacy of drugs in preventing or resolving excessive collagen accumulation in lung. In addition, the relationship between pulmonary fibrosis and emphysema could be studied.

  14. Extensive pulmonary sarcoid reaction in a patient with BMPR-2 associated idiopathic pulmonary arterial hypertension.

    PubMed

    Braam, Evelien A J E; Quanjel, Marian J R; Van Haren-Willems, Jolanda H G M; Van Oosterhout, Matthijs F M; Vink, Aryan; Heijdra, Yvonne F; Kwakkel-van Erp, Johanna M

    2016-01-01

    Pulmonary arterial hypertension is a progressive life-threatening disease characterized by vascular remodeling. There is evidence that varied immune mechanism play an important role in progression of pulmonary hypertension.  We describe a case of a 35-year-old woman with idiopathic pulmonary arterial hypertension (IPAH) and a novel BMPR2 mutation, who underwent a successful lung transplantation.  Extensive granulomatous inflammation was seen in the resected lungs. The granulomatous inflammation found in the histology supports  a sarcoid-like reaction due to pulmonary hypertension in the context of the BMPR2 mutation. PMID:27537724

  15. Self-organized defensive behavior in honeybees.

    PubMed

    Millor, J; Pham-Delegue, M; Deneubourg, J L; Camazine, S

    1999-10-26

    We investigated the defensive behavior of honeybees under controlled experimental conditions. During an attack on two identical targets, the spatial distribution of stings varied as a function of the total number of stings, evincing the classic "pitchfork bifurcation" phenomenon of nonlinear dynamics. The experimental results support a model of defensive behavior based on a self-organizing mechanism. The model helps to explain several of the characteristic features of the honeybee defensive response: (i) the ability of the colony to localize and focus its attack, (ii) the strong variability between different hives in the intensity of attack, as well as (iii) the variability observed within the same hive, and (iv) the ability of the colony to amplify small differences between the targets. PMID:10535970

  16. Defense on the Move: Ant-Based Cyber Defense

    SciTech Connect

    Fink, Glenn A.; Haack, Jereme N.; McKinnon, Archibald D.; Fulp, Errin W.

    2014-04-15

    Many common cyber defenses (like firewalls and IDS) are as static as trench warfare allowing the attacker freedom to probe them at will. The concept of Moving Target Defense (MTD) adds dynamism to the defender side, but puts the systems to be defended themselves in motion, potentially at great cost to the defender. An alternative approach is a mobile resilient defense that removes attackers’ ability to rely on prior experience without requiring motion in the protected infrastructure itself. The defensive technology absorbs most of the cost of motion, is resilient to attack, and is unpredictable to attackers. The Ant-Based Cyber Defense (ABCD) is a mobile resilient defense providing a set of roaming, bio-inspired, digital-ant agents working with stationary agents in a hierarchy headed by a human supervisor. The ABCD approach provides a resilient, extensible, and flexible defense that can scale to large, multi-enterprise infrastructures like the smart electric grid.

  17. The NF-κB inhibitory Proteins IκBα and IκBβ Mediate Disparate Responses to Inflammation in Fetal Pulmonary Endothelial Cells

    PubMed Central

    Tang, Jen-Ruey; Michaelis, Katherine A.; Nozik-Grayck, Eva; Seedorf, Gregory J.; Hartman-Filson, Marlena; Abman, Steven H.; Wright, Clyde J.

    2013-01-01

    Rationale Exposure to intrauterine inflammation impairs lung growth, but paradoxically protects the neonatal pulmonary vasculature from hyperoxic injury. The mechanisms mediating these contradictory effects are unknown. Objective To identify the role of NF-κB in mediating cytoprotective and pro-inflammatory responses to inflammation in the fetal pulmonary endothelium. Methods and Results In newborn rats exposed to intraamniotic lipopolysaccharide (LPS), we found increased expression of the NF-κB target gene manganese superoxide dismutase (MnSOD) in the pulmonary endothelium. Supporting these in vivo findings, LPS induced NF-κB activation and MnSOD expression in isolated fetal pulmonary arterial endothelial cells. Additionally, LPS exposure caused apoptosis, and suppressed cellular growth and induced P-selectin expression. LPS-induced NF-κB activation that proceeded through specific isoforms of the inhibitory protein IκB mediated these diverse responses; NF-κB signaling through IκBα degradation resulted in MnSOD upregulation and preserved cell growth, whereas NF-κB signaling through IκBβ degradation mediated apoptosis and P-selectin expression. Conclusions These findings suggest that selective inhibition of NF-κB activation that results from IκBβ degradation preserves the enhanced antioxidant defense and protects the developing pulmonary vascular endothelium from ongoing inflammatory injury. PMID:23418625

  18. Autophagy and checkpoints for intracellular pathogen defense

    PubMed Central

    Paulus, Geraldine L.C.; Xavier, Ramnik J.

    2015-01-01

    Purpose of review Autophagy plays a crucial role in intracellular defense against various pathogens. Xenophagy is a form of selective autophagy that targets intracellular pathogens for degradation. In addition, several related yet distinct intracellular defense responses depend on autophagy-related (ATG) genes. This review gives an overview of these processes, pathogen strategies to subvert them, and their crosstalk with various cell death programs. Recent findings The recruitment of ATG proteins plays a key role in multiple intracellular defense programs, specifically xenophagy, LC3-associated phagocytosis (LAP), and the IFNγ-mediated elimination of pathogens such as Toxoplasma gondii and murine norovirus. Recent progress has revealed methods employed by pathogens to resist these intracellular defense mechanisms and/or persist in spite of them. The intracellular pathogen load can tip the balance between cell survival and cell death. Further, it was recently observed that LAP is indispensable for the efficient clearance of dying cells. Summary Autophagy-dependent and ATG gene-dependent pathways are essential in intracellular defense against a broad range of pathogens. PMID:25394238

  19. Enhanced Susceptibility to Pulmonary Infection with Burkholderia cepacia in Cftr−/− Mice

    PubMed Central

    Sajjan, Uma; Thanassoulis, George; Cherapanov, Vera; Lu, Annie; Sjolin, Carola; Steer, Brent; Wu, Yi Jun; Rotstein, Ori D.; Kent, Geraldine; McKerlie, Colin; Forstner, Janet; Downey, Gregory P.

    2001-01-01

    Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs of Cftr m1unc−/− (Cftr−/−) and congenic Cftr+/+ controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptible Cftr−/− mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from the Cftr−/− mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages from Cftr−/− mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF. PMID:11447196

  20. Granuloma Formation in Pulmonary Sarcoidosis

    PubMed Central

    Broos, Caroline E.; van Nimwegen, Menno; Hoogsteden, Henk C.; Hendriks, Rudi W.; Kool, Mirjam; van den Blink, Bernt

    2013-01-01

    Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well understood. An impaired immunosuppressive function of regulatory T cells has been suggested to contribute to the exaggerated response. Interestingly, therapeutical agents commonly used in sarcoidosis, such as glucocorticosteroids and anti-TNF agents, interfere with granuloma integrity and restore the immune homeostasis in autoimmune disorders. Increasing insight into their mechanisms of action may contribute to the search for new therapeutical targets in pulmonary sarcoidosis. PMID:24339826

  1. Pulmonary rehabilitation in chronic obstructive pulmonary disease.

    PubMed

    Saey, D; Bernard, S; Gagnon, P; Laviolette, L; Soicher, J; Maltais, F; Esgagne, P; Coats, V; Devost, A-A

    2009-06-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and an important worldwide cause of disability and handicap. Centered around exercise training, pulmonary rehabilitation is a global, multidisciplinary, individualized and comprehensive approach acting on the patient as a whole and not only on the pulmonary component of the disease. Pulmonary rehabilitation is now well recognized as an effective and key intervention in the management of several respiratory diseases particularly in COPD. Modern and effective pulmonary rehabilitation programs are global, multidisciplinary, individualized and use comprehensive approach acting on the patient as a whole and not only on the pulmonary component of the disease. In the last two decades interest for pulmonary rehabilitation is on the rise and a growing literature including several guidelines is now available. This review addresses the recent developments in the broad area of pulmonary rehabilitation as well as new methods to consider in the development of future and better programs. Modern literature for rationale, physiopathological basis, structure, exercise training as well challenges for pulmonary rehabilitation programs are addressed. Among the main challenges of pulmonary rehabilitation, efforts have to be devoted to improve accessibility to early rehabilitation strategies, not only to patients with COPD but to those with other chronic respiratory diseases. PMID:19776711

  2. DNA Damage and Pulmonary Hypertension

    PubMed Central

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  3. DNA Damage and Pulmonary Hypertension.

    PubMed

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  4. Pulmonary Complications due to Esophagectomy

    PubMed Central

    Shirinzadeh, Abulfazl; Talebi, Yashar

    2011-01-01

    Introduction Esophageal carcinoma is the scourge of human beings. Pulmonary complications in patients who have undergone operation are common (20-30% of cases) and there are no suitable tools and ways to predict these complications. Methods During a period of 10 years, from March 1998 to February 2007, 200 patients (150 male and 50 female) underwent Esophagectomy due to esophageal carcinoma in thoracic surgery ward retrospectively. Complications include the length of hospitalization, mechanical ventilation, morbidity and mortality. Patients’ risk factors include age, preoperative chemo-radiotherapy, stage of the disease and preoperative spirometry condition. Results We grouped our patients into three categories: Normal (FEV1 ≥ 80% predicted), mildly impaired (FEV1 65% to 79% predicted), more severely impaired (FEV1 < 65% predicted).Although almost all patients had radiographic pulmonary abnormalities, significant pulmonary complications occurred in 40 patients (20%) which underwent Esophagectomy. Pleural effusion and atelectasia in 160 patients (80%). 24 patients needed chest-tube insertion. 20 patients (10%) developed ARDS. 14 patients (7%) developed chylothorax. 20 patients (10%) of patients died during their postoperative hospital stay. 30 patients (15%) required mechanical ventilation for greater than 48 hours. Conclusion We reviewed a number of preoperative clinical variables to determine whether they contributed to postoperative pulmonary complications as well as other outcomes. In general, age, impaired pulmonary function especially in those patients with FEV1 less than 65% predicted was associated with prolonged hospital length of stay (LOS). In fact pulmonary complications rate after Esophagectomy are high and there was associated mortality and morbidity. PMID:24250962

  5. Plant Defense against Insect Herbivores

    PubMed Central

    Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

    2013-01-01

    Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. PMID:23681010

  6. Synthetic plant defense elicitors

    PubMed Central

    Bektas, Yasemin; Eulgem, Thomas

    2015-01-01

    To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection. PMID:25674095

  7. Nanomaterials for Defense Applications

    NASA Astrophysics Data System (ADS)

    Turaga, Uday; Singh, Vinitkumar; Lalagiri, Muralidhar; Kiekens, Paul; Ramkumar, Seshadri S.

    Nanotechnology has found a number of applications in electronics and healthcare. Within the textile field, applications of nanotechnology have been limited to filters, protective liners for chemical and biological clothing and nanocoatings. This chapter presents an overview of the applications of nanomaterials such as nanofibers and nanoparticles that are of use to military and industrial sectors. An effort has been made to categorize nanofibers based on the method of production. This chapter particularly focuses on a few latest developments that have taken place with regard to the application of nanomaterials such as metal oxides in the defense arena.

  8. [Idiopathic pulmonary trunk aneurysm].

    PubMed

    Uehara, Mayuko; Kuroda, Yosuke; Ohori, Syunsuke; Mawatari, Toru; Morishita, Kiyofumi

    2010-07-01

    Pulmonary trunk aneurysm is generally associated with congenital cardiac defects, pulmonary hypertension, or infection. Idiopathic pulmonary trunk aneurysm without any associated diseases is a rare lesion and has seldom been reported. Here, we report a case of a 68-year-old woman with idiopathic pulmonary trunk aneurysm. The maximum diameter of the aneurysm was 53 mm while she was 142 cm in height. We successfully performed aneurysmorrhaphy and her postoperative course was uneventful. Aneurysmorrhaphy was an effective technique for idiopathic pulmonary trunk aneurysm without pulmonary hypertention. PMID:20662238

  9. The chemistry of defense: theory and practice.

    PubMed Central

    Berenbaum, M R

    1995-01-01

    Defensive chemicals used by organisms for protection against potential consumers are generally products of secondary metabolism. Such chemicals are characteristic of free-living organisms with a limited range of movement or limited control over their movements. Despite the fact that chemical defense is widespread among animals as well as plants, the vast majority of theories advanced to account for patterns of allocation of energy and materials to defensive chemistry derive exclusively from studies of plant-herbivore interactions. Many such theories place an undue emphasis on primary physiological processes that are unique to plants (e.g., photosynthesis), rendering such theories limited in their utility or predictive power. The general failure of any single all-encompassing theory to gain acceptance to date may indicate that such a theory might not be a biologically realistic expectation. In lieu of refining theory, focusing attention on the genetic and biochemical mechanisms that underlie chemical defense allocation is likely to provide greater insights into understanding patterns across taxa. In particular, generalizations derived from understanding such mechanisms in natural systems have immediate applications in altering patterns of human use of natural and synthetic chemicals for pest control. PMID:7816816

  10. Pulmonary endarterectomy after pulmonary infectious embolisms

    PubMed Central

    Heiberg, Johan; Ilkjær, Lars B.

    2013-01-01

    Pulmonary endarterectomy (PEA) is a well-established procedure in the treatment of chronic thromboembolic pulmonary hypertension (CTPH). The procedure is known to increase functional outcome and to raise the 5-year survival rate. We report 2 cases of pulmonary valve endocarditis and secondary embolisms causing sustained pulmonary hypertension. Both were treated with PEA. In none of the cases, a cleavage between the thrombotic masses and the vessel wall was obtainable, and both attempts were therefore inadequate. Based on our reports, we recommend not attempting PEA in cases of CTPH after infectious embolisms. PMID:23248168

  11. Utility of a novel error-stepping method to improve gradient-based parameter identification by increasing the smoothness of the local objective surface: a case-study of pulmonary mechanics.

    PubMed

    Docherty, Paul D; Schranz, Christoph; Chase, J Geoffrey; Chiew, Yeong Shiong; Möller, Knut

    2014-05-01

    Accurate model parameter identification relies on accurate forward model simulations to guide convergence. However, some forward simulation methodologies lack the precision required to properly define the local objective surface and can cause failed parameter identification. The role of objective surface smoothness in identification of a pulmonary mechanics model was assessed using forward simulation from a novel error-stepping method and a proprietary Runge-Kutta method. The objective surfaces were compared via the identified parameter discrepancy generated in a Monte Carlo simulation and the local smoothness of the objective surfaces they generate. The error-stepping method generated significantly smoother error surfaces in each of the cases tested (p<0.0001) and more accurate model parameter estimates than the Runge-Kutta method in three of the four cases tested (p<0.0001) despite a 75% reduction in computational cost. Of note, parameter discrepancy in most cases was limited to a particular oblique plane, indicating a non-intuitive multi-parameter trade-off was occurring. The error-stepping method consistently improved or equalled the outcomes of the Runge-Kutta time-integration method for forward simulations of the pulmonary mechanics model. This study indicates that accurate parameter identification relies on accurate definition of the local objective function, and that parameter trade-off can occur on oblique planes resulting prematurely halted parameter convergence. PMID:23910223

  12. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

  13. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides.

    PubMed

    Hilchie, Ashley L; Wuerth, Kelli; Hancock, Robert E W

    2013-12-01

    Cationic host defense (antimicrobial) peptides were originally studied for their direct antimicrobial activities. They have since been found to exhibit multifaceted immunomodulatory activities, including profound anti-infective and selective anti-inflammatory properties, as well as adjuvant and wound-healing activities in animal models. These biological properties suggest that host defense peptides, and synthetic derivatives thereof, possess clinical potential beyond the treatment of antibiotic-resistant infections. In this Review, we provide an overview of the biological activities of host defense and synthetic peptides, their mechanism(s) of action and new therapeutic applications and challenges that are associated with their clinical use. PMID:24231617

  14. Pulmonary function in microgravity

    NASA Technical Reports Server (NTRS)

    Guy, H. J.; Prisk, G. K.; West, J. B.

    1992-01-01

    We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non-gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS).

  15. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension

    PubMed Central

    Wang, Zhijie; Chesler, Naomi C.

    2011-01-01

    Pulmonary hypertension (PH) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload. These changes, characterized by narrowing and stiffening, occur in both proximal and distal pulmonary arteries (PAs). An important consequence of arterial narrowing is increased pulmonary vascular resistance (PVR). Arterial stiffening, which can occur in both the proximal and distal pulmonary arteries, is an important index of disease progression and is a significant contributor to increased RV afterload in PH. In particular, arterial narrowing and stiffening increase the RV afterload by increasing steady and oscillatory RV work, respectively. Here we review the current state of knowledge of the causes and consequences of pulmonary arterial stiffening in PH and its impact on RV function. We review direct and indirect techniques for measuring proximal and distal pulmonary arterial stiffness, measures of arterial stiffness including elastic modulus, incremental elastic modulus, stiffness coefficient β and others, the changes in cellular function and the extracellular matrix proteins that contribute to pulmonary arterial stiffening, the consequences of PA stiffening for RV function and the clinical implications of pulmonary vascular stiffening for PH progression. Future investigation of the relationship between PA stiffening and RV dysfunction may facilitate new therapies aimed at improving RV function and thus ultimately reducing mortality in PH. PMID:22034607

  16. Pulmonary arteriovenous fistula

    MedlinePlus

    Pulmonary arteriovenous fistula is an abnormal connection between an artery and vein in the lungs. As a result, blood passes ... Pulmonary arteriovenous fistulas are usually the result of abnormal development of the blood vessels of the lung. Most occur in ...

  17. Chronic obstructive pulmonary disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000091.htm Chronic obstructive pulmonary disease To use the sharing features on this page, please enable JavaScript. Chronic obstructive pulmonary disease (COPD) is a common lung disease. Having COPD ...

  18. Who Needs Pulmonary Rehabilitation?

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... other symptoms. Examples of interstitial lung diseases include sarcoidosis and idiopathic pulmonary fibrosis . Cystic fibrosis (CF). CF ...

  19. Familial Pulmonary Fibrosis

    MedlinePlus

    ... are here: Health Information > Condition Information Familial Pulmonary Fibrosis: Overview When two or more members within the ... Associate Professor View full profile More Familial Pulmonary Fibrosis Information Forms Causes Genetic Counseling Print Page Email ...

  20. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...