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Sample records for pulmonary defense mechanisms

  1. Comparison of pulmonary defense mechanisms in Rocky Mountain bighorn (Ovis canadensis canadensis) and domestic sheep.

    PubMed

    Silflow, R M; Foreyt, W J; Taylor, S M; Laegreid, W W; Liggitt, H D; Leid, R W

    1989-10-01

    Alveolar macrophages were obtained from Rocky Mountain bighorn sheep (Ovis canadensis canadensis) and domestic sheep for the purpose of comparing pulmonary host defense mechanisms in the two species. Specific variables studied included (1) characterization of the cell types present in the lung, (2) alveolar macrophage phagocytic and bactericidal functions, (3) measurement of protein levels in lavage fluid, and (4) measurement of cortisol levels in lavage fluid. While phagocytic cell populations were similar between bighorn and domestic sheep, a significantly higher percentage of lymphocytes were present in bighorns than domestics (20% in bighorn versus 6% in domestic sheep). Significant differences were not observed in the phagocytic or bactericidal functions of macrophages between the two species. Significant differences were not observed in either lavage fluid protein levels or in cortisol levels.

  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.

  3. Understanding Defense Mechanisms.

    PubMed

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur.

  4. 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.…

  5. Pulmonary mechanics during mechanical ventilation.

    PubMed

    Henderson, William R; Sheel, A William

    2012-03-15

    The use of mechanical ventilation has become widespread in the management of hypoxic respiratory failure. Investigations of pulmonary mechanics in this clinical scenario have demonstrated that there are significant differences in compliance, resistance and gas flow when compared with normal subjects. This paper will review the mechanisms by which pulmonary mechanics are assessed in mechanically ventilated patients and will review how the data can be used for investigative research purposes as well as to inform rational ventilator management.

  6. Natural host defense mechanisms.

    PubMed

    Heggers, J P

    1979-10-01

    Severe injury, whether the result of a major accident, a large burn, or a complicated surgical operation, often results in sepsis. Under such conditions both specific and nonspecific host defense systems are affected. The individual facets of major concern are chemotaxis, phagocytosis, intracellular killing, complement depletion, and depression of humoral and cellular mediated immunity. The most profound changes occur in cell-mediated immunity. Within a few hours o injury, the number of circulating T cells becomes depleted, concomitantly thoracic duct lymphocytes are markedly reduced. This change is not only quantitative but functional. The clinical impact of these deficient host defense mechanisms lies in the fact that low virulent organisms may become a lethal threat to the injured patient. Currently, investigators are attempting to reverse thse deficiencies through the use of immunotherapy.

  7. Gastroduodenal Mucosal Defense Mechanisms

    PubMed Central

    Said, Hyder; Kaji, Izumi; Kaunitz, Jonathan D.

    2015-01-01

    Purpose of Review To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. Recent Findings There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like-peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. Summary A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and -2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release. PMID:26376476

  8. Control Processes and Defense Mechanisms

    PubMed Central

    HOROWITZ, MARDI; COOPER, STEVEN; FRIDHANDLER, BRAM; PERRY, J. CHRISTOPHER; BOND, MICHAEL; VAILLANT, GEORGE

    1992-01-01

    Defense-mechanism theory and control-process theory are related psychodynamic approaches to explaining and classifying how people ward off emotional upsets. Although both theories explain defensive maneuvers in the same motivational terms, each defines categories different1y. Classic categories define defense mechanisms at a relatively macroscopic level, whereas control-process theory aims at relatively microgenetic analysis of how cognitive maneuvers—involving what is thought, how it is thought, and how it is organized—may generate defensive states. The theories are not contradictory, but they are focused on different levels of observation; it is useful to compare how these classifications are applied to specific case material. PMID:22700114

  9. Mechanisms of defense: development and research perspectives.

    PubMed

    Kernberg, P F

    1994-01-01

    The author offers a selective overview of defense mechanisms. With an eye to clarifying the definition of defense mechanisms and the use of this concept in treatment, she traces the evolution of the concept since its initial formulation, examines the developmental aspects of defenses and the implications for psychopathology, and discusses various recent research studies.

  10. 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,…

  11. 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,…

  12. The Defense Mechanisms of Coronary Patients.

    ERIC Educational Resources Information Center

    Peglar, Marian; Borgen, Fred H.

    1984-01-01

    Tested 73 male inpatients with coronary heart disease on the Defense Mechanisms Inventory, State-Trait Anxiety Inventory, and a perception of health measure. Subjects were followed for five years. Principalization was discovered to be the most successful and projection the least successful defense. (JAC)

  13. The Defense Mechanisms of Coronary Patients.

    ERIC Educational Resources Information Center

    Peglar, Marian; Borgen, Fred H.

    1984-01-01

    Tested 73 male inpatients with coronary heart disease on the Defense Mechanisms Inventory, State-Trait Anxiety Inventory, and a perception of health measure. Subjects were followed for five years. Principalization was discovered to be the most successful and projection the least successful defense. (JAC)

  14. Adaptive defense mechanisms: function and transcendence.

    PubMed

    Metzger, Jesse A

    2014-05-01

    This article reviews the high-adaptive (mature) defense mechanisms, along with case material illustrating each. These defenses are described in terms of not only the specific means by which they serve to ward off anxiety and manage conflict, but also how they often transcend their role as defenses by contributing to the creation of new "products" of value, such as new meanings, perspectives, modes of relating, and works of art or science. This report also discusses the implications of the use of adaptive defenses, especially humor, in the context of psychotherapy. © 2014 Wiley Periodicals, Inc.

  15. Defense mechanisms: 40 years of empirical research.

    PubMed

    Cramer, Phebe

    2015-01-01

    This article reviews research on defense mechanisms carried out over the past 40 years with children, adolescents, adults, and psychiatric patients. Both experimental and observational studies are included.

  16. Host defense mechanisms against pneumonia due to Pseudomonas aeruginosa.

    PubMed

    Pennington, J E; Ehrie, M G; Hickey, W F

    1984-01-01

    Pneumonia due to Pseudomonas aeruginosa is associated with unusually high mortalities. Accordingly, efforts to define better the most important components of lung defenses against this infection are justified as a prelude to defining improved management strategies. In this report, a guinea pig model of experimental aspiration pseudomonas pneumonia was employed for studies of cellular and humoral mechanisms of pulmonary defense. Animals treated with cortisone acetate plus cyclophosphamide experienced decreased survival from pneumonia, and survival rates correlated directly with the degree of myelosuppression. Numbers of pulmonary macrophages and polymorphonuclear neutrophils were reduced in drug-treated animals before impairment of macrophage antibacterial function. Thus, a reduction in numbers of phagocytes alone was sufficient to markedly reduce lung defenses. In additional experiments, normal guinea pigs were vaccinated with a lipopolysaccharide pseudomonas vaccine. Improved survival from pneumonia correlated with high titers of type-specific, heat-stable opsonic antibody. It is concluded that adequate numbers of lung phagocytes, plus type-specific opsonic antibody, represent the ideal status for lung defense against P. aeruginosa infection.

  17. 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

  18. Defense Mechanisms Associated with Borderline Personality Disorder

    PubMed Central

    Zanarini, Mary C.; Weingeroff, Jolie L.; Frankenburg, Frances R.

    2011-01-01

    This study assessed the defensive functioning of 290 criteria-defined borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was administered to 362 axis II inpatients diagnosed using semistructured interviews of proven reliability. Borderline patients had significantly higher scores than axis II comparison subjects on three of the four defense styles assessed by the DSQ: self-sacrificing, maladaptive action, and image-distorting defenses. They also had significantly higher scores than axis II comparison subjects on eight of the 19 defense mechanisms 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 contrast, axis II comparison subjects had a significantly higher score than borderline patients on one mature defense (suppression). When all significant defenses were considered together, three were found to be significant predictors of a borderline diagnosis: acting out, emotional hypochondriasis, and undoing. This model has both good sensitivity (.95) and positive predictive power (.86). Taken together, the results of this study suggest that the defensive profile of borderline patients is distinct from that of patients with other forms of axis II pathology. They also suggest that the defensive triad of acting out, emotional hypochondriasis, and undoing may serve as a useful clinical marker for the borderline diagnosis, particularly in settings where the base rate of the disorder is high. PMID:19379090

  19. 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

  20. 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

  1. Defense Mechanism Card Pull in TAT Stories.

    PubMed

    Cramer, Phebe

    2017-01-01

    This study investigates the question of whether different Thematic Apperception Test (TAT; Murray, 1943 ) cards are likely to prompt stories that are characterized by different defense mechanisms. This condition is known as card pull and refers to the probability that different TAT cards elicit different personality scores for the same variable. If so, the assessment of defense use would be importantly influenced by the TAT cards used in an assessment. TAT stories from 3 different community samples were examined (Ns = 91, 98, 121), using a statistical method developed by Stein et al ( 2014 ). The results indicated that different TAT cards pull for different defenses, as assessed by the Defense Mechanism Manual (DMM: Cramer, 1991b ). However, the nature of card pull was not always consistent across samples. These dissimilarities could be due to group differences, or to the presence of different TAT cards used in the test battery, indicating that card pull is importantly determined by context.

  2. Defense mechanisms and psychological adjustment in childhood.

    PubMed

    Sandstrom, Marlene J; Cramer, Phebe

    2003-08-01

    The association between maturity of defense use and psychological functioning was assessed in a group of 95 elementary school children. Defense mechanisms were measured using a valid and reliable storytelling task, and psychological adjustment was assessed through a combination of parent and self-report questionnaires. Correlational analyses indicated that children who relied on the developmentally immature defense of denial reported higher levels of self-rated social anxiety and depression and received higher ratings of parent-reported internalizing and externalizing behavior problems. However, children who made use of the developmentally mature defense of identification exhibited higher scores on perceived competence in social, academic, conduct, athletic, and global domains. Significantly, there was no relationship between children's use of denial and their level of perceived competence or between children's use of identification and their degree of maladjustment.

  3. 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

  4. 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.

  5. Macrophage defense mechanisms against intracellular bacteria.

    PubMed

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    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.

  6. 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

  7. Mechanisms of Defense: Nepenthe Theory and Psychiatric Symptomatology

    ERIC Educational Resources Information Center

    Azibo, Daudi Ajani ya

    2007-01-01

    Results of exploratory research on defense mechanisms and psychiatric symptomatology are reported about Black students enrolled in classes on the campus of one Historically Black College and University. Theoretical influences are twofold: ego mechanisms of defense conceptualized hierarchically and a culture-specific view of defense mechanism…

  8. Mechanisms of Defense: Nepenthe Theory and Psychiatric Symptomatology

    ERIC Educational Resources Information Center

    Azibo, Daudi Ajani ya

    2007-01-01

    Results of exploratory research on defense mechanisms and psychiatric symptomatology are reported about Black students enrolled in classes on the campus of one Historically Black College and University. Theoretical influences are twofold: ego mechanisms of defense conceptualized hierarchically and a culture-specific view of defense mechanism…

  9. Intrinsic Defense Mechanisms of the Intestinal Epithelium.

    PubMed

    Ramanan, Deepshika; Cadwell, Ken

    2016-04-13

    The intestinal epithelium is a single cell layer that facilitates the absorption of nutrients but also provides a tight barrier to prevent pathogen invasion and dissemination of commensal microbes. Specialized epithelial cells of the gastrointestinal tract achieve this frontline defense by working in concert with lymphoid, myeloid, and stromal cells to secrete an array of factors that limit direct contact between the epithelium and infectious agents. The importance of these mechanisms is underscored by the ability of enteric pathogens to target these mechanisms to achieve invasion and dissemination. This review highlights recent advances in our understanding of these intricate molecular and cellular mechanisms adopted by these cells to promote spatial segregation and barrier maintenance. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Intrinsic Defense Mechanisms of the Intestinal Epithelium

    PubMed Central

    Ramanan, Deepshika; Cadwell, Ken

    2016-01-01

    SUMMARY The intestinal epithelium is a single cell layer that facilitates the absorption of nutrients but also provides a tight barrier to prevent pathogen invasion and dissemination of commensal microbes. Specialized epithelial cells of the gastrointestinal tract achieve this front-line defense by working in concert with lymphoid, myeloid, and stromal cells to secrete an array of factors that limit direct contact between the epithelium and infectious agents. The importance of these mechanisms is underscored by the ability of enteric pathogens to target these mechanisms to achieve invasion and dissemination. This review highlights recent advances in our understanding of these intricate molecular and cellular mechanisms adopted by these cells to promote spatial segregation and barrier maintenance. PMID:27049583

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

    PubMed

    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.

  12. 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

  13. Cell senescence is an antiviral defense mechanism

    PubMed Central

    Baz-Martínez, Maite; Da Silva-Álvarez, Sabela; Rodríguez, Estefanía; Guerra, Jorge; El Motiam, Ahmed; Vidal, Anxo; García-Caballero, Tomás; González-Barcia, Miguel; Sánchez, Laura; Muñoz-Fontela, César; Collado, Manuel; Rivas, Carmen

    2016-01-01

    Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus. Here, we evaluate this hypothesis using vesicular stomatitis virus (VSV) as a model. Our results show that VSV replication is significantly impaired in both primary and tumor senescent cells in comparison with non-senescent cells, and independently of the stimulus used to trigger senescence. Importantly, we also demonstrate a protective effect of senescence against VSV in vivo. Finally, our results identify the SASP as the major contributor to the antiviral defense exerted by cell senescence in vitro, and points to a role activating and recruiting the immune system to clear out the infection. Thus, our study indicates that cell senescence has also a role as a natural antiviral defense mechanism. PMID:27849057

  14. Cell senescence is an antiviral defense mechanism.

    PubMed

    Baz-Martínez, Maite; Da Silva-Álvarez, Sabela; Rodríguez, Estefanía; Guerra, Jorge; El Motiam, Ahmed; Vidal, Anxo; García-Caballero, Tomás; González-Barcia, Miguel; Sánchez, Laura; Muñoz-Fontela, César; Collado, Manuel; Rivas, Carmen

    2016-11-16

    Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus. Here, we evaluate this hypothesis using vesicular stomatitis virus (VSV) as a model. Our results show that VSV replication is significantly impaired in both primary and tumor senescent cells in comparison with non-senescent cells, and independently of the stimulus used to trigger senescence. Importantly, we also demonstrate a protective effect of senescence against VSV in vivo. Finally, our results identify the SASP as the major contributor to the antiviral defense exerted by cell senescence in vitro, and points to a role activating and recruiting the immune system to clear out the infection. Thus, our study indicates that cell senescence has also a role as a natural antiviral defense mechanism.

  15. Ego defense mechanisms in COPD: impact on health-related quality of life and dyspnoea severity.

    PubMed

    Albuquerque, Saulo C; Carvalho, Eduardo R; Lopes, Rebeka S; Marques, Higor S; Macêdo, Danielle S; Pereira, Eanes D; Hyphantis, Thomas N; Carvalho, Andre F

    2011-11-01

    To assess chronic obstructive pulmonary disorder (COPD) patients' defensive profile compared with healthy participants and to test whether specific ego defense mechanisms are associated with health-related quality of life (HRQoL) and self-reported dyspnoea severity. In a cross-sectional study, we assessed, in 80 patients with COPD and 80 age- and gender-matched healthy participants, psychological distress (Hospital Anxiety and Depression Scale) and defense mechanisms/styles (Defense Style Questionnaire). Patients had their HRQoL evaluated with the St. George's Respiratory Questionnaire and underwent a comprehensive clinical evaluation with determination of functional parameters and dyspnoea severity. COPD patients presented higher scores in undoing, acting out, autistic fantasy, denial, and splitting defenses compared with healthy controls. Overall, patients showed a more immature (P = 0.001) and/or neurotic (P = 0.006) defensive profile. Higher scores of denial (P = 0.044), somatization (P = 0.009), and undoing (P = 0.032) defenses were associated with poorer HRQoL, independently of the anticipated significant associations of clinical and psychological distress variables with impaired HRQoL. Somatization was strongly independently associated with more severe self-reported dyspnoea. COPD patients exhibit a relatively immature and neurotic defensive profile. Clinicians and consultation-liaison psychiatrists should consider the patients' underlying personality structure, especially somatization tendencies, since it is independently associated with HRQoL and dyspnoea severity.

  16. An Evaluative Study of the Defense Mechanism Test

    DTIC Science & Technology

    1990-07-01

    defense mechanisms if persons showing in psychotherapy to have very many or rigid defense mechanisms, for example, did not differ in their test results...Investigation of Freudian Defences. Unpublished PhD thesis , University of Exeter, Faculty of Science, 1982.Cooper, C. & Kline, P. An evaluation of the...Defences. Unpublished PhD thesis , University of Exeter, Faculty of Science, 1982. Cooper, C. & Kline, P. An evaluation of the Defense Mechanism Test

  17. Defense mechanisms in adolescent conduct disorder and adjustment reaction.

    PubMed

    Cramer, Phebe; Kelly, Francis D

    2004-02-01

    The use of defense mechanisms by male and female adolescents with a diagnosis of conduct disorder was compared with the defense use of adolescents with a diagnosis of adjustment reaction. Because conduct disorder has been shown to be associated with a developmental lag in several areas of psychological functioning, we expected that these adolescents would show immaturity in the use of defenses. This expectation was confirmed. As compared with adjustment reaction, conduct disordered youths were more likely to use the immature defense of denial and less likely to use the mature defense of identification.

  18. 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; Tavernier, Jan; Poynter, Matthew E.; Parsons, Polly E.; Dixon, Anne E.; Wargo, Matthew J.; 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 effect 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

  19. 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

  20. 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…

  1. Defense Mechanisms in "Pure" Anxiety and "Pure" Depressive Disorders.

    PubMed

    Colovic, Olga; Lecic Tosevski, Dusica; Perunicic Mladenovic, Ivana; Milosavljevic, Maja; Munjiza, Ana

    2016-10-01

    Our study was intended to test whether there are any differences in the way defense mechanisms are used by patients suffering from pure anxiety and those with pure depressive disorders. The sample size was as follows: depressive disorders without psychotic symptoms 30, anxiety disorders 30, and the healthy control group 30. The assessment of defense mechanisms was made using the DSQ-40 questionnaire. Our findings show that "pure" anxiety disorders differ from "pure" depressive disorders only in the use of immature defense mechanisms. The group with depressive disorders was significantly more prone to use immature defense mechanisms than the group with anxiety disorders (p = 0.005), primarily projection (p = 0.001) and devaluation (p = 0.003). These defense mechanisms may therefore be used both to differentiate between anxiety and depressive disorders and also to determine which symptoms (anxiety or depressive disorders) are dominant at any given stage of treatment.

  2. The dimensionality of defense-mechanism parcels in the Defense Style Questionnaire-40.

    PubMed

    Wilkinson, Wayne W; Ritchie, Timothy D

    2015-03-01

    The Defense Style Questionnaire-40 (DSQ-40; Andrews, Singh, & Bond, 1993) uses pairs of items to measure 20 individual defense mechanisms. In a statistical sense, these item pairs represent parcels and are subject to the standards of unidimensionality demanded of parcels in general. Using a 2-facet modeling approach (N = 672), the present study examined the dimensionality of the defense-mechanism parcels in the DSQ-40 and found that the majority of the parcels did not satisfy the criteria for unidimensionality. In addition, the original 3-factor model of defense styles was not tenable with the present data. Overall, the results suggest caution when attempting to assess individual defense mechanisms using the DSQ-40. 2015 APA, all rights reserved

  3. Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense.

    PubMed

    Gabor, Kristin A; Fessler, Michael B

    2017-01-01

    The mevalonic acid synthesis pathway, cholesterol, and lipoproteins play fundamental roles in lung physiology and the innate immune response. Recent literature investigating roles for cholesterol synthesis and trafficking in host defense against respiratory infection was critically reviewed. The innate immune response and the cholesterol biosynthesis/trafficking network regulate one another, with important implications for pathogen invasion and host defense in the lung. The activation of pathogen recognition receptors and downstream cellular host defense functions are critically sensitive to cellular cholesterol. Conversely, microorganisms can co-opt the sterol/lipoprotein network in order to facilitate replication and evade immunity. Emerging literature suggests the potential for harnessing these insights towards therapeutic development. Given that >50% of adults in the U.S. have serum cholesterol abnormalities and pneumonia remains a leading cause of death, the potential impact of cholesterol on pulmonary host defense is of tremendous public health significance and warrants further mechanistic and translational investigation.

  4. Ego Defenses and Reaction to Stress: A Validation Study of the Defense Mechanisms Inventory

    ERIC Educational Resources Information Center

    Gleser, Goldine C.; Sacks, Marilyn

    1973-01-01

    This study investigated the relationship between scores on the Defense Mechanisms Inventory and reaction to an experimental conflict situation in which Ss (85 undergraduate college students) were led to believe that their performance was deficient on a new test of scholastic ability. The pattern of defenses predicted residual posttest estimates of…

  5. Defense mechanisms in schizotypal, borderline, antisocial, and narcissistic personality disorders.

    PubMed

    Perry, J Christopher; Presniak, Michelle D; Olson, Trevor R

    2013-01-01

    Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.

  6. Psychological defense mechanisms among individuals with SCI with adjustment disorder.

    PubMed

    Yazdanshenas Ghazwin, Manijeh; Tavakoli, Seyed Amir Hossein; Latifi, Sahar; Saberi, Hooshang; Derakhshanrad, Nazi; Yekaninejad, Mir Saeed; Sadeghi, Majid; Emami Razavi, Seyed-Hassan; Norouzi Javidan, Abbas; Ghodsi, Seyed-Mohammad

    2017-09-01

    The used psychological defense styles among individuals with spinal cord injury (SCI) with adjustment disorders (AJD) have not yet been described. In the present investigation, the prevalence of AJD among people with SCI has been estimated and the pattern of used defense styles has been identified. Cross-sectional investigation. A tertiary rehabilitation center in Iran. Individuals referred to Brain and Spinal Cord Injury Research Center were invited to participate in a screening interview. AJD was diagnosed based on DSM-V criteria. Those with AJD diagnosis were scheduled for another interview to assess defense mechanisms. Demographic and injury-related variables were recorded. Defense mechanisms were assessed by the 40-item version of the Defense-Style Questionnaire (DSQ-40). Among 114 participants, 32 (28%) were diagnosed with AJD among whom 23 subjects attended the second interview. Mean age and time since injury were 29.57 ± 9.29 years and 11.70 ± 6.34 months, respectively. The majority of patients were using idealization defense mechanism (91.3%). In the second and third place, passive aggression (87.0%) and somatization (82.6%) defense mechanisms were observed, respectively. Neurotic style was dominantly used (11.52 ± 2.26). Sex, marital status, educational level, cause of the injury and injury level were not related to defense style (P: 0.38, 0.69, 0.88, 0.73, and P: 0.32, respectively). Prevalence of AJD is estimated to be 28% among individuals with SCI. The most prevalent defense style was neurotic and the dominant used defense mechanism was "idealization." The role of demographic and injury-related variables in determining the used defense mechanisms was insignificant.

  7. 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

  8. Case series on defense mechanisms in patients for reconstructive hand transplantation: consideration on transplant defense concept.

    PubMed

    Kumnig, Martin; Jowsey, Sheila G; Moreno, Elisa; Brandacher, Gerald; Azari, Kodi; Rumpold, Gerhard

    2014-05-16

    The technical demands of reconstructive hand transplantation (RHT) and need for complex multidisciplinary care have led to intense research efforts to improve patient care and outcomes. However, RHT is an extraordinary life event which carries the potential for long-term consequences including psychological distress, which invokes coping and defense mechanisms. Little is known about the relationship between psychological defense mechanisms and health outcomes in RHT patients. In an effort to elucidate this relationship, we studied seven RHT patients who underwent standardized psychological assessment either pre- or post transplantation. No single defense concept was identified as common to all patients, which we suspect was due in part to the varied mechanisms of hand loss. All seven patients demonstrated diverse psychological reactions to RHT. The self-reported defense styles were associated with psychological adjustment. The patients who reported defenses that distorted reality described less adaptive functioning and psychological well-being. These preliminary findings reveal the varied psychological mechanisms invoked in RHT patients. An assessment of defense mechanisms should be part of multicenter evaluation protocols that address unique psychosocial aspects of RHT in large samples, in order to better guide psychological management.

  9. Defense mechanisms and self-reported violence toward strangers.

    PubMed

    Kim, Myeong; Cogan, Rosemary; Carter, Stacy; Porcerelli, John H

    2005-01-01

    College men who reported committing violence toward strangers (N = 30) and nonviolent college men (N = 30) completed Thematic Apperception Test cards (TAT) and responded to the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Defense mechanisms were coded from the TAT responses with the Defense Mechanism Manual (DMM). The men who reported violence toward strangers had higher DMM Denial scores and higher MMPI-2 Antisocial Practices scores than the nonviolent men. Student violence toward strangers seems to reflect immaturity rather than psychopathy.

  10. Pulmonary collectins play distinct roles in host defense against Mycobacterium avium.

    PubMed

    Ariki, Shigeru; Kojima, Takashi; Gasa, Shinsei; Saito, Atsushi; Nishitani, Chiaki; Takahashi, Motoko; Shimizu, Takeyuki; Kurimura, Yuichiro; Sawada, Norimasa; Fujii, Nobuhiro; Kuroki, Yoshio

    2011-09-01

    Pulmonary collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), play important roles in the innate immunity of the lung. Mycobacterium avium is one of the well-known opportunistic pathogens that can replicate within macrophages. We examined the effects of pulmonary collectins in host defense against M. avium infection achieved via direct interaction between bacteria and collectins. Although both pulmonary collectins bound to M. avium in a Ca(2+)-dependent manner, these collectins revealed distinct ligand-binding specificity and biological activities. SP-A and SP-D bound to a methoxy group containing lipid and lipoarabinomannan, respectively. Binding of SP-D but not SP-A resulted in agglutination of M. avium. A chimeric protein with the carbohydrate recognition domain of SP-D, which chimera revealed a bouquet-like arrangement similar to SP-A, also agglutinated M. avium. The ligand specificity of the carbohydrate recognition domain of SP-D seems to be necessary for agglutination activity. The binding of SP-A strongly inhibited the growth of M. avium in culture media. Although pulmonary collectins did not increase membrane permeability of M. avium, they attenuated the metabolic rate of the bacteria. Observations under a scanning electron microscope revealed that SP-A almost completely covers bacterial surfaces, whereas SP-D binds to certain areas like scattered dots. These observations suggest that a distinct binding pattern of collectins correlates with the difference of their biological activities. Furthermore, the number of bacteria phagocytosed by macrophages was significantly increased in the presence of SP-D. These data indicate that pulmonary collectins play critical roles in host defense against M. avium.

  11. The relationship between emotional intelligence and ego defense mechanisms.

    PubMed

    Pellitteri, John

    2002-03-01

    The author examined the relationship between the components of emotional intelligence (perception of emotion, affect regulation, and emotional knowledge) and personality factors associated with adaptation, represented by the hierarchical model of defense mechanisms (M. Bond, S. Gardner, J. Christian, & J. Sigal, 1983). Bivariate correlation analyses yielded mixed results; the adaptive defense styles were correlated with overall emotional intelligence but not with the emotional perception and regulation components, as was hypothesized. Emotional knowledge was correlated with both adaptive and maladaptive defense styles and with general intelligence, as was expected. Implications for counseling and psychoeducational interventions are suggested.

  12. Gender differences in self-reported defense mechanisms: a study using the new Defense Style Questionnaire-60.

    PubMed

    Petraglia, Jonathan; Thygesen, Kylie Louise; Lecours, Serge; Drapeau, Martin

    2009-01-01

    Studies have shown that men and women differ in their use of defense mechanisms (e.g. Cramer, 1991; Watson and Sinha, 1998). However, how and why this difference exists is still open to debate. The present study explores the relationship between gender and defenses using the Defense Style Questionnaire (DSQ-60; Trijsburg Bond, & Drapeau, 2003). As expected, no significant differences were found in Overall Defensive Functioning (ODF); however, men and women differed in their choice of defense style, defense level, and individual defense mechanisms. Evidence is provided to support the notion that while overall adaptivity of defenses is comparable, men and women rely on different defensive organizations during conflict-laden situations. We discuss the clinical relevance of these results in light of previous findings.

  13. Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

    PubMed

    Elks, Philip M; van der Vaart, Michiel; van Hensbergen, Vincent; Schutz, Esther; Redd, Michael J; Murayama, Emi; Spaink, Herman P; Meijer, Annemarie H

    2014-01-01

    Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments.

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

    PubMed Central

    Han, SeungHye

    2015-01-01

    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

  15. 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.

  16. 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.

  17. Adaptation Mechanisms in the Evolution of Moss Defenses to Microbes.

    PubMed

    Ponce de León, Inés; Montesano, Marcos

    2017-01-01

    Bryophytes, including mosses, liverworts and hornworts are early land plants that have evolved key adaptation mechanisms to cope with abiotic stresses and microorganisms. Microbial symbioses facilitated plant colonization of land by enhancing nutrient uptake leading to improved plant growth and fitness. In addition, early land plants acquired novel defense mechanisms to protect plant tissues from pre-existing microbial pathogens. Due to its evolutionary stage linking unicellular green algae to vascular plants, the non-vascular moss Physcomitrella patens is an interesting organism to explore the adaptation mechanisms developed in the evolution of plant defenses to microbes. Cellular and biochemical approaches, gene expression profiles, and functional analysis of genes by targeted gene disruption have revealed that several defense mechanisms against microbial pathogens are conserved between mosses and flowering plants. P. patens perceives pathogen associated molecular patterns by plasma membrane receptor(s) and transduces the signal through a MAP kinase (MAPK) cascade leading to the activation of cell wall associated defenses and expression of genes that encode proteins with different roles in plant resistance. After pathogen assault, P. patens also activates the production of ROS, induces a HR-like reaction and increases levels of some hormones. Furthermore, alternative metabolic pathways are present in P. patens leading to the production of a distinct metabolic scenario than flowering plants that could contribute to defense. P. patens has acquired genes by horizontal transfer from prokaryotes and fungi, and some of them could represent adaptive benefits for resistance to biotic stress. In this review, the current knowledge related to the evolution of plant defense responses against pathogens will be discussed, focusing on the latest advances made in the model plant P. patens.

  18. Adaptation Mechanisms in the Evolution of Moss Defenses to Microbes

    PubMed Central

    Ponce de León, Inés; Montesano, Marcos

    2017-01-01

    Bryophytes, including mosses, liverworts and hornworts are early land plants that have evolved key adaptation mechanisms to cope with abiotic stresses and microorganisms. Microbial symbioses facilitated plant colonization of land by enhancing nutrient uptake leading to improved plant growth and fitness. In addition, early land plants acquired novel defense mechanisms to protect plant tissues from pre-existing microbial pathogens. Due to its evolutionary stage linking unicellular green algae to vascular plants, the non-vascular moss Physcomitrella patens is an interesting organism to explore the adaptation mechanisms developed in the evolution of plant defenses to microbes. Cellular and biochemical approaches, gene expression profiles, and functional analysis of genes by targeted gene disruption have revealed that several defense mechanisms against microbial pathogens are conserved between mosses and flowering plants. P. patens perceives pathogen associated molecular patterns by plasma membrane receptor(s) and transduces the signal through a MAP kinase (MAPK) cascade leading to the activation of cell wall associated defenses and expression of genes that encode proteins with different roles in plant resistance. After pathogen assault, P. patens also activates the production of ROS, induces a HR-like reaction and increases levels of some hormones. Furthermore, alternative metabolic pathways are present in P. patens leading to the production of a distinct metabolic scenario than flowering plants that could contribute to defense. P. patens has acquired genes by horizontal transfer from prokaryotes and fungi, and some of them could represent adaptive benefits for resistance to biotic stress. In this review, the current knowledge related to the evolution of plant defense responses against pathogens will be discussed, focusing on the latest advances made in the model plant P. patens. PMID:28360923

  19. Defense Mechanisms, Psychosomatic Symptomatology, and Conjugate Lateral Eye Movements

    ERIC Educational Resources Information Center

    Gur, Raquel E.; Gur, Ruben C.

    1975-01-01

    Subjects were classified into left movers, right movers, and bidirectionals according to the characteristic direction of their eye movements in response to questions. The three groups were compared on their preferential use of defense mechanisms and on the number of psychosomatic complaints. (Author)

  20. 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

  1. 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

  2. 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.

  3. Serum Lipoproteins are Critical for Pulmonary Innate Defense against Staphylococcus aureus Quorum Sensing

    PubMed Central

    Manifold-Wheeler, Brett C.; Elmore, Bradley O.; Triplett, Kathleen D.; Castleman, Moriah J.; Otto, Michael; Hall, Pamela R.

    2015-01-01

    Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). Here we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing dependent pathogenesis. Specifically, apoB levels in the lung early post-infection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact post-trauma pneumonia susceptibility to both Gram positive and Gram negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung. PMID:26608923

  4. Serum Lipoproteins Are Critical for Pulmonary Innate Defense against Staphylococcus aureus Quorum Sensing.

    PubMed

    Manifold-Wheeler, Brett C; Elmore, Bradley O; Triplett, Kathleen D; Castleman, Moriah J; Otto, Michael; Hall, Pamela R

    2016-01-01

    Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein-deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low-density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). In this article, we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing-dependent pathogenesis. Specifically, apolipoprotein B levels in the lung early postinfection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact posttrauma pneumonia susceptibility to both Gram-positive and -negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. Control of Lung Defense by Mucins and Macrophages: Ancient defense mechanisms with modern functions

    PubMed Central

    Janssen, William J.; Stefanski, Adrianne L.; Bochner, Bruce S.; Evans, Christopher M.

    2016-01-01

    Due to the need to balance the requirement for efficient respiration in the face of tremendous levels of exposure to endogenous and environmental challenges, it is crucial for the lungs to maintain sustainable defense that minimizes damage caused by exposures and the detrimental effects of inflammation to delicate gas exchange surfaces. Accordingly, epithelial and macrophage defenses constitute essential 1st and 2nd lines of protection that prevent the accumulation of potentially harmful agents in the lungs, and under homeostatic conditions do so effectively without inducing inflammation. Though seemingly distinct, recent data show that epithelial and macrophage mediated defenses are linked through their shared reliance on airway mucins, in particular the polymeric mucin MUC5B. This review highlights our understanding of novel mechanisms that link mucus and macrophage defenses. The roles of phagocytosis and the effects of factors that are contained within mucus on phagocytosis, as well as newly identified roles for mucin glycoproteins in the direct regulation of leukocyte functions are discussed. The emergence of this nascent field of glycoimmunobiology sets forth a new paradigm for considering how homeostasis is maintained under healthy conditions and how it is restored in disease. PMID:27587549

  6. Mechanical circulatory assist for pulmonary embolism.

    PubMed

    Misawa, Y; Fuse, K; Yamaguchi, T; Saito, T; Konishi, H

    2000-11-01

    Optimal management of acute pulmonary embolism remains controversial, despite advances in thrombolytic therapy. Haemodynamic instability and, in particular, right ventricular dysfunction is associated with poor outcomes. Urgent surgical embolectomy has been the treatment of choice in this category of patients. We present two cases in which percutaneous cardiopulmonary support (PCPS) was used as an adjunct to thrombolytic therapy for progressive circulatory collapse secondary to massive acute pulmonary embolism. This experience suggests that PCPS may offer an attractive option for a condition which continues to carry significant morbidity and mortality.

  7. Adaptive midlife defense mechanisms and late-life health.

    PubMed

    Malone, Johanna C; Cohen, Shiri; Liu, Sabrina R; Vaillant, George E; Waldinger, Robert J

    2013-07-01

    A growing body of research suggests that personality characteristics relate to physical health; however, this relation ship has primarily been tested in cross-sectional studies that have not followed the participants into old age. The present study utilizes data from a 70-year longitudinal study to prospectively examine the relationship between the adaptive defense mechanisms in midlife and objectively assessed physical health in late life. In addition to examining the direct effect, we test whether social support mediates this relation ship. The sample consisted of 90 men who were followed for over seven decades beginning in late adolescence. Health ratings from medical records were made at three time points (ages 70, 75, and 80). Defense mechanisms were coded from narratives by trained independent raters (Vaillant, Bond, & Vaillant, 1986). Independent raters assessed social supports between ages 50 and 70. More adaptive defenses in midlife were associated with better physical health at all three time points in late life. These relationships were partially mediated by social support. Findings are consistent with the theory that defense maturity is important for building social relationships, which in turn contribute to better late-life physical health. Psychological interventions aimed at improving these domains may be beneficial for physical health.

  8. Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae.

    PubMed

    Samuelson, Derrick R; Shellito, Judd E; Maffei, Vincent J; Tague, Eric D; Campagna, Shawn R; Blanchard, Eugene E; Luo, Meng; Taylor, Christopher M; Ronis, Martin J J; Molina, Patricia E; Welsh, David A

    2017-06-01

    Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these

  9. Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae

    PubMed Central

    Campagna, Shawn R.; Blanchard, Eugene E.; Ronis, Martin J. J.

    2017-01-01

    Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these

  10. 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

  11. Botryticides affect grapevine leaf photosynthesis without inducing defense mechanisms.

    PubMed

    Petit, Anne-Noëlle; Wojnarowiez, Geneviève; Panon, Marie-Laure; Baillieul, Fabienne; Clément, Christophe; Fontaine, Florence; Vaillant-Gaveau, Nathalie

    2009-02-01

    The effects of the two botryticides, fludioxonil (fdx) and fenhexamid (fhd), were investigated on grapevine leaves (Vitis vinifera L. cv. Pinot noir) following photosynthesis and defense mechanisms. Treatments were carried out in vineyard at the end of flowering. Phytotoxicity of both fungicides was evaluated by measuring variations of leaf photosynthetic parameters and correlated expression of photosynthesis-related genes. Results demonstrated that similar decrease in photosynthesis was caused by fdx and fhd applications. Moreover, the mechanism leading to photosynthesis alteration seems to be the same for both fungicides. Stomatal limitation to photosynthetic gas exchange did not change following treatments indicating that inhibition of photosynthesis was mostly attributed to non-stomatal factors. Nevertheless, fungicides-induced depression of photosynthesis was related neither to a decrease in Rubisco carboxylation efficiency and in the capacity for regeneration of ribulose 1,5-bisphosphate nor to loss in PSII activity. However, fdx and fhd treatments generated repression of genes encoding proteins involved in the photosynthetic process. Indeed, decreased photosynthesis was coupled with repression of PsbP subunit of photosystem II (psbP1), chlorophyll a/b binding protein of photosystem I (cab) and Rubisco small subunit (rbcS) genes. A repression of these genes may participate in the photosynthesis alteration. To our knowledge, this is the first study of photosynthesis-related gene expression following fungicide stress. In the meantime, defense responses were followed by measuring chitinase activity and expression of varied defense-related genes encoding proteins involved in phenylpropanoid synthesis (PAL) or octadecanoid synthesis (LOX), as well as pathogenesis-related protein (Chi4C). No induction of defense was observed in botryticides-treated leaves. To conclude, the photosynthesis is affected without any triggering of plant defense responses.

  12. Defense mechanisms of the respiratory system and aerosol production systems.

    PubMed

    Zarogoulidis, Paul; Darwiche, Kaid; Yarmus, Lonny; Spyratos, Dionysios; Secen, Nevena; Hohenforst-Schmidt, Wolfgang; Katsikogiannis, Nikolaos; Huang, Haidong; Gschwendtner, Andreas; Zarogoulidis, Konstantinos

    2014-03-01

    Aerosolized therapies have been used in everyday clinical practice for decades. Experimentation with different delivery systems have led to the creation of aerosolized insulin, antibiotics, gene therapy and chemotherapy. Several of these therapies are already clinically available while others are being investigated in active clinical trials. The main factors affecting the efficiency and safety of the aerosolized therapies are the production of the aerosol, distribution/deposition of the aerosol throughout the lung parenchyma, respiratory defense mechanisms and tissue/pharmaceutical molecule interactions. Current methods of aerosol production and distribution will be presented along with an overview of the respiratory defense mechanisms. In addition, methods of aerosol evaluation in conjunction with a future perspective of the potential development of aerosol therapies will be presented.

  13. The Venturia Apple Pathosystem: Pathogenicity Mechanisms and Plant Defense Responses

    PubMed Central

    Jha, Gopaljee; Thakur, Karnika; Thakur, Priyanka

    2009-01-01

    Venturia inaequalis is the causal agent of apple scab, a devastating disease of apple. We outline several unique features of this pathogen which are useful for molecular genetics studies intended to understand plant-pathogen interactions. The pathogenicity mechanisms of the pathogen and overview of apple defense responses, monogenic and polygenic resistance, and their utilization in scab resistance breeding programs are also reviewed. PMID:20150969

  14. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris.

    PubMed

    Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel

    2008-07-01

    Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.

  15. Current views on the mechanisms of pulmonary oedema.

    PubMed

    Hurley, J V

    1978-06-01

    Understanding of the causes of pulmonary oedema must be based on knowledge of the mechanism responsible for fluid exchange between the several compartments of the normal lung. Recent physiological studies have clarified the main features of these mechanisms. However in three areas knowledge is still incomplete--the magnitude of the hydrostatic and oncotic forces responsible for fluid movement within the lung, the means by which protein leaks across the wall of small pulmonary vessels and the routes by which fluid and protein pass between the interstitial tissues of the lung and the alveolar space. Further work is needed in these areas. On the basis of this physiological knowledge the mode of development of hydrostatic oedema, the role of lymphatics in pulmonary oedema, and the several stages of pulmonary oedema development that may culminate in alveolar flooding are now clearly understood. Knowledge is less complete about oedema due to increased vascular permeability. In some experimental models, such as alloxan, leakage is due to irreversible injury to the alveolar wall; in other models, including ANTU, oedema formation has been shown to depend upon minor and reversible changes in pulmonary vascular endothelium similar to those that cause exudate formation in areas of acute inflammation. In no instance is detailed information available of both the rate and magnitude of protein leakage and of the morphological basis of increased vascular permeability. Further work is required in this area. Present knowledge allows an adequate explanation of the changes that occur in many clinically important types of pulmonary oedema, including cardiac failure and neurogenic pulmonary oedema. Other types of oedema, notably that which may complicate traumatic shock or extrapulmonary sepsis and high altitude pulmonary oedema, are more complex and the details of their pathogenesis are still obscure.

  16. Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

    PubMed Central

    Schulze-Neick, I; Penny, D; Derrick, G; Dhillon, R; Rigby, M; Kelleher, A; Bush, A; Redington, A

    2000-01-01

    BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.
OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.
DESIGN—Prospective, cross sectional study.
SETTING—Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation.
INTERVENTIONS—Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis.
MAIN OUTCOME MEASURES—Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs).
RESULTS—28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H2O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H2O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H2O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold.
CONCLUSIONS—Acute changes in pulmonary blood flow are associated

  17. Lung microbicidal mechanisms and pulmonary hypertension in septic piglets

    SciTech Connect

    Bowdy, B.D.

    1989-01-01

    These studies sought to determine whether the pulmonary hemodynamic abnormalities elicited in infant piglets in response to an intravascular bacterial challenge are dependent upon the clearance and killing of the organism by an oxygen radical dependent mechanism residing within the pulmonary circulation of the host. Initial studies were conducted to ascertain the effect of dimethylthiourea (DMTU), a relatively selective scavenger of hydroxyl radical, on Group B Streptococcus (GBS)-induced pulmonary abnormalities in young piglets. Lung samples from piglets infused with GBS and evaluated by transmission electron microscopy revealed that the GBS had been taken up by pulmonary intravascular macrophages. To determine clearance characteristics of intravascularly administered GBS as well as oxygen radical involvement in pulmonary bactericidal mechanisms, studies were performed in which GBS was radiolabelled with {sup 111}Indium-oxine and infused into piglets in the presence or absence of DMTU. In accord with the previous study, animals receiving GBS only exhibited profound increases in Ppa and TPR with concomitant arterial hypoxemia, all of which were attenuated by the co-administration of DMTU. Bacterial accumulated to the greatest extent in the lung, followed by the liver and spleen.

  18. Defense Mechanisms in Adolescence as Predictors of Adult Personality Disorders.

    PubMed

    Strandholm, Thea; Kiviruusu, Olli; Karlsson, Linnea; Miettunen, Jouko; Marttunen, Mauri

    2016-05-01

    Our study examines whether defense styles and separate defenses in depressed adolescent outpatients predict adult personality disorders (PDs). We obtained data from consecutive adolescent outpatients who participated in the Adolescent Depression Study at baseline and at the 8-year follow-up (N = 140). Defense styles were divided into mature, neurotic, image-distorting, and immature and a secondary set of analyses were made with separate defenses as predictors of a PD diagnosis. Neurotic, image-distorting, and immature defense styles in adolescence were associated with adulthood PDs. Neurotic defense style associated with cluster B diagnosis and image-distorting defense style associated with cluster A diagnosis. Separate defenses of displacement, isolation, and reaction formation were independent predictors of adult PD diagnosis even after adjusting for PD diagnosis in adolescence. Defense styles and separate defenses predict later PDs and could be used in the focusing of treatment interventions for adolescents.

  19. Hypoxic Pulmonary Vasoconstriction: From Molecular Mechanisms to Medicine.

    PubMed

    Dunham-Snary, Kimberly J; Wu, Danchen; Sykes, Edward A; Thakrar, Amar; Parlow, Leah R G; Mewburn, Jeffrey D; Parlow, Joel L; Archer, Stephen L

    2017-01-01

    Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in pulmonary artery smooth muscle cells (PASMC). This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and hypoxia-inducible factor (HIF)-1α, leading to adverse pulmonary vascular remodeling and pulmonary hypertension (PH). In the nonventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis, which optimizes systemic Po2 without altering pulmonary artery pressure (PAP). In single-lung anesthesia, HPV reduces blood flow to the nonventilated lung, thereby facilitating thoracic surgery. At altitude, global hypoxia causes diffuse HPV, increases PAP, and initiates PH. Exaggerated or heterogeneous HPV contributes to high-altitude pulmonary edema. Conversely, impaired HPV, whether due to disease (eg, COPD, sepsis) or vasodilator drugs, promotes systemic hypoxemia. Genetic and epigenetic abnormalities of this oxygen-sensing pathway can trigger normoxic activation of HIF-1α and can promote abnormal metabolism and cell proliferation. The resulting pseudohypoxic state underlies the Warburg metabolic shift and contributes to the neoplasia-like phenotype of PH. HPV and oxygen sensing are important in human health and disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  20. Mechanisms and strategies of plant defense against Botrytis cinerea.

    PubMed

    AbuQamar, Synan; Moustafa, Khaled; Tran, Lam Son

    2017-03-01

    Biotic factors affect plant immune responses and plant resistance to pathogen infections. Despite the considerable progress made over the past two decades in manipulating genes, proteins and their levels from diverse sources, no complete genetic tolerance to environmental stresses has been developed so far in any crops. Plant defense response to pathogens, including Botrytis cinerea, is a complex biological process involving various changes at the biochemical, molecular (i.e. transcriptional) and physiological levels. Once a pathogen is detected, effective plant resistance activates signaling networks through the generation of small signaling molecules and the balance of hormonal signaling pathways to initiate defense mechanisms to the particular pathogen. Recently, studies using Arabidopsis thaliana and crop plants have shown that many genes are involved in plant responses to B. cinerea infection. In this article, we will review our current understanding of mechanisms regulating plant responses to B. cinerea with a particular interest on hormonal regulatory networks involving phytohormones salicylic acid (SA), jasmonic acid (JA), ethylene (ET) and abscisic acid (ABA). We will also highlight some potential gene targets that are promising for improving crop resistance to B. cinerea through genetic engineering and breeding programs. Finally, the role of biological control as a complementary and alternative disease management will be overviewed.

  1. 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.

  2. Do toxic heavy metals affect antioxidant defense mechanisms in humans?

    PubMed

    Wieloch, Monika; Kamiński, Piotr; Ossowska, Anna; Koim-Puchowska, Beata; Stuczyński, Tomasz; Kuligowska-Prusińska, Magdalena; Dymek, Grażyna; Mańkowska, Aneta; Odrowąż-Sypniewska, Grażyna

    2012-04-01

    The aim of this study was to prove whether anthropogenic pollution affects antioxidant defense mechanisms such as superoxide dismutase (SOD) and catalase (CAT) activity, ferritin (FRT) concentration and total antioxidant status (TAS) in human serum. The study area involves polluted and salted environment (Kujawy region; northern-middle Poland) and Tuchola Forestry (unpolluted control area). We investigated 79 blood samples of volunteers from polluted area and 82 from the control in 2008 and 2009. Lead, cadmium and iron concentrations were measured in whole blood by the ICP-MS method. SOD and CAT activities were measured in serum using SOD and CAT Assay Kits by the standardized colorimetric method. Serum TAS was measured spectrophotometrically by the modified Benzie and Strain (1996) method and FRT concentration-by the immunonefelometric method. Pb and Cd levels and SOD activity were higher in volunteers from polluted area as compared with those from the control (0.0236 mg l(-1) vs. 0.014 mg l(-1); 0.0008 mg l(-1) vs. 0.0005 mg l(-1); 0.137 Um l(-1) vs. 0.055 Um l(-1), respectively). Fe level, CAT activity and TAS were lower in serum of volunteers from polluted area (0.442 g l(-1) vs. 0.476 gl(-1); 3.336 nmol min(-1)ml(-1) vs. 6.017 nmol min(-1)ml(-1); 0.731 Trolox-equivalents vs. 0.936 Trolox-equivalents, respectively), whilst differences in FRT concentration were not significant (66.109 μg l(-1) vs. 37.667 μg l(-1), p=0.3972). Positive correlations between Pb (r=0.206), Cd (r=0.602) and SOD in the inhabitants of polluted area, and between Cd and SOD in the control (r=0.639) were shown. In volunteers from both studied environments TAS-FRT (polluted: r=0.625 vs. control: r=0.837) and Fe-FRT (polluted area: r=0.831 vs. control: r=0.407) correlations, and Pb-FRT (r=0.360) and Pb-TAS (r=0.283) in the control were stated. The higher lead and cadmium concentrations in blood cause an increase of SOD activity. It suggests that this is one of the defense mechanisms of an

  3. Kinetic mechanism of pulmonary carbonyl reductase.

    PubMed

    Matsuura, K; Nakayama, T; Nakagawa, M; Hara, A; Sawada, H

    1988-05-15

    The kinetic mechanism of guinea-pig lung carbonyl reductase was studied at pH 7 in the forward reaction with five carbonyl substrates and NAD(P)H and in the reverse reaction with propan-2-ol and NAD(P)+. In each case the enzyme mechanism was sequential, and product-inhibition studies were consistent with a di-iso ordered bi bi mechanism, in which NAD(P)H binds to the enzyme first and NAD(P)+ leaves last and the binding of cofactor induces isomerization. The kinetic and binding studies of the cofactors and several inhibitors such as pyrazole, benzoic acid, Cibacron Blue and benzamide indicate that the cofactor and Cibacron Blue bind to the free enzyme whereas the other inhibitors bind to the binary and/or ternary complexes.

  4. Kinetic mechanism of pulmonary carbonyl reductase.

    PubMed Central

    Matsuura, K; Nakayama, T; Nakagawa, M; Hara, A; Sawada, H

    1988-01-01

    The kinetic mechanism of guinea-pig lung carbonyl reductase was studied at pH 7 in the forward reaction with five carbonyl substrates and NAD(P)H and in the reverse reaction with propan-2-ol and NAD(P)+. In each case the enzyme mechanism was sequential, and product-inhibition studies were consistent with a di-iso ordered bi bi mechanism, in which NAD(P)H binds to the enzyme first and NAD(P)+ leaves last and the binding of cofactor induces isomerization. The kinetic and binding studies of the cofactors and several inhibitors such as pyrazole, benzoic acid, Cibacron Blue and benzamide indicate that the cofactor and Cibacron Blue bind to the free enzyme whereas the other inhibitors bind to the binary and/or ternary complexes. PMID:3048244

  5. 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

  6. 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.

  7. 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.

  8. The comprehensive assessment of defense style: measuring defense mechanisms in children and adolescents.

    PubMed

    Laor, N; Wolmer, L; Cicchetti, D V

    2001-06-01

    This study introduces the Comprehensive Assessment of Defense Style (CADS), a new method to assess descriptively the defensive behavior of children and adolescents. Parents of 124 children and adolescents referred to a mental health clinic, of 104 nontreated children, and of 15 children whose fathers were treated for posttraumatic stress disorder completed the CADS. Factor analysis of 28 defenses yielded one mature factor, one immature factor of defenses expressed in relations with the environment (other-oriented), and one of defenses expressed in relations with the self (self-oriented). The CADS significantly discriminated between patients and nonpatients. Psychiatric patients used more immature and fewer mature defenses than control subjects, and adolescents used more mature and fewer other-oriented defenses than children. Girls used more mature and fewer other-oriented defenses than boys. The reliability and validity data of the CADS are encouraging. The three defense factors may be implemented for diagnostic and clinical purposes as well as for screening for psychopathology risk in untreated populations.

  9. [Neutrophil extracellular traps: a 2-faced host defense mechanism].

    PubMed

    Camicia, Gabriela; de Larrañaga, Gabriela

    2013-01-19

    Neutrophils play a key role in the innate immune system, providing the first line of host defense. In addition to their ability to eliminate pathogens by phagocytosis and antimicrobial secretions, it has recently been shown that neutrophils can trap and kill microorganisms by the release of extracellular structures composed of DNA and antimicrobial proteins called neutrophil extracellular traps (NETs). Although physiological amounts of NETs are important as antimicrobial agents, high levels of NETs in circulation may result in severe tissue damage. Besides, the excessive generation of NETs or a disruption in their clearance mechanism might be associated with the development of certain autoimmune diseases. This review describes the structure, function and generation of NETs, and their possible implication in the initiation and/or progression of different diseases. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  10. Psychosexual fixation and defense mechanisms in a sample of young Japanese women: a preliminary study.

    PubMed

    Mogami, Tamiko

    2010-08-01

    The present pilot study examined psychosexual fixations and defense mechanisms in a sample of young Japanese women. The Lexical Rorschach count and the Defense Mechanisms Inventory were administered to 24 female college students. Sadism on the Lexical Rorschach count was positively correlated with Reversal of Affect. Phallic fixation on the Lexical Rorschach count was positively correlated with Projection. Psychoanalytic hypotheses about the associations between psychosexual fixations and defense mechanisms were partially confirmed.

  11. Jasmonic acid does not increase oxidative defense mechanisms or common defense-related enzymes in postharvest sugarbeet roots

    USDA-ARS?s Scientific Manuscript database

    Jasmonic acid (JA) treatment significantly reduces rot due to several sugarbeet (Beta vulgaris L.) storage pathogens. However, the mechanisms by which JA protects postharvest sugarbeet roots from disease are unknown. In other plant species and organs, alterations in antioxidant defense mechanisms ...

  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. Pulmonary deposition of a nebulised aerosol during mechanical ventilation.

    PubMed Central

    Thomas, S H; O'Doherty, M J; Fidler, H M; Page, C J; Treacher, D F; Nunan, T O

    1993-01-01

    BACKGROUND: There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. METHODS: Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. RESULTS: Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). CONCLUSIONS: Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients. Images PMID:8493630

  14. 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…

  15. 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…

  16. 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.

  17. Ego defense mechanisms in Pakistani medical students: a cross sectional analysis

    PubMed Central

    2010-01-01

    Background Ego defense mechanisms (or factors), defined by Freud as unconscious resources used by the ego to reduce conflict between the id and superego, are a reflection of how an individual deals with conflict and stress. This study assesses the prevalence of various ego defense mechanisms employed by medical students of Karachi, which is a group with higher stress levels than the general population. Methods A questionnaire based cross-sectional study was conducted on 682 students from five major medical colleges of Karachi over 4 weeks in November 2006. Ego defense mechanisms were assessed using the Defense Style Questionnaire (DSQ-40) individually and as grouped under Mature, Immature, and Neurotic factors. Results Lower mean scores of Immature defense mechanisms (4.78) were identified than those for Neurotic (5.62) and Mature (5.60) mechanisms among medical students of Karachi. Immature mechanisms were more commonly employed by males whereas females employed more Neurotic mechanisms than males. Neurotic and Immature defenses were significantly more prevalent in first and second year students. Mature mechanisms were significantly higher in students enrolled in Government colleges than Private institutions (p < 0.05). Conclusions Immature defense mechanisms were less commonly employed than Neurotic and Mature mechanisms among medical students of Karachi. The greater employment of Neurotic defenses may reflect greater stress levels than the general population. Employment of these mechanisms was associated with female gender, enrollment in a private medical college, and students enrolled in the first 2 years of medical school. PMID:20109240

  18. Ego defense mechanisms in Pakistani medical students: a cross sectional analysis.

    PubMed

    Parekh, Maria A; Majeed, Hina; Khan, Tuba R; Khan, Anum B; Khalid, Salman; Khwaja, Nadia M; Khalid, Roha; Khan, Mohammad A; Rizqui, Ibrahim M; Jehan, Imtiaz

    2010-01-29

    Ego defense mechanisms (or factors), defined by Freud as unconscious resources used by the ego to reduce conflict between the id and superego, are a reflection of how an individual deals with conflict and stress. This study assesses the prevalence of various ego defense mechanisms employed by medical students of Karachi, which is a group with higher stress levels than the general population. A questionnaire based cross-sectional study was conducted on 682 students from five major medical colleges of Karachi over 4 weeks in November 2006. Ego defense mechanisms were assessed using the Defense Style Questionnaire (DSQ-40) individually and as grouped under Mature, Immature, and Neurotic factors. Lower mean scores of Immature defense mechanisms (4.78) were identified than those for Neurotic (5.62) and Mature (5.60) mechanisms among medical students of Karachi. Immature mechanisms were more commonly employed by males whereas females employed more Neurotic mechanisms than males. Neurotic and Immature defenses were significantly more prevalent in first and second year students. Mature mechanisms were significantly higher in students enrolled in Government colleges than Private institutions (p < 0.05). Immature defense mechanisms were less commonly employed than Neurotic and Mature mechanisms among medical students of Karachi. The greater employment of Neurotic defenses may reflect greater stress levels than the general population. Employment of these mechanisms was associated with female gender, enrollment in a private medical college, and students enrolled in the first 2 years of medical school.

  19. Immunocytochemistry of plant defense mechanisms induced upon microbial attack.

    PubMed

    Benhamou, N

    1995-05-01

    During the past few years, cyto- and immunocytochemical techniques have been developed and widely used for locating and identifying various molecules in plant cell compartments. The last decade has witnessed tremendous improvements in molecular cytology, thus allowing an accurate in situ detection of various components thought to play important biological functions in the plant metabolism. The use of immunocytochemistry to investigate resistance mechanisms of plants upon pathogen attack has provided key information on the defense strategy that plants elaborate during a host-pathogen interaction. Of the various proteins induced in response to infection, chitinases and beta-1,3-glucanases have been the focus of particular attention due to their believed antimicrobial activity through the hydrolysis of the main fungal wall components, chitin and beta-1,3-glucans. Attention has also been paid to beta-fructosidase, the enzyme that hydrolyzes sucrose into glucose and fructoside. The marked accumulation of this enzyme upon pathogen infection has led to the consideration that infection may greatly influence the metabolic activity of colonized tissues by creating alterations of source-sink relationships. Another facet of the plant's defense strategy that has been the focus of considerable interest is related to the accumulation of structural compounds, such as hydroxyproline-rich glycoproteins and callose, to reinforce the wall architecture, thus decreasing vulnerability to microbial enzymes. A number of alternatives designed to improve plant protection towards pathogen invasion have been suggested. Among these, the production of transgenic plants expressing constitutively a foreign resistance gene and the pretreatment of plants with elicitors of defense reactions have been the subject of intensive studies at the molecular, biochemical, and cytological levels. Results of such studies clearly demonstrate the important contribution that cyto- and immunocytochemical approaches

  20. An Alternative Form of the Defense Mechanisms Inventory: Assessing Chinese University Students

    ERIC Educational Resources Information Center

    Zhang, Li-Fang

    2016-01-01

    To overcome the major weakness in the response format of the Defense Mechanisms Inventory and to use the information most relevant to the population concerned in the present study, an alternative form of the Defense Mechanisms Inventory (DMI-AF) was designed. The 80 Likert-scaled items in the inventory were tested among 385 university students in…

  1. An Alternative Form of the Defense Mechanisms Inventory: Assessing Chinese University Students

    ERIC Educational Resources Information Center

    Zhang, Li-Fang

    2016-01-01

    To overcome the major weakness in the response format of the Defense Mechanisms Inventory and to use the information most relevant to the population concerned in the present study, an alternative form of the Defense Mechanisms Inventory (DMI-AF) was designed. The 80 Likert-scaled items in the inventory were tested among 385 university students in…

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  4. 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.

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

    PubMed Central

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

    2011-01-01

    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 was dependent upon 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 ICAM-1 is locally expressed and actively participates in this process. Injured gp91phox 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

  6. 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.

  7. Preoptic mechanism for cold-defensive responses to skin cooling

    PubMed Central

    Nakamura, Kazuhiro; Morrison, Shaun F

    2008-01-01

    We recently identified a somatosensory pathway that transmits temperature information from the skin to a median subregion of the preoptic area (POA), a thermoregulatory centre. Here, we investigated in vivo the local neuronal circuit in the rat POA that processes the thermosensory information and outputs thermoregulatory effector signals. Skin cooling-evoked increases in sympathetic thermogenesis in brown adipose tissue, in metabolism and in heart rate were reversed by inhibition of neurons in the median preoptic nucleus (MnPO). Glutamatergic stimulation or disinhibition of MnPO neurons evoked thermogenic, metabolic and cardiac responses that mimicked the cold-defensive responses to skin cooling and were reversed by antagonizing GABAA receptors in the medial preoptic area (MPO), which is thought to contain neurons providing thermoregulatory output to effectors. These results suggest that GABA inhibition of output neurons in the MPO by MnPO neurons that are activated by cool sensory signals from the skin is a core thermoregulatory mechanism within the POA that is essential for the feedforward defence of body temperature against cold challenges in the environment. PMID:18388139

  8. Anomalies and specific functions in the clinical identification of defense mechanisms.

    PubMed

    Perry, J Christopher

    2014-05-01

    Standard teaching about defense mechanisms generally focuses on definitions, which do not readily aid the clinician in identifying defenses whenever individuals use them. This report demonstrates a process by which the clinician can identify when a defense is used, which ones are likely being used, and with what aim. Clinicians first notice that a defense may be operating whenever the other individual presents with anomalies in the expression of affect, behavior, speech, or its content. Some of these anomalies are described. Next, to identify the specific defense or general level of defensive functioning used, the clinician must identify the specific function of the defense in context using a process of guided clinical inference. This report examines 2 verbatim examples from recorded interviews of one case to demonstrate this process. The examples present a microcosm of clinical concerns that have a surprising relationship to the individual's course and prognosis.

  9. Mechanical valves in the pulmonary position: An international retrospective analysis.

    PubMed

    Pragt, Hanna; van Melle, Joost P; Javadikasgari, Hoda; Seo, Dong Man; Stulak, John M; Knez, Igor; Hörer, Jürgen; Muñoz-Guijosa, Christian; Dehaki, Mahyar G; Shin, Hong Ju; Dearani, Joseph A; Dehaki, Maziar G; Pieper, Petronella G; Eulenburg, Christine; Dos, Laura; Ebels, Tjark

    2017-10-01

    Life expectancy of patients with congenital heart disease has improved over the past decades, increasing the need for a durable pulmonary prosthetic valve. Biological valves in various forms have become the valve of choice for pulmonary valve replacement (PVR), but structural valve deterioration is unavoidable in the long term. Use of a mechanical valve could be an alternative, but data on long-term outcomes are sparse. We retrospectively collected and analyzed data on 364 patients with mechanical valves implanted in the pulmonary position between 1965 and 2014. The data originate from medical centers in Barcelona (Spain), Graz (Austria), Groningen (the Netherlands), Munich (Germany), Rochester (United States), Seoul (Republic of Korea), and Tehran (Iran). Median follow-up duration was 4.26 years (range, 0-27 years), mean age at implantation was 27.16 ± 12.2 years. Tetralogy of Fallot was the most common primary cardiac diagnosis, with a subgroup of 69.8%. Freedom from valvular thrombosis was 91% (95% confidence interval [CI], 87%-94%) at 5 years and 86% (95% CI, 81%-91%) at 10 years post-PVR. With a success rate up to 88%, thrombolysis was a successful therapy. Freedom from reoperation was 97% (95% CI, 94%-99%) at 5 years post-PVR and 91% (95% CI, 85%-95%) at 10 years. Mechanical PVR is associated with a limited risk of valvular thrombosis. Thrombolysis was an effective treatment in the majority. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  10. Defense Mechanisms and Utilization in Cancer Patients Undergoing Radiation Therapy: A Pilot Study.

    PubMed

    Porcerelli, John H; Cramer, Phebe; Porcerelli, Daniel J; Arterbery, V Elayne

    2017-06-01

    A group of 49 patients who had been diagnosed with cancer during the preceding year and who were receiving radiation therapy were assessed for their use of defense mechanisms, as well as for their level of psychological distress. In addition, their utilization of medical services was determined. It was predicted that the use of services that were under the patients' control-namely, requesting extra outpatient visits and making trips to the emergency department-would be related to the patients' use of defense mechanisms, whereas a treatment option not under the patients' control-overnight hospitalization based on physicians' assessment of condition-would not be related to defense use. The findings confirmed the hypotheses. Outpatient visits were strongly predicted by defense use, whereas hospitalization was determined by psychological distress. However, emergency department visits were determined by both defense use and psychological distress. In addition, an interaction between defense and distress was found to predict hospitalization.

  11. Factors that influence the suppression of pulmonary antibacterial defenses in mice exposed to ozone

    SciTech Connect

    Gilmour, M.I.; Park, P.; Doerfler, D.; Selgrade, M.J.K.

    1993-01-01

    Exposure to ozone (O3) has been shown to increase susceptibility of mice to bacterial infection; however, the underlying mechanism has not been well elucidated. The study investigated the effect of O3 exposure on the ability of mice to combat an infectious challenge of Streptococcus zooepidemicus. Following a 3-h exposure to either air, 0.4 ppm O3, or 0.8 ppm O3, 5- and 9-week-old mice received an aerosol infection of bacteria. Intrapulmonary killing of the bacteria was impaired in the O3-exposed mice. The effect was most severe at the higher dose of O3 in the younger mice, and showed good correlation to subsequent mortality assessed over a 20-day period. Alveolar macrophages (AM) from O3-exposed mice had an impaired ability to phagocytose the bacteria. Additionally, prostaglandin E2 (PGE2) levels, which are known to depress AM function, were increased in the bronchoalveolar lavage fluid of the younger mice following exposure to O3, while pretreatment with indomethacin in the drinking water blunted the increased of PGE2 and reduced O3 enhanced mortality from 53 to 33%. The data show that O3 inhalation can reduce the defensive capability of the murine lung and that this is associated with a reduction in AM phagocytosis. (Copyright (c) 1993 Taylor Francis.)

  12. Heterogeneous mechanics of the mouse pulmonary arterial network.

    PubMed

    Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A

    2016-10-01

    Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more

  13. Change in coping and defense mechanisms across adulthood: longitudinal findings in a European American sample.

    PubMed

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

    2014-02-01

    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.

  14. 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

  15. 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

  16. Pulmonary complications of neuromuscular disease: a respiratory mechanics perspective.

    PubMed

    Allen, Julian

    2010-03-01

    Paediatric neuromuscular disease compromises both the gas exchange and pump functions of the respiratory system. This can have profound implications for both growth and development of the respiratory system, as well as morbidity and mortality. Aspiration lung disease is common, and leads to increasingly restrictive pulmonary physiology over time. Abnormal lung and chest wall mechanics, and weak respiratory muscles, can combine to cause respiratory failure. Improving the balance between the work of breathing (by decreasing the respiratory load) and the respiratory pump (by improving respiratory muscle strength and decreasing respiratory muscle fatigue) can help prevent the onset of respiratory failure. Airway clearance techniques and non-invasive ventilation are two important tools in this effort. Better ways of assessing the respiratory pump, mechanical function, control and fatigue are needed especially in children.

  17. Weight loss in chronic obstructive pulmonary disease. Mechanisms and implications.

    PubMed

    Agust, Alvar G N; Gari, Patricia G; Sauleda, Jaume; Busquets, Xavier

    2002-01-01

    Weight loss occurs frequently in patients with chronic obstructive pulmonary disease (COPD). Although the precise cellular mechanisms underlying weight loss in COPD are unclear, this is a clinically relevant phenomenon because it contributes to limit the exercise capacity of these patients and, therefore, it jeopardizes their quality of life. More importantly, it is a negative prognostic factor that is independent of the degree of lung function impairment present. Thus, weight loss in COPD constitutes a new therapeutic target. This article reviews the mechanisms and potential consequences of weight loss in COPD and highlights areas that needed future research. It is hoped that a better understanding of its pathogenesis may eventually contribute to the development of new therapeutic strategies that contribute to improve the well-being and/or long-term prognosis of patients suffering from this devastating disease and, potentially, from others characterized also by unexplained weight loss.

  18. Factors that influence the suppression of pulmonary antibacterial defenses in mice exposed to ozone

    SciTech Connect

    Gilmour, M.I.; Park, P.; Doerfler, D.; Selgrade, M.K. )

    1993-05-01

    Exposure to ozone (O3) has been shown to increase susceptibility of mice to bacterial infection; however, the underlying mechanism has not been well elucidated. This study investigated the effect of O3 exposure on the ability of mice to combat an infectious challenge of Streptococcus zooepidemicus. Following a 3-h exposure to either air, 0.4 ppm O3, or 0.8 ppm O3, 5- and 9-week-old mice received an aerosol infection of bacteria. Intrapulmonary killing of the bacteria was impaired in the O3-exposed mice. The effect was most severe at the higher dose of O3 in the younger mice, and showed good correlation to subsequent mortality assessed over a 20-day period. Alveolar macrophages (AM) from O3-exposed mice had an impaired ability to phagocytose the bacteria. Additionally, prostaglandin E2 (PGE2) levels, which are known to depress AM function, were increased in the bronchoalveolar lavage fluid of the younger mice following exposure to O3, while pretreatment with indomethacin in the drinking water blunted the increased of PGE2 and reduced O3 enhanced mortality from 53 to 33%. The data show that O3 inhalation can reduce the defensive capability of the murine lung and that this is associated with a reduction in AM phagocytosis. The defect is more marked in young mice, suggesting that they may be more susceptible to oxidant exposure. Further studies are required to distinguish between direct toxicity of O3 on the AM and indirect suppression due to modulation of pharmacologic or inflammatory mediators.

  19. Object relations and defense mechanisms of a psychopathic serial sexual homicide perpetrator: a TAT analysis.

    PubMed

    Porcerelli, J H; Abramsky, M F; Hibbard, S; Kamoo, R

    2001-08-01

    The case of a 24-year-old African American man who committed serial sexual homicide and who met criteria (Hare, 1991) for psychopathy is presented. His Thematic Apperception Test (Murray, 1943) responses were used to code key aspects of personality organization--object relations and defense mechanisms--via the Social Cognition and Object Relations Scale (Westen, Lohr, Silk, & Kerber, 1989) and the Defense Mechanisms Manual (Cramer, 1991), respectively. Severe object relations pathology and a reliance on the defense mechanism of immature projection and immature denial are noted. Findings are relatively consistent with previous psychodynamic Rorschach studies of psychopathic sexual homicide perpetrators (Gacono, Meloy, & Bridges, 2000; Meloy, Gacono, & Kenney, 1994).

  20. 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

  1. 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.

  2. [Concepts and monitoring of pulmonary mechanic in patients under ventilatory support in intensive care unit].

    PubMed

    Faustino, Eduardo Antonio

    2007-06-01

    In mechanical ventilation, invasive and noninvasive, the knowledge of respiratory mechanic physiology is indispensable to take decisions and into the efficient management of modern ventilators. Monitoring of pulmonary mechanic parameters is been recommended from all the review works and clinical research. The objective of this study was review concepts of pulmonary mechanic and the methods used to obtain measures in the bed side, preparing a rational sequence to obtain this data. It was obtained bibliographic review through data bank LILACS, MedLine and PubMed, from the last ten years. This review approaches parameters of resistance, pulmonary compliance and intrinsic PEEP as primordial into comprehension of acute respiratory failure and mechanic ventilatory support, mainly in acute respiratory distress syndrome (ARDS) and in chronic obstructive pulmonary disease (COPD). Monitoring pulmonary mechanics in patients under mechanical ventilation in intensive care units gives relevant informations and should be implemented in a rational and systematic way.

  3. Ego functions and ego development: defense mechanisms and intelligence as predictors of ego level.

    PubMed

    Cramer, P

    1999-10-01

    This study considers the contribution of two ego functions--intelligence and defense mechanisms--to ego developmental level. Two independent assessments of ego level were related to IQ and defense mechanism use in a sample of 89 young adults. Whereas IQ and defense were themselves found to be unrelated, both variables predicted ego level: The relation with IQ was linear, whereas the relation with defense was curvilinear. In addition, the relation between defense and ego level varied as a function of IQ level. At low levels of IQ, stronger use of Denial and Projection was associated with higher ego levels. At high IQ levels, strong use of Denial was associated with lower ego levels, whereas moderate use of Projection was associated with higher ego levels.

  4. Turning passive into active: a building block of ego and fundamental mechanism of defense.

    PubMed

    Corradi, Richard B

    2007-01-01

    Turning passive into active is an ego function that plays an important role in managing anxiety associated with passive feelings of helplessness and powerlessness. Its use in childhood aids the ego in constructing a basic sense of mastery, a secure sense of being in control, both of oneself and of one's circumstances. Functioning first as a building block of ego, it subsequently becomes a versatile mechanism of defense with utility throughout the life cycle. This article discusses both the developmental and defensive uses of the passive into active mechanism of defense and illustrates them with clinical examples. Often regarded only as a byproduct of defense, its importance in mastering core developmental anxieties and their adult revivals warrants its inclusion in the glossary of discrete defenses.

  5. [The values of the lipid peroxidation-antioxidative defense system as predictors of the poor course of infiltrative pulmonary tuberculosis].

    PubMed

    Volchegorskiĭ, I A; Novoselov, P N; Bolotov, A A

    2008-01-01

    The authors have studied whether an indirect clinical-and-laboratory assessment of the extent of a destructive process in the tuberculous infiltrates and that of concomitant pleural affection can be made from the values of the lipid peroxidation-antioxidative defense (PLO-AOD) system in the blood of patients with infiltrative pulmonary tuberculosis (IPT). Regression analysis has indicated that PLO-AOD values significantly reflect the extent of X-ray verified destructions in the tuberculous infiltrates, concomitant pleural involvements, the specific features of immunity of patients with IPT. The neural network technology used to analyze the baseline PLO-AOD values has been ascertained to permit a reliable prognosis of decay cavity closure 4 months after the initiation of medical treatment and of a need for surgical treatment for IPT.

  6. 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 ...

  7. 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 ...

  8. 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.

  9. [The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

    PubMed

    Evlakhov, V I; Poiasov, I Z

    2012-05-01

    In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

  10. Immature psychological defense mechanisms are associated with greater personal importance of junk food, alcohol, and television.

    PubMed

    Costa, Rui Miguel; Brody, Stuart

    2013-10-30

    Immature psychological defense mechanisms are psychological processes that play an important role in suppressing emotional awareness and contribute to psychopathology. In addition, unhealthy food, television viewing, and alcohol consumption can be among the means to escape self-awareness. In contrast, engaging in, and responding fully to specifically penile-vaginal intercourse (PVI) is associated with indices of better emotional regulation, including less use of immature defense mechanisms. There was a lack of research on the association of immature defense mechanisms with personal importance of junk food, alcohol, television, PVI, and noncoital sex. In an online survey, 334 primarily Scottish women completed the Defense Style Questionnaire (DSQ-40), and rated the personal importance of junk food, alcohol, television, PVI, and noncoital sex. Immature defense mechanisms correlated with importance of junk food, alcohol, and television. Importance of PVI correlated with mature defenses, and less use of some component immature defenses. Importance of alcohol correlated with importance of junk food, television, and noncoital sex. Importance of junk food was correlated with importance of television and noncoital sex. The findings are discussed in terms of persons with poorer self-regulatory abilities having more interest in junk food, television, and alcohol, and less interest in PVI. © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Strain-specific pulmonary defense achieved after repeated airway immunizations with non-typeable haemophilus influenzae in a mouse model.

    PubMed

    Koyama, Jun; Ahmed, Kamruddin; Zhao, Jizi; Saito, Mariko; Onizuka, Shozaburo; Oma, Keita; Watanabe, Kiwao; Watanabe, Hiroshi; Oishi, Kazunori

    2007-01-01

    Strain-specific immune responses may play a critical role in the acute exacerbation of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of surface antigens of NTHi, which may contribute to the strain-specific protective immunity. We examined whether repeated airway immunizations with killed-NTHi strains bearing different P2 molecules were capable of inducing protective immunity against homologous or heterologous strains in the lungs of a mouse model. Three different strains of NTHi were used in this study. Three serial intratracheal (IT) immunizations of a single strain or three different strains of NTHi led to the production of cross-reactive immunoglobulins G and A in bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain enhanced the bacterial clearance of the homologous strain in the lungs, but no enhancement of bacterial clearance was found with three serial IT immunizations of heterologous strains. The enhancement in bacterial clearance, therefore, appears to be primarily strain-specific. Enhanced bacterial clearance of a heterologous strain was also found after three serial IT immunizations of a single strain among two of the three strains employed for bacterial challenge. These findings suggest that P2 molecules and surface antigens other than P2 are involved in the development of pulmonary defense against NTHi in mice. Our data may explain, in part, why patients with COPD experience recurrent NTHi infections.

  12. Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

    PubMed Central

    Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia; Serota, Matthew; Kanterakis, Stathis; Chatterjee, Shampa; Solomides, Charalambos C.; Javvadi, Prashanthi; Koumenis, Constantinos; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2010-01-01

    The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1%or 5%(w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5%dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation. PMID:20426658

  13. 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.

  14. 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

  15. [High altitude pulmonary edema. An experiment of nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans].

    PubMed

    Schwab, Marcos; Jayet, Pierre-Yves; Allemann, Yves; Sartori, Claudio; Scherrer, Urs

    2007-01-01

    High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.

  16. Study of defensive methods and mechanisms in developmental, emotional (internalization), and disruptive behavior (externalization) disorders.

    PubMed

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

    2014-09-18

    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.

  17. The relationship between attachment styles and alexithymia: mediating role of defense mechanisms.

    PubMed

    Besharat, Mohammad Ali; Khajavi, Zeinab

    2013-12-01

    This study examined the mediating role of ego defense mechanisms on the relationship between attachment styles and alexithymia. Four hundred and forty-three Iranian high school students (213 boys, 230 girls) participated in this study. Participants completed Defense Styles Questionnaire (DSQ-40), Adult Attachment Inventory (AAI), and Farsi version of the Toronto Alexithymia Scale (FTAS-20). Results showed a significant negative correlation between secure attachment style and alexithymia, while avoidant and ambivalent attachment styles showed significant positive associations with alexithymia. Regression analysis indicated that defense mechanisms have a mediating role between attachment styles and alexithymia. It can be concluded that a mediation role of ego defense mechanisms on the relationship between attachment styles and alexithymia was partial. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis.

    PubMed

    Sriram, Narayanan; Kalayarasan, Srinivasan; Sudhandiran, Ganapasam

    2008-07-01

    Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.

  19. 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.

  20. Association between defense mechanisms and psychiatric symptoms in North Korean Refugees.

    PubMed

    Jun, Jin Yong; Lee, Yu-Jin G; Lee, So-Hee; Yoo, So Young; Song, Jungeun; Kim, Seog Ju

    2015-01-01

    Defense mechanism may contribute to psychiatric symptoms. Refugees are vulnerable to various psychiatric symptoms, such as depression, anxiety, somatization, and those associated with post-traumatic stress disorder (PTSD), due to their traumatic or stressful experiences. We aimed to investigate the mediating role of each defense mechanism in the occurrence of specific psychiatric symptoms in North Korean refugees. Among 213 North Korean refugees initially recruited, 201 completed the following questionnaires: the Defense Style Questionnaire, the Center for Epidemiological Studies-Depression Scale (CES-D), the State-Trait Anxiety Inventory-State (STAI-S), the somatization subscale of Symptom Check-List-90-Revised (SCL-90-R), and the Impact of Event Scale-Revised (IES-R). Stepwise regression analysis was performed to determine the defense mechanisms more predominantly associated with specific psychiatric symptoms after controlling for age, sex, number of traumatic experiences, and other psychiatric symptoms (depressive symptoms and/or anxiety). Higher levels of depression were independently predicted by greater use of resignation. More use of acting out and less use of humor and sublimation independently predicted higher levels of anxiety. Somatization was independently predicted by more use of inhibition. PTSD symptoms were independently predicted by more use of undoing and isolation. Specific psychiatric symptoms were associated with specific defense mechanisms in North Korean refugees. Our findings suggest that the manifest psychiatric symptoms of refugees may be mediated by their dominant defense mechanism. Copyright © 2014. Published by Elsevier Inc.

  1. Pulmonary Mechanics and Mortality in Mechanically Ventilated Patients without Acute Respiratory Distress Syndrome: A Cohort Study.

    PubMed

    Fuller, Brian M; Page, David; Stephens, Robert J; Roberts, Brian W; Drewry, Anne M; Ablordeppey, Enyo; Mohr, Nicholas M; Kollef, Marin H

    2017-08-25

    Driving pressure has been proposed as a major determinant of outcome in patients with acute respiratory distress syndrome (ARDS), but there is little data examining the association between pulmonary mechanics, include driving pressure, and outcomes in mechanically ventilated patients without ARDS. Secondary analysis from 1,705 mechanically ventilated patients enrolled in a clinical study that examined outcomes associated with the use of early lung-protective mechanical ventilation. The primary outcome was mortality and the secondary outcome was the incidence of ARDS. Multivariable models were constructed to: 1) define the association between pulmonary mechanics (driving pressure, plateau pressure, and compliance) and mortality; and 2) evaluate if driving pressure contributed information beyond that provided by other pulmonary mechanics. The mortality rate for the entire cohort was 26.0%. Compared with survivors, non-survivors had significantly higher driving pressure [15.9 (5.4) vs. 14.9 (4.4), p = 0.005] and plateau pressure [21.4 (5.7) vs. 20.4 (4.6)), p = 0.001]. Driving pressure was independently associated with mortality [adjusted OR, 1.04 (1.01-1.07)]. Models related to plateau pressure also revealed an independent association with mortality, with similar effect size and interval estimates as driving pressure. There were 152 patients that progressed to ARDS (8.9%). Along with driving pressure and plateau pressure, mechanical power [adjusted OR, 1.03 (1.00-1.06)] was also independently associated with ARDS development CONCLUSIONS:: In mechanically ventilated patients, driving pressure and plateau pressure are risk factors for mortality and ARDS, and provide similar information. Mechanical power is also a risk factor for ARDS.

  2. The IκB family member Bcl-3 coordinates the pulmonary defense against Klebsiella pneumoniae infection.

    PubMed

    Pène, Frédéric; Paun, Andrea; Sønder, Søren Ulrik; Rikhi, Nimisha; Wang, Hongshan; Claudio, Estefania; Siebenlist, Ulrich

    2011-02-15

    Bcl-3 is an atypical member of the IκB family that has the potential to positively or negatively modulate nuclear NF-κB activity in a context-dependent manner. Bcl-3's biologic impact is complex and includes roles in tumorigenesis and diverse immune responses, including innate immunity. Bcl-3 may mediate LPS tolerance, suppressing cytokine production, but it also seems to contribute to defense against select systemic bacterial challenges. However, the potential role of Bcl-3 in organ-specific host defense against bacteria has not been addressed. In this study, we investigated the relevance of Bcl-3 in a lung challenge with the Gram-negative pathogen Klebsiella pneumoniae. In contrast to wild-type mice, Bcl-3-deficient mice exhibited significantly increased susceptibility toward K. pneumoniae pneumonia. The mutant mice showed increased lung damage marked by neutrophilic alveolar consolidation, and they failed to clear bacteria in lungs, which correlated with increased bacteremic dissemination. Loss of Bcl-3 incurred a dramatic cytokine imbalance in the lungs, which was characterized by higher levels of IL-10 and a near total absence of IFN-γ. Moreover, Bcl-3-deficient mice displayed increased lung production of the neutrophil-attracting chemokines CXCL-1 and CXCL-2. Alveolar macrophages and neutrophils are important to antibacterial lung defense. In vitro stimulation of Bcl-3-deficient alveolar macrophages with LPS or heat-killed K. pneumoniae recapitulated the increase in IL-10 production, and Bcl-3-deficient neutrophils were impaired in intracellular bacterial killing. These findings suggest that Bcl-3 is critically involved in lung defense against Gram-negative bacteria, modulating functions of several cells to facilitate efficient clearance of bacteria.

  3. A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense

    PubMed Central

    Caughey, George H.

    2008-01-01

    Airways are protected from pathogens by forces allied with innate and adaptive immunity. Recent investigations establish critical defensive roles for leukocyte and mast cell serine-class peptidases garrisoned in membrane-bound organelles-here termed Granule-Associated Serine Peptidases of Immune Defense, or GASPIDs. Some better characterized GASPIDs include neutrophil elastase and cathepsin G (which defend against bacteria), proteinase-3 (targeted by antineutrophil antibodies in Wegener’s vasculitis), mast cell β-tryptase and chymase (which promote allergic inflammation), granzymes A and B (which launch apoptosis pathways in infected host cells), and factor D (which activates complement’s alternative pathway). GASPIDs can defend against pathogens but can harm host cells in the process, and therefore become targets for pharmaceutical inhibition. They vary widely in specificity, yet are phylogenetically similar. Mammalian speciation supported a remarkable flowering of these enzymes as they co-evolved with specialized immune cells, including mast cells, basophils, eosinophils, cytolytic T-cells, natural killer cells, neutrophils, macrophages and dendritic cells. Many GASPIDs continue to evolve rapidly, providing some of the most conspicuous examples of divergent protein evolution. Consequently, students of GASPIDs are rewarded not only with insights into their roles in lung immune defense but also with clues to the origins of cellular specialization in vertebrate immunity. PMID:18516248

  4. HOST DEFENSE AGAINST BACTERIAL ENDOTOXEMIA: MECHANISM IN NORMAL ANIMALS

    PubMed Central

    Skarnes, Robert C.

    1970-01-01

    The present study defines the early response of normal rabbits to the intravenous injection of a single, sublethal dose of endotoxin. Within the first few hours following endotoxin there occurs in the circulating plasma of recipients a decrease in ionized calcium, a threefold increase in the heat-stable, organo-phosphate-resistant esterase level, and a striking increase in the endotoxin-detoxifying capacity. These results are fully consistent with the thesis that circulating plasma represents a principal site of detoxification and that plasma esterases of the nonspecific, carboxylic type are of major concern in defense against circulating endotoxins. PMID:4994446

  5. Activation of Defense Mechanisms against Pathogens in Mosses and Flowering Plants

    PubMed Central

    de León, Inés Ponce; Montesano, Marcos

    2013-01-01

    During evolution, plants have developed mechanisms to cope with and adapt to different types of stress, including microbial infection. Once the stress is sensed, signaling pathways are activated, leading to the induced expression of genes with different roles in defense. Mosses (Bryophytes) are non-vascular plants that diverged from flowering plants more than 450 million years ago, allowing comparative studies of the evolution of defense-related genes and defensive metabolites produced after microbial infection. The ancestral position among land plants, the sequenced genome and the feasibility of generating targeted knock-out mutants by homologous recombination has made the moss Physcomitrella patens an attractive model to perform functional studies of plant genes involved in stress responses. This paper reviews the current knowledge of inducible defense mechanisms in P. patens and compares them to those activated in flowering plants after pathogen assault, including the reinforcement of the cell wall, ROS production, programmed cell death, activation of defense genes and synthesis of secondary metabolites and defense hormones. The knowledge generated in P. patens together with comparative studies in flowering plants will help to identify key components in plant defense responses and to design novel strategies to enhance resistance to biotic stress. PMID:23380962

  6. Activation of Defense Mechanisms against Pathogens in Mosses and Flowering Plants.

    PubMed

    Ponce de León, Inés; Montesano, Marcos

    2013-02-04

    During evolution, plants have developed mechanisms to cope with and adapt to different types of stress, including microbial infection. Once the stress is sensed, signaling pathways are activated, leading to the induced expression of genes with different roles in defense. Mosses (Bryophytes) are non-vascular plants that diverged from flowering plants more than 450 million years ago, allowing comparative studies of the evolution of defense-related genes and defensive metabolites produced after microbial infection. The ancestral position among land plants, the sequenced genome and the feasibility of generating targeted knock-out mutants by homologous recombination has made the moss Physcomitrella patens an attractive model to perform functional studies of plant genes involved in stress responses. This paper reviews the current knowledge of inducible defense mechanisms in P. patens and compares them to those activated in flowering plants after pathogen assault, including the reinforcement of the cell wall, ROS production, programmed cell death, activation of defense genes and synthesis of secondary metabolites and defense hormones. The knowledge generated in P. patens together with comparative studies in flowering plants will help to identify key components in plant defense responses and to design novel strategies to enhance resistance to biotic stress.

  7. Cellular defense mechanisms against lead toxicity in the vascular system.

    PubMed

    Shinkai, Yasuhiro; Kaji, Toshiyuki

    2012-01-01

    Lead is a toxic heavy metal that can cause a range of health problems. In this context, the vascular system is a particular target of the deleterious effects of lead. Lead exerts its toxicity through substitution of other divalent cations such as calcium and zinc, resulting in disruption of homeostasis. Based on the evidence that lead up-regulates endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (GRP78) and/or antioxidant proteins such as hemeoxygenase-1, it is believed that the heavy metal is able to induce ER and/or oxidative stress in cells. These events also suggest that the unfolded protein response (UPR) system and the antioxidant defense system Kelch-like ECH-associated protein 1-nuclear factor (NF)-E2-related factor 2 (Keap1-Nrf2) play a critical role in adaptive response to lead. In this review, we summarize recent progress in lead toxicity in terms of cellular defense systems, including stress proteins and transcription factors involved in the vascular system.

  8. 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

  9. 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.

  10. 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.

  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. An empirical look at the Defense Mechanism Test (DMT): reliability and construct validity.

    PubMed

    Ekehammar, Bo; Zuber, Irena; Konstenius, Marja-Liisa

    2005-07-01

    Although the Defense Mechanism Test (DMT) has been in use for almost half a century, there are still quite contradictory views about whether it is a reliable instrument, and if so, what it really measures. Thus, based on data from 39 female students, we first examined DMT inter-coder reliability by analyzing the agreement among trained judges in their coding of the same DMT protocols. Second, we constructed a "parallel" photographic picture that retained all structural characteristic of the original and analyzed DMT parallel-test reliability. Third, we examined the construct validity of the DMT by (a) employing three self-report defense-mechanism inventories and analyzing the intercorrelations between DMT defense scores and corresponding defenses in these instruments, (b) studying the relationships between DMT responses and scores on trait and state anxiety, and (c) relating DMT-defense scores to measures of self-esteem. The main results showed that the DMT can be coded with high reliability by trained coders, that the parallel-test reliability is unsatisfactory compared to traditional psychometric standards, that there is a certain generalizability in the number of perceptual distortions that people display from one picture to another, and that the construct validation provided meager empirical evidence for the conclusion that the DMT measures what it purports to measure, that is, psychological defense mechanisms.

  13. Expression and mechanism of BRP-39 in bleomycin-induced pulmonary fibrosis in rat.

    PubMed

    Du, Chunxian; Yang, Yibing; Lin, Yuhui; Yang, Jiong

    2014-09-01

    The purpose of the study was to explore the effects of breast regression protein 39 (BRP-39) in bleomycin-induced pulmonary fibrosis and its mechanism in pulmonary fibrosis by studying change in BRP-39 to provide a novel direction for the treatment of idiopathic pulmonary fibrosis. SPF grade male C57BL/6 rats were randomly divided into three groups, including bleomycin group, bleomycin+ BRP-39 recombinant protein group and control group. HE and Masson staining were applied to test the change in lung tissue after being treated by BRP-39, ELISA was applied to test the expression of TGF-β1 in different groups, and Western blot was used to test the expression of BRP-39 in rat lung tissue. Expression of BRP-39 increased, the fibrosis was obvious, and lung tissue collagen increased in bleomycin-induced pulmonary fibrosis in rat lung tissue. Increasing BRP-39 protein level and intratracheal bleomycin medication to establish pulmonary fibrosis model can aggravate pulmonary fibrosis. Along with the increase in BRP-39 protein level, TGF-β1 expression level also increased in lung tissue. Western blot results showed the expression of BRP-39, and TGF-β1 had the same trend in different groups. BRP-39 has effects in bleomycin-induced rat pulmonary fibrosis. Change in BRP-39 can affect the process of bleomycin-induced pulmonary fibrosis. The mechanism of BRP-3 in pulmonary fibrosis may work by regulating TGF-β1.

  14. 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.

  15. CXCR1/CXCR2 antagonism is effective in pulmonary defense against Klebsiella pneumoniae infection.

    PubMed

    Wei, Jing; Peng, Jing; Wang, Bing; Qu, Hong; Wang, Shiyi; Faisal, Aziz; Cheng, Jia-Wei; Gordon, John R; Li, Fang

    2013-01-01

    Klebsiella pneumoniae-associated pathology is largely mediated by neutrophilic inflammation. In this study, we administered Klebsiella pneumoniae to experimental guinea pig groups and the ELR-CXC chemokine antagonist CXCL8(3-72), ceftazidime, and dexamethasone to different groups, respectively. After 24 h, we assessed the animal's pulmonary inflammatory levels, including gross histopathology, airway neutrophilia, lung myeloperoxidase levels, expressions of CXCL8 and TNF, and airway bacterial loads. Compared with ceftazidime and dexamethasone treatments, the administration of the ELR-CXC chemokine antagonist CXCL8(3-72) alone was more effective than other methods, although it did not markedly attenuate the bacterial load. These results suggest new methods for the treatment of Klebsiella pneumoniae pathology.

  16. Mechanism of change in pulmonary shunt flow with hemorrhage.

    PubMed

    Colley, P S; Cheney, F W; Butler, J

    1977-02-01

    In the presence of regional atelectasis, hemorrhage increases the pulmonary shunt fraction (Qs/Qt). We wanted to determine if the increase in Qs/Qt occurs due to inhibition of hypoxic vasoconstriction or due to hydrostatic effects associated with a collapsed lung and decrease in cardiac output. We compared the effects of hemorrhage on flow to a hypoxic lung (Qh) produced in two ways in anesthetized dogs. In six dogs atelectasis of one lung was produced by bronchial occlusion and in a second group of six dogs one lung was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% O2. Hemorrhage (20 ml/kg) had no effect on Qh/Qt in dogs with a nitrogen-ventilated lung suggesting that hemorrhage did not inhibit hypoxic vasoconstriction. In contrast, hemorrhage caused a marked increase in Qh/Qt in dogs with a collapsed lung because the flow to the inflated ventilated lung fell, while flow to the collapsed lung did not change. The increase in Qs/Qt in the dogs with atelectasis can be explained solely on the basis of mechanical effects produced by the differences in lung heights and alveolar pressures between ventilated and atelectatic lung.

  17. Cellular and molecular mechanisms of chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J

    2014-03-01

    Chronic obstructive pulmonary disease is associated with chronic inflammation affecting predominantly lung parenchyma and peripheral airways and results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, and T lymphocytes, which are recruited from the circulation. Oxidative stress plays a key role in driving this inflammation. The pulmonary inflammation may enhance the development and growth of lung cancer. The peripheral inflammation extends into the circulation, resulting in systemic inflammation with the same inflammatory proteins. Systemic inflammation may worsen comorbidities. Treatment of pulmonary inflammation may therefore have beneficial effects.

  18. Pulmonary embolism in mechanically ventilated patients requiring computed tomography: Prevalence, risk factors, and outcome.

    PubMed

    Minet, Clémence; Lugosi, Maxime; Savoye, Pierre Yves; Menez, Caroline; Ruckly, Stéphane; Bonadona, Agnès; Schwebel, Carole; Hamidfar-Roy, Rebecca; Dumanoir, Perrine; Ara-Somohano, Claire; Ferretti, Gilbert R; Timsit, Jean-François

    2012-12-01

    To estimate the rate of pulmonary embolism among mechanically ventilated patients and its association with deep venous thrombosis. Prospective cohort study. Medical intensive care unit of a university-affiliated teaching hospital. mechanically ventilated patients requiring a thoracic contrast-enhanced computed tomography scan for any medical reason. a diagnosis of pulmonary embolism before intensive care unit admission, an allergy to contrast agents, and age younger than 18 yrs. All the mechanically ventilated patients requiring a thoracic computed tomography underwent the standard imaging protocol for pulmonary embolism detection. Therapeutic anticoagulation was given immediately after pulmonary embolism diagnosis. All the included patients underwent a compression ultrasound of the four limbs within 48 hrs after the computed tomography scan to detect deep venous thrombosis. Of 176 included patients, 33 (18.7%) had pulmonary embolism diagnosed by computed tomography, including 20 (61%) with no clinical suspicion of pulmonary embolism. By multiple logistic regression, independent risk factors for pulmonary embolism were male gender, high body mass index, history of cancer, past medical history of deep venous thrombosis, coma, and high platelet count. Previous prophylactic anticoagulant use was not a risk factor for pulmonary embolism. Of the 176 patients, 35 (19.9%) had deep venous thrombosis by compression ultrasonography, including 20 (57.1%) in the lower limbs and 24 (68.6%) related to central venous catheters. Of the 33 pulmonary embolisms, 11 (33.3%) were associated with deep venous thrombosis. The pulmonary embolism risk was increased by lower-limb deep venous thrombosis (odds ratio 4.0; 95% confidence interval 1.6-10) but not upper-limb deep venous thrombosis (odds ratio 0.6; 95% confidence interval 0.1-2.9). Crude comparison of patients with and without pulmonary embolism shows no difference in length of stay or mortality. In mechanically ventilated patients

  19. 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…

  20. 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…

  1. Signal Mechanisms of Vascular Remodeling in the Development of Pulmonary Arterial Hypertension.

    PubMed

    Li, Ming-xing; Jiang, De-qi; Wang, Yan; Chen, Qing-zhuang; Ma, Yan-jiao; Yu, Shan-shan; Wang, Yong

    2016-02-01

    Pulmonary artery hypertension (PAH) is a chronic progressive disease characterized by persistent elevation of pulmonary arterial vascular pressure. The disease severely limits the function of the right ventricle, causing organ failure and finally leading to death. Despite significant advances in pharmacological treatments, PAH remains an incurable disease with high morbidity and mortality. The histopathological change of PAH is featured by remodeling of the pulmonary vascular. Abnormal proliferation of pulmonary artery smooth muscle cells in peripheral vascular is 1 major pathological finding of pulmonary vascular remodeling. Current therapeutics available for PAH primarily aim at inhibiting the pulmonary vasoconstriction and resisting pulmonary vascular remodeling. To date, only some inhibitors targeting proliferative signaling pathways have been used to suppress the proliferation of pulmonary artery smooth muscle cells and reverse pulmonary vascular remodeling. However, because of serious side effects, their clinical use is limited, and more validation is needed before the inhibitors can be transferred into clinical use. This review will focus on signal mechanisms of vascular remodeling in the development of PAH and give an overview of recent advances in research on inhibitors targeting proliferative pathways.

  2. 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.

  3. Pulmonary pathophysiology and lung mechanics in anesthesiology: a case-based overview.

    PubMed

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

    2012-12-01

    Anesthesia, surgical requirements, and patients' unique pathophysiology all combine to make the accumulated knowledge of respiratory physiology and lung mechanics vital in patient management. This article take a case-based approach to discuss how the complex interactions between anesthesia, surgery, and patient disease affect patient care with respect to pulmonary pathophysiology and clinical decision making. Two disparate scenarios are examined: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass. The impacts of important concepts in pulmonary physiology and respiratory mechanics on clinical management decisions are discussed.

  4. Ego Defense Mechanisms and Types of Object Relations in Adults With ADHD.

    PubMed

    de Almeida Silva, Vanessa; Louzã, Mario Rodrigues; da Silva, Maria Aparecida; Nakano, Eduardo Yoshio

    2016-11-01

    This research evaluates the personality structure of adults with ADHD from a psychodynamic perspective. The hypothesis was that possible structural characteristics in personality could be correlated with this syndrome. Assessment tools for ego functions (Bell Object Relations and Reality Testing Inventory [BORRTI-Form O], Defense Style Questionnaire ( DSQ-40)) were applied to a sample of 90 adults with ADHD, recruited in a specialized clinic. Among the ADHD sample, 84.4% of the participants were identified as having object relations pathologies. Pathological elevations were observed mainly in the Alienation, Egocentricity, and Insecure Attachment subscales. Statistically, significant differences were found especially in the use of immature and neurotic defense mechanisms, compared with normative data. The findings indicate that adults with ADHD make more use of immature and neurotic defense mechanisms, and presented pathological internalized object relations that are typical of an archaic and poorly structured egoic structure. © The Author(s) 2012.

  5. Affective temperaments and ego defense mechanisms associated with somatic symptom severity in a large sample.

    PubMed

    Hyphantis, Thomas N; Taunay, Tauily C; Macedo, Danielle S; Soeiro-de-Souza, Márcio G; Bisol, Luísa W; Fountoulakis, Konstantinos N; Lara, Diogo R; Carvalho, André F

    2013-09-05

    Several complex mechanisms including biological, psychological and social factors may contribute to the development of bodily symptoms. Affective temperaments may represent heritable subclinical manifestations of mood disorders, and the concept of ego defense mechanisms has also provided a model for the comprehension of psychopathology. The relationship between affective temperaments, defensive functioning and somatic symptom severity remains unknown. We obtained data from a subsample of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). Participants completed the Affective and Emotional Temperament Composite Scale (AFECTS), the Defense Style Questionnaire (DSQ-40) and the Symptom Checklist-90-Revised (SCL-90-R). SCL-90-R Somatization scale was used as outcome variable. Among 9937 participants (4472 male; 45%), individuals with dysphoric, cyclothymic and depressive temperaments and those who adopted displacement, somatisation and passive aggression as their predominant defense mechanisms presented high somatic symptom severity. Participants with dysphoric temperament and those with higher displacement scores were more likely to endorse numerous bodily symptoms after controlling for age, gender, education and depressive symptoms. Moderator analysis showed that the relationship of dysphoric temperament with somatic symptom severity was much more powerful in people who adopted displacement as their predominant defense. The data was collected from a convenience web-based sample. The study was cross-sectional. There was no information on the presence of established physical illness. Affective temperaments and defense mechanisms are associated with somatic symptom severity independently of depressive symptoms. These two personality theories provide distinct but interacting views for comprehension of somatic symptom formation. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Immune and Inflammatory Mechanisms in Pulmonary Arterial Hypertension

    PubMed Central

    El Chami, Hala; Hassoun, Paul M.

    2012-01-01

    Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917

  7. [Hypervolemic redistribution mechanism in pulmonary edema in patients with isolated left ventricular failure].

    PubMed

    Shteĭngardt, Iu N; Inzel', T N

    1981-04-01

    The authors examined 90 patients with ischemic heart disease and isolated left-ventricular insufficiency by impedance plethysmography and determined the body total water content by means of tritium oxide in 32 of them. It was established that there is no essential increase in total body water and volumes of circulating blood and plasma at the peak of manifestations of isolated left-ventricular insufficiency. The redistribution of some of the blood from the periphery of systemic circulation to the center, mainly into the pulmonary circulation, possibly plays the principle role in the genesis of pulmonary circulation hypervolemia and pulmonary edema in approximately half of the cases. The same mechanism with its reverse direction occurs in successful treatment and correction of hypervolemia of pulmonary circulation and pulmonary edema.

  8. Defense mechanisms after brief cognitive-behavior group therapy for panic disorder: one-year follow-up.

    PubMed

    Heldt, Elizeth; Blaya, Carolina; Kipper, Leticia; Salum, Giovanni A; Otto, Michael W; Manfro, Gisele G

    2007-06-01

    Changes in defense mechanisms have been shown in long-term psychodynamic treatment. The aim of this study was to examine the changes that occurred after brief cognitive-behavior group therapy in the defense style of panic disorder patients that had failed to respond to pharmacotherapy. Forty-seven patients participated in the study and severity of panic disorder was evaluated by Clinical Global Impression. Defense mechanisms were evaluated by the Defense Style Questionnaire. Patients decreased the use of maladaptive defenses after cognitive-behavior group therapy, and the change in immature defenses was maintained at 1-year follow-up evaluation (p = 0.022). These modifications were associated with reduction of symptoms (F = 0.359; p = 0.047). These findings are consistent with the hypothesis that defense styles are malleable in short-term treatment and are, at least partially, symptom-state dependent.

  9. 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

  10. 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…

  11. 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...

  12. 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…

  13. 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...

  14. 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…

  15. Family Defense Mechanisms: The Concept and Its Utility to Family Scientists, Practitioners, and Educators.

    ERIC Educational Resources Information Center

    Schwebel, Andrew I.

    1993-01-01

    Notes that interpersonal conflict among family members and between spouses can cause dissatisfaction and threaten feasibility of marriage. Defines Family Defense Mechanisms (FDMs) as fixed patterns of behaviors that, when followed by spouses and other family members, enable them to better manage their interpersonal differences and conflict.…

  16. 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…

  17. 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…

  18. Antimicrobial peptides: modes of mechanism, modulation of defense responses.

    PubMed

    Rahnamaeian, Mohammad

    2011-09-01

    Complicated schemes of classical breeding and their drawbacks, environmental risks imposed by agrochemicals, decrease of arable land, and coincident escalating damages of pests and pathogens have accentuated the necessity for highly efficient measures to improve crop protection. During co-evolution of host-microbe interactions, antimicrobial peptides (AMPs) have exhibited a brilliant history in protecting host organisms against devastation by invading pathogens. Since the 1980s, a plethora of AMPs has been isolated from and characterized in different organisms. Nevertheless the AMPs expressed in plants render them more resistant to diverse pathogens, a more orchestrated approach based on knowledge of their mechanisms of action and cellular targets, structural toxic principle, and possible impact on immune system of corresponding transgenic plants will considerably improve crop protection strategies against harmful plant diseases. This review outlines the current knowledge on different modes of action of AMPs and then argues the waves of AMPs’ ectopic expression on transgenic plants’ immune system.

  19. The physician's quality of life: Relationship with ego defense mechanisms and object relations.

    PubMed

    Miranda, Benedito; Louzã, Mário Rodrigues

    2015-11-01

    To assess whether ego defense mechanisms and object relations (the way an individual subjectively experiences his/her relationships with others) are related to quality of life among physicians. In this cross-sectional mail survey, 602 physicians from Botucatu, SP, Brazil, were sent a socio-demographic questionnaire, the Bell Object Relations and Reality Testing Inventory-Form O (BORRTI-O), the Defense Style Questionnaire-40 (DSQ-40), and the World Health Organization Abbreviated Instrument for Quality of Life Assessment (WHOQOL-BREF). 198 questionnaires (33%) with valid responses were obtained. High BORRTI-O scores (indicative of pathology) on the alienation, egocentricity and insecure attachment subscales were associated with reduced WHOQOL-BREF scores for the psychological health and social relationship domains. Immature ego defense mechanisms were associated with lower WHOQOL-BREF scores for all domains. No significant associations of WHOQOL-BREF scores with working hours, workplace or monthly income were observed in the study population WHOQOL-BREF scores correlated with mature defense mechanisms and normal object relations, suggesting an association between psychological maturity and quality of life among physicians. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Activation of Host Defense Mechanisms by Elevated Production of H2O2 in Transgenic Plants.

    PubMed Central

    Wu, G.; Shortt, B. J.; Lawrence, E. B.; Leon, J.; Fitzsimmons, K. C.; Levine, E. B.; Raskin, I.; Shah, D. M.

    1997-01-01

    Active oxygen species have been postulated to perform multiple functions in plant defense, but their exact role in plant resistance to diseases is not fully understood. We have recently demonstrated H2O2-mediated disease resistance in transgenic potato (Solanum tuberosum) plants expressing a foreign gene encoding glucose oxidase. In this study we provide further evidence that the H2O2-mediated disease resistance in potato is effective against a broad range of plant pathogens. We have investigated mechanisms underlying the H2O2-mediated disease resistance in transgenic potato plants. The constitutively elevated levels of H2O2 induced the accumulation of total salicylic acid severalfold in the leaf tissue of transgenic plants, although no significant change was detected in the level of free salicylic acid. The mRNAs of two defense-related genes encoding the anionic peroxidase and acidic chitinase were also induced. In addition, an increased accumulation of several isoforms of extracellular peroxidase, including a newly induced one, was observed. This was accompanied by a significant increase in the lignin content of stem and root tissues of the transgenic plants. The results suggest that constitutively elevated sublethal levels of H2O2 are sufficient to activate an array of host defense mechanisms, and these defense mechanisms may be a major contributing factor to the H2O2-mediated disease resistance in transgenic plants. PMID:12223817

  1. 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. © 2015 Institute of Zoology, Chinese Academy of Sciences.

  2. Attachment style and defense mechanisms in parents who abuse their children.

    PubMed

    Cramer, Phebe; Kelly, Francis D

    2010-09-01

    Adult attachment style, defense mechanisms, and personal history of abuse was studied in a group of abusive parents. As a group, these parents made unusually high use of the defense of denial; this was especially true of those with a Fearful attachment style. However, the use of Identification was characteristic of those with a Preoccupied attachment style. Further, personal abuse history was related to adult attachment style. Those who reported having been abused as a child were less likely to have a Secure attachment style, and a history of physical or sexual abuse was associated with a Preoccupied style. In general, these findings support the deactivating/hyperactivating defensive theory of Mikulincer et al (Emotion Regulation in Couples and Families: Pathways to Dysfunction and Health. 2006; pp 77-99. Washington (WA): American Psychological Association).

  3. 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

  4. Convergent evolution of defense mechanisms in oribatid mites (Acari, Oribatida) shows no "ghosts of predation past".

    PubMed

    Pachl, Patrick; Domes, Katja; Schulz, Garvin; Norton, Roy A; Scheu, Stefan; Schaefer, Ina; Maraun, Mark

    2012-11-01

    Oribatid mites are diverse and abundant terrestrial soil arthropods that are involved in decomposition of organic matter and nutrient cycling. As indicated by fossils starting from the Devonian, they evolved varied mechanisms and structures for defense from predators. We investigated four of these defensive structures (ptychoid body, hologastry, mineralization and opisthonotal glands) and used ancestral character state reconstruction to determine whether they evolved convergently and how many times this may have happened. Phylogenetic trees based on 18S rDNA were constructed for 42 oribatid mite species and two outgroup taxa using likelihood and Bayesian algorithms. The results suggest that at least three of the four defensive structures evolved convergently several times; for opisthonotal glands convergent evolution remains equivocal. This high level of convergence indicates that predation has been an important factor throughout the evolution of oribatid mites, contributing to morphological diversity and potentially also to species richness, as there are indications that some taxa radiated after the evolution of defense structures. Despite the ancientness of oribatid mites, defense structures seems to have been rarely lost, suggesting that they still are functional and necessary to reduce predation, rather than being 'ghosts of predation past'. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Self-injury, psychiatric symptoms, and defense mechanisms: findings in an Italian nonclinical sample.

    PubMed

    Sarno, I; Madeddu, F; Gratz, K L

    2010-04-01

    This study provides data on the rates, characteristics, and correlates of self-injury (SI) in an Italian nonclinical sample, a population previously unexamined within the SI literature. This study examined the associations between SI and defense mechanisms, as well as the differences between self-injurers (episodic and recurrent) and non self-injurers with regard to the severity and variety of their psychiatric symptoms and psychological distress. Five hundred and seventy-eight university students (82.5% female; mean age=22.3; S.D.=3.4) were administered a battery of self-report questionnaires, including the "Deliberate Self Harm Inventory" for SI, the Response Evaluation Measure-71 for defense mechanisms, and the "Symptom Checklist-90-Revised" for psychological distress and psychiatric symptoms. One hundred and nineteen participants (20.6%) reported having engaged in SI at least once during their lifetime. Individuals with recurrent SI (SI>or=5) reported significantly higher levels of all psychiatric symptoms and many maladaptive defense mechanisms than individuals without SI. Results also provided evidence for differences between individuals with recurrent and episodic SI. Results suggest that recurrent self-injurers are distinguished from both episodic self-injurers and non self-injurers by their greater use of maladaptive defense mechanisms, rather than their lesser use of adaptive defenses. Further, results suggest that recurrent self-injurers differ from episodic self-injurers not in terms of the severity of their psychiatric symptoms, but the variety and number of these symptoms. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  6. 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.

  7. The molecular genetics and cellular mechanisms underlying pulmonary arterial hypertension.

    PubMed

    Machado, Rajiv D

    2012-01-01

    Pulmonary arterial hypertension (PAH) is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards.

  8. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Cancer survival probability as a function of ego defense (adaptive) mechanisms versus depressive symptoms.

    PubMed

    Beresford, Thomas P; Alfers, Julie; Mangum, Laura; Clapp, Lori; Martin, Brandon

    2006-01-01

    Psychological treatment studies, uncontrolled for ego defense (adaptive) styles, report conflicting survival results. The authors hypothesized that "immature" adaptive styles and frequent depression symptoms would independently predict lower survival rates. This study followed 86 consecutive, mostly late-stage, cancer outpatients for up to 5 years; their survival data were analyzed in relation to the Beck Depression Inventory and the Defense Style Questionnaire scores at study entry. Cumulative survival probability curves contrasted the extreme cases: the most (N=15) to the least (N=21) depressed, and the "immature" (N=14) to the "mature" (N=16) adaptors. Depression did not separate the groups until 30 months after diagnosis. Ego defense style separated them at 8 months; by 18 months, the "immature" survival probability had dropped to 50%, versus 87% for the "mature." At 36 months, survival probabilities were 19% and 57%, respectively. These data direct clinical attention toward ego defense mechanisms as indicators of distress and lowered survival in cancer patients. They further suggest that the maturity of adaptive mechanisms must be controlled for in behavioral-treatment trials of cancer patients.

  10. 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.

  11. Higher Pulmonary Dead Space May Predict Prolonged Mechanical Ventilation After Cardiac Surgery

    PubMed Central

    Ong, Thida; Stuart-Killion, Regan B.; Daniel, Brian M.; Presnell, Laura B.; Zhuo, Hanjing; Matthay, Michael A.; Liu, Kathleen D.

    2009-01-01

    Summary Children undergoing congenital heart surgery are at risk for prolonged mechanical ventilation and length of hospital stay. We investigated the prognostic value of pulmonary dead space fraction as a non-invasive, physiologic marker in this population. In a prospective, cross-sectional study, we measured pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery. Measurements were obtained with a bedside, non-invasive cardiac output (NICO) monitor (Respironics Novametrix, Inc., Wallingford, CT). Median pulmonary dead space fraction was 0.46 (25–75% IQR 0.34–0.55). Pulmonary dead space fraction significantly correlated with duration of mechanical ventilation and length of hospital stay in the entire cohort (rs=0.51, P=0.0002; rs=0.51, P=0.0002) and in the subset of patients without residual intracardiac shunting (rs=0.45, P=0.008; rs=0.49, P=0.004). In a multivariable logistic regression model, pulmonary dead space fraction remained an independent predictor for prolonged mechanical ventilation in the presence of cardiopulmonary bypass time and ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (OR 2.2; 95% CI 1.14–4.38; P=0.02). The area under the receiver operator characteristic curve for this model was 0.91. Elevated pulmonary dead space fraction is associated with prolonged mechanical ventilation and hospital stay in pediatric patients who undergo surgery for congenital heart disease and has additive predictive value in identifying those at risk for longer duration of mechanical ventilation. Pulmonary dead space may be a useful prognostic tool for clinicians in patients who undergo congenital heart surgery. PMID:19382217

  12. Psychoticism, Immature Defense Mechanisms and a Fearful Attachment Style are Associated with a Higher Homophobic Attitude.

    PubMed

    Ciocca, Giacomo; Tuziak, Bogdan; Limoncin, Erika; Mollaioli, Daniele; Capuano, Nicolina; Martini, Alessia; Carosa, Eleonora; Fisher, Alessandra D; Maggi, Mario; Niolu, Cinzia; Siracusano, Alberto; Lenzi, Andrea; Jannini, Emmanuele A

    2015-09-01

    Homophobic behavior and a negative attitude toward homosexuals are prevalent among the population. Despite this, few researches have investigated the psychologic aspects associated with homophobia, as psychopathologic symptoms, the defensive system, and attachment styles. The aim of this study was to investigate the psychologic factors mentioned earlier and their correlation with homophobia. Five hundred fifty-one university students recruited, aged 18-30, were asked to complete several psychometric evaluation. In particular, Homophobia Scale (HS) was used to assess homophobia levels, the Symptoms Check List Revised (SCL-90-R) for the identification of psychopathologic symptoms, the Defence Style Questionnaire (DSQ-40) for the evaluation of defense mechanisms and the Relationship Questionnaire (RQ) for attachment styles. After a regression analysis, we found a significant predictive value of psychoticism (β = 0.142; P = 0.04) and of immature defense mechanisms (β = 0.257; P < 0.0001) for homophobia, while neurotic defense mechanisms (β = -0.123; P = 0.02) and depressive symptoms (β = -0.152; P = 0.04) have an opposite role. Moreover, categorical constructs of the RQ revealed a significant difference between secure and fearful attachments styles in levels of homophobia (secure = 22.09 ± 17.22 vs. fearful = 31.07 ± 25.09; P < 0.05). Finally, a gender difference to HS scores and a significant influence of male sex was found (β = 0.213; P < 0.0001). We demonstrated the involvement of psychoticism and immature defense mechanisms in homophobic attitudes, while a contrasting role is played by neurotic defense mechanisms and depressive symptoms. Moreover, secure attachment is an indicator of low levels of homophobia compared with the subjects demonstrating a fearful style of attachment. Hence, in the assessment of homophobia and in the relevant programs of prevention, it is necessary to consider the

  13. [Defense mechanisms as outcome measure in short-term psychotherapy related to symptoms, severity and overall functioning: a preliminary study].

    PubMed

    Coccanari de' Fornari, Maria Antonietta; Piccione, Michele; Maiello, Luca; Giampà, Alessio

    2011-01-01

    The assessment of defense mechanisms in psychotherapy is currently one of the most used ways to evaluate the effectiveness of psychotherapy. In literature there are few reports on defense mechanisms changes by short-term treatments. To determine whether the defense mechanisms are changed after twelve sessions of short-term psychotherapy related to psychopathological symptoms, severity and overall functioning. Twenty patients (12 F and 8 M; age 38.4) affected by anxiety and mood disorders were recruited to the study between November 2008 and July 2009 and were assessed with the Defense Style Questionnaire-88 (DSQ-88), scale Symptom Checklist-90-Revised (SCL-90-R), scale Clinical Global Impression (CGI) and scale Valutazione Globale del Funzionamento (VGF) at the beginning and after short-term psychotherapy. Half the sample also assumed drugs. The treatment was supportive-expressive psychotherapy of Luborsky, a short focal dynamic therapy, characterized by the integration of supportive and expressive techniques. Both patients showed a significant decrease in immature defenses and a significant-increase in mature defenses (p < 0.01). Mature defenses were significantly correlated with severity (r = -0632; p = 0.003) and overall functioning (r = 0529; p = 0.01). Immature and mature defenses seem to be a useful outcome measure in short-term psychotherapy as well as severity and overall functioning and the combined treatment may be most effective in reducing immature defenses.

  14. 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

  15. Anthropometric characteristics of the pubic arch and proper function of the defense mechanisms against hernia formation.

    PubMed

    López-Cano, M; Munhequete, E G; Hermosilla-Pérez, E; Armengol-Carrasco, M; Rodríguez-Baeza, A

    2005-03-01

    In 33 inguinal regions, we determined the anthropometric characteristics of the pubic arch and the anatomic structures of the suprainguinal space and assessed whether there is a relationship between anatomic features and function of the defense mechanisms. There was a low position of the pubic arch (pubic tubercle and interspinal line distance >75 mm) in 23 cases. The low-pubic-arch group showed a significantly longer inguinal ligament and a greater angle made by the superior border of the suprainguinal space and the inguinal ligament at its medial insertion. The position of the pubic arch correlated significantly with the diameter of the internal ring, the length of the inguinal ligament, and the angle made by the superior border of the suprainguinal space and the medial insertion of the inguinal ligament. A low pubic arch would represent an unfavorable condition for an adequate function of the anatomic defense mechanism against hernia.

  16. Atrial flutter following pulmonary vein isolation: what is the mechanism?

    PubMed

    Yamada, Takumi; Kay, G Neal

    2013-10-01

    A 70-year-old man with atrial flutter (AFL) following pulmonary vein (PV) isolation (PVI) underwent electrophysiologic testing. The AFL exhibited positive P waves in the inferior leads and lead V1. Left atrial activation mapping revealed 2 remote sites with early activation that were located at the antrum of the left superior PV roof and the left inferior PV bottom. A single irrigated radiofrequency ablation targeting the earliest PV activation at the left PV carina eliminated the AFL. This case demonstrated that PV carina tachycardia with multiple conduction gaps and inter-PV conduction after PVI might mimic double focal atrial tachycardias. © 2013 Wiley Periodicals, Inc.

  17. When the Guns Fall Silent: a Leader’s Guide to Understanding Defensive Coping Mechanisms

    DTIC Science & Technology

    2011-05-19

    Ego, and Superego. An entire chapter is dedicated to the introduction of the psychological theorist Sigmund Freud but only a small section is used to...awareness.” 18 Though some may find the study of Freud to be outdated and hard to prove because it is based on the unconscious; review of this theory...Intellectualization, and Undoing. Allen stated, “ Freud believed that exaggerated use of such defense mechanisms result in neuroses; anxiety-driven

  18. Development of a Q-sort version of the Defense Mechanism Rating Scales (DMRS-Q) for clinical use.

    PubMed

    Di Giuseppe, Mariagrazia; Perry, J Christopher; Petraglia, Jonathan; Janzen, Jennifer; Lingiardi, Vittorio

    2014-05-01

    This report focuses on the need to provide clinicians with a reliable and valid measure for detecting patient defense mechanisms "inside psychotherapy." To avoid the limitations of existing methods, we designed a Q-sort based on the theoretical definitions and criteria of the Defense Mechanisms Rating Scales (DMRS-Q), but one that does not require transcripts of clinical interviews or sessions and may be applied without specific training on defenses. The DMRS-Q is sensitive to changes in psychotherapy and its scores correlate significantly with various aspects of mental functioning, making it potentially available for the psychotherapy process and outcome research as well. We report the results of using the DMRS-Q on a systematic single case study with the aim of detecting changes in defense mechanisms during a long-term psychodynamic psychotherapy. The DMRS-Q reveals change both in quantitative scores and in the literary Defensive Profile Narrative. © 2014 Wiley Periodicals, Inc.

  19. Inducible maize defense mechanisms against the corn borer Sesamia nonagrioides: a transcriptome and biochemical approach.

    PubMed

    Rodríguez, Víctor M; Santiago, Rogelio; Malvar, Rosa Ana; Butrón, Ana

    2012-01-01

    In spite of multiple studies elucidating individual defense mechanisms against stalk borer feeding, little information is available about the plant response to these members of Lepidoptera. Four maize inbred lines were cultivated in a greenhouse and challenged with larvae of the corn borer Sesamia nonagrioides. Transcriptome and biochemical analyses were performed to elucidate the maize response mechanisms to this insect. General plant defense mechanisms were activated, including the jasmonic acid biosynthetic pathway, proteinase inhibitors, and four defense-related transcription factors. Interestingly, gene ontology analysis shows that maize plants undergo cell-wall reorganization after being attacked. These results were confirmed through biochemical analyses showing that the concentration of some cell-wall-related compounds significantly changed after plant infestation in a genotype-dependent way. In conclusion, maize plants respond to the attack of the corn borer S. nonagrioides through cell-wall fortification, activating genes involved in cell-wall organization, which finally is reflected in a higher concentration of some cell-wall components, especially in resistant genotypes.

  20. Diverse mechanisms evolved by DNA viruses to inhibit early host defenses.

    PubMed

    Crow, Marni S; Lum, Krystal K; Sheng, Xinlei; Song, Bokai; Cristea, Ileana M

    In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent on the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments.

  1. Respiratory drive and pulmonary mechanics during haemodialysis with ultrafiltration in ventilated patients.

    PubMed

    Huang, C C; Tsai, Y H; Lin, M C; Yang, C T; Hsieh, M J; Lan, R S

    1997-10-01

    The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.

  2. 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.

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

    PubMed Central

    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 110nm 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 110nm 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

  4. The chemical defense ecology of marine unicellular plankton: constraints, mechanisms, and impacts.

    PubMed

    Wolfe, G V

    2000-04-01

    The activities of unicellular microbes dominate the ecology of the marine environment, but the chemical signals that determine behavioral interactions are poorly known. In particular, chemical signals between microbial predators and prey contribute to food selection or avoidance and to defense, factors that probably affect trophic structure and such large-scale features as algal blooms. Using defense as an example, I consider physical constraints on the transmission of chemical information, and strategies and mechanisms that microbes might use to send chemical signals. Chemical signals in a low Re, viscosity-dominated physical environment are transferred by molecular diffusion and laminar advection, and may be perceived at nanomolar levels or lower. Events that occur on small temporal and physical scales in the "near-field" of prey are likely to play a role in cell-cell interactions. On the basis of cost-benefit optimization and the need for rapid activation, I suggest that microbial defense system strategies might be highly dynamic. These strategies include compartmented and activated reactions, utilizing both pulsed release of dissolved signals and contact-activated signals at the cell surface. Bioluminescence and extrusome discharge are two visible manifestations of rapidly activated microbial defenses that may serve as models for other chemical reactions as yet undetected due to the technical problems of measuring transient chemical gradients around single cells. As an example, I detail an algal dimethylsulfoniopropionate (DMSP) cleavage reaction that appears to deter protozoan feeding and explore it as a possible model for a rapidly activated, short-range chemical defense system. Although the exploration of chemical interactions among planktonic microbes is in its infancy, ecological models from macroorganisms provide useful hints of the complexity likely to be found.

  5. 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

  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. [Pneumomediastinum: an aspect of pulmonary barotrauma during mechanical ventilation of acute respiratory distress syndrome].

    PubMed

    Aissaoui, Y; En-Nafaa, I; Chkoura, K; Boughalem, M; Kamili, N Drissi

    2014-06-01

    Mechanical ventilation is a fundamental treatment of acute respiratory distress syndrome (ARDS). Despite compliance with the recommendations of protective mechanical ventilation, it can results in serious complications including the pulmonary barotrauma. This is often manifested by a pneumothorax. This observation describes an unusual aspect of barotrauma which is pneumomediastinum. The authors also point out the role of chest imaging in the management of mechanical ventilation during ARDS. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Priming by rhizobacterium protects tomato plants from biotrophic and necrotrophic pathogen infections through multiple defense mechanisms.

    PubMed

    Ahn, Il-Pyung; Lee, Sang-Woo; Kim, Min Gab; Park, Sang-Ryeol; Hwang, Duk-Ju; Bae, Shin-Chul

    2011-07-01

    A selected strain of rhizobacterium, Pseudomonas putida strain LSW17S (LSW17S), protects tomato plants (Lycopersicon esculentum L. cv. Seokwang) from bacterial speck by biotrophic Pseudomonas syringae pv. tomato strain DC3000 (DC3000) and bacterial wilt by necrotrophic Ralstonia solanacearum KACC 10703 (Rs10703). To investigate defense mechanisms induced by LSW17S in tomato plants, transcription patterns of pathogenesis-related (PR) genes and H(2)O(2) production were analyzed in plants treated with LSW17S and subsequent pathogen inoculation. LSW17S alone did not induce transcriptions of employed PR genes in leaves and roots. DC3000 challenge following LSW17S triggered rapid transcriptions of PR genes and H(2)O(2) production in leaves and roots. Catalase infiltration with DC3000 attenuated defense-related responses and resistance against DC3000 infection. Despite depriving H(2)O(2) production and PR1b transcription by the same treatment, resistance against Rs10703 infection was not deterred significantly. H(2)O(2) is indispensable for defense signaling and/or mechanisms primed by LSW17S and inhibition of bacterial speck, however, it is not involved in resistance against bacterial wilt.

  9. Defense mechanisms of Pseudomonas aeruginosa PAO1 against quantum dots and their released heavy metals.

    PubMed

    Yang, Yu; Mathieu, Jacques M; Chattopadhyay, Soma; Miller, Jeffrey T; Wu, Tianpin; Shibata, Tomohiro; Guo, Wenhua; Alvarez, Pedro J J

    2012-07-24

    The growing use of quantum dots (QDs) in numerous applications increases the possibility of their release to the environment. Bacteria provide critical ecosystem services, and understanding their response to QDs is important to assess the potential environmental impacts of such releases. Here, we analyze the microbial response to sublethal exposure to commercial QDs, and investigate potential defense and adaptation mechanisms in the model bacterium Pseudomonas aeruginosa PAO1. Both intact and weathered QDs, as well as dissolved metal constituents, up-regulated czcABC metal efflux transporters. Weathered QDs also induced superoxide dismutase gene sodM, which likely served as a defense against oxidative stress. Interestingly, QDs also induced antibiotic resistance (ABR) genes and increased antibiotic minimum inhibitory concentrations by 50 to 100%, which suggests up-regulation of global stress defense mechanisms. Extracellular synthesis of nanoparticles (NPs) was observed after exposure to dissolved Cd(NO(3))(2) and SeO(2). With extended X-ray absorption fine structure (EXAFS), we discerned biogenic NPs such as CdO, CdS, CdSe, and selenium sulfides. These results show that bacteria can mitigate QD toxicity by turning on energy-dependent heavy-metal ion efflux systems and by mediating the precipitation of dissolved metal ions as less toxic and less bioavailable insoluble NPs.

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

    PubMed

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

    2014-11-06

    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.

  11. Priming by Rhizobacterium Protects Tomato Plants from Biotrophic and Necrotrophic Pathogen Infections through Multiple Defense Mechanisms

    PubMed Central

    Ahn, Il-Pyung; Lee, Sang-Woo; Kim, Min Gab; Park, Sang-Ryeol; Hwang, Duk-Ju; Bae, Shin-Chul

    2011-01-01

    A selected strain of rhizobacterium, Pseudomonas putida strain LSW17S (LSW17S), protects tomato plants (Lycopersicon esculentum L. cv. Seokwang) from bacterial speck by biotrophic Pseudomonas syringae pv. tomato strain DC3000 (DC3000) and bacterial wilt by necrotrophic Ralstonia solanacearum KACC 10703 (Rs10703). To investigate defense mechanisms induced by LSW17S in tomato plants, transcription patterns of pathogenesis-related (PR) genes and H2O2 production were analyzed in plants treated with LSW17S and subsequent pathogen inoculation. LSW17S alone did not induce transcriptions of employed PR genes in leaves and roots. DC3000 challenge following LSW17S triggered rapid transcriptions of PR genes and H2O2 production in leaves and roots. Catalase infiltration with DC3000 attenuated defense-related responses and resistance against DC3000 infection. Despite depriving H2O2 production and PR1b transcription by the same treatment, resistance against Rs10703 infection was not deterred significantly. H2O2 is indispensable for defense signaling and/or mechanisms primed by LSW17S and inhibition of bacterial speck, however, it is not involved in resistance against bacterial wilt. PMID:21710203

  12. Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism

    PubMed Central

    Whitfield, Nathan L.; Bearden, Shawn E.; St. Leger, Judy; Nilson, Erika; Gao, Yan; Madden, Jane A.

    2010-01-01

    Hypoxic pulmonary vasoconstriction (HVC), an intrinsic and assumed ubiquitous response of mammalian pulmonary blood vessels, matches regional ventilation to perfusion via an unknown O2-sensing mechanism. Global pulmonary hypoxia experienced by individuals suffering from chronic obstructive pulmonary disease or numerous hypoventilation syndromes, including sleep apnea, often produces maladaptive pulmonary hypertension, but pulmonary hypertension is not observed in diving mammals, where profound hypoxia is routine. Here we examined the response of cow and sea lion pulmonary arteries (PA) to hypoxia and observed the expected HVC in the former and a unique hypoxic vasodilation in resistance vessels in the latter. We then used this disparate response to examine the O2-sensing mechanism. In both animals, exogenous H2S mimicked the vasoactive effects of hypoxia in isolated PA. H2S-synthesizing enzymes, cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfur transferase, were identified in lung tissue from both animals by one-dimensional Western blot analysis and immunohistochemistry. The relationship between H2S production/consumption and O2 was examined in real time by use of amperometric H2S and O2 sensors. H2S was produced by sea lion and cow lung homogenate in the absence of O2, but it was rapidly consumed when O2 was present. Furthermore, consumption of exogenous H2S by cow lung homogenate, PA smooth muscle cells, and heart mitochondria was O2 dependent and exhibited maximal sensitivity at physiologically relevant Po2 levels. These studies show that HVC is not an intrinsic property of PA and provide further evidence for O2-dependent H2S metabolism in O2 sensing. PMID:19889863

  13. 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.

  14. Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection

    PubMed Central

    Yajima, Toshitaka

    2011-01-01

    Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

  15. 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.

  16. 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

  17. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    EPA Science Inventory

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  18. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    EPA Science Inventory

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  19. [Path causal analysis of a model of a functional organization between defense mechanisms and coping strategies].

    PubMed

    Gouvernet, B; Mouchard, J; Combaluzier, S

    2015-10-01

    In the psychological literature, two concepts are often used to approach psychological and social adaptation: defense mechanisms and coping strategies. Many empirical studies deal with these strategies independently of each other. However, the nature of their relationship is still debated, making empirical studies necessary jointly evaluating these two types of strategies to better reflect the adaptive process. To test Chabrol and Callahan's theoretical model of the relationship between defence mechanisms and coping strategies. According to theses authors, defence mechanisms and coping strategies are distinct mechanisms, functionally organized: defenses appear first and modulate the emergence of coping strategy defenses through threat representation. Ninety-four young adult volunteers completed the Coping Inventory for Stressful Situations (CISS), the Defense Style Questionnaire (DSQ-40) and the Perceived Stress Scale (PSS14). The data were treated according to the structural equation modeling method. Overall, the results support the theoretical model proposed by Chabrol and Callahan. The statistical model provides a good fit to the data (chi(2)/df=18.62/22=.85, P=.67, RMSEA=.00 (90% CI: .00-.07), CFI=1, TLI=1.04). It explains from 7 to 24% of coping variability scores (Avoidant Coping: R(2)=.07, P<.01; emotional coping and problem-focused coping: R(2)=24, P<.01). Results also show that the relationships between defence mechanisms and copings strategies are mediated by perceived distress and perceived controllability. Defence impact on coping strategies is not the same whether one considers problem-focused coping or emotional and avoidant coping. Immature and mature defences' impact on problem-focused coping is underpinned by a simple mediation: perceived controllability. Defences' impact on emotional coping and avoidant coping is more complex and underpinned by a double mediation: first by the perceived controllability and then, in a second time, the perceived

  20. 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

  1. Defense mechanisms of Solanum tuberosum L. in response to attack by plant-pathogenic bacteria.

    PubMed

    Poiatti, Vera A D; Dalmas, Fernando R; Astarita, Leandro V

    2009-01-01

    The natural resistance of plants to disease is based not only on preformed mechanisms, but also on induced mechanisms. The defense mechanisms present in resistant plants may also be found in susceptible ones. This study attempted to analyze the metabolic alterations in plants of the potato Solanum tuberosum L. cv. Agata that were inoculated with the incompatible plant-pathogenic bacteria X. axonopodis and R. solanacearum, and the compatible bacterium E. carotovora. Levels of total phenolic compounds, including the flavonoid group, and the activities of polyphenol oxidase (PPO) and peroxidase (POX) were evaluated. Bacteria compatibility was evaluated by means of infiltration of tubers. The defense response was evaluated in the leaves of the potato plants. Leaves were inoculated depending on their number and location on the stem. Multiple-leaf inoculation was carried out on basal, intermediate, and apical leaves, and single inoculations on intermediate leaves. Leaves inoculated with X. axonopodis and with R. solanacearum showed hypersensitive responses within 24 hours post-inoculation, whereas leaves inoculated with E. carotovora showed disease symptoms. Therefore, the R. solanacearum isolate used in the experiments did not exhibit virulence to this potato cultivar. Regardless of the bacterial treatments, the basal leaves showed higher PPO and POX activities and lower levels of total phenolic compounds and flavonoids, compared to the apical leaves. However, basal and intermediate leaves inoculated with R. solanacearum and X. axonopodis showed increases in total phenolic compounds and flavonoid levels. In general, multiple-leaf inoculation showed the highest levels of total phenolics and flavonoids, whereas the single inoculations resulted in the highest increase in PPO activity. The POX activity showed no significant difference between single- and multiple-leaf inoculations. Plants inoculated with E. carotovora showed no significant increase in defense mechanisms

  2. Effect of Pulmonary Blood Flow upon Lung Mechanics*

    PubMed Central

    Giannelli, Stanley; Ayres, Stephen M.; Buehler, M. E.

    1967-01-01

    Airway pressure was continuously recorded in an isolated horizontally mounted canine heart-lung preparation during abrupt, stepwise 100-200 ml inflations to 20-25 cm water pressure, and subsequent deflations. With each change in volume there was a steep rise or fall in pressure, followed by stress relaxation to a static equilibrium airway pressure. Comparison was made between the nonperfused state and during perfusion with whole blood at 100 ml/kg dog wt per min, and left atrial pressure of 10 mm Hg. Pressure tracings were similar during deflation in the perfused and the nonperfused lung. During inflation, in the middle range of lung inflation volumes, the peak inflation and equilibrium airway pressures were greater in the nonperfused state; maximum difference of static pressures in nine preparations averaged 146% of perfused values and the average stress relaxation difference from eight of these was 276%. Lung distensibility was the same with packed red cells or plasma perfusates and was not changed by varying the perfusion rate up to 220 ml/kg per min. During cyclic ventilation, dynamic compliance was similarly greater in the perfused than in the nonperfused state in the middle range of inflation volumes. Static distention of the vascular bed produced similar results with progressive improvement in distensibility in mid-inflation range up to a hydrostatic pressure of 15 cm blood. These data suggest that the distended pulmonary vascular bed provides structural airway support which facilitates entry of gas into the terminal respiratory units at diminished pressure. PMID:6061740

  3. 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.

  4. Plant defense mechanisms are activated during biotrophic and necrotrophic development of Colletotricum graminicola in maize.

    PubMed

    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

    2012-03-01

    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.

  5. Mechanisms of carbon nanotube-induced pulmonary fibrosis: a physicochemical characteristic perspective.

    PubMed

    Duke, Katherine S; Bonner, James C

    2017-10-06

    Carbon nanotubes (CNTs) are engineered nanomaterials (ENMs) with numerous beneficial applications. However, they could pose a risk to human health from occupational or consumer exposures. Rodent models demonstrate that exposure to CNTs via inhalation, instillation, or aspiration results in pulmonary fibrosis. The severity of the fibrogenic response is determined by various physicochemical properties of the nanomaterial such as residual metal catalyst content, rigidity, length, aggregation status, or surface charge. CNTs are also increasingly functionalized post-synthesis with organic or inorganic agents to modify or enhance surface properties. The mechanisms of CNT-induced fibrosis involve oxidative stress, innate immune responses of macrophages, cytokine and growth factor production, epithelial cell injury and death, expansion of the pulmonary myofibroblast population, and consequent extracellular matrix accumulation. A comprehensive understanding of how physicochemical properties affect the fibrogenic potential of various types of CNTs should be considered in combination with genetic variability and gain or loss of function of specific genes encoding secreted cytokines, enzymes, or intracellular cell signaling molecules. Here, we cover the current state of the literature on mechanisms of CNT-exposed pulmonary fibrosis in rodent models with a focus on physicochemical characteristics as principal drivers of the mechanisms leading to pulmonary fibrosis. For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  6. Involvement of serotonin mechanism in methamphetamine-induced chronic pulmonary toxicity in rats.

    PubMed

    Wang, Y; Liu, M; Wang, H M; Bai, Y; Zhang, X H; Sun, Y X; Wang, H L

    2013-07-01

    The widest distribution and the highest uptake of methamphetamine (MA) in the human body occurred in the lungs, so that more and more attention should be paid to MA-induced pulmonary toxicity. MA induces the release of serotonin, which is an important mediator in pulmonary disease. The purpose of this study is to investigate the chronic response of the lung to MA and its potential mechanism in rats. Models of the chronic toxicity of MA were established with MA of 5 mg/kg and 10 mg/kg (intraperitoneally, twice per day) for 5 weeks. It was found that the high dose of MA induced rat pulmonary toxicity: crowded lung parenchyma, thickened septum, reduced number of alveolar sacs, inflammatory cell infiltration, and pulmonary arteriolar remodeling. In addition, MA resulted in a significant increase in the lung serotonin concentration and the marked upregulation of tryptophan hydroxylase 1, vesicular monoamine transporter 2, serotonin transporter, and downregulation of monoamine oxidase-A. These findings suggest that MA induced chronic pulmonary toxicity, which is concerned with the elevated serotonin concentration in rat lungs by increased synthesis, reduced metabolism, augmented accumulation, and promoted release of serotonin.

  7. A Defensive Kicking Behavior in Response to Mechanical Stimuli Mediated by Drosophila Wing Margin Bristles.

    PubMed

    Li, Jiefu; Zhang, Wei; Guo, Zhenhao; Wu, Sophia; Jan, Lily Yeh; Jan, Yuh-Nung

    2016-11-02

    Mechanosensation, one of the fastest sensory modalities, mediates diverse behaviors including those pertinent for survival. It is important to understand how mechanical stimuli trigger defensive behaviors. Here, we report that Drosophila melanogaster adult flies exhibit a kicking response against invading parasitic mites over their wing margin with ultrafast speed and high spatial precision. Mechanical stimuli that mimic the mites' movement evoke a similar kicking behavior. Further, we identified a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle that forms an array along the wing margin as being essential sensory components for this behavior. Our electrophysiological recordings demonstrated that the mechanosensitivity of recurved bristles requires Nanchung and Nanchung-expressing neurons. Together, our results reveal a novel neural mechanism for innate defensive behavior through mechanosensation. We discovered a previously unknown function for recurved bristles on the Drosophila melanogaster wing. We found that when a mite (a parasitic pest for Drosophila) touches the wing margin, the fly initiates a swift and accurate kick to remove the mite. The fly head is dispensable for this behavior. Furthermore, we found that a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle are essential for its mechanosensitivity and the kicking behavior. In addition, touching different regions of the wing margin elicits kicking directed precisely at the stimulated region. Our experiments suggest that recurved bristles allow the fly to sense the presence of objects by touch to initiate a defensive behavior (perhaps analogous to touch-evoked scratching; Akiyama et al., 2012). Copyright © 2016 the authors 0270-6474/16/3611275-08$15.00/0.

  8. Error in intensive care: psychological repercussions and defense mechanisms among health professionals.

    PubMed

    Laurent, Alexandra; Aubert, Laurence; Chahraoui, Khadija; Bioy, Antoine; Mariage, André; Quenot, Jean-Pierre; Capellier, Gilles

    2014-11-01

    To identify the psychological repercussions of an error on professionals in intensive care and to understand their evolution. To identify the psychological defense mechanisms used by professionals to cope with error. Qualitative study with clinical interviews. We transcribed recordings and analysed the data using an interpretative phenomenological analysis. Two ICUs in the teaching hospitals of Besançon and Dijon (France). Fourteen professionals in intensive care (20 physicians and 20 nurses). None. We conducted 40 individual semistructured interviews. The participants were invited to speak about the experience of error in ICU. The interviews were transcribed and analyzed thematically by three experts. In the month following the error, the professionals described feelings of guilt (53.8%) and shame (42.5%). These feelings were associated with anxiety states with rumination (37.5%) and fear for the patient (23%); a loss of confidence (32.5%); an inability to verbalize one's error (22.5%); questioning oneself at a professional level (20%); and anger toward the team (15%). In the long term, the error remains fixed in memory for many of the subjects (80%); on one hand, for 72.5%, it was associated with an increase in vigilance and verifications in their professional practice, and on the other hand, for three professionals, it was associated with a loss of confidence. Finally, three professionals felt guilt which still persisted at the time of the interview. We also observed different defense mechanisms implemented by the professional to fight against the emotional load inherent in the error: verbalization (70%), developing skills and knowledge (43%), rejecting responsibility (32.5%), and avoidance (23%). We also observed a minimization (60%) of the error during the interviews. It is important to take into account the psychological experience of error and the defense mechanisms developed following an error because they appear to determine the professional's capacity to

  9. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    PubMed Central

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  10. 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.

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

    PubMed

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

    2015-09-30

     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.  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.  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.  There was a significant association between academic

  12. 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

  13. 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

  14. 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.

  15. Mechanical Thrombectomy for Early Treatment of Massive Pulmonary Embolism

    SciTech Connect

    Reekers, Jim A. Baarslag, Henk Jan; Koolen, Maria G.J.; Delden, Otto van; Beek, Edwin J.R. van

    2003-06-15

    We report our technique and results of percutaneous mechanical thrombectomy in a consecutive series of eight patients with massive PE. We also discuss the possible role of mechanical PE thrombectomy. Eight consecutive patients with acute massive PE, with or without hemodynamic impairment, were treated with mechanical thrombectomy. We used a modified 7-fr hydrolyzer catheter. The treatment was combined with systemic fibrinolysis. From the logistic and technical point we encountered no problems. All patients showed significant improvement while still in the angiography suite. There were no bleeding complications and no other events related to the procedure. Despite the clinical improvement, one patient died shortly after the procedure from cardiac failure. In all patients there was an acute increase in PO2 to normal values. Only a mean of about 50% of all local thrombus could be removed (range 30-80%). The mean PAP pre-intervention decreased only minimally from 42.5 mmHg to 36.3 mm Hg post-intervention (not significant). In three patients, the PAP continues to remain high at follow-up. The most important feature of mechanical thrombectomy for massive PE is the immediate improvement of the cardiac output, PO2, and clinical situation, overcoming the first critical hours after massive PE. The amount of thrombus reduction seems not to be an important parameter.

  16. 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

  17. 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

  18. Viewing loved faces inhibits defense reactions: a health-promotion mechanism?

    PubMed

    Guerra, Pedro; Sánchez-Adam, Alicia; Anllo-Vento, Lourdes; Ramírez, Isabel; Vila, Jaime

    2012-01-01

    We have known for decades that social support is associated with positive health outcomes. And yet, the neurophysiological mechanisms underlying this association remain poorly understood. The link between social support and positive health outcomes is likely to depend on the neurophysiological regulatory mechanisms underlying reward and defensive reactions. The present study examines the hypothesis that emotional social support (love) provides safety cues that activate the appetitive reward system and simultaneously inhibit defense reactions. Using the startle probe paradigm, 54 undergraduate students (24 men) viewed black and white photographs of loved (romantic partner, father, mother, and best friend), neutral (unknown), and unpleasant (mutilated) faces. Eye-blink startle, zygomatic major activity, heart rate, and skin conductance responses to the faces, together with subjective ratings of valence, arousal, and dominance, were obtained. Viewing loved faces induced a marked inhibition of the eye-blink startle response accompanied by a pattern of zygomatic, heart rate, skin conductance, and subjective changes indicative of an intense positive emotional response. Effects were similar for men and women, but the startle inhibition and the zygomatic response were larger in female participants. A comparison between the faces of the romantic partner and the parent who shares the partner's gender further suggests that this effect is not attributable to familiarity or arousal. We conclude that this inhibitory capacity may contribute to the health benefits associated with social support.

  19. 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.

  20. Greater tactile sensitivity and less use of immature psychological defense mechanisms predict women's penile-vaginal intercourse orgasm.

    PubMed

    Brody, Stuart; Houde, Stephanie; Hess, Ursula

    2010-09-01

    Previous research has suggested that diminished tactile sensitivity might be associated with reduced sexual activity and function. Research has also demonstrated significant physiological and psychological differences between sexual behaviors, including immature psychological defense mechanisms (associated with various psychopathologies) impairing specifically women's orgasm from penile-vaginal intercourse (PVI). To examine the extent to which orgasm triggered by PVI (distinguished from other sexual activities) is associated with both greater tactile sensitivity and lesser use of immature psychological defenses. Seventy French-Canadian female university students (aged 18-30) had their finger sensitivity measured with von Frey type microfilaments, completed the Defense Style Questionnaire and a short form of the Marlowe-Crowne social desirability scale, and provided details of the 1 month (and ever) frequencies of engaging in, and having an orgasm from, PVI, masturbation, anal intercourse, partner masturbation, and cunnilingus. Logistic and linear regression prediction of orgasm triggered by PVI from tactile sensitivity, age, social desirability responding, and immature psychological defenses. Having a PVI orgasm in the past month was associated with greater tactile sensitivity (odds ratio=4.0 for each filament point) and less use of immature defense mechanisms (odds ratio=5.1 for each scale point). Lifetime PVI orgasm was associated only with less use of immature defense mechanisms (and lower social desirability responding score). Orgasms triggered by other activities were not associated with either tactile sensitivity or immature defense mechanisms. Tactile sensitivity was also associated with greater past month PVI frequency (inclusion of PVI frequency in a logistic regression model displaced tactile sensitivity), and lesser use of immature defenses was associated with greater past month PVI and PVI orgasm frequencies. Both diminished physical sensitivity and the

  1. Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus.

    PubMed

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

    2015-01-14

    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.

  2. 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

  3. Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke.

    PubMed

    Amatngalim, Gimano D; Schrumpf, Jasmijn A; Henic, Almira; Dronkers, Esther; Verhoosel, Renate M; Ordonez, Soledad R; Haagsman, Henk P; Fuentes, Maria E; Sridhar, Sriram; Aarbiou, Jamil; Janssen, Richard A J; Lekkerkerker, Annemarie N; Hiemstra, Pieter S

    2017-02-08

    Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity of airway epithelial cells. It has been proposed that a decrease in antibacterial lung defense contributes to an increased susceptibility to microbial infection in smokers and patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression in the epithelium contributes to this lower defense is largely unknown. We investigated the bacterial killing activity and expression of AMPs by air-liquid interface-cultured primary bronchial epithelial cells from COPD patients and non-COPD (ex-)smokers that were stimulated with nontypeable Haemophilus influenzae (NTHi). In addition, the effect of cigarette smoke on AMP expression and the activation of signaling pathways was determined. COPD cell cultures displayed reduced antibacterial activity, whereas smoke exposure suppressed the NTHi-induced expression of AMPs and further increased IL-8 expression in COPD and non-COPD cultures. Moreover, smoke exposure impaired NTHi-induced activation of NF-κB, but not MAP-kinase signaling. Our findings demonstrate that the antibacterial activity of cultured airway epithelial cells induced by acute bacterial exposure was reduced in COPD and suppressed by cigarette smoke, whereas inflammatory responses persisted. These findings help to explain the imbalance between protective antibacterial and destructive inflammatory innate immune responses in COPD.

  4. Accuracy of pulmonary auscultation to detect abnormal respiratory mechanics: a cross-sectional diagnostic study.

    PubMed

    Xavier, Glaciele Nascimento; Duarte, Antonio Carlos Magalhães; Melo-Silva, César Augusto; dos Santos, Carlos Eduardo Ventura Gaio; Amado, Veronica Moreira

    2014-12-01

    Pulmonary auscultation is a method used in clinical practice for the evaluation and detection of abnormalities relating to the respiratory system. This method has limitations, as it depends on the experience and hearing acuity of the examiner to determine adventitious sounds. In this context, it's important to analyze whether there is a correlation between auscultation of lung sounds and the behavior of the respiratory mechanical properties of the respiratory system in patients with immediate postoperative cardiac surgery.

  5. 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.

  6. 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.

  7. Dynamic Shaping of the Defensive Peripersonal Space through Predictive Motor Mechanisms: When the "Near" Becomes "Far".

    PubMed

    Bisio, Ambra; Garbarini, Francesca; Biggio, Monica; Fossataro, Carlotta; Ruggeri, Piero; Bove, Marco

    2017-03-01

    The hand blink reflex is a subcortical defensive response, known to dramatically increase when the stimulated hand is statically positioned inside the defensive peripersonal space (DPPS) of the face. Here, we tested in a group of healthy human subjects the hand blink reflex in dynamic conditions, investigating whether the direction of the hand movements (up-to/down-from the face) could modulate it. We found that, on equal hand position, the response enhancement was present only when the hand approached to (and not receded from) the DPPS of the face. This means that, when the hand is close to the face but the subject is planning to move the hand down, the predictive motor system can anticipate the consequence of the movement: the "near" becomes "far." We found similar results both in passive movement condition, when only afferent (visual and proprioceptive) information can be used to estimate the final state of the system, and in motor imagery task, when only efferent (intentional) information is available to predict the consequences of the movement. All these findings provide evidence that the DPPS is dynamically shaped by predictive mechanisms run by the motor system and based on the integration of feedforward and sensory feedback signals.SIGNIFICANCE STATEMENT The defensive peripersonal space (DPPS) has a crucial role for survival, and its modulation is fundamental when we interact with the environment, as when we move our arms. Here, we focused on a defensive response, the hand blink reflex, known to increase when a static hand is stimulated inside the DPPS of the face. We tested the hand blink reflex in dynamic conditions (voluntary, passive, and imagined movements) and we found that, on equal hand position, the response enhancement was present only when the hand approached to (and not receded from) the DPPS of the face. This suggests that, through the integration of efferent and afferent signals, the safety boundary around the body is continuously shaped by

  8. Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse

    PubMed Central

    Jackson, Isabel L.; Zhang, Yuji; Bentzen, Søren M.; Hu, Jingping; Zhang, Angel; Vujaskovic, Zeljko

    2016-01-01

    Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury. PMID:27845360

  9. 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

  10. Using the TAT to Assess the Relation Between Gender Identity and the Use of Defense Mechanisms.

    PubMed

    Cramer, Phebe

    2017-01-01

    The purpose of this study is to explore whether 2 different dimensions of personality, when assessed at an implicit level with the Thematic Apperception Test (TAT; Murray, 1943 ) will show a theoretically meaningful coherence not demonstrated when 1 is assessed at an implicit level and the other at an explicit level. Gender identity and defense mechanisms were assessed implicitly using the TAT. Gender identity was compared with a self-report measure of gender-related attributes assessed at the explicit level. The results showed a theoretically meaningful coherence when different dispositions were assessed at the same level, but a lack of agreement when similar dispositions were assessed at different levels. The study is based on a secondary analysis of data from 2 previously published papers (Cramer, 1998 ; Cramer & Westergren, 1999 ).

  11. Learning to recognize ego defense mechanisms: results of a structured teaching experience for psychiatric residents.

    PubMed

    Beresford, Thomas P

    2005-01-01

    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. This study hypothesized that mean test scores would increase significantly over 8 weeks in a course on practical EDM recognition. Second-year residents from two successive classes (n = 25) were tested in the first and the last course sessions using a 10-item, multiple-choice test. Correct answer mean scores were compared using Student's t test. Test scores demonstrated an increase in the mean percentage of correct answers between the two time points: 54% versus 82%. These data suggest that clinical EDM recognition can be systematically taught and that learning can be measured appropriately.

  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.

  13. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    PubMed

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring.

  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.

  15. Pulmonary antifibrotic mechanisms aspirin-triggered lipoxin A(4) synthetic analog.

    PubMed

    Guilherme, Rafael F; Xisto, Debora G; Kunkel, Steven L; Freire-de-Lima, Célio G; Rocco, Patricia R M; Neves, Josiane S; Fierro, Iolanda M; Canetti, Claudio; Benjamim, Claudia F

    2013-12-01

    No successful therapies are available for pulmonary fibrosis, indicating the need for new treatments. Lipoxins and their 15-epimers, aspirin-triggered lipoxins (ATL), present potent antiinflammatory and proresolution effects (Martins et al., J Immunol 2009;182:5374-5381). We show that ATLa, an ATL synthetic analog, therapeutically reversed a well-established pulmonary fibrotic process induced by bleomycin (BLM) in mice. We investigated the mechanisms involved in its effect and found that systemic treatment with ATLa 1 week after BLM instillation considerably reversed the inflammatory response, total collagen and collagen type 1 deposition, vascular endothelial growth factor, and transforming growth factor (TGF)-β expression in the lung and restored surfactant protein C expression levels. ATLa also inhibited BLM-induced apoptosis and cellular accumulation in bronchoalveolar lavage fluid and in the lung parenchyma as evaluated by light microscopy and flow cytometry (Ly6G(+), F4/80(+), CD11c(+), CD4(+), and B220(+) cells) assays. Moreover, ATLa inhibited the lung production of IL-1β, IL-17, TNF-α, and TGF-β induced by BLM-challenged mice. ATLa restored the balance of inducible nitric oxide synthase-positive and arginase-positive cells in the lungs, suggesting a prevalence of M2 versus M1 macrophages. Together, these effects improved pulmonary mechanics because ATLa treatment brought to normal levels lung resistance and elastance, which were clearly altered at 7 days after BLM challenge. Our findings support ATLa as a promising therapeutic agent to treat lung fibrosis.

  16. Simple mechanical thrombectomy with intrapulmonary arterial thrombolysis in pulmonary thromboembolism: a small case series

    PubMed Central

    Ahmed, Khurshid; Munawar, Muhammad; Andina Munawar, Dian; Hartono, Beny

    2014-01-01

    Pulmonary thromboembolism (PTE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. We report a series of three patients who presented with acute and subacute submassive PTE. They were successfully treated by simple catheter-based mechanical thrombectomy and intrapulmonary arterial thrombolysis. Mechanical fragmentation and aspiration of thrombus was performed by commonly used J-wire, multi-purpose and Judkin Right guiding catheters and this obviated the need of specific thrombectomy devices. PMID:25593584

  17. Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease.

    PubMed

    Jin, Zhixian; Pan, Xinghua; Zhou, Kaihua; Bi, Hong; Wang, Liyan; Yu, Lu; Wang, Qing

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality, worldwide. Given that the foremost risk factor leading to the development of COPD is cigarette smoke, the initial treatment for COPD is smoking cessation. Even after smoking cessation, inflammation, apoptosis and oxidative stress can persist and continue to contribute to COPD. Although current therapies for COPD (which are primarily based on anti-inflammatory drugs such as corticosteroids, theophylline and bronchodilators) reduce airway obstruction, limit COPD exacerbation and improve the patient's health-related quality-of-life, none can prevent disease progression or reduce mortality. Recent advances in stem cell research have provided novel insight into the potential of bone marrow mesenchymal stem cells (MSCs) in the treatment of several pulmonary diseases. This review article discusses the biological effects and mechanisms of action of MSC transplantation in COPD, and highlights the foundation that MSCs provide for novel therapeutic approaches in COPD.

  18. Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Reddy, Raghu M; Guntupalli, Kalpalatha K

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD.

  19. Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Reddy, Raghu M; Guntupalli, Kalpalatha K

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD. PMID:18268918

  20. Effect of expiratory flow increase technique on pulmonary function of infants on mechanical ventilation.

    PubMed

    Almeida, Celize C B; Ribeiro, Jose D; Almeida-Júnior, Armando A; Zeferino, Angelica M B

    2005-01-01

    Although chest physiotherapy techniques are commonly used in the treatment of respiratory diseases, there are, however, few studies in the literature on the effectiveness of these techniques in paediatric patients. The purpose of the present study was to evaluate the effect of the expiratory flow increase technique (EFIT) on the pulmonary function of infants on invasive mechanical pulmonary ventilation. A prospective, non-randomized study design was used, with consecutive enrolment conducted in the paediatric intensive care unit (PICU) of a university hospital. All infants with acute obstructive respiratory failure who were on invasive mechanical pulmonary ventilation between April 2001 and April 2003 were included in this study. Respiratory rate, PaO2, PaCO2, SatO2, PaO2/FiO2, P(A-a)O2/PaO2, PaO2/PAO2, VD/VT, dynamic compliance, inspiratory and expiratory resistance values were compared before and after application of the EFIT. Blood gas and pulmonary function measurements were recorded before and after EFIT. Repeated-measures analysis of variance (ANOVA) was used. The results were considered statistically significant when p values were < 0.05. Twenty-two infants were enrolled. There was a significant increase in respiratory rate, SatO2 and PaO2/PAO2 and a significant decrease in P(A-a)O2/PaO2 after application of the EFIT. There was a short-term improvement in the oxygenation of infants who were submitted to the EFIT. Additional studies are necessary to establish the efficacy and effectiveness of this technique.

  1. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. In Vivo NMR Metabolic Profiling of Fabrea salina Reveals Sequential Defense Mechanisms against Ultraviolet Radiation

    PubMed Central

    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

  3. 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

    2011-01-05

    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. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Strong down-regulation of glycophorin genes: A host defense mechanism against rotavirus infection.

    PubMed

    Salas, Antonio; Marco-Puche, Guillermo; Triviño, Juan Carlos; Gómez-Carballa, Alberto; Cebey-López, Miriam; Rivero-Calle, Irene; Vilanova-Trillo, Lucía; Rodríguez-Tenreiro, Carmen; Gómez-Rial, José; Martinón-Torres, Federico

    2016-10-01

    The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection. Most interesting was the inhibition of genes of the glycophorins A and B (GYPA/B) family, which are the major sialoglycoproteins of the human erythrocyte membrane and receptor of several viruses for host invasion. RV infection induces a complex and global response in the host. The strong inhibition of glycophorins suggests a novel defense mechanism of the host to prevent viral infection, inhibiting the expression of receptors used by the virus for infection. The present results add further support to the systemic nature of RV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. [Pulmonary mechanics and small airways in patent ductus arteriosus and interventricular communication, in relation to pulmonary arterial flow and pressure].

    PubMed

    Martínez-Guerra, M L; Fernández-Bonetti, P; Peraza, C; Lupi-Herrera, E

    1982-01-01

    Eighteen patients with ventricular septal defect or patent ductus arteriosus were studied to investigate the effects of an increase of pulmonary hypertension. In general group II showed similar results as previously reported in patients with atrial septal defect without pulmonary hypertension. In group I, we found an increased frequency of functional abnormalities in the small airways. We do not have a definitive explanation for the origin of these differences.

  6. Ultrashort Single-Walled Carbon Nanotubes Insert into a Pulmonary Surfactant Monolayer via Self-Rotation: Poration and Mechanical Inhibition.

    PubMed

    Yue, Tongtao; Xu, Yan; Li, Shixin; Luo, Zhen; Zhang, Xianren; Huang, Fang

    2017-03-22

    It has been widely accepted that longer single-walled carbon nanotubes (SWCNTs) exhibit higher toxicity by causing severe pneumonia once inhaled, yet relatively little is known regarding the potential toxicity of ultrashort SWCNTs, which are of central importance to the development of suitable vehicles for biomedical applications. Here, by combining coarse-grained molecular dynamics (CGMD), pulling simulations, and scaling analysis, we demonstrate that the inhalation toxicity of ultrashort SWCNTs (1.5 nm < l < 5.5 nm) can be derived from the unique behaviors on interaction with the pulmonary surfactant monolayer (PSM), which is located at the air-water interface of alveoli and forms the frontline of the lung host defense. Molecular dynamics (MD) simulations suggest that ultrashort SWCNTs spontaneously insert into the PSM via fast self-rotation. Further translocation toward the water or air phase involves overcoming a high free-energy barrier, indicating that removal of inhaled ultrashort SWCNTs from the PSM is difficult, possibly leading to the accumulation of SWCNTs in the PSM, with prolonged retention and increased inflammation potentials. Under certain conditions, the inserted SWCNTs are found to open hydrophilic pores in the PSM via a mechanism that mimics that of the antimicrobial peptide. Besides, the mechanical property of the PSM is inhibited by the deposited ultrashort SWCNTs through segregation of the inner lipid molecules from the outer phase. Our results bring to the forefront the concern of the inhalation toxicity of ultrashort SWCNTs and provide guidelines for future design of inhaled nanodrug carriers with minimized side effects.

  7. Molecular physiopathogenetic mechanisms and development of new potential therapeutic strategies in persistent pulmonary hypertension of the newborn.

    PubMed

    Distefano, Giuseppe; Sciacca, Pietro

    2015-02-08

    Persistent pulmonary hypertension of the newborn (PPHN) is a cyanogenic plurifactorial disorder characterized by failed postnatal drop of pulmonary vascular resistance and maintenance of right-to-left shunt across ductus arteriosus and foramen ovale typical of intrauterine life. The pathogenesis of PPHN is very complex and can result from functional (vasoconstriction) or structural (arteriolar remodeling, reduced pulmonary vessels density) anomalies of pulmonary circulation. Etiopathogenetic factors heterogeneity can strongly condition therapeutical results and prognosis of PPHN that is particularly severe in organic forms that are usually refractory to selective pulmonary vasodilator therapy with inhaled nitric oxide. This paper reports the more recent acquisitions on molecular physiopathogenetic mechanisms underlying functional and structural forms of PPHN and illustrates the bases for adoption of new potential treatment strategies for organic PPHN. These strategies aim to reverse pulmonary vascular remodeling in PPHN with arteriolar smooth muscle hypertrophy and stimulate pulmonary vascular and alveolar growth in PPHN associated with lung hypoplasia.In order to restore lung growth in this severe form of PPHN, attention is focused on the results of studies of mesenchymal stem cells and their therapeutical paracrine effects on bronchopulmonry dysplasia, a chronic neonatal lung disease characterized by arrested vascular and alveolar growth and development of pulmonary hypertension.

  8. 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. © 2015 Phycological Society of America.

  9. [The influence of self-improving based group psychotherapy in defense mechanisms for the clients with social anxiety disorder].

    PubMed

    Feng, Yuan; Xiao, Rang; Qiu, Chang-jian; Wu, Wei-li; Wang, Wei; Nie, Xiao-jing; Zhu, Chun-yan; Zhang, Wei

    2008-11-01

    To evaluate the influence and therapeutic effect of self-improving based group psychotherapy which bases on pathopsychology mechanism of social anxiety disorder (SAD) in denfense mechanisms for the client with SAD. 70 psychotherapy clients and inpatients with SAD were involved in this group psychotherapy voluntarily. Every group had six to eight clients with SAD and two psychotherapists. Psychotherapy was conducted once a week with 2 to 2. 5 hours for a period of 8 weeks. The evaluation of the therapeutic effect contains the subjective perception of the clients with SAD, Liebowitz Social Anxiety Scale (LSAS), and Defense Style Questionnaire (DSQ). 65 clients with SAD completed the therapy. The clients reported self and social functions were improved after 8 weeks therapy. The total score of LSAS after the therapy was significantly lower than that of before the therapy (Z = -5.673, P=0.000). A significant decrease in immature defense machanism and in neurotic defense machanism were observed (Z = -4.866, -2.973; P=0.000, 0.003 respectively). And a trend of increasing the use of mature defense machanism was also observed (Z = -2.780, P=0.005). Self-improving based group psychotherapy can encourage the clients with SAD accept themselves and cure the social anxiety symptoms. And there was a increasing use of mature defense machanism. These imply the clinic application value of the studied group psychotherapy.

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

    PubMed

    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

    2015-06-05

    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.

  11. 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

  12. 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

  13. 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

  14. [Mechanisms of pathogenicity and host defense in infections by intracellular parasitic microbes].

    PubMed

    Mitsuyama, M; Suzuki, K

    2000-09-01

    Mycobacterium tuberculosis is one of the intracellular parasitic bacteria escaping the intracellular killing inside macrophages. The aim of this symposium was to get some insight into the mechanism of pathogenicity and host defense in M. tuberculosis infection, which has not yet been elucidated well, by the presentation of up-to-date knowledge on these aspect in infection with different intracellular parasitic microbes. Dr. Yoshikai (Nagoya Univ.) indicated that TLR is involved in the initial response of host against S. choleraesuis. Among the cytokines contributing to the induction of specific immunity, the importance of IL-15 was emphasized, based on their own experimental data using IL-15 transgenic mice and the application of anti-IL-15 antibody in vivo. Dr. Yoshida (Kyushu Univ.) reviewed the mechanisms of intracellular growth of Legionellae. Several genes so far identified as essential genes in intra-macrophage growth appeared to be similar to those encoding type 3 secretion system observed in Shigellae. There is a significant strain difference in the growth of L. pneumophila inside macrophages and such difference seemed to be under the control of a gene at chromosome 13, Lgn 1. The investigation of difference in the mode of escape among various Legionella. spp. may provide a novel mechansim in bacterial invasion and escape. Dr. Kawamura (Kyoto Univ.) summarized some new reports on the molecular mechanism of the inhibition of P-L fusion by M. tuberculosis. He emphasized the importance of the alteration in phagosomal maturation as indicated by the accumulation of TACO protein. The possible involvement of TLR in the recognition of Mycobacterial cells and its LAM was discussed. Dr. Kawakami (Ryukyu Univ.) first discussed the possibility that Cryptococcus neoformans, a fungal pathogen, could be regarded as one of the intracellular parasitic microbes. His presentation mainly focused on the TH1-Th2 balance in the expression of host defense against C. neoformans in

  15. Microbial signature-triggered plant defense responses and early signaling mechanisms.

    PubMed

    Wu, Shujing; Shan, Libo; He, Ping

    2014-11-01

    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.

  16. Plant storage proteins with antimicrobial activity: novel insights into plant defense mechanisms.

    PubMed

    Cândido, Elizabete de Souza; Pinto, Michelle Flaviane Soares; Pelegrini, Patrícia Barbosa; Lima, Thais Bergamin; Silva, Osmar Nascimento; Pogue, Robert; Grossi-de-Sá, Maria Fátima; Franco, Octávio Luiz

    2011-10-01

    Storage proteins perform essential roles in plant survival, acting as molecular reserves important for plant growth and maintenance, as well as being involved in defense mechanisms by virtue of their properties as insecticidal and antimicrobial proteins. These proteins accumulate in storage vacuoles inside plant cells, and, in response to determined signals, they may be used by the different plant tissues in response to pathogen attack. To shed some light on these remarkable proteins with dual functions, storage proteins found in germinative tissues, such as seeds and kernels, and in vegetative tissues, such as tubercles and leaves, are extensively discussed here, along with the related mechanisms of protein expression. Among these proteins, we focus on 2S albumins, Kunitz proteinase inhibitors, plant lectins, glycine-rich proteins, vicilins, patatins, tarins, and ocatins. Finally, the potential use of these molecules in development of drugs to combat human and plant pathogens, contributing to the development of new biotechnology-based medications and products for agribusiness, is also presented.

  17. 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

  18. Brief report: self-harm is associated with immature defense mechanisms but not substance use in a nonclinical Scottish adolescent sample.

    PubMed

    Brody, Stuart; Carson, Carron Maryjane

    2012-06-01

    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 Questionnaire; DSQ-40) revealed that a history of DSH was associated with more use of immature defense mechanisms by not with substance use or recent alcohol use. More research and clinical attention might be given to immature defense mechanisms in cases of DSH. Copyright © 2011 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  19. Right ventricular ejection efficiency: a new echocardiographic measure of mechanical performance in chronic pulmonary hypertension.

    PubMed

    López-Candales, Angel; Lopez, Francisco R; Trivedi, Setu; Elwing, Jean

    2014-04-01

    The severity of pulmonary vascular resistance (PVR) is known to be a critical determinant of right ventricular (RV) systolic function; this relationship remains poorly characterized. We therefore, designed a study to examine the relationship that exists between echocardiographically measured PVR and maximal tricuspid annular plane systolic excursion (TAPSE) to gain some insight regarding RV ejection efficiency (RVEe) in patients with chronic pulmonary hypertension (cPH). Standard echocardiographic measures of RV size and systolic performance were recorded from 95 patients (age 54 ± 15 years and pulmonary artery systolic pressures [PASP] that range from 20 to 125 mmHg). For this study, RVEe was defined as TAPSE/Echocardiographic PVR. A strong negative correlation (R(2) = -0.51, P < 0.001) was seen between TAPSE and PASP; however, a power curve trend line fit the relationship between RVEe and PASP (R(2) = 0.77; P < 0.01). In a multiple regression analysis, abnormal pulmonary pressures were better identified when RVEe (P < 0.0001) was used. Based on these results, it appears that measurement of RVEe might be extremely useful for the assessment of RV mechanics and plasticity. The power curve relationship clearly demonstrates that minimal changes in PASP (up to 50 mmHg) result in dramatic reductions in RVEe. A steady decline in RVEe, though at a lower rate, continues to occur with increasing PASP. Additional studies are required using RVEe into a functional RV imaging algorithm and determine if RVEe correlates with development of symptoms, response to therapy and overall clinical outcomes. © 2013, Wiley Periodicals, Inc.

  20. Mitochondrial and endoplasmic reticulum dysfunction and related defense mechanisms in critical illness-induced multiple organ failure.

    PubMed

    Thiessen, Steven E; Van den Berghe, Greet; Vanhorebeek, Ilse

    2017-02-17

    Patients with critical illness-induced multiple organ failure suffer from a very high morbidity and mortality, despite major progress in intensive care. The pathogenesis of this condition is complex and incompletely understood. Inadequate tissue perfusion and an overwhelming inflammatory response with pronounced cellular damage have been suggested to play an important role, but interventions targeting these disturbances largely failed to improve patient outcome. Hence, new therapeutic perspectives are urgently needed. Cellular dysfunction, hallmarked by mitochondrial dysfunction and endoplasmic reticulum stress, is increasingly recognized as an important contributor to the development of organ failure in critical illness. Several cellular defense mechanisms are normally activated when the cell is in distress, but may fail or respond insufficiently to critical illness. This insight may open new therapeutic options by stimulating these cellular defense mechanisms. This review summarizes the current understanding of the role of mitochondrial dysfunction and endoplasmic reticulum stress in critical illness-induced multiple organ failure and gives an overview of the corresponding cellular defense mechanisms. Therapeutic perspectives based on these cellular defense mechanisms are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom.

    PubMed

    Oliveira Neto, Joselito de; Silveira, João Alison de Moraes; Serra, Daniel Silveira; Viana, Daniel de Araújo; Borges-Nojosa, Diva Maria; Sampaio, Célia Maria Souza; Monteiro, Helena Serra Azul; Cavalcante, Francisco Sales Ávila; Evangelista, Janaina Serra Azul Monteiro

    2017-10-01

    This study have analyzed the pulmonary function in an experimental model of acute lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella) (3.0 μg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h and 24 h after inoculation. The C. d. cascavella venom led to an increase in Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all groups when compared to the control, particularly at 12 h and 24 h. The Histeresivity (η) increased 6 h, 12 h and 24 h after inoculation. There was a decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed significant morphological changes such as atelectasis, emphysema, hemorrhage, polymorphonuclear inflammatory infiltrate, edema and congestion. After a challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12 and 24 h. This venom caused mechanical and histopathological changes in the lung tissue; however, its mechanisms of action need further studies in order to better elucidate the morphofunctional lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Mechanisms to Mitigate the Trade-Off between Growth and Defense.

    PubMed

    Karasov, Talia L; Chae, Eunyoung; Herman, Jacob J; Bergelson, Joy

    2017-04-01

    Plants have evolved an array of defenses against pathogens. However, mounting a defense response frequently comes with the cost of a reduction in growth and reproduction, carrying critical implications for natural and agricultural populations. This review focuses on how costs are generated and whether and how they can be mitigated. Most well-characterized growth-defense trade-offs stem from antagonistic crosstalk among hormones rather than an identified metabolic expenditure. A primary way plants mitigate such costs is through restricted expression of resistance; this can be achieved through inducible expression of defense genes or by the concentration of defense to particular times or tissues. Defense pathways can be primed for more effective induction, and primed states can be transmitted to offspring. We examine the resistance (R) genes as a case study of how the toll of defense can be generated and ameliorated. The fine-scale regulation of R genes is critical to alleviate the burden of their expression, and the genomic organization of R genes into coregulatory modules reduces costs. Plants can also recruit protection from other species. Exciting new evidence indicates that a plant's genotype influences the microbiome composition, lending credence to the hypothesis that plants shape their microbiome to enhance defense. © 2017 American Society of Plant Biologists. All rights reserved.

  3. [Analysis of the risk factors of pulmonary fungal infections related to mechanical ventilation and prognosis of the patients].

    PubMed

    Li, Ming; Chen, Zhuang-gui; Zhang, Chang-ran; Lin, Jian-cong; Zeng, Mian

    2008-03-01

    To investigate the risk factors of pulmonary fungal infections related to mechanical ventilation and the prognosis of patients. A retrospective case-controlled study was conducted to analyze the culture results of the pulmonary secretions in patients with pulmonary fungal and nonfungal infections in association with mechanical ventilations. The risk factors of pulmonary fungal infections related to mechanical ventilation were identified and their impact on the clinical outcome of the patients was evaluated. Of the 127 patients included in this study, 81 (63.78%) were positive and 46 (36.22%) negative for pulmonary fungal infections according to the diagnostic criteria of ventilator-associated pneumonia (VAP). The mortality of the patients with fungal infection was 82.7%, significantly higher than that of patients with non-fungal infection (67.39%, chi2=3.910, P<0.05). Univariate analysis and multivariate logistic regression showed that such factors as old age, duration of mechanical ventilation, tracheal intubation or incision for over 7 days, diabetes, blood glucose over 6.1 mmol/L, multi-organ dysfunction, combined use of antibiotics, at least 3-time changes antibiotics, administration of glucocorticosteroid for over 7 days, and immunodepressant use were all the independence risk factors of pulmonary fungal infection related to mechanical ventilation. Old age, multi-organ dysfunction, blood glucose over 6.1 mmol/L, glucocorticosteroid use for over 7 days, anesthetic use for over 3 days and high APACHE III scores were the risk factors for mortality in patients with the infections. Pulmonary fungal infection associated to mechanical ventilation is often the results of presence of multiple risk factors, and early identification of these factors for timely antifungal treatment may improve the prognostics of the patients and help reduce the mortality rate.

  4. The Role of Defense Mechanisms, Personality and Demographical Factors on Complicated Grief following Death of a loved one by Cancer.

    PubMed

    Rahimian Boogar, Isaac; Talepasand, Siavash

    2015-04-01

    Identification of the risk factors and psychological correlates of prolonged grief disorder is vital for health promotions in relatives of persons who died of cancer. The aim of this research was to investigate the role of defense mechanisms, character dimension of personality and demographic factors on complicated grief following a loss of a family member to cancer. A number of 226 persons who had lost a family member to cancer in a cancer institute at Tehran University of Medical Science were selected through compliance sampling and completed the Inventory of complicated Grief-Revised (ICG-R), the Defense Styles Questionnaire (DSQ), the Character dimension of Temperament and Character Inventory (TCI), and the Demographical questionnaire. Data were analyzed by stepwise multiple regression analysis, using the PASW version 18. Findings revealed that neurotic defense style had a significant positive predictive role in the complicated grief; and cooperativeness, age of the deceased person, self-transcendence and mature defense style had a significant negative predictive role in complicated grief (p<0.001). R2 was 0.73 for the final model (p<.001). The results revealed that two character dimensions (low cooperativeness and self-transcendence), high neurotic defense style and young age of the deceased person were involved in the psychopathological course of the complicated and prolonged grief. It was concluded that personality characteristics of the grieving persons and demographics of the deceased person should be addressed in designing tailored interventions for complicated grief.

  5. The Role of Defense Mechanisms, Personality and Demographical Factors on Complicated Grief following Death of a loved one by Cancer

    PubMed Central

    Rahimian Boogar, Isaac; Talepasand, Siavash

    2015-01-01

    Objective: Identification of the risk factors and psychological correlates of prolonged grief disorder is vital for health promotions in relatives of persons who died of cancer. The aim of this research was to investigate the role of defense mechanisms, character dimension of personality and demographic factors on complicated grief following a loss of a family member to cancer. Method: A number of 226 persons who had lost a family member to cancer in a cancer institute at Tehran University of Medical Science were selected through compliance sampling and completed the Inventory of complicated Grief-Revised (ICG-R), the Defense Styles Questionnaire (DSQ), the Character dimension of Temperament and Character Inventory (TCI), and the Demographical questionnaire. Data were analyzed by stepwise multiple regression analysis, using the PASW version 18. Results: Findings revealed that neurotic defense style had a significant positive predictive role in the complicated grief; and cooperativeness, age of the deceased person, self-transcendence and mature defense style had a significant negative predictive role in complicated grief (p<0.001). R2 was 0.73 for the final model (p<.001). Conclusion: The results revealed that two character dimensions (low cooperativeness and self-transcendence), high neurotic defense style and young age of the deceased person were involved in the psychopathological course of the complicated and prolonged grief. It was concluded that personality characteristics of the grieving persons and demographics of the deceased person should be addressed in designing tailored interventions for complicated grief. PMID:26884783

  6. Diminished pulmonary function in pectus excavatum: from denying the problem to finding the mechanism

    PubMed Central

    Obermeyer, Robert J.; Nuss, Donald

    2016-01-01

    Background Recently, technical improvement in the ability to measure lung function and the severity of chest deformity have enabled progress in understanding the mechanism of limitations of lung function in pectus excavatum. Methods After establishing that most patients with pectus excavatum do have symptoms of exercise intolerance, easy fatigability, and shortness of breath with exertion, lung function has been evaluated by a variety of methods in different centers. Spirometry, plethysmography, exercise testing, oculo electronic plethysmography, and imaging methods have been used to assess lung function in pectus excavatum and its response to surgery. Results Not all patients with pectus excavatum have subnormal static pulmonary function testing; some have above-average values. However, in more than 1500 adult and pediatric surgical patients with anatomically severe pectus excavatum at a single center, the bell curve of FVC, FEV1, and FEF 25-75 is shifted to significantly lower values in pectus excavatum. The curve is shifted to higher values after operation by approximately one standard deviation. Previous work has demonstrated that patients with more anatomically severe pectus excavatum are more likely to have diminished PFT’s. A mechanism for this effect is seen by oculo electronic plethysmography, which demonstrates that the depressed portion of the chest does not move on respiration. After Nuss procedure, the chest wall motion used to create suction to draw air into the lungs is indistinguishable from that of persons with a normal chest, and the intrathoracic volume is markedly increased. Conclusions Pectus excavatum is accompanied in most patients by diminished static pulmonary function. Correction by Nuss procedure results in improvement in chest wall motion; this improvement in the thoracic bellows action is accompanied by improvement in pulmonary function testing. PMID:27747180

  7. Pulmonary Antifibrotic Mechanisms Aspirin-Triggered Lipoxin A4 Synthetic Analog

    PubMed Central

    Guilherme, Rafael F.; Xisto, Debora G.; Kunkel, Steven L.; Freire-de-Lima, Célio G.; Rocco, Patricia R.M.; Neves, Josiane S.; Fierro, Iolanda M.; Canetti, Claudio

    2013-01-01

    No successful therapies are available for pulmonary fibrosis, indicating the need for new treatments. Lipoxins and their 15-epimers, aspirin-triggered lipoxins (ATL), present potent antiinflammatory and proresolution effects (Martins et al., J Immunol 2009;182:5374–5381). We show that ATLa, an ATL synthetic analog, therapeutically reversed a well-established pulmonary fibrotic process induced by bleomycin (BLM) in mice. We investigated the mechanisms involved in its effect and found that systemic treatment with ATLa 1 week after BLM instillation considerably reversed the inflammatory response, total collagen and collagen type 1 deposition, vascular endothelial growth factor, and transforming growth factor (TGF)-β expression in the lung and restored surfactant protein C expression levels. ATLa also inhibited BLM-induced apoptosis and cellular accumulation in bronchoalveolar lavage fluid and in the lung parenchyma as evaluated by light microscopy and flow cytometry (Ly6G+, F4/80+, CD11c+, CD4+, and B220+ cells) assays. Moreover, ATLa inhibited the lung production of IL-1β, IL-17, TNF-α, and TGF-β induced by BLM-challenged mice. ATLa restored the balance of inducible nitric oxide synthase–positive and arginase-positive cells in the lungs, suggesting a prevalence of M2 versus M1 macrophages. Together, these effects improved pulmonary mechanics because ATLa treatment brought to normal levels lung resistance and elastance, which were clearly altered at 7 days after BLM challenge. Our findings support ATLa as a promising therapeutic agent to treat lung fibrosis. PMID:23848293

  8. Assessment of safety of lactobacillus strains based on resistance to host innate defense mechanisms.

    PubMed

    Asahara, Takashi; Takahashi, Masatoshi; Nomoto, Koji; Takayama, Hiroo; Onoue, Masaharu; Morotomi, Masami; Tanaka, Ryuichiro; Yokokura, Teruo; Yamashita, Naoya

    2003-01-01

    Seven Lactobacillus strains belonging to four species were evaluated for pathogenicity as well as for in vitro sensitivity to the bactericidal mechanisms of macrophages in a rabbit infective endocarditis (IE) model. Two bacteremia-associated strains, L. rhamnosus PHLS A103/70 and L. casei PHLS A357/84, as well as the L. rhamnosus type strain and the probiotic L. rhamnosus strain ATCC 53103, showed moderate infectivity, and the virulence of the probiotic L. casei strain Shirota and type strains such as L. acidophilus ATCC 4356(T) and L. gasseri DSM 20243(T) in the model was negligible. The strains that showed pathogenic potential in the rabbit IE model (PHLS A357/84, PHLS A103/70, and ATCC 53103) were more resistant than strain Shirota to intracellular killing activity by mouse macrophages in vitro and also to bactericidal nitrogen intermediates, such as nitric oxide and NO(2)(-) ions. These results suggest that resistance to host innate defense systems, which would function at inflammatory lesions, should be considered in the safety assessment of Lactobacillus strains.

  9. Changes of defense mechanisms and personality profile during group analytic treatment.

    PubMed

    Vlastelica, Mirela; Jurcević, Slavica; Zemunik, Tatijana

    2005-12-01

    Researching efficiency of group-analytic treatment and following Foulkes' principle of the "group-as-a-whole", the methodology was applied. That enabled the evaluation of expected changes of group members individually, as well as the group-as-a-whole. In this study three small groups (20 patients) were followed up and changes were evaluated after second and after fourths years of group analysis. Two measuring instruments--The Life Style Index and Defence Mechanisms Scale (LS-DM) and Minnesota Multiphase Personality Inventory (MMPI-201) were applied. Each member of the group was assessed by self-evaluation as well as the group-as-a-whole. The results of the research indicated that changes of the personality occurred. Changes consisted in lowering of defensive activities that was tending towards more mature defences. Changes also consisted in lowering ratings on the pathological parts of the MMPI-scales reflecting shifting of the conflict level. The results could be predictive for positive outcome of group analysis. More studies are needed.

  10. [Adaptation of self-image level and defense mechanisms in elderly patients with complicated stoma].

    PubMed

    Ortiz-Rivas, Miriam Karina; Moreno-Pérez, Norma Elvira; Vega-Macías, Héctor Daniel; Jiménez-González, María de Jesús; Navarro-Elías, María de Guadalupe

    2014-01-01

    Ostomy patients face a number of problems that impact negatively on their personal welfare. The aim of this research is determine the nature and intensity of the relationship between the level of self-concept adaptive mode and the consistent use of coping strategies of older adults with a stoma. Quantitative, correlational and transversal. VIVEROS 03 and CAPS surveys were applied in 3 hospitals in the City of Durango, México. The study included 90 older adults with an intestinal elimination stoma with complications. Kendall's Tau-b coefficient was the non-parametric test used to measure this association. Most older adults analyzed (61.3 < % < 79.9) are not completely adapted to the condition of living with an intestinal stoma. There is also a moderate positive correlation (0,569) between the level of adaptation of the older adults with a stoma and the conscious use of coping strategies. The presence of an intestinal stoma represents a physical and psychological health problem that is reflected in the level of adaptation of the self-image. Elderly people with a stoma use only a small part of defense mechanisms as part of coping process. This limits their ability to face the adversities related to their condition, potentially causing major health complications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  11. 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.

  12. Interactions of regional respiratory mechanics and pulmonary ventilatory impairment in pulmonary emphysema: assessment with dynamic MRI and xenon-133 single-photon emission CT.

    PubMed

    Suga, K; Tsukuda, T; Awaya, H; Matsunaga, N; Sugi, K; Esato, K

    2000-06-01

    Dynamic MRI and (133)Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the (133)Xe retention index (RI) on three-dimensional (133)Xe SPECT displays. By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater (133)Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p < 0.0001 and p < 0.05, respectively). The removal of (133)Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p < 0.01 and p < 0.001, respectively). In a total of 40 studies of the 28 patients including post-LVRS studies, normalized MADM and MACWM correlated with percent predicted FEV(1) (r = 0.881, p < 0.0001; and r = 0.906, p < 0.0001, respectively), and also with (133)Xe RI in each hemithorax (r = -0.871, p < 0 0.0001; and r = -0.901, p < 0 0.0001, respectively.) This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.

  13. Asthma and pulmonary arterial hypertension: do they share a key mechanism of pathogenesis?

    PubMed Central

    Said, S.I.; Hamidi, S.A.; Bosc, L. Gonzalez

    2010-01-01

    Although largely distinct and seemingly unrelated, asthma and pulmonary arterial hypertension (PAH) have important pathological features in common, including inflammation, smooth muscle contraction and remodelling. We hypothesised that these common features could be explained by one shared mechanism of pathogenesis: activation of the transcription factor NFAT (nuclear factor of activated T-cells). If this concept is validated, it could lead to the introduction of novel therapeutic strategies against both lung disorders. In several experimental models, airway remodelling is accompanied by remodelling of smaller pulmonary arteries, validating the hypothesis of their similar pathogenesis. In addition, lungs of vasoactive intestinal peptide (VIP) knockout mice express airway hyperresponsiveness with airway inflammation and PAH with vascular remodelling, with both sets of pathological findings being reversible with VIP treatment. Preliminary data suggest that absence of the VIP gene leads to activation of the calcineurin–NFAT pathway, and that VIP is probably a physiological inhibitor of this pathway. Enough evidence exists to support the views that asthma and PAH share important pathological features, probably related to NFAT activation, and that VIP may be a physiological modulator of this mechanism. PMID:20356986

  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. 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. Copyright

  16. 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.

  17. Plant structural complexity and mechanical defenses mediate predator-prey interactions in an odonate-bird system.

    PubMed

    Grof-Tisza, Patrick; LoPresti, Eric; Heath, Sacha K; Karban, Richard

    2017-03-01

    Habitat-forming species provide refuges for a variety of associating species; these refuges may mediate interactions between species differently depending on the functional traits of the habitat-forming species. We investigated refuge provisioning by plants with different functional traits for dragonfly and damselfly (Odonata: Anisoptera and Zygoptera) nymphs emerging from water bodies to molt into their adult stage. During this period, nymphs experience high levels of predation by birds. On the shores of a small pond, plants with mechanical defenses (e.g., thorns and prickles) and high structural complexity had higher abundances of odonate exuviae than nearby plants which lacked mechanical defenses and exhibited low structural complexity. To disentangle the relative effects of these two potentially important functional traits on nymph emergence-site preference and survival, we conducted two fully crossed factorial field experiments using artificial plants. Nymphs showed a strong preference for artificial plants with high structural complexity and to a lesser extent, mechanical defenses. Both functional traits increased nymph survival but through different mechanisms. We suggest that future investigations attempt to experimentally separate the elements contributing to structural complexity to elucidate the mechanistic underpinnings of refuge provisioning.

  18. Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease.

    PubMed

    Gaffen, S L; Herzberg, M C; Taubman, M A; Van Dyke, T E

    2014-05-01

    The innate and adaptive immune systems are both crucial to oral disease mechanisms and their impact on systemic health status. Greater understanding of these interrelationships will yield opportunities to identify new therapeutic targets to modulate disease processes and/or increase host resistance to infectious or inflammatory insult. The topics addressed reflect the latest advances in our knowledge of the role of innate and adaptive immune systems and inflammatory mechanisms in infectious diseases affecting the oral cavity, including periodontitis and candidiasis. In addition, several potential links with systemic inflammatory conditions, such as cardiovascular disease, are explored. The findings elucidate some of the defense mechanisms utilized by host tissues, including the role of IL-17 in providing immunity to oral candidiasis, the antimicrobial defense of mucosal epithelial cells, and the pro-resolution effects of the natural inflammatory regulators, proresolvins and lipoxins. They also describe the role of immune cells in mediating pathologic bone resorption in periodontal disease. These insights highlight the potential for therapeutic benefit of immunomodulatory interventions that bolster or modulate host defense mechanisms in both oral and systemic disease. Among the promising new therapeutic approaches discussed here are epithelial cell gene therapy, passive immunization against immune cell targets, and the use of proresolvin agents.

  19. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism.

    PubMed

    Ren, Dongmei; Villeneuve, Nicole F; Jiang, Tao; Wu, Tongde; Lau, Alexandria; Toppin, Henry A; Zhang, Donna D

    2011-01-25

    The major obstacle in cancer treatment is the resistance of cancer cells to therapies. Nrf2 is a transcription factor that regulates a cellular defense response and is ubiquitously expressed at low basal levels in normal tissues due to Keap1-dependent ubiquitination and proteasomal degradation. Recently, Nrf2 has emerged as an important contributor to chemoresistance. High constitutive expression of Nrf2 was found in many types of cancers, creating an environment conducive for cancer cell survival. Here, we report the identification of brusatol as a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells and A549 xenografts to cisplatin and other chemotherapeutic drugs. Mechanistically, brusatol selectively reduces the protein level of Nrf2 through enhanced ubiquitination and degradation of Nrf2. Consequently, expression of Nrf2-downstream genes is reduced and the Nrf2-dependent protective response is suppressed. In A549 xenografts, brusatol and cisplatin cotreatment induced apoptosis, reduced cell proliferation, and inhibited tumor growth more substantially when compared with cisplatin treatment alone. Additionally, A549-K xenografts, in which Nrf2 is expressed at very low levels due to ectopic expression of Keap1, do not respond to brusatol treatment, demonstrating that brusatol-mediated sensitization to cisplatin is Nrf2 dependent. Moreover, a decrease in drug detoxification and impairment in drug removal may be the primary mechanisms by which brusatol enhances the efficacy of chemotherapeutic drugs. Taken together, these results clearly demonstrate the effectiveness of using brusatol to combat chemoresistance and suggest that brusatol can be developed into an adjuvant chemotherapeutic drug.

  20. 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

  1. 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.

  2. Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

    PubMed

    Shaler, Christopher R; Horvath, Carly; Lai, Rocky; Xing, Zhou

    2012-01-01

    Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

  3. Mechanisms for Induction of Pulmonary Capillary Hemorrhage by Diagnostic Ultrasound: Review and Consideration of Acoustical Radiation Surface Pressure.

    PubMed

    Miller, Douglas L

    2016-12-01

    Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas-body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustical radiation surface pressure (ARSP) at a tissue-air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiologic conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound.

  4. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

    PubMed Central

    Benoist, David; Stones, Rachel; Drinkhill, Mark J.; Benson, Alan P.; Yang, Zhaokang; Cassan, Cecile; Gilbert, Stephen H.; Saint, David A.; Cazorla, Olivier; Steele, Derek S.; Bernus, Olivier

    2012-01-01

    Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. PMID:22427523

  5. 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.

  6. Unsuccessful percutaneous mechanical thrombectomy in fibrin-rich high-risk pulmonary thromboembolism.

    PubMed

    Vidmar, Jernej; Serša, Igor; Kralj, Eduard; Popovič, Peter

    2015-01-01

    We report a case of unsuccessful percutaneous mechanical thrombectomy in treatment of a high-risk pulmonary embolism (PE). Pulmonary thromboemboli are commonly expected as a homogenous mass, rich with red blood cell content, which respond well to percutaneous mechanical thrombectomy (PMT). Catheter-based approach or surgical embolectomy are two treatment options that are usually considered for treatment of high-risk PE when the thrombolytic therapy fails or it is contraindicated due to a patient's persisting hemodynamic compromise. Currently, selection criteria for PE treatment options are based mostly on the assessment of patient's history. The aim of this report is to highlight a possible treatment complication in PMT of structurally heterogeneous thrombotic mass due to PMT inadequacy. A 32 year-old male with polytrauma was admitted to an intensive care unit after a right-sided nephrectomy and evacuation of retroperitoneal hematoma. The patient initial haemostatic disorder was improved by administration of blood preparations, an anti-fibrinolytic agent and concentrates of fibrinogen. On the third day he presented sudden onset of hemodynamic instability and was incapable of standard CTA diagnostic procedure. Urgent and relevant investigations including transthoracic and transesophageal echocardiogram confirmed a high-risk PE. PMT was performed due to contraindications for systemic thrombolysis. Long-term PMT was attempted using aspiration with several devices. No major improvement was achieved in any of the treatments and the patient died. Autopsy confirmed a large heterogeneous thrombotic mass in the pulmonary trunk folding to the right main artery. Additional histological analysis revealed a high fibrin-rich content in the peripheral surroundings of the thrombus. In the case, it was confirmed that the outcome of PMT was directly influenced by mechanical and histological features of the thromboembolus in high-risk PE. Formation of a rather complex thromboembolus

  7. Gender differences in defense mechanisms, ways of coping with stress and sense of identity in adolescent suicide attempts.

    PubMed

    Foto-Özdemir, Dilşad; Akdemir, Devrim; Çuhadaroğlu-Çetin, Füsun

    2016-01-01

    The main aim of this study was to investigate the gender differences in defense mechanisms, ways of coping with stress and identity formation in relation to adolescent suicidal behavior. This study involved 64 adolescents between 12-17 years of age, who were admitted to the emergency service with a suicide attempt. They were evaluated with a semi-structured clinical interview (K-SADS), Ways of Coping Inventory (WCI), Defense Mechanisms Inventory (DMI) and Sense of Identity Assessment Form (SIAF). 60.9% (n = 39) of the adolescents were female, and 39.1% (n=25) were male. There were no statistically significant differences between the girls and the boys with respect to the clinical characteristics of the suicide attempt and the rate of psychiatric disorders. Of the 64 adolescents with suicide attempt, 47 (73.4%) had at least one, and 26 (40.6%) had more than one psychiatric disorder according to K-SADS. Disruptive behavior disorders were more frequent in males, whereas depression was more frequent in girls. The data indicated the importance of identity confusion, major depression and ADHD in adolescents with suicide attempt in both genders. 43.6% (n=17) of the girls and 36% (n=9) of the boys obtained scores higher than the cut-off point of SIAF indicating identity confusion. Professional help seeking and NSSI behaviors before the suicide attempt were more common in adolescents with identity confusion. While there were differences between genders with respect to the defense mechanisms used, no significant difference was found in terms of ways of coping. Evaluation of DMI scores revealed that the turning against object subscale score was significantly higher in boys compared to girls. While evaluating the adolescents at risk, their defense mechanisms, way of coping and sense of identity, as well as their psychiatric diagnosis should be assessed in detail in order to identify the suicidal thoughts and prevent possible suicide attempts.

  8. From emotional abuse in childhood to psychopathology in adulthood: a path mediated by immature defense mechanisms and self-esteem.

    PubMed

    Finzi-Dottan, Ricky; Karu, Toby

    2006-08-01

    The present study examined the course traveled from childhood emotional abuse to adulthood psychopathology. One hundred ninety-six undergraduate students age 20 to 45 (M = 27; SD = 8.17), answered self-report questionnaires assessing emotional abuse in childhood (Childhood Trauma Questionnaire), parental attitudes (Parental Bonding Instrument), psychopathological symptomatology (Brief Symptom Inventory), self-esteem (Rosenberg Self-Esteem Scale), and defense mechanism organization (Defense Style Questionnaire). Results indicated that reported psychopathological symptomatology highly exceeded the Israeli norm. Structure Equation Modeling provided a statistically significant explanation (52%) of the target variable of psychopathological symptomatology. According to the path model, emotional abuse in childhood and perceptions of controlling and noncaring parents had an indirect effect on the psychopathology. This was mediated by immature defenses and low self-esteem. We conclude that the manifest psychopathology among adults who suffered emotional abuse in childhood is produced by the detrimental effect of abuse on personality, and takes the form of immature defense organization and damaged self-representation.

  9. 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…

  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 review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

    PubMed Central

    Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D

    2016-01-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734

  12. Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development.

    PubMed

    Pan, Jie; Copland, Ian; Post, Martin; Yeger, Herman; Cutz, Ernest

    2006-01-01

    Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (Po2 approximately 20 mmHg), stretch-induced 5-HT release was not affected by Ca2+-free medium or nifedipine (50 microM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid ( approximately 5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

  13. 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.

  14. Mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ARDS.

    PubMed

    Baedorf Kassis, Elias; Loring, Stephen H; Talmor, Daniel

    2016-08-01

    The driving pressure of the respiratory system has been shown to strongly correlate with mortality in a recent large retrospective ARDSnet study. Respiratory system driving pressure [plateau pressure-positive end-expiratory pressure (PEEP)] does not account for variable chest wall compliance. Esophageal manometry can be utilized to determine transpulmonary driving pressure. We have examined the relationships between respiratory system and transpulmonary driving pressure, pulmonary mechanics and 28-day mortality. Fifty-six patients from a previous study were analyzed to compare PEEP titration to maintain positive transpulmonary end-expiratory pressure to a control protocol. Respiratory system and transpulmonary driving pressures and pulmonary mechanics were examined at baseline, 5 min and 24 h. Analysis of variance and linear regression were used to compare 28 day survivors versus non-survivors and the intervention group versus the control group, respectively. At baseline and 5 min there was no difference in respiratory system or transpulmonary driving pressure. By 24 h, survivors had lower respiratory system and transpulmonary driving pressures. Similarly, by 24 h the intervention group had lower transpulmonary driving pressure. This decrease was explained by improved elastance and increased PEEP. The results suggest that utilizing PEEP titration to target positive transpulmonary pressure via esophageal manometry causes both improved elastance and driving pressures. Treatment strategies leading to decreased respiratory system and transpulmonary driving pressure at 24 h may be associated with improved 28 day mortality. Studies to clarify the role of respiratory system and transpulmonary driving pressures as a prognosticator and bedside ventilator target are warranted.

  15. [Participation of gonads in pulmonary silicosis].

    PubMed

    Ruse, M; Dascălu, R; Suciu, I; Zergreanu, O

    1976-05-01

    A survey is given on the participation of endocrine glands in the pulmonary silicosis. At the same time a new clinical and experimental contribution to the question of the appearance of a hypogonadotropic hypogonadism is given. The frequency of this hypogonadism increases with the severity of the pulmonary silicosis. The immunological opinions as well as the neuroergonal ones concerning the pathogenesis of pulmonary silicosis gave the possibility of a better explanation of the mechanisms, by means of which also other organs may be attacked in pulmonary silicosis. The neuroendocrine system gives a defensive answer to the aggressive silicotic pulmonary process, which in general slowly progresses, but which may also be certain hormones from the group of the glucocorticosteroids in the adrenal cortex. The intervention into the axis hypothalamus-hypophysis-adrenal cortex has been provided in all defence processes of the organism against every aggression. By the functional or organic damage of the neuroendocrine system, by the immediate toxic effect of silicium dioxide or the monosilicium acid as well as by the effect of the secondary hypoxia in pulmonary silicosis an insufficiency in the stimulation and excretion of certain hormones develops. The origin of this insufficiency is found in the hypothalamo-hypophyseal centres, and the effects extend to all endocrine glands which depend on the system hypothalamus-hypophysis. This mechanism is made responsible for the appearance of a hypogonadotropic insufficiency of gonads in the course of a pulmonary silicosis and is proved clinically and experimentally in the cases investigated by the authors

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

    PubMed

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

    2013-12-01

    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".

  17. 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.

  18. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

    PubMed

    Su, J; Hilberg, O; Howard, L; Simonsen, U; Hughes, A D

    2016-12-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  19. 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.

  20. Mechanisms and Modifications of Naturally Occurring Host Defense Peptides for Anti-HIV Microbicide Development

    PubMed Central

    Eade, Colleen R.; Wood, Matthew P.; Cole, Alexander M.

    2014-01-01

    Despite advances in the treatment of HIV infection, heterosexual transmission of HIV remains high, and vaccines to prevent HIV acquisition have been unfruitful. Vaginal microbicides, on the other hand, have demonstrated considerable potential for HIV prevention, and a variety of compounds have been screened for their activity and safety as anti-HIV microbicides. Among these are the naturally occurring host defense peptides, small peptides from diverse lineages with intrinsic antiviral activity. Naturally occurring host defense peptides with anti-HIV activity are promising candidates for vaginal microbicide development. Their structural variance and accompanying mechanistic diversity provide a wide range of inhibitors whose antiviral activity can be exerted at nearly every stage of the HIV lifecycle. Additionally, peptide modification has been explored as a method for improving the anti-HIV activity of host defense peptides. Structure- and sequence-based alterations have achieved varying success in improving the potency and specificity of anti-HIV peptides. Overall, peptides have been discovered or engineered to inhibit HIV with therapeutic indices of >1000, encouraging their advancement toward clinical trials. Here we review the naturally occurring anti-HIV host defense peptides, demonstrating their breadth of mechanistic diversity, and exploring approaches to enhance and optimize their activity in order to expedite their development as safe and effective anti-HIV vaginal microbicides. PMID:22264047

  1. Transcriptional analysis of defense mechanisms in upland tetraploid switchgrass to greenbugs

    USDA-ARS?s Scientific Manuscript database

    Background: Aphid infestation of switchgrass (Panicum virgatum) has the potential to reduce yields and biomass quality. Although switchgrass-greenbug (Schizaphis graminum; GB) interactions have been studied at the whole plant level, little information is available on plant defense responses at the m...

  2. Mechanisms of particle-induced pulmonary inflammation in a mouse model: exposure to wood dust.

    PubMed

    Määttä, Juha; Lehto, Maili; Leino, Marina; Tillander, Sari; Haapakoski, Rita; Majuri, Marja-Leena; Wolff, Henrik; Rautio, Sari; Welling, Irma; Husgafvel-Pursiainen, Kirsti; Savolainen, Kai; Alenius, Harri

    2006-09-01

    Repeated airway exposure to wood dust has long been known to cause adverse respiratory effects such as asthma and chronic bronchitis and impairment of lung function. However, the mechanisms underlying the inflammatory responses of the airways after wood dust exposure are poorly known. We used a mouse model to elucidate the mechanisms of particle-induced inflammatory responses to fine wood dust particles. BALB/c mice were exposed to intranasally administered fine (more than 99% of the particles had a particle size of < or = 5 microm, with virtually identical size distribution) birch or oak dusts twice a week for 3 weeks. PBS, LPS, and titanium dioxide were used as controls. Intranasal instillation of birch or oak dusts elicited influx of inflammatory cells to the lungs in mice. Enhancement of lymphocytes and neutrophils was seen after oak dust exposure, whereas eosinophil infiltration was higher after birch dust exposure. Infiltration of inflammatory cells was associated with an increase in the mRNA levels of several cytokines, chemokines, and chemokine receptors in lung tissue. Oak dust appeared to be a more potent inducer of these inflammatory mediators than birch dust. The results from our in vivo mouse model show that repeated airway exposure to wood dust can elicit lung inflammation, which is accompanied by induction of several proinflammatory cytokines and chemokines. Oak and birch dusts exhibited quantitative and qualitative differences in the elicitation of pulmonary inflammation, suggesting that the inflammatory responses induced by the wood species may rise via different cellular mechanisms.

  3. Bone marrow mesenchymal stem cells attenuate silica-induced pulmonary fibrosis via paracrine mechanisms.

    PubMed

    Li, Xiaoli; Wang, Yan; An, Guoliang; Liang, Di; Zhu, Zhonghui; Lian, Ximeng; Niu, Piye; Guo, Caixia; Tian, Lin

    2017-03-15

    The purpose of this study was to investigate the anti-fibrotic effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung injury and fibrosis in vivo and in vitro. In vivo, rats were exposed to 50mg/ml silica intratracheally. The rats were sacrificed on day 15 or day 30 after intravenous injection of BMSCs. Histopathological examination demonstrated that BMSCs decreased the blue areas of collagen fibers and the number of nodules. Alveolar epithelium was damaged by silica, but it was restored by BMSCs. In vitro, BMSCs co-cultured with RLE-6TN cells in 6-Transwell plates were evaluated to determine the possible mechanism. The results demonstrated that BMSCs downregulated the expression of collagen I and III. BMSCs reversed morphological abnormalities and reduced the proliferation of RLE-6TN cells. These data showed that BMSCs did not give rise to alveolar epithelial cells directly, while the levels of hepatocyte growth factor, keratinocyte growth factor and bone morphogenetic protein -7 increased and expression of tumor necrosis factor-α and transforming growth factor-β1 decreased in the 6TN+Silica+BMSCs group compared with the 6TN+Silica group. Our results revealed that BMSCs exerted anti-fibrotic effects on silica-induced pulmonary fibrosis, which might be associated with paracrine mechanisms rather than differentiation.

  4. Diffuse persistent pulmonary interstitial emphysema secondary to mechanical ventilation in bronchiolitis.

    PubMed

    Toledo Del Castillo, Blanca; Gordillo, Isabel; Rubio García, Elena; Fernández Lafever, Sarah Nicole; Gonzalez Cortés, Rafael; Urbano Villaescusa, Javier; López González, Jorge; Solana García, María José; López-Herce Cid, Jesús

    2016-11-03

    Persistent interstitial pulmonary emphysema (PIE) is a rare disease and it is even more uncommon in full-term infants, like our patient. When conservative management is not successful, surgical treatment should be considered. In our case, ECMO support was iniciated to keep the patient ventilated in order to allow the lung to heal using lung protection strategies. We report an 18-day-old male infant with bronchiolitis that required mechanical ventilation with high positive airway pressures due to severe respiratory insufficiency. Chest X-rays and computed tomography scan revealed a severely hyperinflated left lung with extensive destructive changes and multiple small bullae. These findings were consistent with diffuse persistent interstitial emphysema (PIE), probably due to mechanical ventilation. The patient required high frequency oscillatory ventilation, inotropic support and continuous renal replacement therapy. He eventually suffered a cardiac arrest that required cardiopulmonary resuscitation and ECMO during 5 days with progressive clinical improvement and normalization of the X-ray. We present a patient with diffuse persistent interstitial emphysema who, despite an unfavorable evolution with different mechanical ventilation strategies, had a good response after ECMO assistance.

  5. Pulmonary gas exchange in anaesthetised horses mechanically ventilated with oxygen or a helium/oxygen mixture.

    PubMed

    Staffieri, F; Bauquier, S H; Moate, P J; Driessen, B

    2009-11-01

    It is unknown whether administration of gas-mixtures high in inspired fraction of oxygen (FiO2) under general anaesthesia may increase formation of pulmonary atelectasis and impair gas exchange. To evaluate the effects of different FiO2 on pulmonary gas exchange in isoflurane-anaesthetised horses breathing a helium/oxygen (He/O2) mixture. Thirty healthy mature horses were sedated with i.v. acepromazine (0.02 mg/kg bwt), detomidine (0.002 mg/kg bwt) and xylazine (02-0.4 mg/kg bwt). General anaesthesia was induced with i.v. 5% guaifenesin to effect, diazepam (0.1 mg/kg bwt) and ketamine (2 mg/kg bwt), and maintained with isoflurane. Fifteen horses (Group HX) were ventilated mechanically with gas mixtures of successively increasing FiO2 (0.25-030, 0.50-0.55, > 0.90), obtained by blending 02 with Heliox (70% He/30% O2). The other 15 horses (Group O) were ventilated immediately with 100% O2 (FiO2 > 0.90). After 20 min of ventilation at the different FiO2 levels in Group HX and after 60 min in Group O, PaO2 and PaCO2 were measured and the alveolar to arterial PO2 gradient (P(A-a)O2) was calculated. Data analysis included robust categorical regression with clustering on horse (P < 0.05). Inhalation of a He/O2 mixture with FiO2 as low as 0.25-030 ensured adequate arterial oxygenation and was associated with a smaller P(A-a)O2 gradient than inhalation of pure O2 (P < 0.05). In Group HX, PaO2 increased with each rise in FiO2 and so did P(A-a)O2 (P < 0.05). The PaO2 was significantly lower and the P(A-a)O2 higher in Group O compared to Group HX at a FiOz >0.90 (P < 0.05). Administration of a He/O2 gas mixture low in FiO2 can better preserve lung function than ventilation with pure oxygen. A step-wise increase of FiO2 using a He/O2 gas mixture might offer advantages with respect to pulmonary gas exchange over an immediate exposure to 100% 2O2.

  6. 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.

  7. Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation.

    PubMed

    Harvey, C J; O'Doherty, M J; Page, C J; Thomas, S H; Nunan, T O; Treacher, D F

    1997-04-01

    Increased delivery of aerosol to a model lung (attached to a mechanical ventilator) has been demonstrated with an ultrasonic nebulizer as compared to a jet nebulizer. This study examined whether the increased aerosol deposition with an ultrasonic nebulizer could also be demonstrated in vivo. Seven patients (6 male and 1 female) were studied during mechanical ventilalion (Siemens Servo 900C, Middlesex, UK) after open heart surgery. Two studies were performed in each patient. In the first study, aerosol was delivered via a Siemens Servo 945 nebulizer system (high setting) driving a System 22 Acorn jet nebulizer (Medic-Aid, Sussex, UK) containing 3 mL (99m)technetium-labelled human serum albumin (99mTc-HSA) (50 microg; activity 74 MBq). In the second study, a DP100 ultrasonic nebulizer (DP Medical, Meylan, France) containing 12 mL 99mTc-HSA (50 microg; activity 185 MBq) was used. Pulmonary deposition was quantified using a gamma camera. The humidification of the circuit and the ventilator settings were kept constant according to the patient's clinical requirements. The total lung aerosol deposition (mean+/-SD), as a percentage of initial nebulizer activity, was greater using the ultrasonic nebulizer than using the jet nebulizer (53+/-1.4 vs 2.3+/-0.9%; p<0.002). The ultrasonic nebulizer was also associated with a reduction in the time required to complete nebulization (9 vs 21 min, respectively) (p<0.0001). Use of the DP100 ultrasonic nebulizer more than doubled lung deposition compared with the System 22 jet nebulizers in mechanically-ventilated patients. Their efficiency, speed of drug delivery, and compatibility with mechanical ventilator circuits make ultrasonic nebulizers potentially attractive for use during mechanical ventilation.

  8. A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice

    PubMed Central

    Theodoro-Júnior, Osmar Aparecido; Righetti, Renato Fraga; Almeida-Reis, Rafael; Martins-Oliveira, Bruno Tadeu; Oliva, Leandro Vilela; Prado, Carla Máximo; Saraiva-Romanholo, Beatriz Mangueira; Leick, Edna Aparecida; Pinheiro, Nathalia Montouro; Lobo, Yara Aparecida; Martins, Mílton de Arruda; Oliva, Maria Luiza Vilela; Tibério, Iolanda de Fátima Lopes Calvo

    2017-01-01

    Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management. PMID:28216579

  9. A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice.

    PubMed

    Theodoro-Júnior, Osmar Aparecido; Righetti, Renato Fraga; Almeida-Reis, Rafael; Martins-Oliveira, Bruno Tadeu; Oliva, Leandro Vilela; Prado, Carla Máximo; Saraiva-Romanholo, Beatriz Mangueira; Leick, Edna Aparecida; Pinheiro, Nathalia Montouro; Lobo, Yara Aparecida; Martins, Mílton de Arruda; Oliva, Maria Luiza Vilela; Tibério, Iolanda de Fátima Lopes Calvo

    2017-02-14

    Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management.

  10. Intraoperative mechanical and chemical pleurodesis with 50 % glucose solution for secondary spontaneous pneumothorax in patients with pulmonary emphysema.

    PubMed

    Tsukioka, Takuma; Inoue, Kiyotoshi; Oka, Hiroko; Mizuguchi, Shinjiro; Morita, Ryuhei; Nishiyama, Noritoshi

    2013-08-01

    Secondary spontaneous pneumothorax is life-threatening for patients with pulmonary emphysema. To prevent recurrence, intraoperative pleurodesis is performed in addition to bullectomy. We report the therapeutic process and effectiveness of adding mechanical plus chemical pleurodesis, with a 50 % glucose solution, to bullectomy, for patients with pulmonary emphysema-related pneumothorax. The subjects were 20 patients (19 men and 1 woman; mean age 68 years) with pulmonary emphysema-related pneumothorax. After bullectomy was completed, 500 mL of a 50 % glucose solution was injected into the pleural cavity, followed by mechanical pleurodesis performed via ablation of the parietal pleura. The volume of pleural effusion decreased on postoperative day (POD) 1, and the temperature decreased on POD 2. The blood sugar levels increased on the day of surgery but decreased on POD 1. The mean postoperative follow-up period was 521 days. One patient died of pneumonia on POD 24. All other patients survived without pneumothorax recurrence. These results demonstrated the effectiveness of our treatment process for pulmonary emphysema-related pneumothorax. The fact that no patient experienced pneumothorax recurrence suggests that mechanical and chemical pleurodesis with 50 % glucose solution might be effective prophylaxis.

  11. 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

  12. The Integrity of the Esophageal Mucosa. Balance Between Offensive and Defensive Mechanisms

    PubMed Central

    Orlando, Roy C.

    2010-01-01

    Heartburn is the most common and characteristic symptom of gastroesophageal reflux disease. It ultimately results from contact of refluxed gastric acid with nociceptors within the esophageal mucosa and transmission of this peripheral signal to the central nervous system for cognition. Healthy esophageal epithelium provides an effective barrier between refluxed gastric acid and esophageal nociceptors; but this barrier is vulnerable to attack and damage, particularly by acidic gastric contents. How gastric acid is countered by defensive elements within the esophageal mucosa is a major focus of this discussion. When the defense is successful, the subject is asymptomatic and when unsuccessful, the subject experiences heartburn. Those with heartburn commonly fall into one of three endoscopic types: nonerosive reflux disease, erosive esophagitis and Barrett's esophagus. Although what determines endoscopic type remains unknown; it is proposed herein that inflammation plays a key, modulating role. PMID:21126700

  13. The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms.

    PubMed

    Orlando, Roy C

    2010-12-01

    Heartburn is the most common and characteristic symptom of gastroesophageal reflux disease. It ultimately results from contact of refluxed gastric acid with nociceptors within the esophageal mucosa and transmission of this peripheral signal to the central nervous system for cognition. Healthy esophageal epithelium provides an effective barrier between refluxed gastric acid and esophageal nociceptors; but this barrier is vulnerable to attack and damage, particularly by acidic gastric contents. How gastric acid is countered by defensive elements within the esophageal mucosa is a major focus of this discussion. When the defense is successful, the subject is asymptomatic and when unsuccessful, the subject experiences heartburn. Those with heartburn commonly fall into one of three endoscopic types: nonerosive reflux disease, erosive esophagitis and Barrett's esophagus. Although what determines endoscopic type remains unknown; it is proposed herein that inflammation plays a key, modulating role.

  14. Assessment of pulmonary mechanics and breathing patterns during posturally induced glossoptosis in infants.

    PubMed Central

    Cozzi, F; Bonanni, M; Cozzi, D A; Orfei, P; Piacenti, S

    1996-01-01

    Respiratory mechanics were studied in nine infants with glossoptosis-apnoea syndrome to determine whether glossoptosis may account for signs of both inspiratory and expiratory airway obstruction. Airflow, oesophageal pressure, inspiratory and expiratory time (Ti and Te), and inspiratory and expiratory resistance (Ri and Re) were measured before and during ventilatory phases characterised by glossoptotic pharyngeal obstruction, induced by turning the infants onto their backs. In addition, an attempt was made to correlate the abnormalities in pulmonary mechanics with the clinical features. During partial glossoptotic pharyngeal obstruction, a significant increase was observed in Te and Re and variable changes in Ti and Ri. During severe obstruction, the infants displayed obstructed inspiratory efforts often associated with stridor, as well as obstructed expiratory efforts often associated with audible grunting and retarded expiratory flow pattern. The expiratory grunt was loudest over the neck and mimicked bronchospasm over the chest. These findings indicate that glossoptotic pharyngeal obstruction induces functional airway obstruction which may affect both inspiration and expiration. Expiratory airway obstruction seems, at least in part, to be due to active braking of expiratory flow. PMID:8758127

  15. 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.

  16. Molecular mechanism of BjCHI1-mediated plant defense against Botrytis cinerea infection.

    PubMed

    Gao, Ying; Zhao, Kaijun

    2017-01-02

    Plant chitinases are a group of proteins associated with defense against pathogen attack. BjCHI1 is the first characterized chitinase containing two chitin binding domains (CBDs). Investigations have shown that BjCHI1 inhibits growth of fungal phytopathogens and agglutinates Gram-negative bacteria. Our recent studies revealed that expression of BjCHI1 mRNA is largely induced upon infection of Botrytis cinerea via a R2R3-MYB transcription factor BjMYB1 interacting with a W box-like element (Wbl-4) in the BjCHI1 promoter. The enhanced expression pattern of BjMYB1 was similar to that of BjCHI1 and associated with resistant phenotype against B. cinerea. These findings suggest that BjCHI1 is involved in host defense against fungal attack through interaction with BjMYB1. Here, we review the recent studies on BjCHI1 and propose a model of BjCHI1-mediated plant defense against fungal attack.

  17. 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

  18. Influence of dietary carbohydrate on zinc-deficiency-induced changes in oxidative defense mechanisms and tissue oxidative damage in rats.

    PubMed

    Kim, S H; Keen, C L

    1999-10-01

    The aim of this study was to determine the effect of dietary carbohydrate type on the expression of zinc (Zn) deficiency in rats with respect to tissue oxidative damage and defense mechanisms. Rats were fed diets containing adequate (+Zn) or low concentrations (-Zn) of Zn. Both fructose- and glucose-based diets were tested. Pair-fed controls were also studied to evaluate changes in the oxidative defense system which are secondary to Zn-deficiency-induced anorexia. Plasma and liver Zn concentrations and CuZn superoxide dismutase activities were lower in the -Zn rats than in the +Zn rats. Liver glutathione (GSH) and disulfide glutathione concentrations were higher in the -Zn rats than in the +Zn rats; this difference was most pronounced in the fructose groups. Liver and heart selenium glutathione peroxidase (Se-GSH-Px) activities were lower in the -Zn-fructose group than in the +Zn-fructose group. Liver Se-GSH-Px activity was higher in the fructose groups than in the glucose groups. Liver GSH reductase (GSH-Red) activity was lower in the -Zn-fructose group than in its control group. Liver glutamine synthetase activity was lower in the -Zn-glucose group and in the fructose groups than in the glucose control group. Liver thiobarbituric acid reactive substance (TBARS) production was similar among the groups. Collectively, these results support the concept that Zn deficiency can result in an impaired oxidant defense system. Based on the observation that pair-fed control animals also showed evidence of oxidative damage, we suggest that one factor that contributes to the effect of Zn deficiency is the reduction in caloric intake that occurs in these animals. Fructose feeding resulted in increased activities of several of the oxidant defense enzymes. Protein oxidative damage assessed by glutamine synthetase activity was increased by both Zn deficiency and fructose feeding.

  19. 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

  20. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models.

    PubMed

    Yu, Wencheng; Guo, Fang; Song, Xiaoxia

    2017-12-01

    Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p < 0.05) significance of airsacculitis and fibrosis scores of lung tissues, as well as expression of TGF-β1, TNF-α and PDGF, but the expression of Cav-1 was higher (p < 0.05). Compared with the N group, the fibrosis score was significantly lower and the protein expression of Cav-1 was significantly higher in the P group (p < 0.05). Additionally, the expression of Cav-1 was negatively correlated with the airsacculitis and fibrosis scores (r = -0.506, p < 0.01; r = -0.676, p < 0.01) as well as expression of TGF-β1, TNF-α and PDGF (r = -0.590, p < 0.01; r = -0.530, p < 0.01; r = -0.553, p < 0.01). Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and

  2. The use of the insanity defense as a jail diversion mechanism for mentally ill persons charged with misdemeanors.

    PubMed

    Schaefer, Michele N; Bloom, Joseph D

    2005-01-01

    Heightened awareness and concern regarding the large number of mentally ill misdemeanants in jails has led to a search for alternatives to jail and to the development nationwide of jail diversion programs for offenders with mental illness. Two such mechanisms-diversion to civil commitment and the use of mental health courts-are briefly reviewed. In Oregon, however, a rather unique mechanism is used to defer mentally ill misdemeanants (in addition to felons) from the criminal justice system: the insanity defense, with subsequent placement of the individual under Psychiatric Security Review Board jurisdiction. Statistics regarding such use from 1978 to 2001 are provided. The authors compare and contrast this jail alternative with both mental health courts and diversion to civil commitment, and discuss questions related to the feasibility of larger-scale use of this mechanism.

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

    PubMed Central

    Neo, Boon Hwa; Kandhi, Sharath

    2011-01-01

    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 H2O2 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 β1-subunit small interfering RNA-transfected BPAs demonstrated increased aerobic K+ force and inhibition of further contraction to hypoxia, associated with an attenuation of H2O2-elicited relaxation and VASP phosphorylation. Thus, decreases in both a sGC/cGMP-dependent and a dimerization-dependent activation of PKG by H2O2 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

  4. 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

  5. Intracellular infections in Drosophila melanogaster: host defense and mechanisms of pathogenesis.

    PubMed

    Péan, Claire B; Dionne, Marc S

    2014-01-01

    The fruit-fly Drosophila melanogaster has emerged as a powerful model to study innate immunity against intracellular pathogens. To combat infection, the fly relies on multiple lines of defense, many of which are shared with mammals and arthropod vectors of human diseases. In addition to conserved immune pathways, the ease of performing sophisticated genetic screens has allowed the identification of novel host immune factors and novel pathogen virulence factors. Recently, some groups have exploited this to simultaneously analyze the host and pathogen genetics of intracellular infection. This review aims to unravel the Drosophila immune response against intracellular pathogens, highlighting recent discoveries. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Use of experimental airborne infections for monitoring altered host defenses.

    PubMed Central

    Gardner, D E

    1982-01-01

    The success or failure of the respiratory system to defend itself against airborne infectious agents largely depends upon the efficiency of the pulmonary defenses to maintain sterility and to dispose of unwanted substances. Both specific and nonspecific host defenses cooperate in the removal and inactivation of such agents. Several studies have shown that these defenses are vulnerable to a wide range of environmental agents and that there is a good relationship between exposure to pollutant and the impaired resistance to pulmonary disease. There are numerous immunological, biochemical and physiological techniques that are routinely used to identify and to characterize individual impairments of these defenses. Based on these effects, various hypotheses are proposed as to what health consequences could be expected from these effects. The ultimate test is whether the host, with its compromised defense mechanisms, is still capable of sustaining the total injury and continuing to defend itself against opportunistic pathogens. This paper describes the use of an experimental airborne infectious disease model capable of predicting subtle changes in host defenses at concentrations below which there are any other overt toxicological effects. Such sensitivity is possible because the model measure not just a single "health" parameter, but instead is capable of reflecting the total responses caused by the test chemical. Images FIGURE 3. PMID:7060549

  7. Increased proliferation and decreased membrane permeability as defense mechanisms of Fusobacterium nucleatum against human neutrophilic peptide-1.

    PubMed

    Keskin, Mutlu; Könönen, Eija; Söderling, Eva; Isik, Gülden; Firatli, Erhan; Uitto, Veli-Jukka; Gürsoy, Ulvi Kahraman

    2014-12-01

    Human neutrophilic peptides (HNPs) constitute a class of host defense molecules, which contribute to the non-oxidative killing of bacteria and other microorganisms. Since the adaptability is crucial to bacterial survival in changing environments, it is of interest to know how Fusobacterium nucleatum, the major bridge organism connecting early and late colonizers in dental biofilms, defends itself against HNPs. This study aimed to examine the planktonic growth, membrane permeability, and biofilm formation characteristics as defense mechanisms of F. nucleatum against HNP-1. In all experiments, the type strain of F. nucleatum (ssp. nucleatum ATCC 25586) and two clinical strains (ssp. nucleatum AHN 9508 and ssp. polymorphum AHN 9910) were used. Planktonic growth (measured in colony forming units), capsular polysaccharide production (visualized by Ziehl-Neelsen stain), membrane permeability (demonstrated as N-phenyl-1-naphthylamine uptake), biofilm formation, and established biofilm development (measured as total mass and polysaccharide levels) were analyzed in the presence of 0 μg/ml (control), 1 μg/ml, 5 μg/ml, and 10 μg/ml of HNP-1. Planktonic growth of the strains AHN 9508 and ATCC 25586 were significantly (p<0.05) increased in the presence of HNP-1, while their membrane permeability decreased (p<0.005) in the planktonic form. HNP-1 decreased the biofilm formation of the strains ATCC 25586 and AHN 9910, whereas it increased the growth of the strain AHN 9508 in established biofilms. Capsule formation and polysaccharide production were not observed in any strain. We conclude that the inhibition of the membrane permeability and the increase in planktonic and established biofilm growth could act as bacterial defense mechanisms against neutrophilic defensins. In addition, this strain-dependent survival ability against HNP-1 may explain the variation in the virulence of different F. nucleatum strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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

  9. Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2013-06-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

  10. A modified squeeze-out mechanism for generating high surface pressures with pulmonary surfactant

    PubMed Central

    Keating, Eleonora; Zuo, Yi Y.; Tadayyon, Seyed M.; Petersen, Nils O.; Possmayer, Fred; Veldhuizen, Ruud A.W.

    2017-01-01

    The exact mechanism by which pulmonary surfactant films reach the very low surface tensions required to stabilize the alveoli at end expiration remains uncertain. We utilized the nanoscale sensitivity of atomic force microscopy (AFM) to examine phospholipid (PL) phase transition and multilayer formation for two Langmuir–Blodgett (LB) systems: a simple 3 PL surfactant-like mixture and the more complex bovine lipid extract surfactant (BLES). AFM height images demonstrated that both systems develop two types of liquid condensed (LC) domains (micro- and nano-sized) within a liquid expanded phase (LE). The 3 PL mixture failed to form significant multilayers at high surface pressure (π while BLES forms an extensive network of multilayer structures containing up to three bilayers. A close examination of the progression of multilayer formation reveals that multilayers start to form at the edge of the solid-like LC domains and also in the fluid-like LE phase. We used the elemental analysis capability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to show that multilayer structures are enriched in unsaturated PLs while the saturated PLs are concentrated in the remaining interfacial monolayer. This supports a modified squeeze-out model where film compression results in the hydrophobic surfactant protein-dependent formation of unsaturated PL-rich multilayers which remain functionally associated with a monolayer enriched in disaturated PL species. This allows the surface film to attain low surface tensions during compression and maintain values near equilibrium during expansion. PMID:22206628

  11. Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

    PubMed Central

    Sunil, Vasanthi R.

    2013-01-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3h) resulted in rapid (within 3h) and persistent (up to 72h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24h post-exposure. Ozone also induced the appearance of 8-hydroxy-2′-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3–24h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning. PMID:23492811

  12. Strain differences in the immune mechanisms of resistance of immunocompetent rats to pulmonary aspergillosis.

    PubMed

    Mirkov, Ivana; Demenesku, Jelena; Popov Aleksandrov, Aleksandra; Ninkov, Marina; Glamoclija, Jasmina; Kataranovski, Dragan; Kataranovski, Milena

    2015-09-01

    Although the relevance of genetically-based variations in susceptibility to pulmonary aspergillosis was shown in immunocompromised mice and is indicated in humans, there is virtually no information concerning variations in antifungal immune responses in resistant individuals. We have shown recently the relevance of proinflammatory cytokine (interferon-γ/IFN-γ and interleukin-17/IL-17) responses in resistance to sublethal Aspergillus fumigatus infection of non-suppressed Dark Agouti (DA) rats (strain known of a substantial immune reactivity to noxious insults). In this study, anti-fungal immune activities of leukocytes recovered from lungs by enzyme digestion (phagocytosis, oxidative activity, hyphal killing, CD11b expression, as well as production of IFN-γ, IL-17 and Th2/anti-inflammatory cytokines interleukin-4/IL-4 and interleukin-10/IL-10) were investigated in less reactive Albino Oxford (AO) and compared to DA rats. Elimination of fungus from lungs of AO rats was associated with lower degree of leukocyte infiltration and of the majority of their basic effector activities in comparison to DA rats. Lower production of IFN-γ by pulmonary leukocytes was observed early (day 1) post infection (p.i.) in AO compared to DA rats, but without changes in IL-4. Both strains responded to infection by an increase of IL-17 and IL-10, but production of cytokines was higher (from days 7 p.i. and 3 p.i. for IL-17 and IL-10, respectively) in AO compared to DA rats. The levels and pattern of IFN-γ and IL-4 responses by draining lymph node (dLN) cells were similar in both strains and basically corresponded to those of lung leukocytes. In contrast, similar levels of draining lymph node cell production of IL-17 and IL-10 were observed in both strains with lack of changes in mRNA, what suggests additional stimulation of these cytokines in lungs of AO rats. The knowledge of strain differences in the immune-based strategies in response of immunocompetent hosts to A. fumigatus might

  13. Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium.

    PubMed

    Dusio, Giuseppina F; Cardani, Diego; Zanobbio, Laura; Mantovani, Martina; Luchini, Patrizia; Battini, Lorenzo; Galli, Valentina; Diana, Angela; Balsari, Andrea; Rumio, Cristiano

    2011-07-01

    The innate immune system is present throughout the female reproductive tract and functions in synchrony with the adaptive immune system to provide protection in a way that enhances the chances for fetal survival, while protecting against potential pathogens. Recent data show that activation of Toll-like receptor (TLR)2 and 4 by low-molecular weight hyaluronic acid (LMW-HA) in the epidermis induces secretion of the antimicrobial peptide β-defensin 2. In the present work, we show that LMW-HA induces vaginal epithelial cells to release different antimicrobial peptides, via activation of TLR2 and TLR4. Further, we found that LMW-HA favors repair of vaginal epithelial injury, involving TLR2 and TLR4, and independently from its classical receptor CD44. This wound-healing activity of LMW-HA is dependent from an Akt/phosphatidylinositol 3 kinase pathway. Therefore, these findings suggest that the vaginal epithelium is more than a simple physical barrier to protect against invading pathogens: on the contrary, this surface acts as efficient player of innate host defense, which may modulate its antimicrobial properties and injury restitution activity, following LMW-HA stimulation; this activity may furnish an additional protective activity to this body compartment, highly and constantly exposed to microbiota, ameliorating the self-defense of the vaginal epithelium in both basal and pathological conditions.

  14. Assessing ego defense mechanisms by questionnaire: psychometric properties and psychopathological correlates of the Greek version of the Plutchik's Life Style Index.

    PubMed

    Hyphantis, Thomas; Goulia, Panagiota; Floros, George D; Iconomou, Gregoris; Pappas, Argiro-Irene; Karaivazoglou, Katerina; Assimakopoulos, Konstantinos

    2011-11-01

    The Life Style Index (LSI; Plutchik, Kellerman, & Conte, 1979 ) was designed to assess defense mechanisms, assuming that their use is related to specific affective states and diagnostic concepts. We aimed to assess the psychometric properties of its Greek version and its relation to psychopathological symptoms. The LSI was back-translated into Greek and was administered to 1,261 participants. Six factors were identified, 5 of them largely corresponding to the original version's defenses (compensation, denial, projection, reaction formation, and repression). The sixth factor, named regressive emotionality, included mainly the original scale's regression and displacement factors. Test-retest reliabilities, internal consistencies, and construct validity were quite satisfactory. Most defenses were able to discriminate psychiatric patients from healthy participants and were associated with specific psychopathological symptoms in a theoretically expected mode, further supporting the validity of the Greek version. Our findings suggest that the LSI, based on both psychoevolutionary and psychoanalytic theory, can provide a solid ground for assessing ego defense mechanisms.

  15. Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress.

    PubMed

    Gupta, Rupali; Singh, Akanksha; Srivastava, Madhumita; Singh, Vivek; Gupta, M M; Pandey, Rakesh

    2017-02-03

    Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M. incognita stress. These microbes not only augmented bacoside A production (1.5 fold) but also strengthened host resistance via enhancement in chlorophyll a, defense enzymes and phenolic compounds like gallic acid, syringic acid, ferulic acid and cinnamic acid. Furthermore, elevated lignification and callose deposition in the microbial combination treated plants corroborate well with the above findings. Overall, the results provide novel insights into the underlying mechanisms of priming by beneficial microbes and underscore their capacity to trigger bacoside A production in B. monnieri under biotic stress.

  16. Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress

    PubMed Central

    Gupta, Rupali; Singh, Akanksha; Srivastava, Madhumita; Singh, Vivek; Gupta, M. M.; Pandey, Rakesh

    2017-01-01

    Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M. incognita stress. These microbes not only augmented bacoside A production (1.5 fold) but also strengthened host resistance via enhancement in chlorophyll a, defense enzymes and phenolic compounds like gallic acid, syringic acid, ferulic acid and cinnamic acid. Furthermore, elevated lignification and callose deposition in the microbial combination treated plants corroborate well with the above findings. Overall, the results provide novel insights into the underlying mechanisms of priming by beneficial microbes and underscore their capacity to trigger bacoside A production in B. monnieri under biotic stress. PMID:28157221

  17. Overview of reviews: mechanical interventions for the treatment and management of chronic obstructive pulmonary disease.

    PubMed

    Lisy, Karolina; White, Heath; Pearson, Alan

    2014-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and non-reversible airflow limitation and symptoms of breathlessness, sputum production and cough. COPD is the fourth most common cause of mortality worldwide and represents a significant social and economic burden. As such, effective strategies that might be employed to treat COPD and manage symptoms need to be investigated. This overview aimed to summarize the existing evidence available in the Cochrane Library regarding the use of mechanical interventions used for the treatment and management of COPD. Systematic reviews that included adult participants with diagnosed COPD who received a mechanical intervention were included. Five reviews were included, and due to the heterogeneity of these reviews, direct and indirect comparisons of the effects of the intervention were not possible. Instead, data of the effectiveness of each intervention were extracted and summarized in tables and discussed as a narrative summary. Interventions included non-invasive positive pressure ventilation (NPPV), positive airway pressure (PEP) devices and neuromuscular electrical stimulation (NMES). Evidence regarding the effectiveness of NPPV was limited, and available data do not support the use of NPPV for patients with stable COPD. NPPV might, however, be of benefit as a weaning strategy for intubated patients and for patients experiencing respiratory failure; however, more research is required. Although PEP devices are considered as a safe airway clearance technique, data do not reveal a clear clinical benefit to their use. NMES is also regarded as safe for patients with COPD, and might also be beneficial in improving exercise tolerance and improving quality of life for patients with COPD. © 2014 Wiley Publishing Asia Pty Ltd.

  18. 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

  19. Epidemiology and Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: Risk Factors and Mechanisms.

    PubMed

    Medrek, Sarah; Safdar, Zeenat

    2016-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when thromboemboli travel to the pulmonary vasculature, fail to resolve, and cause elevated pulmonary arterial pressure. Untreated, this disease leads to progressive right heart failure and death. It develops in approximately 1% to 5% of patients who suffer an acute pulmonary embolism (PE) and has an overall incidence of 3 to 30 per million in the general population. While it is not entirely evident why most but not all people are able to clear this clot burden, there are known risk factors for the development of CTEPH. These include signs of right heart strain at the time of incident PE, inherited coagulopathies, inflammatory conditions, hypothyroidism, and a history of splenectomy. Since CTEPH can be treated both surgically and medically, it is critical to understand the pathophysiology of the disease so affected patients can be identified and diagnosed appropriately.

  20. Epidemiology and Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: Risk Factors and Mechanisms

    PubMed Central

    Medrek, Sarah; Safdar, Zeenat

    2016-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when thromboemboli travel to the pulmonary vasculature, fail to resolve, and cause elevated pulmonary arterial pressure. Untreated, this disease leads to progressive right heart failure and death. It develops in approximately 1% to 5% of patients who suffer an acute pulmonary embolism (PE) and has an overall incidence of 3 to 30 per million in the general population. While it is not entirely evident why most but not all people are able to clear this clot burden, there are known risk factors for the development of CTEPH. These include signs of right heart strain at the time of incident PE, inherited coagulopathies, inflammatory conditions, hypothyroidism, and a history of splenectomy. Since CTEPH can be treated both surgically and medically, it is critical to understand the pathophysiology of the disease so affected patients can be identified and diagnosed appropriately. PMID:28289493

  1. Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation.

    PubMed

    de Prost, Nicolas; Costa, Eduardo L; Wellman, Tyler; Musch, Guido; Winkler, Tilo; Tucci, Mauro R; Harris, R Scott; Venegas, Jose G; Vidal Melo, Marcos F

    2011-11-01

    Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional (18)F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10(-3)/min; P < 0.05). The increased (18)F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10-50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. (18)F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs (P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs (P < 0.001). In contrast, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.

  2. Oxidative stress and antioxidant defense mechanisms linked to exercise during cardiopulmonary and metabolic disorders.

    PubMed

    Fisher-Wellman, Kelsey; Bell, Heather K; Bloomer, Richard J

    2009-01-01

    Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS), evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary "signal" for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.

  3. 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.

  4. CRISPR-mediated defense mechanisms in the hyperthermophilic archaeal genus Sulfolobus

    PubMed Central

    Manica, Andrea; Schleper, Christa

    2013-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-mediated virus defense based on small RNAs is a hallmark of archaea and also found in many bacteria. Archaeal genomes and, in particular, organisms of the extremely thermoacidophilic genus Sulfolobus, carry extensive CRISPR loci each with dozens of sequence signatures (spacers) able to mediate targeting and degradation of complementary invading nucleic acids. The diversity of CRISPR systems and their associated protein complexes indicates an extensive functional breadth and versatility of this adaptive immune system. Sulfolobus solfataricus and S. islandicus represent two of the best characterized genetic model organisms in the archaea not only with respect to the CRISPR system. Here we address and discuss in a broader context particularly recent progress made in understanding spacer recruitment from foreign DNA, production of small RNAs, in vitro activity of CRISPR-associated protein complexes and attack of viruses and plasmids in in vivo test systems. PMID:23535277

  5. 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

  6. 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.

  7. 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

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

    PubMed Central

    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

  9. Proteomic investigation of the effect of salicylic acid on Arabidopsis seed germination and establishment of early defense mechanisms.

    PubMed

    Rajjou, Loïc; Belghazi, Maya; Huguet, Romain; Robin, Caroline; Moreau, Adrien; Job, Claudette; Job, Dominique

    2006-07-01

    The influence of salicylic acid (SA) on elicitation of defense mechanisms in Arabidopsis (Arabidopsis thaliana) seeds and seedlings was assessed by physiological measurements combined with global expression profiling (proteomics). Parallel experiments were carried out using the NahG transgenic plants expressing the bacterial gene encoding SA hydroxylase, which cannot accumulate the active form of this plant defense elicitor. SA markedly improved germination under salt stress. Proteomic analyses disclosed a specific accumulation of protein spots regulated by SA as inferred by silver-nitrate staining of two-dimensional gels, detection of carbonylated (oxidized) proteins, and neosynthesized proteins with [35S]-methionine. The combined results revealed several processes potentially affected by SA. This molecule enhanced the reinduction of the late maturation program during early stages of germination, thereby allowing the germinating seeds to reinforce their capacity to mount adaptive responses in environmental water stress. Other processes affected by SA concerned the quality of protein translation, the priming of seed metabolism, the synthesis of antioxidant enzymes, and the mobilization of seed storage proteins. All the observed effects are likely to improve seed vigor. Another aspect revealed by this study concerned the oxidative stress entailed by SA in germinating seeds, as inferred from a characterization of the carbonylated (oxidized) proteome. Finally, the proteomic data revealed a close interplay between abscisic signaling and SA elicitation of seed vigor.

  10. [Officer in charge, that unknown being - an explorative, qualitative study of unconscious fears, wishes, and defense mechanisms].

    PubMed

    Beck, Thomas; Kumnig, Martin; Breuss, Margit; Mitmansgruber, Horst; Schusser, Sandra; Andreatta, Pia; Mader, Maria; Schüßler, Gerhard

    2013-01-01

    The stress and coping strategies found among emergency relief personnel have been studied in detail but without considering their function in the team. However, specifically officers in charge have to be addressed and investigated separately. This study focuses on the unconscious desires, fears, and defense mechanisms present in order to improve our understanding of the stress experienced during operations. Four officers in charge were interviewed concerning their stressful experiences during operations. These interviews were then coded and analysed using the JAKOB Narrative Analysis ("Klinische Erzählanalyse JAKOB", Boothe et al. 2002). The recorded unconscious desires included solidarity, phallic integrity, generativity, unconscious fears destruction, loss of power/influence, and social hostility, and as defense strategies rationalism, repression/denial, and idealization. The analysis of the interviews shows a high reliability between the raters (0.74-0.79). The greatest burden for officers in charge is a loss of safety. Especially being confronted with strains in their own team leads to stress, which shows that the methods used for stress management following critical incidents is not sufficient.

  11. Modulatory effects of deltamethrin on antioxidant defense mechanisms and lipid peroxidation in Carassius auratus gibelio liver and intestine.

    PubMed

    Dinu, Diana; Marinescu, Diana; Munteanu, Maria Cristina; Staicu, Andreea Cristina; Costache, Marieta; Dinischiotu, Anca

    2010-04-01

    Pyrethroids, such as deltamethrin, are toxic substances that lead to generation of reactive oxygen species, which harm living organisms. We assessed the level and patterns of imbalance evolved by a single dose of 2 microg/L deltamethrin on the lipid peroxidation (LPO) and the antioxidant defense system of Carassius auratus gibelio liver and intestine, and monitored the recovery dynamics of these parameters during a 14-day post-exposure period. LPO and antioxidative defense mechanisms displayed different responses in the investigated tissues. Sudden increase of LPO in the liver, persisting at this elevated level throughout the test period, was observed on the third day post-exposure, while in the intestine significant enhancement of this parameter was recorded from the seventh day. Reduced glutathione (GSH) showed a transient increase in the liver, and was depleted in the intestine by the second day of exposure, with signs of recovery by the end of the experimental tenure. In the liver of fish a temporary inhibition of superoxide dismutase (SOD) and catalase (CAT) activity, and activation of glutathione peroxidase (GPX), glutathione transferase (GST), and glutathione reductase (GR) enzymes was observed, with maximum thresholds recorded on the third and second days, respectively. In the intestine a relevant increase in CAT and GST activity up to the second day and almost complete recovery by the end of the experiment was recorded, while for GR a continuous enhancement was apparent.

  12. Host defence to pulmonary mycosis

    PubMed Central

    Mody, Christopher H; Warren, Peter W

    1999-01-01

    OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease. DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search. STUDY SELECTION: Articles were identified by a MEDLINE search of ‘exp lung/’ or ‘exp lung diseases/’ and ‘exp fungi/’. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses. DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search. DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects. CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal

  13. Activation of AMPK inhibits PDGF-induced pulmonary arterial smooth muscle cells proliferation and its potential mechanisms.

    PubMed

    Song, Yang; Wu, Yuanyuan; Su, Xiaofan; Zhu, Yanting; Liu, Lu; Pan, Yilin; Zhu, Bo; Yang, Lan; Gao, Li; Li, Manxiang

    2016-05-01

    The aims of the present study were to examine signaling mechanisms for PDGF-induced pulmonary arterial smooth muscle cells (PASMC) proliferation and to determine the effect of AMPK activation on PDGF-induced PASMC proliferation and its underlying mechanisms. PDGF activated PI3K/Akt/mTOR signaling pathway, and this in turn up-regulated Skp2 and consequently reduced p27 leading to PASMC proliferation. Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation. PASMC lacking AMPKα2 were resistant to the inhibitory effect of metformin on PDGF-induced cell proliferation. Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Our study suggests that the activation of AMPK negatively regulates mTOR activity to suppress PASMC proliferation and therefore has a potential value in the prevention and treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

  14. beta-cell apoptosis and defense mechanisms: lessons from type 1 diabetes.

    PubMed

    Eizirik, D L; Darville, M I

    2001-02-01

    Increased evidence suggests that apoptosis is the main mode of beta-cell death in early type 1 diabetes. Cytokines mediate beta-cell apoptosis, and in this article, we discuss some of the cytokine-modified genes that may contribute to beta-cell survival or death. The gene encoding for the inducible form of nitric oxide synthase is induced by interleukin (IL)-1beta or IL-1beta plus gamma-interferon in rodent and human islets, respectively. This leads to nitric oxide (NO) formation, which contributes to a major extent to beta-cell necrosis and to a minor extent to the process of beta-cell apoptosis. The main mode of cell death induced by cytokines in human beta-cells is apoptosis, whereas cytokines lead to both necrosis and apoptosis in rat and mouse beta-cells. It is suggested that the necrotic component in rodent islets is due to NO-induced mitochondrial impairment and consequent decreased ATP production. Human islets, possessing better antioxidant defenses, are able to preserve glucose oxidation and ATP production, and can thus complete the apoptotic program after the death signal delivered by cytokines. We propose that this death signal results from cytokine-induced parallel and/or sequential changes in the expression of multiple proapoptotic and prosurvival genes. The identity of these "gene modules" and of the transcription factors regulating them remains to be established.

  15. Lifestyle and host defense mechanisms of the dung beetle, Euoniticellus intermedius: the toll signaling pathway.

    PubMed

    Hull, Rodney; Alaouna, Mohamed; Khanyile, Lucky; Byrne, Marcus; Ntwasa, Monde

    2013-01-01

    The dung beetle, Euoniticellus intermedius (Reiche) (Coleoptera: Scarabaeidae) is an important ecological and agricultural agent. Their main activity, the burying of dung, improves quality of the soil and reduces pests that could cause illness in animals. E. intermedius are therefore important for agriculture and for good maintenance of the environment, and are regarded as effective biological control agents for parasites of the gastrointestinal tract in livestock. The ability of E. intermedius to co-exist comfortably with many microorganisms, some of which are important human pathogens, stimulated our interest in its host defense strategies. The aim of this study was to investigate the Toll signaling pathway, which is strongly activated by fungi. Gene expression associated with fungal infection was analyzed by using 2-D gel electrophoresis and mass spectroscopy. Furthermore, the partial adult transcriptome was investigated for the presence of known immune response genes by using high-throughput sequencing and bioinformatics. The results presented here suggest that E. intermedius responds to fungal challenge via the Toll signaling pathway.

  16. Host-Microbe Interactions and Defense Mechanisms in the Development of Amoebic Liver Abscesses

    PubMed Central

    Santi-Rocca, Julien; Rigothier, Marie-Christine; Guillén, Nancy

    2009-01-01

    Summary: Amoebiasis by Entamoeba histolytica is a major public health problem in developing countries and leads to several thousand deaths per year. The parasite invades the intestine (provoking diarrhea and dysentery) and the liver, where it forms abscesses (amoebic liver abscesses [ALAs]). The liver is the organ responsible for filtering blood coming from the intestinal tract, a task that implies a particular structure and immune features. Amoebae use the portal route and break through the sinusoidal endothelial barrier to reach the hepatic parenchyma. When faced with systemic and cell-mediated defenses, trophozoites adapt to their new environment and modulate host responses, leading to parasite survival and the formation of inflammatory foci. Cytopathogenic effects and the onset of inflammation may be caused by diffusible products originating from parasites and/or immune cells either by their secretion or by their release after cell death. Liver infection thus results from the interplay between E. histolytica and hepatic cells. Despite its importance in terms of public health burden, the lack of integrated data on ALA genesis means that we have only an incomplete description of the initiation and development of hepatic amoebiasis. Here, we review the main steps of ALA development as well as the responses triggered in both the host and the parasite. Transcriptome studies highlighted parasite factors involved in adherence to human cells, cytopathogenic effects, and adaptative and stress responses. An understanding of their role in ALA development will help to unravel the host-pathogen interactions and their evolution throughout the infection. PMID:19136434

  17. 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.

  18. Lifestyle and Host Defense Mechanisms of the Dung Beetle, Euoniticellus intermedius: The Toll Signaling Pathway

    PubMed Central

    Hull, Rodney; Alaouna, Mohamed; Khanyile, Lucky; Byrne, Marcus; Ntwasa, Monde

    2013-01-01

    The dung beetle, Euoniticellus intermedius (Reiche) (Coleoptera: Scarabaeidae) is an important ecological and agricultural agent. Their main activity, the burying of dung, improves quality of the soil and reduces pests that could cause illness in animals. E. intermedius are therefore important for agriculture and for good maintenance of the environment, and are regarded as effective biological control agents for parasites of the gastrointestinal tract in livestock. The ability of E. intermedius to co-exist comfortably with many microorganisms, some of which are important human pathogens, stimulated our interest in its host defense strategies. The aim of this study was to investigate the Toll signaling pathway, which is strongly activated by fungi. Gene expression associated with fungal infection was analyzed by using 2-D gel electrophoresis and mass spectroscopy. Furthermore, the partial adult transcriptome was investigated for the presence of known immune response genes by using high-throughput sequencing and bioinformatics. The results presented here suggest that E. intermedius responds to fungal challenge via the Toll signaling pathway. PMID:24735102

  19. 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

  20. Sulfur volatiles in guava (Psidium guajava L.) leaves: possible defense mechanism.

    PubMed

    Rouseff, Russell L; Onagbola, Ebenezer O; Smoot, John M; Stelinski, Lukasz L

    2008-10-08

    Volatiles from crushed and intact guava leaves (Psidium guajava L.) were collected using static headspace SPME and determined using GC-PFPD, pulsed flame photometric detection, and GC-MS. Leaf volatiles from four common citrus culitvars were examined similarly to determine the potential component(s) responsible for guava's protective effect against the Asian citrus psyllid (Diaphorina citri Kuwayama), which is the insect vector of Huanglongbing (HLB) or citrus greening disease. Seven sulfur volatiles were detected: hydrogen sulfide, sulfur dioxide, methanethiol, dimethyl sulfide (DMS), dimethyl disulfide (DMDS), methional, and dimethyl trisulfide (DMTS). Identifications were based on matching linear retention index values on ZB-5, DB-Wax, and PLOT columns and MS spectra in the case of DMDS and DMS. DMDS is an insect toxic, defensive volatile produced only by wounded guava but not citrus leaves and, thus, may be the component responsible for the protective effect of guava against the HLB vector. DMDS is formed immediately after crushing, becoming the major headspace volatile within 10 min. Forty-seven additional leaf volatiles were identified from LRI and MS data in the crushed guava leaf headspace.

  1. Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block.

    PubMed

    Kato, K; Evans, A M; Kozlowski, R Z

    1999-03-01

    We investigated the effects of the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on endothelin-1 (ET-1)-induced constriction of rat small pulmonary arteries (diameter 100-400 microm) in vitro, following endothelium removal. ET-1 (30 nM) induced a sustained constriction of rat pulmonary arteries in physiological salt solution. Arteries preconstricted with ET-1 were relaxed by niflumic acid (IC50: 35.8 microM) and NPPB (IC50: 21.1 microM) in a reversible and concentration-dependent manner. However, at concentrations known to block Ca++-activated Cl- channels, DIDS (pulmonary arteries were preincubated with these Cl- channel blockers. When L-type Ca++ channels were blocked by nifedipine (10 microM), the ET-1-induced (30 nM) constriction was inhibited by only 5.8%. However, niflumic acid (30 microM) and NPPB (30 microM) inhibited the ET-1-induced constriction by approximately 53% and approximately 60%, respectively, both in the continued presence of nifedipine and in Ca++-free physiological salt solution. The Ca++ ionophore A23187 (10 microM) also evoked a sustained constriction of pulmonary arteries. Surprisingly, the A23187-induced constriction was also inhibited in a reversible and concentration-dependent manner by niflumic acid (IC50: 18.0 microM) and NPPB (IC50: 8.8 microM), but not by DIDS (mechanism by which niflumic acid and NPPB inhibit pulmonary artery constriction is independent of Cl- channel blockade. One possibility is that these compounds may block the Ca++-dependent contractile processes.

  2. Mechanism of valve failure and efficacy of reintervention through catheterization in patients with bioprosthetic valves in the pulmonary position

    PubMed Central

    Callahan, Ryan; Bergersen, Lisa; Baird, Christopher W; Porras, Diego; Esch, Jesse J; Lock, James E; Marshall, Audrey C

    2017-01-01

    Background: Surgical and transcatheter bioprosthetic valves (BPVs) in the pulmonary position in patients with congenital heart disease may ultimately fail and undergo transcatheter reintervention. Angiographic assessment of the mechanism of BPV failure has not been previously described. Aims: The aim of this study was to determine the mode of BPV failure (stenosis/regurgitation) requiring transcatheter reintervention and to describe the angiographic characteristics of the failed BPVs and report the types and efficacy of reinterventions. Materials and Methods: This is a retrospective single-center review of consecutive patients who previously underwent pulmonary BPV placement (surgical or transcatheter) and subsequently underwent percutaneous reintervention from 2005 to 2014. Results: Fifty-five patients with surgical (41) and transcutaneous pulmonary valve (TPV) (14) implantation of BPVs underwent 66 catheter reinterventions. The surgically implanted valves underwent fifty reinterventions for indications including 16 for stenosis, seven for regurgitation, and 27 for both, predominantly associated with leaflet immobility, calcification, and thickening. Among TPVs, pulmonary stenosis (PS) was the exclusive failure mode, mainly due to loss of stent integrity (10) and endocarditis (4). Following reintervention, there was a reduction of right ventricular outflow tract gradient from 43 ± 16 mmHg to 16 ± 10 mmHg (P < 0.001) and RVp/AO ratio from 0.8 ± 0.2 to 0.5 ± 0.2 (P < 0.001). Reintervention with TPV placement was performed in 45 (82%) patients (34 surgical, 11 transcatheter) with no significant postintervention regurgitation or paravalvular leak. Conclusion: Failing surgically implanted BPVs demonstrate leaflet calcification, thickness, and immobility leading to PS and/or regurgitation while the mechanism of TPV failure in the short- to mid-term is stenosis, mainly from loss of stent integrity. This can be effectively treated with a catheter-based approach

  3. Pulmonary Mycobacterial Granuloma

    PubMed Central

    Shaler, Christopher R.; Kugathasan, Kapilan; McCormick, Sarah; Damjanovic, Daniela; Horvath, Carly; Small, Cherrie-Lee; Jeyanathan, Mangalakumari; Chen, Xiao; Yang, Ping-Chang; Xing, Zhou

    2011-01-01

    The granuloma, a hallmark of host defense against pulmonary mycobacterial infection, has long been believed to be an active type 1 immune environment. However, the mechanisms regarding why granuloma fails to eliminate mycobacteria even in immune-competent hosts, have remained largely unclear. By using a model of pulmonary Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, we have addressed this issue by comparing the immune responses within the airway luminal and granuloma compartments. We found that despite having a similar immune cellular profile to that in the airway lumen, the granuloma displayed severely suppressed type 1 immune cytokine but enhanced chemokine responses. Both antigen-presenting cells (APCs) and T cells in granuloma produced fewer type 1 immune molecules including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and nitric oxide. As a result, the granuloma APCs developed a reduced capacity to phagocytose mycobacteria and to induce T-cell proliferation. To examine the molecular mechanisms, we compared the levels of immune suppressive cytokine IL-10 in the airway lumen and granuloma and found that both granuloma APCs and T cells produced much more IL-10. Thus, IL-10 deficiency restored type 1 immune activation within the granuloma while having a minimal effect within the airway lumen. Hence, our study provides the first experimental evidence that, contrary to the conventional belief, the BCG-induced lung granuloma represents a symbiotic host-microbe microenvironment characterized by suppressed type 1 immune activation. PMID:21406169

  4. Regional right ventricular remodeling and function in children with idiopathic pulmonary arterial hypertension vs those with pulmonary valve stenosis: Insights into mechanics of right ventricular dysfunction.

    PubMed

    Driessen, Mieke M P; Meijboom, Folkert J; Hui, Wei; Dragulescu, Andreea; Mertens, Luc; Friedberg, Mark K

    2017-06-01

    Right ventricular (RV) pressure overload in the context of pulmonary stenosis (PS) has a much better prognosis than in the context of idiopathic pulmonary arterial hypertension (iPAH), which may be related to differences in global and regional RV remodeling and systolic function. We compared RV mechanics in children with PS to those with iPAH, aiming to identify mechanisms and markers of RV dysfunction. Eighteen controls, 18 iPAH and 16 PS patients were retrospectively studied. Age, BSA, and sex distribution were comparable. Two-dimensional echocardiography, blood flow and tissue Doppler, and longitudinal RV deformation were analyzed. ANCOVA-including RV systolic pressure (RVSP) and length as covariates-was used to compare patient groups. RV systolic pressure was higher in iPAH vs PS (96.8±25.4 vs 75.4±18.9 mm Hg, P=.011). Compared to controls, PS patients showed mild dilation (P<.01) and decreased longitudinal deformation (P<.001) at the RV apex. Compared to both PS and controls, iPAH patients showed marked spherical RV dilation (P<.001), reduced global, RV free wall and septal longitudinal deformation (iPAH -22.07%±4.35% vs controls -28.18%±1.69%; -9.98%±4.30% vs -17.45%±2.52%; P<.001) and RV postsystolic shortening (P<.001). RV transverse shortening (radial performance) was increased in PS (31.75%±10.35%; P<.001) but reduced in iPAH (-1.62%±11.11% vs controls 12.00%±7.74%; P<.001). Children with iPAH demonstrate adverse global and regional RV remodeling and mechanics compared to those with PS. Mechanisms of RV systolic dysfunction in iPAH include decreased longitudinal deformation, decreased or absent transverse shortening, and postsystolic shortening. These markers may be useful to identify children at risk of RV failure. © 2017, Wiley Periodicals, Inc.

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

    PubMed

    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.

  6. 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.

  7. Simultaneous generation of methane, carbon dioxide, and carbon monoxide from choline and ascorbic acid: a defensive mechanism against reductive stress?

    PubMed

    Ghyczy, Miklós; Torday, Csilla; Boros, Mihály

    2003-06-01

    Indirect evidence suggests that an abnormal increase in reducing power (reductive stress) may be associated with abnormal clinical states. We have recently proposed that under such conditions biomolecules with electrophilic methyl groups (EMGs) bound to positively charged nitrogen or sulfur moieties may act as electron acceptors and that this poising mechanism may entail the generation of methane gas. Here we report for the first time the generation of methane by rat liver mitochondria. We also report the formation of methane from choline in the presence of hydrogen peroxide, catalytic iron, and ascorbic acid. In this system, carbon monoxide and carbon dioxide are formed from the ascorbate molecule in parallel with methane generation. In view of these findings, we try to explain the essential role of biomolecules with EMG moiety. We hypothesize that this concerted reaction may be a defensive response to reductive stress and may provide the protection needed against redox imbalance in living systems.

  8. 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

  9. Priming for JA-dependent defenses using hexanoic acid is an effective mechanism to protect Arabidopsis against B. cinerea.

    PubMed

    Kravchuk, Zhana; Vicedo, Begonya; Flors, Víctor; Camañes, Gemma; González-Bosch, Carmen; García-Agustín, Pilar

    2011-03-01

    Soil drench treatments with hexanoic acid can effectively protect Arabidopsis plants against Botrytis cinerea through a mechanism based on a stronger and faster accumulation of JA-dependent defenses. Plants impaired in ethylene, salicylic acid, abscisic acid or glutathion pathways showed intact protection by hexanoic acid upon B. cinerea infection. Accordingly, no significant changes in the SA marker gene PR-1 in either the SA or ABA hormone balance were observed in the infected and treated plants. In contrast, the JA signaling pathway showed dramatic changes after hexanoic acid treatment, mainly when the pathogen was present. The impaired JA mutants, jin1-2 and jar1, were unable to display hexanoic acid priming against the necrotroph. In addition, hexanoic acid-treated plants infected with B. cinerea showed priming in the expression of the PDF1.2, PR-4 and VSP1 genes implicated in the JA pathways. Moreover, JA and OPDA levels were primed at early stages by hexanoic acid. Treatments also stimulated increased callose accumulation in response to the pathogen. Although callose accumulation has proved an effective IR mechanism against B. cinerea, it is apparently not essential to express hexanoic acid-induced resistance (HxAc-IR) because the mutant pmr4.1 (callose synthesis defective mutant) is protected by treatment. We recently described how hexanoic acid treatments can protect tomato plants against B. cinerea by stimulating ABA-dependent callose deposition and by priming OPDA and JA-Ile production. We clearly demonstrate here that Hx-IR is a dependent plant species, since this acid protects Arabidopsis plants against the same necrotroph by priming JA-dependent defenses without enhancing callose accumulation.

  10. The evolution of defense mechanisms correlate with the explosive diversification of autodigesting Coprinellus mushrooms (Agaricales, Fungi).

    PubMed

    Nagy, László G; Házi, Judit; Szappanos, Balázs; Kocsubé, Sándor; Bálint, Balázs; Rákhely, Gábor; Vágvölgyi, Csaba; Papp, Tamás

    2012-07-01

    Bursts of diversification are known to have contributed significantly to the extant morphological and species diversity, but evidence for many of the theoretical predictions about adaptive radiations have remained contentious. Despite their tremendous diversity, patterns of evolutionary diversification and the contribution of explosive episodes in fungi are largely unknown. Here, using the genus Coprinellus (Psathyrellaceae, Agaricales) as a model, we report the first explosive fungal radiation and infer that the onset of the radiation correlates with a change from a multilayered to a much simpler defense structure on the fruiting bodies. We hypothesize that this change constitutes a key innovation, probably relaxing constraints on diversification imposed by nutritional investment into the development of protective tissues of fruiting bodies. Fossil calibration suggests that Coprinellus mushrooms radiated during the Miocene coinciding with global radiation of large grazing mammals following expansion of dry open grasslands. In addition to diversification rate-based methods, we test the hard polytomy hypothesis, by analyzing the resolvability of internal nodes of the backbone of the putative radiation using Reversible-Jump MCMC. We discuss potential applications and pitfalls of this approach as well as how biologically meaningful polytomies can be distinguished from alignment shortcomings. Our data provide insights into the nature of adaptive radiations in general by revealing a deceleration of morphological diversification through time. The dynamics of morphological diversification was approximated by obtaining the temporal distribution of state changes in discrete traits along the trees and comparing it with the tempo of lineage accumulation. We found that the number of state changes correlate with the number of lineages, even in parts of the tree with short internal branches, and peaks around the onset of the explosive radiation followed by a slowdown, most

  11. Rate of oral intake and effects of mechanical insufflation-exsufflation on pulmonary complications in patients with duchenne muscular dystrophy

    PubMed Central

    Miura, Toshihiko; Takami, Akiyoshi; Makino, Misato; Ishikawa, Akira; Ishikawa, Yuka

    2017-01-01

    [Purpose] In Duchenne muscular dystrophy, it increases risks of difficulties of expectoration of secretion, asphyxia, aspiration pneumonia because of decreased cough function. The aim of this study is to prove that manually assisted coughing or mechanical insufflation-exsufflation prevents pulmonary complication and contribute to continue oral intake safely and continue rate of oral intake in Duchenne muscular dystrophy. [Subjects and Methods] We investigated the status of using ventilator, manually assisted coughing or mechanical insufflation-exsufflation, and oral intake or not. In addition, we inspected the frequency of fever (over 37 °C) needed antibiotics from medical records for index of respiratory tract infection, and compared with every period of using mechanical insufflation-exsufflation from respiratory evaluation on cough peak flow. [Results] Fifty-eight patients participated in this study. There were 45 Full-time noninvasive positive pressure ventilation patients. Forty-three in 45 Full-time noninvasive positive pressure ventilation patients (95.6%) avoided tracheostomy and continued noninvasive positive pressure ventilation because they continued oral intake without tracheal intubation due to the respiratory acute exacerbation by asphyxia or aspiration pneumonia. [Conclusion] Duchenne muscular dystrophy patients can continue oral intake safely while preventing pulmonary complication by using manually assisted coughing or mechanical insufflation-exsufflation. PMID:28356637

  12. Attachment, penetration and early host defense mechanisms during the infection of filamentous brown algae by Eurychasma dicksonii.

    PubMed

    Tsirigoti, Amerssa; Beakes, Gordon W; Hervé, Cécile; Gachon, Claire M M; Katsaros, Christos

    2015-05-01

    Eurychasma dicksonii is one of the most common and widespread marine pathogens and attacks a broad spectrum of more than 45 brown algal species. The present study focuses on the mechanism used by the pathogen to attach on the host cell wall and force its way into algal cells. Ultrastructural examination revealed a needle-like structure which develops within the attached spore and extends along its main axis. Particular cell wall modifications are present at the basal part of the spore (adhesorium pad) and guide the needle-like tool to penetrate perpendicularly the host cell wall. The unique injection mechanism is shared with Haptoglossa species which suggests that this is an important characteristic of early diverging oomycetes. Furthermore, the encystment and adhesion mechanism of E. dicksonii shows significant similarities with other oomycetes, some of which are plant pathogens. Staining and immunolabelling techniques showed the deposition of β-1,3-glucans on the host cell wall at the pathogen penetration site, a strategy similar to physical responses previously described only in infected plant cells. It is assumed that the host defense in terms of callose-like deposition is an ancient response to infection.

  13. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

    PubMed

    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  14. “Expiratory holding” approach in measuring end-expiratory pulmonary artery wedge pressure for mechanically ventilated patients

    PubMed Central

    Yang, Wanjie; Zhao, Xuefeng; Feng, Qingguo; An, Youzhong; Wei, Kai; Wang, Wei; Li, Chang; Cheng, Xiuling

    2013-01-01

    Objective To accurately measure the end-expiratory pulmonary artery wedge pressure (PAWP) with the “expiration holding” function on the ventilator and the “pulmonary artery wedge pressure review” software on the monitor. Materials and methods Fifty prospective measurements were made on 12 patients undergoing pulmonary artery catheter and mechanical ventilation. All measurements were divided into <8 mmHg or ≥8 mmHg subgroups according to respiratory variability, and they were then subdivided into either an airway pressure display measurement group (AM group) or an expiration holding (EH) group for comparison. Results In all measurements, the two groups showed similar levels of accuracy; however, for the time spent for measurement, the EH group was much faster than the airway pressure display measurement group (P<0.001). Additionally, the EH group was associated with lower medical costs. Conclusion The expiration holding approach measured the PAWP more accurately, more quickly, and with reduced costs in comparison to the airway pressure display approach. PMID:24133370

  15. 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

  16. Combined nutritional support in patients with chronic obstructive pulmonary disease (COPD), under mechanical ventilation (MV).

    PubMed

    Grigorakos, Leonidas; Sotiriou, Evangelia; Markou, Nikolaos; Stratouli, Stamatina; Boutzouka, Eleni; Philntisis, George; Baltopoulos, George

    2009-01-01

    The importance of nutrition is clearly established in the management of the critically ill patient: malnutrition contributes to immune incompetence, poor wound healing, increased postoperative complication and prolonged hospital stay. The interaction between nutritional status, nutritional supply and respiratory function is important in the management of the Chronic Obstructive pulmonary Disease (COPD) patients under mechanical ventilation (MV). In the present study was analyzed the benefits of combined nutritional support in patients with COPD under MV. One hundred ninety two (192) patients with COPD were admitted to our Intensive Care Unit (ICU), due to severe respiratory failure of whom 163 (84.9%) patients were under MV. In 18 (11.04%) patients after the 10th day under MV and due to severe malnutrition (serum albumin < 2.5 gm/dl, total lymphocyte count (TLC) < 900/mm3), added in the enteral nutrition (EN) of 1800 Kcals and parenteral nutrition (PN) of 2000 Kcals, at high concentration in lipids from central venous catheter. Seven (38.89%) patients on the 4th day, after combined nutrition, had a positive balance of nitrogen and normal level of the nutritional indices, 4 (22.22%) were on normal level on the 5th day, 3 (16.67%) on the 6th day, 1 (5.56%) on the 7th day after combined nutrition. We had no complications from the combination of EN and PN. Conclusively, of these 18 patients that were given both EN and PN, 15 (83.33%) were weaned from MV and continued the combined nutritional support for 3 days, while 3 (16.67%) died during the combination of EN and PN, without having achieved a normal level of the indices of nutrition and without a positive balance of nitrogen. In this study was found that: 1. patients with COPD under MV rapidly developed malnutrition, 2. the combination EN and PN without complications contribute to the weaning from MV, 3. positive nitrogen balance and normal increases of nutrition are achieved after the 4th day of combined nutrition

  17. 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

  18. Comparative capacitative calcium entry mechanisms in canine pulmonary and renal arterial smooth muscle cells

    PubMed Central

    Wilson, Sean M; Mason, Helen S; Smith, Gregory D; Nicholson, Neil; Johnston, Louise; Janiak, Robert; Hume, Joseph R

    2002-01-01

    Experiments were performed to determine whether capacitative Ca2+ entry (CCE) can be activated in canine pulmonary and renal arterial smooth muscle cells (ASMCs) and whether activation of CCE parallels the different functional structure of the sarcoplasmic reticulum (SR) in these two cell types. The cytosolic [Ca2+] was measured by imaging fura-2-loaded individual cells. Increases in the cytosolic [Ca2+] due to store depletion in pulmonary ASMCs required simultaneous depletion of both the inositol 1,4,5-trisphosphate (InsP3)- and ryanodine (RY)-sensitive SR Ca2+ stores. In contrast, the cytosolic [Ca2+] rises in renal ASMCs occurred when the SR stores were depleted through either the InsP3 or RY pathways. The increase in the cytosolic [Ca2+] due to store depletion in both pulmonary and renal ASMCs was present in cells that were voltage clamped and was abolished when cells were perfused with a Ca2+-free bathing solution. Rapid quenching of the fura-2 signal by 100 μM Mn2+ following SR store depletion indicated that extracellular Ca2+ entry increased in both cell types and also verified that activation of CCE in pulmonary ASMCs required the simultaneous depletion of the InsP3- and RY-sensitive SR Ca2+ stores, while CCE could be activated in renal ASMCs by the depletion of either of the InsP3- or RY-sensitive SR stores. Store depletion Ca2+ entry in both pulmonary and renal ASMCs was strongly inhibited by Ni2+ (0.1–10 mM), slightly inhibited by Cd2+ (200–500 μM), but was not significantly affected by the voltage-gated Ca2+ channel (VGCC) blocker nisoldipine (10 μM). The non-selective cation channel blocker Gd3+ (100 μM) inhibited a portion of the Ca2+ entry in 6 of 18 renal but not pulmonary ASMCs. These results provide evidence that SR Ca2+ store depletion activates CCE in parallel with the organization of intracellular Ca2+ stores in canine pulmonary and renal ASMCs. PMID:12231648

  19. Local mechanical stimulation induces components of the pathogen defense response in parsley

    PubMed Central

    Gus-Mayer, Sabine; Naton, Beatrix; Hahlbrock, Klaus; Schmelzer, Elmon

    1998-01-01

    Cell suspension cultures of parsley (Petroselinum crispum) have previously been used as a suitable system for studies of the nonhost resistance response to Phytophthora sojae. In this study, we replaced the penetrating fungus by local mechanical stimulation by using a needle of the same diameter as a fungal hypha, by local application of a structurally defined fungus-derived elicitor, or by a combination of the two stimuli. Similar to the fungal infection hypha, the local mechanical stimulus alone induced the translocation of cytoplasm and nucleus to the site of stimulation, the generation of intracellular reactive oxygen intermediates (ROI), and the expression of some, but not all, elicitor-responsive genes. When the elicitor was applied locally to the cell surface without mechanical stimulation, intracellular ROI also accumulated rapidly, but morphological changes were not detected. A combination of the mechanical stimulus with simultaneous application of low doses of elicitor closely simulated early reactions to fungal infection, including cytoplasmic aggregation, nuclear migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were impaired at high elicitor concentrations. Neither papilla formation nor hypersensitive cell death occurred under the conditions tested. These results suggest that mechanical stimulation by the invading fungus is responsible for the observed intracellular rearrangements and may trigger some of the previously demonstrated changes in the activity of elicitor-responsive genes, whereas chemical stimulation is required for additional biochemical processes. As yet unidentified signals may be involved in papilla formation and hypersensitive cell death. PMID:9653198

  20. First evidence for toxic defense based on the multixenobiotic resistance (MXR) mechanism in Daphnia magna.

    PubMed

    Campos, Bruno; Altenburger, Rolf; Gómez, Cristian; Lacorte, Silvia; Piña, Benjamin; Barata, Carlos; Luckenbach, Till

    2014-03-01

    The water flea Daphnia magna is widely used as test species in ecotoxicological bioassays. So far, there is no information available to which extent ATP binding cassette (ABC) transporter based multixenobiotic resistance (MXR) counteracts adverse chemical effects in this species. This, however, would be important for assessing to which extent the bio-active potential of a compound determined with this species depends on this cellular defense. We here present molecular, functional and toxicological studies that provide first evidence for ABC transporter-based MXR in D. magna. We cloned putatively MXR-related partial abcb1, abcc1/3, abcc4 and abcc5 coding sequences; respective transcripts were constitutively expressed in different D. magna life stages. MXR associated efflux activity was monitored in D. magna using the fluorescent substrate dyes rhodamine 123, rhodamine B and calcein-AM combined with inhibitors of human ABCB1 and/or ABCC transporter activities reversin 205, MK571 and cyclosporin A. With inhibitors present, efflux of dye substrates was reduced in D. magna in a concentration-dependent mode, as indicated by elevated accumulation of the dyes in D. magna tissues. In animals pre-exposed to mercury, pentachlorophenol or dacthal applied as inducers of ABC transporter expression, levels of some ABC transporter transcripts were increased in some cases showing that these genes can be chemically induced. Likewise, pre-exposure of animals to these chemicals decreased dye accumulation in tissue, indicating enhanced MXR transporter activity, likely associated with higher transporter protein levels. Toxicity assays with toxic transporter substrates mitoxantrone and chlorambucil that were applied singly and in combination with inhibitors were performed to study the tolerance role of Abcb1 and Abcc efflux transporters in D. magna. Joint toxicities of about half of the binary combinations of test compounds applied (substrate/inhibitor, substrate/substrate, inhibitor

  1. The antifibrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fibrosis.

    PubMed

    Liang, Haihai; Xu, Chaoqian; Pan, Zhenwei; Zhang, Ying; Xu, Zhidan; Chen, Yingzhun; Li, Tianyu; Li, Xuelian; Liu, Ying; Huangfu, Longtao; Lu, Ying; Zhang, Zhihua; Yang, Baofeng; Gitau, Samuel; Lu, Yanjie; Shan, Hongli; Du, Zhimin

    2014-06-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high-lethality fibrotic lung disease characterized by excessive fibroblast proliferation, extracellular matrix accumulation, and, ultimately, loss of lung function. Although dysregulation of some microRNAs (miRs) has been shown to play important roles in the pathophysiological processes of IPF, the role of miRs in fibrotic lung diseases is not well understood. In this study, we found downregulation of miR-26a in the lungs of mice with experimental pulmonary fibrosis and in IPF, which resulted in posttranscriptional derepression of connective tissue growth factor (CTGF), and induced collagen production. More importantly, inhibition of miR-26a in the lungs caused pulmonary fibrosis in vivo, whereas overexpression of miR-26a repressed transforming growth factor (TGF)-β1-induced fibrogenesis in MRC-5 cells and attenuated experimental pulmonary fibrosis in mice. Our study showed that miR-26a was downregulated by TGF-β1-mediated phosphorylation of Smad3. Moreover, miR-26a inhibited the nuclear translocation of p-Smad3 through directly targeting Smad4, which determines the nuclear translocation of p-Smad2/Smad3. Taken together, our experiments demonstrated the antifibrotic effects of miR-26a in fibrotic lung diseases and suggested a new strategy for the prevention and treatment of IPF using miR-26a. The current study also uncovered a novel positive feedback loop between miR-26a and p-Smad3, which is involved in pulmonary fibrosis.

  2. Molecular Mechanism of Dihydropyridine Ca(2+) Channel Blockers in Pulmonary Hypertension.

    PubMed

    Yamamura, Aya

    2016-01-01

     Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease of unidentified pathogenesis. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. In pulmonary arterial smooth muscle cells (PASMCs), an increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) triggers vasoconstriction and stimulates cell proliferation leading to vascular remodeling. However, dihydropyridine-type voltage-dependent Ca(2+) channel blockers are only effective in very few patients with IPAH (<10%). It is unclear why dihydropyridine Ca(2+) channel blockers are not therapeutically effective in a majority of IPAH patients. We have previously shown that extracellular Ca(2+)-sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, and it contributes to enhanced [Ca(2+)]cyt responses and augmented cell proliferation. In this study, the effects of dihydropyridine Ca(2+) channel blockers on [Ca(2+)]cyt responses mediated by CaSR were examined in IPAH-PASMCs. Nifedipine (dihydropyridines) enhanced the CaSR-mediated increase in [Ca(2+)]cyt in IPAH-PASMCs, but not in PASMCs from normal subjects. Nicardipine (dihydropyridines) and Bay K 8644 (a dihydropyridine Ca(2+) channel activator) also augmented the CaSR-mediated [Ca(2+)]cyt increase in IPAH-PASMCs. In contrast, non-dihydropyridine Ca(2+) channel blockers such as diltiazem (benzothiazepines) and verapamil (phenylalkylamines) had no effect on the [Ca(2+)]cyt response in IPAH-PASMCs. Finally, in monocrotaline-induced pulmonary hypertensive rats, nifedipine caused further increase in right ventricular systolic pressure and thus right ventricular hypertrophy. In conclusion, dihydropyridine Ca(2+) channel blockers could exacerbate symptoms of pulmonary hypertension in IPAH patients with upregulated CaSR in PASMCs.

  3. Mechanical stress is associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot.

    PubMed

    Tang, Dalin; Yang, Chun; Del Nido, Pedro J; Zuo, Heng; Rathod, Rahul H; Huang, Xueying; Gooty, Vasu; Tang, Alexander; Billiar, Kristen L; Wu, Zheyang; Geva, Tal

    2016-03-01

    Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  4. Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation.

    PubMed

    Dreyfuss, D; Saumon, G

    1993-11-01

    Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation

  5. Oxidative Stress and Pulmonary Fibrosis

    PubMed Central

    Cheresh, Paul; Kim, Seok-Jo; Tulasiram, Sandhya; Kamp, David W.

    2012-01-01

    Oxidative stress is implicated as an important molecular mechanism underlying fibrosis in a variety of organs, including the lungs. However, the causal role of reactive oxygen species (ROS) released from environmental exposures and inflammatory / interstitial cells in mediating fibrosis as well as how best to target an imbalance in ROS production in patients with fibrosis are not firmly established. We focus on the role of ROS in pulmonary fibrosis and, where possible, highlight overlapping molecular pathways in other organs. The key origins of oxidative stress in pulmonary fibrosis (e.g. environmental toxins, mitochondria / NADPH oxidase of inflammatory and lung target cells, and depletion of antioxidant defenses) are reviewed. The role of alveolar epithelial cell (AEC) apoptosis by mitochondria- and p53-regulated death pathways are examined. We emphasize an emerging role for the endoplasmic reticulum (ER) in pulmonary fibrosis. After briefly summarizing how ROS trigger a DNA damage response, we concentrate on recent studies implicating a role for mitochondrial DNA (mtDNA) damage and repair mechanisms focusing on 8-oxoguanine DNA glycosylase (Ogg1) as well as crosstalk between ROS production, mtDNA damage, p53, Ogg1, and mitochondrial aconitase (ACO2). Finally, the association between ROS and TGF-β1-induced fibrosis is discussed. Novel insights into the molecular basis of ROS-induced pulmonary diseases and, in particular, lung epithelial cell death may promote the development of unique therapeutic targets for managing pulmonary fibrosis as well as fibrosis in other organs and tumors, and in aging; diseases for which effective management is lacking. PMID:23219955

  6. Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): study protocol for a randomized controlled trial.

    PubMed

    Bignami, Elena; Guarnieri, Marcello; Saglietti, Francesco; Maglioni, Enivarco Massimo; Scolletta, Sabino; Romagnoli, Stefano; De Paulis, Stefano; Paternoster, Gianluca; Trumello, Cinzia; Meroni, Roberta; Scognamiglio, Antonio; Budillon, Alessandro Maria; Pota, Vincenzo; Zangrillo, Alberto; Alfieri, Ottavio

    2017-06-07

    There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization. The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery. ClinicalTrials.gov, ID: NCT02090205 . Registered on 8 March 2014.

  7. Pulmonary Right Ventricular Resynchronization in Congenital Heart Disease: Acute Improvement in Right Ventricular Mechanics and Contraction Efficiency.

    PubMed

    Janoušek, Jan; Kovanda, Jan; Ložek, Miroslav; Tomek, Viktor; Vojtovič, Pavel; Gebauer, Roman; Kubuš, Peter; Krejčíř, Miroslav; Lumens, Joost; Delhaas, Tammo; Prinzen, Frits

    2017-09-01

    Electromechanical discoordination may contribute to long-term pulmonary right ventricular (RV) dysfunction in patients after surgery for congenital heart disease. We sought to evaluate changes in RV function after temporary RV cardiac resynchronization therapy. Twenty-five patients aged median 12.0 years after repair of tetralogy of Fallot and similar lesions were studied echocardiographically (n=23) and by cardiac catheterization (n=5) after primary repair (n=4) or after surgical RV revalvulation for significant pulmonary regurgitation (n=21). Temporary RV cardiac resynchronization therapy was applied in the presence of complete right bundle branch block by atrial-synchronized RV free wall pacing in complete fusion with spontaneous ventricular depolarization using temporary electrodes. The q-RV interval at the RV free wall pacing site (mean 77.2% of baseline QRS duration) confirmed pacing from a late activated RV area. RV cardiac resynchronization therapy carried significant decrease in QRS duration (P<0.001) along with elimination of the right bundle branch block QRS morphology, increase in RV filling time (P=0.002), pulmonary artery velocity time integral (P=0.006), and RV maximum +dP/dt (P<0.001), and decrease in RV index of myocardial performance (P=0.006). RV mechanical synchrony improved: septal-to-lateral RV mechanical delay decreased (P<0.001) and signs of RV dyssynchrony pattern were significantly abolished. RV systolic stretch fraction reflecting the ratio of myocardial stretching and contraction during systole diminished (P=0.001). In patients with congenital heart disease and right bundle branch block, RV cardiac resynchronization therapy carried multiple positive effects on RV mechanics, synchrony, and contraction efficiency. © 2017 American Heart Association, Inc.

  8. 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.

  9. 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

  10. Innovations in Defense Acquisition: Asymmetric Information, Mechanism Design and Prediction Markets

    DTIC Science & Technology

    2011-02-03

    is a fair characterization to say that prediction markets may be very straightforward in basic principle , but in practice the devil is certainly in...experimental economics and game theory /mechanism design. He also has research interests in strategic and competitive dynamics, particularly applied to...School in 1988, Dr. Gates work as an economist at the Jet Propulsion Laboratory in Pasadena, CA. Dr. Gates’ research interests include game theory

  11. Reactive oxygen species and antioxidant defense mechanisms in the oral cavity: a literature review.

    PubMed

    San Miguel, Symone M; Opperman, Lynne A; Allen, Edward P; Svoboda, Kathy K H

    2011-01-01

    Through dental procedures and environment, periodontal tissues are exposed to many types of reactive oxygen species (ROS). Recently, various forms of antioxidants have been introduced as an approach to fight dental diseases and improve general gingival health. This article focuses on the classification of antioxidants and the link between oxidative stress and periodontal disease. The protective mechanisms of antioxidants and how routine dental procedures may increase ROS is discussed. The final section reviews the effect of tobacco products on gingival health and disease.

  12. 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.

  13. Drought resistance in rice seedlings conferred by seed priming : role of the anti-oxidant defense mechanisms.

    PubMed

    Goswami, Alakananda; Banerjee, Rahul; Raha, Sanghamitra

    2013-10-01

    Seed priming is a method by which seeds are subjected to different stress conditions to impart stress adaptation in seedlings germinating and growing under stressful situations. Drought stress is a major reason behind failure of crops. We studied the effects of hydropriming, dehydration priming (induced by PEG), and osmopriming (induced by NaCl and KH(2)PO(4)) on subsequent germination, growth and anti-oxidant defense mechanisms of 2-week-old rice seedlings under continuing dehydration stress. Unprimed seeds grown in PEG showed significantly lower germination and growth along with significantly higher reactive oxygen species (ROS) and lipid peroxidation levels. Among the priming methods, 5 % PEG priming was found to be the best in terms of germination and growth rate along with the lowest amount of ROS and lipid peroxidation (malondialdehyde [MDA]) values. MDA levels were reduced significantly by all of the priming methods. Hence, reduction of lipid peroxidation may be a key factor underlying the drought tolerance produced by the priming treatments. Glutathione peroxidase (GPX) activity seemed to bear an excellent correlation with oxidative stress resistance through seed priming. The PEG priming produced minimum peroxidative damage and superior germination and growth rate along with efficient GPX activity, overexpressed MnSOD and maintenance of HSP70 expression in normal as well as in drought condition. Therefore, in PEG-primed seeds the existence of robust protective mechanisms is definitely indicated.

  14. Digestive physiology of the pig symposium: involvement of gut chemosensing in the regulation of mucosal barrier function and defense mechanisms.

    PubMed

    Kaji, I; Akiba, Y; Kaunitz, J D

    2013-05-01

    Meal ingestion is followed by release of numerous hormones from enteroendocrine cells interspersed among the epithelial cells lining the intestine. Recently, the de-orphanization of G protein-coupled receptor (GPCR)-type nutrient receptors, expressed on the apical membranes of enteroendocrine cells, has suggested a plausible mechanism whereby luminal nutrients trigger the release of gut hormones. Activation of nutrient receptors triggers intracellular signaling mechanisms that promote exocytosis of hormone-containing granules into the submucosal space. Hormones released by foregut enteroendocrine cells include the glucagon-like peptides (GLP) affecting glycemic control (GLP-1) and releasing pro-proliferative, hypertrophy-inducing growth factors (GLP-2). The foregut mucosa, being exposed to pulses of concentrated HCl, is protected by a system of defense mechanisms, which includes epithelial bicarbonate and mucus secretion and augmentation of mucosal blood flow. We have reported that luminal co-perfusion of AA with nucleotides in anesthetized rats releases GLP-2 into the portal vein, associated with increased bicarbonate and mucus secretion and mucosal blood flow. The GLP-2 increases bicarbonate secretion via release of vasoactive intestinal peptide (VIP) from myenteric nerves. Luminal bile acids also release gut hormones due to activation of the bile-acid receptor known as G Protein-Coupled Receptor (GPR) 131, G Protein Bile Acid Receptor (GPBAR) 1, or Takeda G Protein-Coupled Receptor (TGR) 5, also expressed on enteroendocrine cells. The GLP are metabolized by dipeptidyl peptidase IV (DPPIV), an enzyme of particular interest to pharmaceutical, because its inhibition increases plasma concentrations of GLP-1 to treat diabetes. We have also reported that DPPIV inhibition enhances the secretory effects of nutrient-evoked GLP-2. Understanding the release mechanism and the metabolic pathways of gut hormones is of potential utility to the formulation of feedstuff

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

    PubMed Central

    Akamatsu, Akira; Shimamoto, Ko; Kawano, Yoji

    2016-01-01

    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

  16. Triggers and mechanisms of skeletal muscle wasting in chronic obstructive pulmonary disease.

    PubMed

    Langen, R C J; Gosker, H R; Remels, A H V; Schols, A M W J

    2013-10-01

    Skeletal muscle wasting contributes to impaired exercise capacity, reduced health-related quality of life and is an independent determinant of mortality in chronic obstructive pulmonary disease. An imbalance between protein synthesis and myogenesis on the one hand, and muscle proteolysis and apoptosis on the other hand, has been proposed to underlie muscle wasting in this disease. In this review, the current understanding of the state and regulation of these processes governing muscle mass in this condition is presented. In addition, a conceptual mode of action of disease-related determinants of muscle wasting including disuse, hypoxemia, malnutrition, inflammation and glucocorticoids is provided by overlaying the available associative clinical data with causal evidence, mostly derived from experimental models. Significant progression has been made in understanding and managing muscle wasting in chronic obstructive pulmonary disease. Further examination of the time course of muscle wasting and specific disease phenotypes, as well as the application of systems biology and omics approaches in future research will allow the development of tailored strategies to prevent or reverse muscle wasting in chronic obstructive pulmonary disease. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

  17. 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

    2013-08-09

    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.

  18. Amyotrophic lateral sclerosis: impact of pulmonary follow-up and mechanical ventilation on survival. A study of 114 cases.

    PubMed

    Sanjuán-López, Pilar; Valiño-López, Paz; Ricoy-Gabaldón, Jorge; Verea-Hernando, Héctor

    2014-12-01

    To study the impact of ventilatory management and treatment on the survival of patients with amyotrophic lateral sclerosis (ALS). Retrospective analysis of 114 consecutive patients admitted to a general hospital, evaluating demographic data, type of presentation, clinical management, treatment with mechanical ventilation and survival. descriptive and Kaplan-Meier estimator. Sixty four patients presented initial bulbar involvement. Overall mean survival after diagnosis was 28.0 months (95%CI, 21.1-34.8). Seventy patients were referred to the pulmonary specialist (61.4%) and 43 received non-invasive ventilation (NIV) at 12.7 months (median) after diagnosis. Thirty seven patients continued to receive NIV with no subsequent invasive ventilation. The mean survival of these patients was 23.3 months (95%CI, 16.7-28.8), higher in those without bulbar involvement, although below the range of significance. Survival in the 26 patients receiving programmed NIV was higher than in the 11 patients in whom this was indicated without prior pulmonary assessment (considered following diagnosis, P<.012, and in accordance with the start of ventilation, P<.004). A total of 7 patients were treated invasively; mean survival in this group was 72 months (95%CI, 14.36-129.6), median 49.6±17.5 (95%CI, 15.3-83.8), and despite the difficulties involved in home care, acceptance and tolerance was acceptable. Long-term mechanical ventilation prolongs survival in ALS. Programmed pulmonary assessment has a positive impact on survival of ALS patients and is key to the multidisciplinary management of this disease. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  19. Usefulness of open lung biopsy in mechanically ventilated patients with undiagnosed diffuse pulmonary infiltrates: influence of comorbidities and organ dysfunction

    PubMed Central

    Lim, Seong Yong; Suh, Gee Young; Choi, Jae Chol; Koh, Won Jung; Lim, Si Young; Han, Joungho; Lee, Kyung Soo; Shim, Young Mog; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung

    2007-01-01

    Background The purpose of this study was to evaluate the clinical usefulness of open lung biopsy (OLB) in patients undergoing mechanical ventilation for diffuse pulmonary infiltrates of unknown etiology. Methods This was a 10-year retrospective study in a 10-bed medical intensive care unit. The medical records of 36 ventilator-dependent patients who underwent OLB for the diagnosis of unknown pulmonary infiltrates from 1994 to 2004 were reviewed retrospectively. Data analyzed included demographic data, Charlson age–comorbidity score, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, ventilation variables, and radiological patterns. Diagnostic yield, effect on subsequent treatment changes, and complications of OLB were also assessed. Results A specific clinico-pathologic diagnosis was obtained for 31 patients (86%). The most common diagnoses were interstitial pneumonia (n = 17, including 8 acute interstitial pneumonia) and viral pneumonia (n = 4). Therapeutic modifications were made in 64% of patients. Patients who received OLB less than 1 week after initiation of mechanical ventilation were more likely to survive (63% versus 11%; P = 0.018). There were no major complications associated with the procedure. Factors independently associated with survival were the Charlson age-comorbidity score, number of organ dysfunction and the PaO2/FiO2 ratio on the day of the OLB. Conclusion OLB can provide a specific diagnosis in many ventilator-dependent patients with undiagnosed pulmonary infiltrate. Early OLB seems to be useful in critically ill patients with isolated respiratory failure. PMID:17725820

  20. Changes in dead space/tidal volume ratio and pulmonary mechanics after surfactant replacement therapy in respiratory distress syndrome of the newborn infants.

    PubMed Central

    Chung, E. H.; Ko, S. Y.; Kim, I. Y.; Chang, Y. S.; Park, W. S.

    2001-01-01

    This study was performed to elucidate the mechanism of improved oxygenation after surfactant replacement therapy in respiratory distress syndrome (RDS) of the newborn infants. In 26 newborns with RDS, end tidal-CO2 tension (PetCO2), arterial blood gas analysis and pulmonary function tests were measured at baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in dead space/tidal volume ratio (VD/VT ratio=(PaCO2-PetCO2)/PaCO2), oxygenation index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO2) were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A-a)DO2 improved, and VD/VT ratio decreased progressively after surfactant administration, becoming significantly different from the baseline at 30 min and thereafter with administration of surfactant. Pulmonary mechanics did not change significantly during the observation period. VD/VT ratio showed close correlation with OI and (A-a)DO2, but not with pulmonary mechanics. These results suggest that decreased physiologic dead space resulting from the recruitment of atelectatic alveoli rather than improvement in pulmonary mechanics is primarily responsible for the improved oxygenation after surfactant therapy in the RDS of newborn. PMID:11289401

  1. Innate immune memory: towards a better understanding of host defense mechanisms.

    PubMed

    Quintin, Jessica; Cheng, Shih-Chin; van der Meer, Jos W M; Netea, Mihai G

    2014-08-01

    Innate immunity is classically defined as unable to build up immunological memory. Recently however, the assumption of the lack of immunological memory within innate immune responses has been reconsidered. Plants and invertebrates lacking adaptive immune system can be protected against secondary infections. It has been shown that mammals can build cross-protection to secondary infections independently of T-lymphocytes and B-lymphocytes. Moreover, recent studies have demonstrated that innate immune cells such as NK cells and monocytes can display adaptive characteristics, a novel concept for which the term trained immunity has been proposed. Several mechanisms are involved in mediating innate immune memory, among which epigenetic histone modifications and modulation of recognition receptors on the surface of innate immune cells are likely to play a central role. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

    PubMed

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-10-01

    The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage.

  3. A novel mechanism underlying the basic defensive response of macrophages against Mycobacterium infection.

    PubMed

    Iyoda, Takuya; Takada, Muneaki; Fukatsu, Yoshinobu; Kumokoshi, Shunsuke; Fujisawa, Tatsuya; Shimada, Tomokazu; Shimokawa, Noriko; Matsunaga, Takuya; Makino, Kimiko; Doi, Norio; Terada, Hiroshi; Fukai, Fumio

    2014-05-01

    Following inhalation of Mycobacterium tuberculosis, including bacillus Calmette-Guérin (BCG), pathogens enter and grow inside macrophages by taking advantage of their phagocytic mechanisms. Macrophages often fail to eliminate intracellular M. tuberculosis, leading to the induction of host macrophage death. Despite accumulating evidence, the molecular mechanisms underlying M. tuberculosis infection-induced cell death remain controversial. In this study, we show the involvement of two distinct pathways triggered by TLR2 and β2 integrin in BCG infection-induced macrophage apoptosis. First, BCG infection induced activation of ERK1/2, which in turn caused phosphorylation/activation of the proapoptotic protein Bim in mouse macrophage-like Raw 264.7 cells. BCG-infected Raw cells treated with U0126, an MEK/ERK inhibitor, led to the suppression of Bim phosphorylation alongside a remarkable increase in the number of viable macrophages. Small interfering RNA-mediated knockdown of Bim rescued the macrophages from the apoptotic cell death induced by BCG infection. Stimulation with Pam3CSK, a TLR2 agonist, induced macrophage apoptosis with a concomitant increase in the phosphorylation/activation of MEK/ERK and Bim. These observations indicate the important role of the TLR2/MEK/ERK/Bim pathway in BCG infection-induced macrophage apoptosis. Second, we used the β2 integrin agonists C3bi and fibronectin to show that the β2 integrin-derived signal was involved in BCG infection-induced apoptosis, independent of MEK/ERK activation. Interestingly, latex beads coated with Pam3CSK and C3bi were able to induce apoptosis in macrophages to the same extent and specificity as that induced by BCG. Taken together, two distinct pattern-recognition membrane receptors, TLR2 and β2 integrin, acted as triggers in BCG infection-induced macrophage apoptosis, in which MEK/ERK activation played a crucial role following the engagement of TLR2.

  4. Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

    PubMed Central

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-01-01

    The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

  5. A simulation tool to study high-frequency chest compression energy transfer mechanisms and waveforms for pulmonary disease applications.

    PubMed

    O'Clock, George D; Lee, Yong Wan; Lee, Jongwon; Warwick, Warren J

    2010-07-01

    High-frequency chest compression (HFCC) can be used as a therapeutic intervention to assist in the transport and clearance of mucus and enhance water secretion for cystic fibrosis patients. An HFCC pump-vest and half chest-lung simulation, with 23 lung generations, has been developed using inertance, compliance, viscous friction relationships, and Newton's second law. The simulation has proven to be useful in studying the effects of parameter variations and nonlinear effects on HFCC system performance and pulmonary system response. The simulation also reveals HFCC waveform structure and intensity changes in various segments of the pulmonary system. The HFCC system simulation results agree with measurements, indicating that the HFCC energy transport mechanism involves a mechanically induced pulsation or vibration waveform with average velocities in the lung that are dependent upon small air displacements over large areas associated with the vest-chest interface. In combination with information from lung physiology, autopsies and a variety of other lung modeling efforts, the results of the simulation can reveal a number of therapeutic implications.

  6. An active one-lobe pulmonary simulator with compliance control for medical training in neonatal mechanical ventilation.

    PubMed

    Baldoli, Ilaria; Tognarelli, Selene; Cecchi, Francesca; Scaramuzzo, Rosa Teresa; Ciantelli, Massimiliano; Gentile, Marzia; Cuttano, Armando; Laschi, Cecilia; Menciassi, Arianna; Boldrini, Antonio; Dario, Paolo

    2014-06-01

    Mechanical ventilation is a current support therapy for newborns affected by respiratory diseases. However, several side effects have been observed after treatment, making it mandatory for physicians to determine more suitable approaches. High fidelity simulation is an efficient educational technique that recreates clinical experience. The aim of the present study is the design of an innovative and versatile neonatal respiratory simulator which could be useful in training courses for physicians and nurses as for mechanical ventilation. A single chamber prototype, reproducing a pulmonary lobe both in size and function, was designed and assembled. Volume and pressure within the chamber can be tuned by the operator through the device control system, in order to simulate both spontaneous and assisted breathing. An innovative software-based simulator for training neonatologists and nurses within the continuing medical education program on respiratory disease management was validated. Following the clinical needs, three friendly graphic user interfaces were implemented for simulating three different clinical scenarios (spontaneous breathing, controlled breathing and triggered/assisted ventilation modalities) thus providing physicians with an active experience. The proposed pulmonary simulator has the potential to be included in the range of computer-driven technologies used in medical training, adding novel functions and improving simulation results.

  7. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury.

    PubMed

    Rachmale, Sonal; Li, Guangxi; Wilson, Gregory; Malinchoc, Michael; Gajic, Ognjen

    2012-11-01

    Optimal titration of inspired oxygen is important to prevent hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence of the deleterious effects of hyperoxia; however, there is a paucity of data about F(IO(2)) practice and oxygen exposure among patients in ICUs. We therefore sought to assess excessive F(IO(2)) exposure in mechanically ventilated patients with acute lung injury and to evaluate the effect on pulmonary outcomes. From a database of ICU patients with acute lung injury identified by prospective electronic medical record screening, we identified those who underwent invasive mechanical ventilation for > 48 hours from January 1 to December 31, 2008. Ventilator settings, including F(IO(2)) and corresponding S(pO(2)), were collected from the electronic medical record at 15-min intervals for the first 48 hours. Excessive F(IO(2)) was defined as F(IO(2)) > 0.5 despite S(pO(2)) > 92%. The association between the duration of excessive exposure and pulmonary outcomes was assessed by change in oxygenation index from baseline to 48 hours and was analyzed by univariate and multivariate linear regression analysis. Of 210 patients who met the inclusion criteria, 155 (74%) were exposed to excessive F(IO(2)) for a median duration of 17 hours (interquartile range 7.5-33 h). Prolonged exposure to excessive F(IO(2)) correlated with worse oxygenation index at 48 hours in a dose-response manner (P < .001.). Both exposure to higher F(IO(2)) and longer duration of exposure were associated with worsening oxygenation index at 48 hours (P < .001), more days on mechanical ventilation, longer ICU stay, and longer hospital stay (P = .004). No mortality difference was noted. Excessive oxygen supplementation is common in mechanically ventilated patients with ALI and may be associated with worsening lung function.

  8. Preventive effects of Citrus reticulata essential oil on bleomycin-induced pulmonary fibrosis in rats and the mechanism.

    PubMed

    Zhou, Xian-mei; Zhao, Yang; He, Cui-cui; Li, Jian-xin

    2012-02-01

    were significantly lower than those in the model group (Plt;0.01); the SOD levels in serum and pulmonary tissues of the EOCR (50, 100 and 200 mg/kg) groups were markedly increased compared with the model group (Plt;0.01 ), while the MDA levels in both serum and pulmonary tissues were markedly reduced (Plt;0.05); the Col I level in pulmonary tissues of the EOCR (100 and 200 mg/kg per day) groups were markedly lower than that of the model group (Plt;0.01); the protein and mRNA expressions of CTGF in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were down-regulated compared with the model group (Plt;0.01). The results indicate that EOCR has preventive effects on BLM-induced pulmonary fibrosis in rats. The mechanism may be via adjusting the unbalance of oxidation and antioxidation, down-regulating CTGF protein and mRNA expressions, and reducing collagen deposition and fibrosis.

  9. Ego mechanisms of defense are associated with patients' preference of treatment modality independent of psychological distress in end-stage renal disease.

    PubMed

    Hyphantis, Thomas; Katsoudas, Spiros; Voudiclari, Sonia

    2010-03-24

    Several parameters mediate the selection of treatment modality in end-stage renal disease (ESRD). The nephrology community suggests that patient preference should be the prime determinant of modality choice. We aimed to test whether ego mechanisms of defense are associated with patients' treatment modality preferences, independent of psychological distress. In 58 eligible ESRD patients who had themselves chosen their treatment modality, we administered the Symptom Distress Checklist-90-R and the Defense Style Questionnaire. Thirty-seven patients (53.4%) had chosen hemodialysis and 21 (46.6%) peritoneal dialysis. Patients who preferred peritoneal dialysis were younger (odds ratio [OR], 0.89; 95% confidence interval [CI]: 0.804-0.988), had received more education (OR, 8.84; 95% CI: 1.301-60.161), and were twice as likely to adopt an adaptive defense style as compared to patients who preferred hemodialysis (57.1% vs 27.0%, respectively; P < 0.033). On the contrary, the latter were more likely to adopt an image-distorting defense style (35.1% vs 14.3%; P = 0.038) and passive-aggressive defenses (OR, 0.73: 95% CI: 0.504-1.006). These results were independent of psychological distress. Our findings indicate that the patient's personality should be taken into account, if we are to better define which modalities are best suited to which patients. Also, physicians should bear in mind passive-aggressive behaviors that warrant attention and intervention in patients who preferred hemodialysis.

  10. The antiviral defense mechanisms in mandarin fish induced by DNA vaccination against a rhabdovirus.

    PubMed

    Chen, Zhong-Yuan; Lei, Xiao-Ying; Zhang, Qi-Ya

    2012-06-15

    Plasmid DNAs containing Siniperca chuatsi rhabdovirus (SCRV) glycoprotein gene (pcDNA-G) and nucleoprotein gene (pcDNA-N) were constructed, and used to determine the antiviral immune response elicited by DNA vaccination in mandarin fish. In vitro and in vivo expression of the plasmid constructs was confirmed in transfected cells and muscle tissues of vaccinated fish by Western blot, indirect immunofluorescence or RT-PCR analysis. Fish injected with pcDNA-G exhibited protective effect against SCRV challenge with a relative percent survival (RPS) of 77.5%, but no significant protection (RPS of 2.5%) was observed in fish vaccinated with pcDNA-N. Immunohistochemical analysis showed that vaccination with pcDNA-G decreased histological lesions and suppressed the virus replication in fish target organs, e.g. kidney, liver, spleen, gill and heart. Transcriptional analysis further revealed that the expression levels of type I IFN system genes including interferon regulation factor-7 (IRF-7) gene, myxovirus resistance (Mx) gene and virus inhibitory protein (Viperin) gene were strongly up-regulated after injection with pcDNA-G, whereas the level of transcription of immunoglobulin M (IgM) gene did not show a statistically significant change. These results reveal that type I IFN antiviral immune response is rapidly triggered by the plasmid DNA containing rhabdovirus glycoprotein gene in fish, which offers an explanation of molecular mechanisms for DNA vaccination inducing mandarin fish resist to SCRV disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. High level resistance against rhizomania disease by simultaneously integrating two distinct defense mechanisms.

    PubMed

    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 HrpZ(Psph) protein in a secreted form (SP/HrpZ(Psph)) 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.

  12. Cell wall composition as a maize defense mechanism against corn borers.

    PubMed

    Barros-Rios, Jaime; Malvar, Rosa A; Jung, Hans-Joachim G; Santiago, Rogelio

    2011-04-01

    European and Mediterranean corn borers are two of the most economically important insect pests of maize (Zea mays L.) in North America and southern Europe, respectively. Cell wall structure and composition were evaluated in pith and rind tissues of resistant and susceptible inbred lines as possible corn borer resistance traits. Composition of cell wall polysaccharides, lignin concentration and composition, and cell wall bound forms of hydroxycinnamic acids were measured. As expected, most of the cell wall components were found at higher concentrations in the rind than in the pith tissues, with the exception of galactose and total diferulate esters. Pith of resistant inbred lines had significantly higher concentrations of total cell wall material than susceptible inbred lines, indicating that the thickness of cell walls could be the initial barrier against corn borer larvae attack. Higher concentrations of cell wall xylose and 8-O-4-coupled diferulate were found in resistant inbreds. Stem tunneling by corn borers was negatively correlated with concentrations of total diferulates, 8-5-diferulate and p-coumarate esters. Higher total cell wall, xylose, and 8-coupled diferulates concentrations appear to be possible mechanisms of corn borer resistance.

  13. [Biventricular-pulmonary interaction as the prime mechanism in the adaptation of the human heart to orthostatic posture].

    PubMed

    Guazzi, M; Maltagliati, A; Tamborini, G

    1997-01-01

    The purpose was to identify the basic circulatory adjustments to the erect position in man and what the role may be of the heart-lung coupling. Requirements for this study are that: subjects be normal, changes in posture be gradual; pulmonary venous flow, ventricular filling and output be assessed; the methods be noninvasive. In 10 normal men (mean age 34 +/- 8 years) the flow pattern in the right upper pulmonary vein and through the atrioventricular mitral valve, and the right and left ventricular (RV and LV) end-diastolic dimensions were assessed with Doppler echocardiography, in the supine position, after 20, 40 and 60 degrees tilting for 10 min. At 20 degrees displacement: blood pressure, heart rate, stroke volume and LV dimension did not change: RV dimension reduced: pulmonary venous forward flow velocity diminished during systole (X wave) and rose in diastole (Y wave); E wave velocity of the mitral flow and the E/A ratio reduced (consistent with a lower atrioventricular pressure gradient); difference between duration of the pulmonary venous flow reversal during atrial contraction (Z wave) and duration of the mitral A wave (the difference is an index of LV end-diastolic pressure) also diminished, suggesting an improvement of LV compliance. Tilting at 40 and 60 degrees were associated with increase in heart rate and diastolic blood pressure; decrease in systolic blood pressure and stroke volume; reduction of diastolic dimension of both ventricles; some enhancement of the flow changes already described. X was related to stroke volume while supine (r = 0.75; p < 0.01) and not during tilting; at any level of tilting, X/Y ratio was inversely related to the E/A ratio and directly related to the difference in duration between Z and A. During vertical displacement, blood shifts from lungs to systemic circulation resulting in: contribution to replenishment of the arterial side of the circuit; enhancement in LV compliance, due to reduction of RV diastolic volume

  14. 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.

  15. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

    PubMed Central

    Chandran, Preethi K.; Kuttan, Ramadasan

    2008-01-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

  16. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns.

    PubMed

    Chandran, Preethi K; Kuttan, Ramadasan

    2008-09-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins-haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury.

  17. 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.

  18. Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

    PubMed Central

    Wan Ngah, Wan Zurinah; Abdul Karim, Norwahidah

    2017-01-01

    During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts. PMID:28243354

  19. Bacteria and smoke-water extract improve growth and induce the synthesis of volatile defense mechanisms in Vitis vinifera L.

    PubMed

    Salomon, María Victoria; Piccoli, Patricia; Funes Pinter, Iván; Stirk, Wendy Ann; Kulkarni, Manoj; van Staden, Johannes; Bottini, Rubén

    2017-09-19

    Sustainable agricultural practices have been developed as alternative to the use of agrochemicals, and viticulture is not exempt of that. Plant growth promoting rhizobacteria (PGPR) and smoke water extracts (SW) are environmentally-friendly alternative to those agrochemicals. The aim of this study was to investigate the single or combined effects of SW and the PGPR Pseudomonas fluorescens (Pf) and Bacillus licheniformis (Bl) on the physiology and biochemistry of grapevines plants. After 38 days, single applications of SW solutions and bacterial suspensions increase rooting and root length. Combined treatments had a slight positive effect compared to the water control. At the end of 60-days pot trial, grapevine treated with 1:1000 SW and Pf applied alone showed increases in stem length, leaf area and fresh weight of the roots, shoot and leaves, although not significantly differences from the water control were found. In addition, Pf augmented chlorophyll relative content, all treatments decreased the stomatal conductance (mainly 1:500 SW, Pf and 1:1000 SW + Bl), as well as lipid peroxidation in roots (mainly in bacterial treatments), and induced the synthesis of mono and sesquiterpenes in leaves, where the effect was enhanced in combined treatments. In conclusion, PGPR and SW are effective to improve growth of V. vinifera cuttings as well as to increase the plants defense mechanisms that may help them to cope with biotic and abiotic stresses. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Increase in cardiac output and PEEP as mechanism of pulmonary optimization.

    PubMed

    Curiel, C; Martínez, R; Pinto, V; Rosales, A; D'Empaire, G; Sánchez De Leon, R

    1995-03-01

    The influence of cardiac output (CO) and PEEP on pulmonary shunt (Qs/Qt) has been the subjects of considerable investigation but findings are controversial. The role of CO and PEEP on 19 isolated rabbit lung preparations perfused with hypoxic mixture (6% CO2, 10% O2, and 84% N2), which resulted in a constant oxygen venous pressure (64 +/- 5.6 mmHg) has been studied. The first group of 11 preparations were used to study the influence of CO modifications with room air ventilation on the Qs/Qt when the CO rises in 48%; in the second group simultaneous modifications in CO and PEEP (0.5 and 10 cm H2O) were performed. A positive correlation (p < 0.01) in Qs/Qt (0.048 +/- 0.04 to 0.12933 +/- 0.09) was found when the CO increased in the first experimental group, the fluid filtration rate (FFR) also increased and the pulmonary vascular resistance (PVR) remained stable. In the second group an increase of 5 and 10 cm H2O of PEEP at constant CO reduced the Qs/Qt (0.0361 +/- 0.02 to 0.0184 +/- 0.006) while it increased the arterio-venous oxygen difference, PVR and FFR. During high CO conditions increase of 5 and 10 cm H2O of PEEP reduced the Qs/Qt (0.099 +/- 0.03 to 0.027 +/- 0.02) and FFR. These data suggest that when the Qs/Qt is increased, the use of PEEP can compensate the ventilation/perfusion alterations and restore pulmonary gas exchange.

  1. Postoperative pulmonary function in coronary artery bypass graft surgery patients undergoing early tracheal extubation: a comparison between short-term mechanical ventilation and early extubation.

    PubMed

    Nicholson, Donna J; Kowalski, Stephen E; Hamilton, G Andrew; Meyers, Michael P; Serrette, Carl; Duke, Peter C

    2002-02-01

    To evaluate the effect of a short period of mechanical ventilation (3 hours) versus immediate extubation (within 1 hour of surgery) on pulmonary function, gas exchange, and pulmonary complications after coronary artery bypass graft (CABG) surgery. Prospective randomized study. University teaching hospital. Thirty-five patients undergoing CABG surgery. Patients were randomized into 2 groups. Patients in group I were extubated as soon as possible after surgery. Patients in group II were ventilated for a minimum of 3 hours after surgery. Patients in both groups were extubated only after achieving predetermined extubation criteria. Patients who did not meet the criteria for extubation within the predetermined set time limit (90 minutes in group I and 6 hours in group II) were withdrawn from the study. Pulmonary function tests (vital capacity, forced expiratory volume in 1 second, total lung capacity, functional residual capacity), arterial blood gases, and chest radiographs were done preoperatively and postoperatively. Pulmonary complications were recorded. Demographic data were similar between groups. The mean time to extubation in group I was 45.7 plus minus 27.6 minutes and in group II was 201.4 plus minus 21 minutes (p < 0.01). Two patients in group I and 1 patient in group II did not meet the extubation criteria within the predetermined set time limit and were excluded from the study. In both groups, there was a significant decline in pulmonary function but no differences between groups at 24 or 72 hours after surgery. There were no differences between groups in blood gases, atelectasis scores, or pulmonary complications. The data suggest that extending mechanical ventilation after CABG surgery does not affect pulmonary function. Provided that routine extubation criteria are met, patients can be safely extubated early (within 1 hour) after major cardiac surgery without concerns of further pulmonary derangement. Copyright 2002, Elsevier Science (USA). All rights

  2. Chest physiotherapy effectiveness to reduce hospitalization and mechanical ventilation length of stay, pulmonary infection rate and mortality in ICU patients.

    PubMed

    Castro, Antonio A M; Calil, Suleima Ramos; Freitas, Súsi Andréa; Oliveira, Alexandre B; Porto, Elias Ferreira

    2013-01-01

    Although physiotherapy is an integral part of the multiprofessional team in most ICUs there is only limited evidence concerning the effectiveness of its procedures. The objectives of this study were to verify if physiotherapy care provided within 24 h/day for hospitalized patients in the ICU reduce the length of stay, mechanical ventilation support, pulmonary infection and mortality compared to a physiotherapy care provided within 6 h/day. A cohort study was designed to assess differences between one hospital where patients were given physiotherapy care for 24 h/day and another hospital with only 6 h/day. We considered the following as outcome measurements: clinical diagnosis, medication in use, presence of associated diseases, APACHE II and SOFA scores, ICU and mechanical ventilation length of stay, development of pulmonary infections and survival. One hundred and forty-six patients were enrolled. Patients admitted in the service A presented a lower length of stay in mechanical ventilation (p < 0.0001), ICU stay (p = 0.0003), respiratory infections (p = 0.0043) than patients admitted in service B. No difference was found for APACHE II score (p = 0.8) and SOFA scores (p = 0.2) between groups. The mortality risk was OR 1.3 (1.01-2.33) (p = 0.04) for patients in the service B. The presence of a physiotherapist in the intensive care unit contributes decisively to the early recovery of the patient, reducing mechanical ventilation support need, number of hospitalization days, incidence of respiratory infection and risk of mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Pulmonary function in advanced pulmonary hypertension.

    PubMed Central

    Burke, C M; Glanville, A R; Morris, A J; Rubin, D; Harvey, J A; Theodore, J; Robin, E D

    1987-01-01

    Pulmonary mechanical function and gas exchange were studied in 33 patients with advanced pulmonary vascular disease, resulting from primary pulmonary hypertension in 18 cases and from Eisenmenger physiology in 15 cases. Evidence of airway obstruction was found in most patients. In addition, mean total lung capacity (TLC) was only 81.5% of predicted and 27% of our subjects had values of TLC less than one standard deviation below the mean predicted value. The mean value for transfer factor (TLCO) was 71.8% of predicted and appreciable arterial hypoxaemia was present, which was disproportionate to the mild derangements in pulmonary mechanics. Patients with Eisenmenger physiology had significantly lower values of arterial oxygen tension (PaO2) (p less than 0.05) and of maximum mid expiratory flow (p less than 0.05) and significantly higher pulmonary arterial pressure (p less than 0.05) than those with primary pulmonary hypertension, but no other variables were significantly different between the two subpopulations. It is concluded that advanced pulmonary vascular disease in patients with primary pulmonary hypertension and Eisenmenger physiology is associated not only with severe hypoxaemia but also with altered pulmonary mechanical function. PMID:3433237

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

    PubMed

    Ward, William O; Ledbetter, Allen D; Schladweiler, Mette C; Kodavanti, Urmila P

    2015-01-01

    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 analysis of these changes will allow us to better understand the mechanism of pulmonary injury and inflammation. Male Wistar Kyoto rats (10-12 week) were exposed to air, or ozone (0.25, 0.5 or 1.0 ppm) for 4 h and pulmonary injury and inflammation were assessed at 0-h or 20-h (n = 8/group). Lung gene expression profiling was assessed at 0-h (air and 1.0 ppm ozone, n = 3-4/group). At 20-h bronchoalveolar lavage, fluid protein and neutrophils increased at 1 ppm ozone. Numerous genes involved in acute inflammatory response were up-regulated along with changes in genes involved in cell adhesion and migration, steroid metabolism, apoptosis, cell cycle control and cell growth. A number of NRF2 target genes were also induced after ozone exposure. Based on expression changes, Rela, SP1 and TP3-mediated signaling were identified to be mediating downstream changes. Remarkable changes in the processes of endocytosis provide the insight that ozone-induced lung injury and inflammation are likely initiated by changes in cell membrane components and receptors likely from oxidatively modified lung lining lipids and proteins. In conclusion, ozone-induced injury and inflammation are preceded by changes in gene targets for cell adhesion/migration, apoptosis, cell cycle control and growth regulated by Rela, SP1 and TP53, likely mediated by the process of endocytosis and altered steroid receptor signaling.

  5. Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice.

    PubMed

    Mahmoud, Motamed Elsayed; Fereig, Ragab; Nishikawa, Yoshifumi

    2017-04-01

    Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii infection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-γ) to anhedonic and despair-related behaviors in T. gondii-infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas in T. gondii-infected mice, treatment normalized kynurenine/tryptophan (Kyn/Trp) ratios in both plasma and brain tissue. Additionally, T. gondii infection failed to induce anhedonic and despair-like behaviors or increase the Kyn/Trp ratio in immunocompromised (IFN-γ(-/-)) mice, whereas sickness behavior was observed in both immunocompetent and IFN-γ(-/-) mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn/Trp ratios in T. gondii-infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection with T. gondii resulted in IFN-γ production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors. Copyright © 2017 American

  6. Dual mechanism of bacterial lethality for a cationic sequence-random copolymer that mimics host-defense antimicrobial peptides.

    PubMed

    Epand, Raquel F; Mowery, Brendan P; Lee, Sarah E; Stahl, Shannon S; Lehrer, Robert I; Gellman, Samuel H; Epand, Richard M

    2008-05-23

    Flexible sequence-random polymers containing cationic and lipophilic subunits that act as functional mimics of host-defense peptides have recently been reported. We used bacteria and lipid vesicles to study one such polymer, having an average length of 21 residues, that is active against both Gram-positive and Gram-negative bacteria. At low concentrations, this polymer is able to permeabilize model anionic membranes that mimic the lipid composition of Escherichia coli, Staphylococcus aureus, or Bacillus subtilis but is ineffective against model zwitterionic membranes, which explains its low hemolytic activity. The polymer is capable of binding to negatively charged vesicles, inducing segregation of anionic lipids. The appearance of anionic lipid-rich domains results in formation of phase-boundary defects through which leakage can occur. We had earlier proposed such a mechanism of membrane disruption for another antimicrobial agent. Experiments with the mutant E. coli ML-35p indicate that permeabilization is biphasic: at low concentrations, the polymer permeabilizes the outer and inner membranes; at higher polymer concentrations, permeabilization of the outer membrane is progressively diminished, while the inner membrane remains unaffected. Experiments with wild-type E. coli K12 show that the polymer blocks passage of solutes into the intermembrane space at high concentrations. Cell membrane integrity in E. coli K12 and S. aureus exhibits biphasic dependence on polymer concentration. Isothermal titration calorimetry indicates that the polymer associates with the negatively charged lipopolysaccharide of Gram-negative bacteria and with the lipoteichoic acid of Gram-positive bacteria. We propose that this polymer has two mechanisms of antibacterial action, one predominating at low concentrations of polymer and the other predominating at high concentrations.

  7. Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells.

    PubMed

    Feinstein, Wei P; Zhu, Bing; Leavesley, Silas J; Sayner, Sarah L; Rich, Thomas C

    2012-03-15

    Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

  8. Effect of lung resection on pleuro-pulmonary mechanics and fluid balance.

    PubMed

    Salito, C; Bovio, D; Orsetti, G; Salati, M; Brunelli, A; Aliverti, A; Miserocchi, G

    2016-01-15

    The aim of the study was to determine in human patients the effect of lung resection on lung compliance and on pleuro-pulmonary fluid balance. Pre and post-operative values of compliance were measured in anesthetized patients undergoing resection for lung cancer (N=11) through double-lumen bronchial intubation. Lung compliance was measured for 10-12 cm H2O increase in alveolar pressure from 5 cm H2O PEEP in control and repeated after resection. No air leak was assessed and pleural fluid was collected during hospital stay. A significant negative correlation (r(2)=0.68) was found between compliance at 10 min and resected mass. Based on the pre-operative estimated lung weight, the decrease in compliance following lung resection exceeded by 10-15% that expected from resected mass. Significant negative relationships were found by relating pleural fluid drainage flow to the remaining lung mass and to post-operative lung compliance. Following lung re-expansion, data suggest a causative relationship between the decrease in compliance and the perturbation in pleuro-pulmonary fluid balance.

  9. Senescence hypothesis for the pathogenetic mechanism of chronic obstructive pulmonary disease.

    PubMed

    Aoshiba, Kazutetsu; Nagai, Atsushi

    2009-12-01

    We report herein that pulmonary emphysematous lesions appear to be a dynamic phenomenon that involves not only the gradual loss of alveolar structure but also apoptosis, cellular proliferation, and cellular senescence. Cellular proliferation compensates for increased alveolar cell apoptosis in patients with chronic obstructive pulmonary disease (COPD). However, smoking, age, and the increased cell cycle turnover that compensates for apoptosis accelerate alveolar cell senescence, thereby halting cellular proliferation and tipping the balance toward apoptosis, which, in turn, promotes the formation of emphysematous lesions. As a result, alveolar cells disappear and the emphysematous lesions progress. At the same time, cellular senescence is believed to induce inflammation. More specifically, senescent alveolar cells induce inflammation by producing various inflammatory cytokines in tissue. Lymphocytes and Clara cells may also age more rapidly in the lungs of patients with COPD. Lymphocyte senescence may induce an autoimmune reaction and increase susceptibility to infection, and Clara cell senescence may impair airway regeneration as well as sustain airway inflammation. Thus, cellular senescence may be involved in arrested tissue repair, chronic inflammation, and increased susceptibility to infection, which are the typical features of COPD.

  10. Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes.

    PubMed

    Habib, M P; Dunn, A M; Sobonya, R E; Baumgartener, C C; Newell, J D; Halonen, M

    1988-03-01

    Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.

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

    PubMed

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

    2017-09-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly

  12. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    PubMed

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  13. Structural and Mechanical Adaptations of Right Ventricular Free Wall Myocardium to Pulmonary-Hypertension Induced Pressure Overload

    PubMed Central

    Hill, Michael R.; Simon, Marc A.; Valdez-Jasso, Daniela; Zhang, Will; Champion, Hunter C.; Sacks, Michael S.

    2014-01-01

    Right ventricular (RV) failure in response to pulmonary hypertension (PH) is a severe disease that remains poorly understood. PH-induced pressure overload leads to changes in the RV free wall (RVFW) that eventually results in RV failure. While the development of computational models can benefit our understanding of the onset and progression of PH-induced pressure overload, detailed knowledge of the underlying structural and biomechanical events remains limited. The goal of the present study was to elucidate the structural and biomechanical adaptations of RV myocardium subjected to sustained pressure overload in a rat model. Hemodynamically confirmed severe chronic RV pressure overload was induced in Sprague-Dawley rats via pulmonary artery banding. Extensive tissue-level biaxial mechanical and histomorphological analyses were conducted to assess the remodeling response in the RV free wall. Simultaneous myofiber hypertrophy and longitudinal re-orientation of myo- and collagen fibers was observed, with both fiber types becoming more highly aligned. Transmural myo- and collagen fiber orientations were co-aligned in both the normal and diseased state. The overall tissue stiffness increased, with larger increases in longitudinal versus circumferential stiffness. Interestingly, estimated myofiber stiffness increased while the collagen fiber stiffness remained unchanged. The latter was attributed to longitudinal fiber re-orientation, which increased the degree of anisotropy. Increased mechanical coupling between the two axes was attributed to the increased fiber alignment. The increased myofiber stiffness was consistent with clinical results showing titin-associated increased sarcomeric stiffening observed in PH patients. These results further our understanding of the underlying adaptive and maladaptive remodeling mechanisms and may lead to improved techniques for prognosis, diagnosis, and treatment for PH. PMID:25164124

  14. Salicylic acid-mediated and RNA-silencing defense mechanisms cooperate in the restriction of systemic spread of plum pox virus in tobacco.

    PubMed

    Alamillo, Josefa M; Saénz, Pilar; García, Juan Antonio

    2006-10-01

    Plum pox virus (PPV) is able to replicate in inoculated leaves of Nicotiana tabacum, but is defective in systemic movement in this host. However, PPV produces a systemic infection in transgenic tobacco expressing the silencing suppressor P1/HC-Pro from tobacco etch virus (TEV). In this work we show that PPV is able to move to upper non-inoculated leaves of tobacco plants expressing bacterial salicylate hydroxylase (NahG) that degrades salicylic acid (SA). Replication and accumulation of PPV is higher in the locally infected leaves of plants deficient in SA or expressing TEV P1/HC-Pro silencing suppressor. Accumulation of viral derived small RNAs was reduced in the NahG transgenic plants, suggesting that SA might act as an enhancer of the RNA-silencing antiviral defense in tobacco. Besides, expression of SA-mediated defense transcripts, such as those of pathogenesis-related (PR) proteins PR-1 and PR-2 or alternative oxidase-1, as well as that of the putative RNA-dependent RNA polymerase NtRDR1, is induced in response to PPV infection, and the expression patterns of these defense transcripts are altered in the TEV P1/HC-Pro transgenic plants. Long-distance movement of PPV is highly enhanced in NahG x P1/HC-Pro double-transgenic plants and systemic symptoms in these plants reveal that the expression of an RNA-silencing suppressor and the lack of SA produce additive but distinct effects. Our results suggest that SA might act as an enhancer of the RNA-silencing antiviral defense in tobacco, and that silencing suppressors, such as P1/HC-Pro, also alter the SA-mediated defense. Both an RNA-silencing and an SA-mediated defense mechanism could act together to limit PPV infection.

  15. Defense Concept - Mechanized Division

    DTIC Science & Technology

    1975-06-06

    Sfrnf t.F0SSi51! war s^nario. of momentum, the greater the d?^.LSre?uion^f th0 importance greater the^dvantaLf^°Sich accrSs L ?hp hL? b ;)!Ctivei the...8217TIrT ■^^^.^■M ::: S: *’ :ii£ B - ■ Jsi ^-rj;^: ?v-’iisÜiLiSü TT" ^^"» 1 > ever, substantially different from the existing doctrinal forms of...stroncpolnts betwe-n b ’.t- talions may or may not be. .Small towns and villages remain the "knot in the web," just as they are in Fuller’s Island

  16. Visualization of pulmonary clearance mechanisms via noninvasive optical imaging validated by near-infrared flow cytometry.

    PubMed

    Zhou, Haiying; Gunsten, Sean P; Zhegalova, Natalia G; Bloch, Sharon; Achilefu, Samuel; Christopher Holley, J; Schweppe, Daniel; Akers, Walter; Brody, Steven L; Eades, William C; Berezin, Mikhail Y

    2015-05-01

    In vivo optical imaging with near-infrared (NIR) probes is an established method of diagnostics in preclinical and clinical studies. However, the specificities of these probes are difficult to validate ex vivo due to the lack of NIR flow cytometry. To address this limitation, we modified a flow cytometer to include an additional NIR channel using a 752 nm laser line. The flow cytometry system was tested using NIR microspheres and cell lines labeled with a combination of visible range and NIR fluorescent dyes. The approach was verified in vivo in mice evaluated for immune response in lungs after intratracheal delivery of the NIR contrast agent. Flow cytometry of cells obtained from the lung bronchoalveolar lavage demonstrated that the NIR dye was taken up by pulmonary macrophages as early as 4-h post-injection. This combination of optical imaging with NIR flow cytometry extends the capability of imaging and enables complementation of in vivo imaging with cell-specific studies.

  17. 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 con