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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. 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

  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. 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

  14. 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.

  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. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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…

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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…

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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)

  3. 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.

  4. 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

  5. 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.

  6. 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

  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. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

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

    PubMed

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

    2014-03-01

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

  14. 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.

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

    SciTech Connect

    Mendel, J.E.

    1984-08-01

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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  3. 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

  4. 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

  5. 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.)

  6. 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.

  7. 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.

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

    PubMed Central

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

    2016-01-01

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

  9. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. [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.

  12. 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.

  13. 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.

  14. 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.

  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. [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.

  17. 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 ...

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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).

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. In Defense of a Heuristic Interpretation of Quantum Mechanics

    ERIC Educational Resources Information Center

    Healy, Eamonn F.

    2010-01-01

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

  7. 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.

  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. 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…

  11. 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…

  12. 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…

  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. 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.

  15. 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

  16. 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

  17. 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

  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. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. [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.

  8. Pulmonary Hypertension in Scleroderma

    MedlinePlus

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels ... with scleroderma are at increased risk for developing PH from several mechanisms. Frequently patients with scleroderma have ...

  9. 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.

  10. 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

  11. 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.

  12. 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.

  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. 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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

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

    PubMed

    Silva, Rafael; Oyarzún, Manuel; Olloquequi, Jordi

    2015-06-01

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

  3. 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.

  4. 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

  5. [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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2002-06-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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…

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. 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

  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. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. “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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Pulmonary edema

    MedlinePlus

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

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

    PubMed Central

    2011-01-01

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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Pulmonary embolus

    MedlinePlus

    ... clot - lung; Embolus; Tumor embolus; Embolism - pulmonary; DVT-pulmonary embolism; Thrombosis - pulmonary embolism ... Main symptoms of a pulmonary embolism include chest pain that may be any of the following: Under the breastbone or on one side Sharp or stabbing ...

  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. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    PubMed Central

    Colvin, Kelley L.; Yeager, Michael E.

    2015-01-01

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

  11. 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.

  12. 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

  13. Innovations in Defense Acquisition Auctions: Lessons Learned and Alternative Mechanism Designs

    DTIC Science & Technology

    2008-02-21

    Engines, Turbines , and Components $93,321 3 29—Engine Accessories $13,109 3 30—Mechanical Power Transmission Equipment $53,183 5 31— Bearings $9,760 1... balls . In this urn, there are α black balls and β white balls (recall that α + β = 100). An individual player (be it a buyer or seller) infers the...true number of black and white balls in the urn (the true values of α and β) from the information received from its draws (the number of black and

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

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

    PubMed Central

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

    2016-01-01

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

  2. Visualization of Pulmonary Clearance Mechanisms via Noninvasive Optical Imaging Validated by Near-Infrared Flow Cytometry

    PubMed Central

    Zhou, Haiying; Gunsten, Sean P.; Zhegalova, Natalia G.; Bloch, Sharon; Achilefu, Samuel; Holley, J. Christopher; Schweppe, Daniel; Akers, Walter; Brody, Steven L.; Eades, William; Berezin, Mikhail Y.

    2016-01-01

    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 four-hours 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. PMID:25808737

  3. Pulmonary angiography

    MedlinePlus

    ... Pulmonary arteriography; Pulmonary angiogram; Angiogram of the lungs Images Pulmonary arteries References Jackson JE, Meaney JFM. Angiography. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  4. Pulmonary Rehabilitation

    MedlinePlus

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

  5. Effects of alveolar hypoxia on the pulmonary circulation and lung mechanics after cromolyn sodium and U-60,257 in lambs.

    PubMed

    Taylor, B J; Sziszak, T L; Sziszak, T J; Dang, A Q

    1992-08-01

    Because alveolar hypoxia (HYP) triggers pulmonary mast cell degranulation with elaboration of vasoactive mediators such as leukotrienes, we investigated the effects of aerosolized cromolyn sodium (CS), a mast cell stabilizing agent, and U-60,257(U) (a leukotriene blocker) on the circulation, lung mechanics and thromboxane (TXB2) levels in 11 lambs during acute exposure to HYP. Studies were performed in awake, chronically instrumented animals, once after placebo (saline) and again after CS (100 mg; n = 5) or U (90 mg; n = 6). Pulmonary arterial pressure increased 42% during HYP after saline, and 32% and 19% after CS and U, respectively. Pulmonary vascular resistance did not change during HYP after CS or U. Systemic arterial pressure was unchanged after saline and CS but decreased after U; systemic vascular resistance dropped after both CS and U. No changes were seen in tidal volume, lung compliance or airway resistance during HYP after saline or either drug, but minute ventilation increased during HYP in all studies. TXB2 increased during HYP after saline in both studies and was not altered by CS. In contrast, after U, TXB2 decreased. Thus, U more effectively blunted the pulmonary vascular response to HYP than CS and resulted in mild systemic hypotension. The drop in TXB2 after U suggests leukotriene-induced thromboxane synthesis contributes to regulation of pulmonary, and possibly, systemic vasoactivity.

  6. Noninvasive mechanical ventilation with average volume assured pressure support (AVAPS) in patients with chronic obstructive pulmonary disease and hypercapnic encephalopathy

    PubMed Central

    2013-01-01

    Background Non-invasive mechanical ventilation (NIV) in patients with acute respiratory failure has been traditionally determined based on clinical assessment and changes in blood gases, with NIV support pressures manually adjusted by an operator. Bilevel positive airway pressure-spontaneous/timed (BiPAP S/T) with average volume assured pressure support (AVAPS) uses a fixed tidal volume that automatically adjusts to a patient’s needs. Our study assessed the use of BiPAP S/T with AVAPS in patients with chronic obstructive pulmonary disease (COPD) and hypercapnic encephalopathy as compared to BiPAP S/T alone, upon immediate arrival in the Emergency-ICU. Methods We carried out a prospective interventional match-controlled study in Guayaquil, Ecuador. A total of 22 patients were analyzed. Eleven with COPD exacerbations and hypercapnic encephalopathy with a Glasgow Coma Scale (GCS) <10 and a pH of 7.25-7.35 were assigned to receive NIV via BiPAP S/T with AVAPS. Eleven patients were selected as paired controls for the initial group by physicians who were unfamiliar with our study, and these patients were administered BiPAP S/T. Arterial blood gases, GCS, vital signs, and ventilatory parameters were then measured and compared between the two groups. Results We observed statistically significant differences in favor of the BiPAP S/T + AVAPS group in GCS (P = .00001), pCO2 (P = .03) and maximum inspiratory positive airway pressure (IPAP) (P = .005), among others. However, no significant differences in terms of length of stay or days on NIV were observed. Conclusions BiPAP S/T with AVAPS facilitates rapid recovery of consciousness when compared to traditional BiPAP S/T in patients with chronic obstructive pulmonary disease and hypercapnic encephalopathy. Trial registration Current Controlled Trials application ref is ISRCTN05135218 PMID:23497021

  7. Dietary abscisic acid ameliorates influenza-virus-associated disease and pulmonary immunopathology through a PPARγ-dependent mechanism.

    PubMed

    Hontecillas, Raquel; Roberts, Paul C; Carbo, Adria; Vives, Cristina; Horne, William T; Genis, Sandra; Velayudhan, Binu; Bassaganya-Riera, Josep

    2013-06-01

    The anti-inflammatory phytohormone abscisic acid (ABA) modulates immune and inflammatory responses in mouse models of colitis and obesity. ABA has been identified as a ligand of lanthionine synthetase C-like 2, a novel therapeutic target upstream of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. The goal of this study was to investigate the immune modulatory mechanisms underlying the anti-inflammatory efficacy of ABA against influenza-associated pulmonary inflammation. Wild-type (WT) and conditional knockout mice with defective PPARγ expression in lung epithelial and hematopoietic cells (cKO) treated orally with or without ABA (100 mg/kg diet) were challenged with influenza A/Udorn (H3N2) to assess ABA's impact in disease, lung lesions and gene expression. Dietary ABA ameliorated disease activity and lung inflammatory pathology, accelerated recovery and increased survival in WT mice. ABA suppressed leukocyte infiltration and monocyte chemotactic protein 1 mRNA expression in WT mice through PPARγ since this effect was abrogated in cKO mice. ABA ameliorated disease when administered therapeutically on the same day of the infection to WT but not mice lacking PPARγ in myeloid cells. We also show that ABA's greater impact is between days 7 and 10 postchallenge when it regulates the expression of genes involved in resolution, like 5-lipoxygenase and other members of the 5-lipoxygenase pathway. Furthermore, ABA significantly increased the expression of the immunoregulatory cytokine interleukin-10 in WT mice. Our results show that ABA, given preventively or therapeutically, ameliorates influenza-virus-induced pathology by activating PPARγ in pulmonary immune cells, suppressing initial proinflammatory responses and promoting resolution.

  8. Mechanisms of corticosteroid resistance in severe asthma and chronic obstructive pulmonary disease (COPD).

    PubMed

    Adcock, Ian M; Marwick, John; Casolari, Paolo; Contoli, Marco; Chung, Kian Fan; Kirkham, Paul; Papi, Alberto; Caramori, Gaetano

    2010-01-01

    Inhaled glucocorticoids, also know as corticosteroids (ICS), revolutionized the treatment of asthma by suppressing airways inflammation and ICS therapy now forms the basis of treatment of asthma of all severities. More recently and usually in combination with a long-acting β-agonist (LABA), ICS use has been established in the treatment of chronic obstructive pulmonary disease (COPD). In asthma, ICS improves asthma control, lung function and prevents exacerbations, including hospital admissions and probably decreases mortality. Similar effects are seen in COPD but to a much lesser degree, however, an improvement in symptoms such as breathlessness and reduction in exacerbations occur particularly in more advanced disease with ICS. Chronic inflammation is a feature of both asthma and COPD, although there are differences in the site and characteristics of the inflammatory response. ICS have proven to be less effective in patients with severe asthma, smoking asthmatics and in patients with COPD. ICS act by binding to and activating specific cytosolic receptors (GR), which then translocate to the nucleus where they regulate gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. GR is able to selective repress specific inflammatory genes by differing actions on specific intracellular signalling pathways and transcription factors such as nuclear factor κB and on kinases pathways. Abnormal activation of these pathways may result in glucocorticoid resistance. Although, ICS/LABA combinations will remain the main focus of treatment of airways diseases in the near future; other combinations that improve the efficacy of ICS by reducing the abnormal activation of pathways that cause glucocorticoid resistance will be developed.

  9. Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus?

    PubMed

    Shvedova, A A; Kisin, E R; Porter, D; Schulte, P; Kagan, V E; Fadeel, B; Castranova, V

    2009-02-01

    Nanotechnology is an emerging science involving manipulation of materials at the nanometer scale. There are several exciting prospects for the application of engineered nanomaterials in medicine. However, concerns over adverse and unanticipated effects on human health have also been raised. In fact, the same properties that make engineered nanomaterials attractive from a technological and biomedical perspective could also make these novel materials harmful to human health and the environment. Carbon nanotubes are cylinders of one or several coaxial graphite layer(s) with a diameter in the order of nanometers, and serve as an instructive example of the Janus-like properties of nanomaterials. Numerous in vitro and in vivo studies have shown that carbon nanotubes and/or associated contaminants or catalytic materials that arise during the production process may induce oxidative stress and prominent pulmonary inflammation. Recent studies also suggest some similarities between the pathogenic properties of multi-walled carbon nanotubes and those of asbestos fibers. On the other hand, carbon nanotubes can be readily functionalized and several studies on the use of carbon nanotubes as versatile excipients for drug delivery and imaging of disease processes have been reported, suggesting that carbon nanotubes may have a place in the armamentarium for treatment and monitoring of cancer, infection, and other disease conditions. Nanomedicine is an emerging field that holds great promise; however, close attention to safety issues is required to ensure that the opportunities that carbon nanotubes and other engineered nanoparticles offer can be translated into feasible and safe constructs for the treatment of human disease.

  10. 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.

  11. Hyperosmolarity Invokes Distinct Anti-Inflammatory Mechanisms in Pulmonary Epithelial Cells: Evidence from Signaling and Transcription Layers

    PubMed Central

    Wright, Franklin L.; Gamboni, Fabia; Moore, Ernest E.; Nydam, Trevor L.; Mitra, Sanchayita; Silliman, Christopher C.; Banerjee, Anirban

    2014-01-01

    Hypertonic saline (HTS) has been used intravenously to reduce organ dysfunction following injury and as an inhaled therapy for cystic fibrosis lung disease. The role and mechanism of HTS inhibition was explored in the TNFα and IL-1β stimulation of pulmonary epithelial cells. Hyperosmolar (HOsm) media (400 mOsm) inhibited the production of select cytokines stimulated by TNFα and IL-1β at the level of mRNA translation, synthesis and release. In TNFα stimulated A549 cells, HOsm media inhibited I-κBα phosphorylation, NF-κB translocation into the nucleus and NF-κB nuclear binding. In IL-1β stimulated cells HOsm inhibited I-κBα phosphorylation without affecting NF-κB translocation or nuclear binding. Incubation in HOsm conditions inhibited both TNFα and IL-1β stimulated nuclear localization of interferon response factor 1 (IRF-1). Additional transcription factors such as AP-1, Erk-1/2, JNK and STAT-1 were unaffected by HOsm. HTS and sorbitol supplemented media produced comparable outcomes in all experiments, indicating that the effects of HTS were mediated by osmolarity, not by sodium. While not affecting MAPK modules discernibly in A549 cells, both HOsm conditions inhibit IRF-1 against TNFα or IL-1β, but inhibit p65 NF-kB translocation only against TNFα but not IL-1β. Thus, anti-inflammatory mechanisms of HTS/HOsm appear to disrupt cytokine signals at distinct intracellular steps. PMID:25479425

  12. Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation.

    PubMed

    Zhang, Yang; Liu, Gongjian; Dull, Randal O; Schwartz, David E; Hu, Guochang

    2014-07-15

    The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury.

  13. Dysfunctionality of the xylem in Olea europaea L. Plants associated with the infection process by Verticillium dahliae Kleb. Role of phenolic compounds in plant defense mechanism.

    PubMed

    Báidez, Ana G; Gómez, Pedro; Del Río, José A; Ortuño, Ana

    2007-05-02

    Xylem ultrastructural modification and the possible participation of phenolic compounds in the natural defense or resistance mechanisms of olive plants infected with Verticillium dahliae Kleb. were studied. Microscopic study showed that the mycelium propagated and passed from one element to another through the pit. The formation of tyloses and aggregates contributed to obstruction of the xylem lumen. In vivo changes in the levels of these phenolic compounds in infected olive plants and their antifungal activity against Verticillium dahliae Kleb., as revealed by in vitro study, strongly suggest that they are involved in natural defense or resistance mechanisms in this plant material, the most active being quercetin and luteolin aglycons, followed by rutin, oleuropein, luteolin-7-glucoside, tyrosol, p-coumaric acid, and catechin. .

  14. A novel mechanical lung model of pulmonary diseases to assist with teaching and training

    PubMed Central

    Chase, J Geoffrey; Yuta, Toshinori; Mulligan, Kerry J; Shaw, Geoffrey M; Horn, Beverley

    2006-01-01

    Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS). The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP) therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp. PMID:16919173

  15. Possible involvement of self-defense mechanisms in the preferential vulnerability of the striatum in Huntington's disease

    PubMed Central

    Francelle, Laetitia; Galvan, Laurie; Brouillet, Emmanuel

    2014-01-01

    HD is caused by a mutation in the huntingtin gene that consists in a CAG repeat expansion translated into an abnormal poly-glutamine (polyQ) tract in the huntingtin (Htt) protein. The most striking neuropathological finding in HD is the atrophy of the striatum. The regional expression of mutant Htt (mHtt) is ubiquitous in the brain and cannot explain by itself the preferential vulnerability of the striatum in HD. mHtt has been shown to produce an early defect in transcription, through direct alteration of the function of key regulators of transcription and in addition, more indirectly, as a result of compensatory responses to cellular stress. In this review, we focus on gene products that are preferentially expressed in the striatum and have down- or up-regulated expression in HD and, as such, may play a crucial role in the susceptibility of the striatum to mHtt. Many of these striatal gene products are for a vast majority down-regulated and more rarely increased in HD. Recent research shows that some of these striatal markers have a pro-survival/neuroprotective role in neurons (e.g., MSK1, A2A, and CB1 receptors) whereas others enhance the susceptibility of striatal neurons to mHtt (e.g., Rhes, RGS2, D2 receptors). The down-regulation of these latter proteins may be considered as a potential self-defense mechanism to slow degeneration. For a majority of the striatal gene products that have been identified so far, their function in the striatum is unknown and their modifying effects on mHtt toxicity remain to be experimentally addressed. Focusing on these striatal markers may contribute to a better understanding of HD pathogenesis, and possibly the identification of novel therapeutic targets. PMID:25309327

  16. [Pulmonary strongyloidiasis].

    PubMed

    Lozada, Heiler; Daza, Jorge E

    2016-10-01

    Strongyloidiasis is an infection caused by the parasite Strongyloides stercoralis, which can be asymptomatic and means a high morbidity and mortality in immunocompromised hosts, severe malnutrition and coinfection with HTLV-1 virus. The parasite has the potential to produce and multiply internal autoinfection in humans, thus an hyperinfection can be developed. A case of pulmonary infection by this parasite is presented in this study, infection which advanced into a respiratory failure and required mechanical ventilation and hemodynamic support in an intensive care unit. The standard treatment combined with ivermectin and albendazole was provided, achieving an appropriate response.

  17. Mechanisms of optimal defense patterns in Nicotiana attenuata: flowering attenuates herbivory-elicited ethylene and jasmonate signaling.

    PubMed

    Diezel, Celia; Allmann, Silke; Baldwin, Ian T

    2011-12-01

    To defend themselves against herbivore attack, plants produce secondary metabolites, which are variously inducible and constitutively deployed, presumably to optimize their fitness benefits in light of their fitness costs. Three phytohormones, jasmonates (JA) and their active forms, the JA-isoleucine (JA-Ile) and ethylene (ET), are known to play central roles in the elicitation of induced defenses, but little is known about how this mediation changes over ontogeny. The Optimal Defense Theory (ODT) predicts changes in the costs and benefits of the different types of defenses and has been usefully extrapolated to their modes of deployment. Here we studied whether the herbivore-induced accumulation of JA, JA-Ile and ET changed over ontogeny in Nicotiana attenuata, a native tobacco in which inducible defenses are particularly well studied. Herbivore-elicited ET production changed dramatically during six developmental stages, from rosette through flowering, decreasing with the elongation of the first corollas during flower development. This decrease was largely recovered within a day after flower removal by decapitation. A similar pattern was found for the herbivore-induced accumulation of JA and JA-Ile. These results are consistent with ODT predictions and suggest that the last steps in floral development control the inducibility of at least three plant hormones, optimizing defense-growth tradeoffs.

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

    PubMed

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

    2016-08-01

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

  19. Pulmonary Hypertension

    PubMed Central

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

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

    NASA Astrophysics Data System (ADS)

    Masoumi, Nafiseh

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

  1. Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms.

    PubMed

    Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Konstantinos; Loridas, Spyridon

    2013-08-27

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

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

    EPA Science Inventory

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

  3. Extrapolation of a non-linear autoregressive model of pulmonary mechanics.

    PubMed

    Langdon, Ruby; Docherty, Paul D; Chiew, Yeong Shiong; Chase, J Geoffrey

    2017-02-01

    For patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is an essential therapy in the intensive care unit (ICU). Suboptimal PEEP levels in MV can cause ventilator induced lung injury, which is associated with increased mortality, extended ICU stay, and high cost. The ability to predict the outcome of respiratory mechanics in response to changes in PEEP would thus provide a critical advantage in personalising and improving care. Testing the potentially dangerous high pressures would not be required to assess their impact. A nonlinear autoregressive (NARX) model was used to predict airway pressure in 19 data sets from 10 mechanically ventilated ARDS patients. Patient-specific NARX models were identified from pressure and flow data over one, two, three, or four adjacent PEEP levels in a recruitment manoeuvre. Extrapolation of NARX model elastance functions allowed prediction of patient responses to PEEP changes to higher or lower pressures. NARX model predictions were more successful than those using a well validated first order model (FOM). The most clinically important results were for extrapolation up one PEEP step of 2cmH2O from the highest PEEP in the training data. When the NARX model was trained on one PEEP level, the mean RMS residual for the extrapolation PEEP level was 0.52 (90% CI: 0.47-0.57) cmH2O, compared to 1.50 (90% CI: 1.38-1.62) cmH2O for the FOM. When trained on four PEEP levels, the NARX result was 0.50 (90% CI: 0.42-0.58) cmH2O, and was 1.95 (90% CI: 1.71-2.19) cmH2O for the FOM. The results suggest that a full recruitment manoeuvre may not be required for the NARX model to obtain a useful estimate of the pressure waveform at higher PEEP levels. The methodology could thus allow clinicians to make informed decisions about ventilator PEEP settings while reducing the risk associated with high PEEP, and subsequent high peak airway pressures.

  4. The GraS Sensor in Staphylococcus aureus Mediates Resistance to Host Defense Peptides Differing in Mechanisms of Action

    PubMed Central

    Chaili, Siyang; Cheung, Ambrose L.; Bayer, Arnold S.; Xiong, Yan Q.; Waring, Alan J.; Memmi, Guido; Donegan, Niles; Yang, Soo-Jin

    2015-01-01

    Staphylococcus aureus uses the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). Assay conditions simulated bloodstream (pH 7.5) or phagolysosomal (pH 5.5) pH contexts. S. aureus strains were more susceptible to HDPs at pH 7.5 than at pH 5.5, and each HDP exerted a distinct effect signature. The impacts of ΔgraS and ΔΕL on HDP resistance were peptide and pH dependent. Both mutants exhibited defects in ANX response to hNP-1 or hBD-2 at pH 7.5, but only hNP-1 did so at pH 5.5. Both mutants exhibited hyper-PRM, -ANX, and -CDP responses to RP-1 at both pHs and hypo-ENR at pH 5.5. The actions correlated with ΔgraS or ΔΕL hypersusceptibility to hNP-1 or RP-1 (but not hBD-2) at pH 7.5 and to all study HDPs at pH 5.5. An exogenous EL mimic protected mutant strains from hNP-1 and hBD-2 but not RP-1, indicating that GraS and its EL play nonredundant roles in S. aureus survival responses to specific HDPs. These findings suggest that GraS mediates specific resistance countermeasures to HDPs in immune contexts that are highly relevant to S. aureus pathogenesis in humans. PMID:26597988

  5. Ovine pulmonary surfactant induces killing of Pasteurella haemolytica, Escherichia coli, and Klebsiella pneumoniae by normal serum.

    PubMed Central

    Brogden, K A

    1992-01-01

    Pulmonary surfactant has been shown to play an increasingly important role in bacterial clearance at the alveolar surface in the lung. This study describes a bactericidal mechanism in which ovine pulmonary surfactant induces killing of Pasteurella haemolytica by normal serum. To demonstrate killing, six bacterial species were incubated first with pulmonary surfactant for 60 min at 37 degrees C and then with serum for an additional 60 min at 37 degrees C. P. haemolytica type A1 strains 82-25 and L101, a P. haemolytica type 2 strain, Escherichia coli, and Klebsiella pneumoniae were susceptible and Pasteurella multocida, Serratia marcescens, and Pseudomonas aeruginosa were not susceptible to killing by ovine pulmonary surfactant and normal serum. No bacteria incubated with bovine pulmonary surfactant were killed by normal serum. Although the species origin of pulmonary surfactant was selective, the species origin of serum was not. P. haemolytica incubated with ovine pulmonary surfactant was killed by fetal calf serum, gnotobiotic calf serum, pooled normal sheep serum, pooled normal rabbit serum, and pooled guinea pig serum. Ultrastructurally, killed P. haemolytica suspensions contained dead cells and cells distorted with vacuoles between the cytoplasmic membrane and the cytoplasm. The mechanism of killing did not correlate with concentrations of complement or lysozyme or titers of residual antibody in either the pulmonary surfactant or the serum, and killing was reduced by preincubation of surfactant with P. haemolytica lipopolysaccharide. Preliminary characterization of both surfactant and serum implicate a low-molecular-weight proteinaceous component in the surfactant and serum albumin in the serum. This mechanism may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system. Images PMID:1452351

  6. PULMONARY CIRCULATION AT EXERCISE

    PubMed Central

    NAEIJE, R; CHESLER, N

    2012-01-01

    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40–50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease. PMID:23105961

  7. Pulmonary circulation at exercise.

    PubMed

    Naeije, Robert; Chesler, N

    2012-01-01

    The pulmonary circulation is a high-flow and low-pressure circuit, with an average resistance of 1 mmHg/min/L in young adults, increasing to 2.5 mmHg/min/L over four to six decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20 to 25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40 to 50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease.

  8. Pulmonary hypertension and hepatic cirrhosis.

    PubMed

    Téllez Villajos, L; Martínez González, J; Moreira Vicente, V; Albillos Martínez, A

    2015-01-01

    Pulmonary hypertension is a relatively common phenomenon in patients with hepatic cirrhosis and can appear through various mechanisms. The most characteristic scenario that binds portal and pulmonary hypertension is portopulmonary syndrome. However, hyperdynamic circulation, TIPS placement and heart failure can raise the mean pulmonary artery pressure without increasing the resistances. These conditions are not candidates for treatment with pulmonary vasodilators and require a specific therapy. A correct assessment of hemodynamic, ultrasound and clinical variables enables the differential diagnosis of each situation that produces pulmonary hypertension in patients with cirrhosis.

  9. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

    PubMed Central

    Lammers, Steven R.; Kao, Phil H.; Qi, H. Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R.; Shandas, Robin

    2008-01-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Time course of respiratory mechanics and pulmonary structural remodelling in acute lung injury.

    PubMed

    Rocco, Patricia R M; Facchinetti, Livia D; Ferreira, Halina C; Negri, Elnara M; Capelozzi, Vera L; Faffe, Debora S; Zin, Walter A

    2004-10-12

    The aim of this study was to evaluate the time course of in vivo and in vitro respiratory mechanics and examine whether these parameters could reflect the temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.) injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue resistances increased from control in PQ1 and PQ3 and returned to control values in PQ8, in accordance with the magnitude of bronchoconstriction. Viscoelastic/inhomogeneous pressure, tissue elastance, the number of polymorphonuclear cells, and collagen fibre content in lung parenchyma increased in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1, returned to control values after 3 weeks, and was correlated with the volume fraction of collapsed alveoli. In conclusion, there is a restoration of normal alveolar-capillary lung units with a gradual improvement in airway and tissue resistances and static elastance. However, the on-going fibrotic process kept elevated tissue elastance and viscoelastic/inhomogeneous pressure.

  13. Cobalt chloride speciation, mechanisms of cytotoxicity on human pulmonary cells, and synergistic toxicity with zinc.

    PubMed

    Bresson, Carole; Darolles, Carine; Carmona, Asuncion; Gautier, Céline; Sage, Nicole; Roudeau, Stéphane; Ortega, Richard; Ansoborlo, Eric; Malard, Véronique

    2013-02-01

    Cobalt is used in numerous industrial sectors, leading to occupational diseases, particularly by inhalation. Cobalt-associated mechanisms of toxicity are far from being understood and information that could improve knowledge in this area is required. We investigated the impact of a soluble cobalt compound, CoCl(2)·6H(2)O, on the BEAS-2B lung epithelial cell line, as well as its impact on metal homeostasis. Cobalt speciation in different culture media, in particular soluble and precipitated cobalt species, was investigated via theoretical and analytical approaches. The cytotoxic effects of cobalt on the cells were assessed. Upon exposure of BEAS-2B cells to cobalt, intracellular accumulation of cobalt and zinc was demonstrated using direct in situ microchemical analysis based on ion micro-beam techniques and analysis after cell lysis by inductively coupled plasma mass spectrometry (ICP-MS). Microchemical imaging revealed that cobalt was rather homogeneously distributed in the nucleus and in the cytoplasm whereas zinc was more abundant in the nucleus. The modulation of zinc homeostasis led to the evaluation of the effect of combined cobalt and zinc exposure. In this case, a clear synergistic increase in toxicity was observed as well as a substantial increase in zinc content within cells. Western blots performed under the same coexposure conditions revealed a decrease in ZnT1 expression, suggesting that cobalt could inhibit zinc release through the modulation of ZnT1. Overall, this study highlights the potential hazard to lung function, of combined exposure to cobalt and zinc.

  14. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

    PubMed

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha

    2015-09-01

    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action.

  15. Pulmonary Hypertension and Pulmonary Vasodilators.

    PubMed

    Keller, Roberta L

    2016-03-01

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

  16. Pulmonary Edema

    MedlinePlus

    ... suddenly or develop over time. Sudden (acute) pulmonary edema symptoms Extreme shortness of breath or difficulty breathing ( ... fatal if not treated. Long-term (chronic) pulmonary edema symptoms Having more shortness of breath than normal ...

  17. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  18. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  19. Pulmonary Embolism

    MedlinePlus

    ... pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  20. Lysozyme- and chitinase activity in latex bearing plants of genus Euphorbia--A contribution to plant defense mechanism.

    PubMed

    Sytwala, Sonja; Günther, Florian; Melzig, Matthias F

    2015-10-01

    Occurrence of latices in plants is widespread, there are 40 families of plants characterized to establish lactiferous structures. Latices exhibit a constitutive part of plant defense due to the stickiness. The appearance of proteins incorporated in latices is well characterized, and hydrolytic active proteins are considerable. A lot of plants constitute so-called pathogenesis-related (PR) proteins, to overcome stressful conditions. In our investigation we are focused on latex bearing plants of Euphorbiaceae Juss., and investigated the appearance of chitinase- and lysozyme activity in particular. The present outcomes represent a comprehensive study, relating to the occurrence of lysozyme and chitinase activity of genus Euphorbia at the first time. 110 different species of genus Euphorbia L. were tested, and the appearance of chitinase and lysozyme were determined in different quantities. The appearance itself, and the physicochemical properties of latices indicate an efficient interaction for plant defense against pathogen attack.

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

    PubMed

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

    2015-11-01

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

  2. Pulmonary Hypertension

    MedlinePlus

    ... on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart to your lungs to pick up oxygen. PH causes symptoms such as shortness of ...

  3. Induction of DIMBOA accumulation and systemic defense responses as a mechanism of enhanced resistance of mycorrhizal corn (Zea mays L.) to sheath blight.

    PubMed

    Song, Yuan Yuan; Cao, Man; Xie, Li Jun; Liang, Xiao Ting; Zeng, Ren Sen; Su, Yi Juan; Huang, Jing Hua; Wang, Rui Long; Luo, Shi Ming

    2011-11-01

    Arbuscular mycorrhizas are the most important symbioses in terrestrial ecosystems and they enhance the plant defense against numerous soil-borne pathogenic fungi and nematodes. Two corn (Zea mays) varieties, Gaoyou-115 that is susceptible to sheath blight disease caused by Rhizoctonia solani and Yuenong-9 that is resistant, were used for mycorrhizal inoculation in this study. Pre-inoculation of susceptible Gaoyou-115 with arbuscular mycorrhizal fungus (AMF) Glomus mosseae significantly reduced the disease incidence and disease severity of sheath blight of corn. HPLC analysis showed that AMF inoculation led to significant increase in 2,4-dihydroxy-7-methoxy-2 H-1,4-benzoxazin-3(4 H)-one (DIMBOA) accumulation in the roots of both corn varieties and in leaves of resistant Yuenong-9. R. solani inoculation alone did not result in accumulation of DIMBOA in both roots and leaves of the two corn varieties. Our previous study showed that DIMBOA strongly inhibited mycelial growth of R. solani in vitro. Real-time PCR analysis showed that mycorrhizal inoculation itself did not affect the transcripts of most genes tested. However, pre-inoculation with G. mosseae induced strong responses of three defense-related genes PR2a, PAL, and AOS, as well as BX9, one of the key genes in DIMBOA biosynthesis pathway, in the leaves of corn plants of both Yuenong-9 and Gaoyou-115 after the pathogen attack. Induction of defense responses in pre-inoculated plants was much higher and quicker than that in non-inoculated plants upon R. solani infection. These results indicate that induction of accumulation of DIMBOA, an important phytoalexin in corn, and systemic defense responses by AMF, plays a vital role in enhanced disease resistance of mycorrhizal plants of corn against sheath blight. This study also suggests that priming is an important mechanism in mycorrhiza-induced resistance.

  4. Unravelling the networks dictating host resistance versus tolerance during pulmonary infections.

    PubMed

    Meunier, Isabelle; Kaufmann, Eva; Downey, Jeffrey; Divangahi, Maziar

    2017-03-01

    The appearance of single cell microorganisms on earth dates back to more than 3.5 billion years ago, ultimately leading to the development of multicellular organisms approximately 3 billion years later. The evolutionary burst of species diversity and the "struggle for existence", as proposed by Darwin, generated a complex host defense system. Host survival during infection in vital organs, such as the lung, requires a delicate balance between host defense, which is essential for the detection and elimination of pathogens and host tolerance, which is critical for minimizing collateral tissue damage. Whereas the cellular and molecular mechanisms of host defense against many invading pathogens have been extensively studied, our understanding of host tolerance as a key mechanism in maintaining host fitness is extremely limited. This may also explain why current therapeutic and preventive approaches targeting only host defense mechanisms have failed to provide full protection against severe infectious diseases, including pulmonary influenza virus and Mycobacterium tuberculosis infections. In this review, we aim to outline various host strategies of resistance and tolerance for effective protection against acute or chronic pulmonary infections.

  5. Immune defense against pneumonic plague

    PubMed Central

    Smiley, Stephen T.

    2009-01-01

    Summary Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection. PMID:18837787

  6. Clustered regularly interspaced short palindromic repeats (CRISPRs): the hallmark of an ingenious antiviral defense mechanism in prokaryotes.

    PubMed

    Al-Attar, Sinan; Westra, Edze R; van der Oost, John; Brouns, Stan J J

    2011-04-01

    Many prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences (repeats), interspaced by highly variable sequences referred to as spacers. The spacers originate from either phages or plasmids and comprise the prokaryotes' 'immunological memory'. CRISPR-associated (cas) genes encode conserved proteins that together with CRISPRs make-up the CRISPR/Cas system, responsible for defending the prokaryotic cell against invaders. CRISPR-mediated resistance has been proposed to involve three stages: (i) CRISPR-Adaptation, the invader DNA is encountered by the CRISPR/Cas machinery and an invader-derived short DNA fragment is incorporated in the CRISPR array. (ii) CRISPR-Expression, the CRISPR array is transcribed and the transcript is processed by Cas proteins. (iii) CRISPR-Interference, the invaders' nucleic acid is recognized by complementarity to the crRNA and neutralized. An application of the CRISPR/Cas system is the immunization of industry-relevant prokaryotes (or eukaryotes) against mobile-genetic invasion. In addition, the high variability of the CRISPR spacer content can be exploited for phylogenetic and evolutionary studies. Despite impressive progress during the last couple of years, the elucidation of several fundamental details will be a major challenge in future research.

  7. Transforming Defense

    DTIC Science & Technology

    2005-09-01

    or agency each week?” 47 By way of just one example, Madrid’s La Razon reported on September 13 , 2004, that Spain would lose U.S. bases to Portugal...public release, distribution unlimited 13 . SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...DEFENSE 7 responsibilities. The homeland security JOC envisions a layered and comprehensive defense requiring geographical and functional integra- tion. 13

  8. Reperfusion pulmonary edema

    SciTech Connect

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. )

    1989-02-17

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B{sub 4} and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

  9. The potential impact of the pulmonary microbiome on immunopathogenesis of Aspergillus-related lung disease.

    PubMed

    Kolwijck, Eva; van de Veerdonk, Frank L

    2014-11-01

    Aspergillosis is an infection or allergic response caused by fungi of the genus Aspergillus. The most common forms of aspergillosis are allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis. Aspergillus also plays an important role in fungal sensitized asthma. Humans inhale Aspergillus spores every day and when the host is immunocompromised, Aspergillus spp. may cause severe pulmonary disease. There is increasing evidence that the microbiome plays a significant role in immune regulation, chronic inflammatory diseases, metabolism, and other physiological processes, including recovery from the effects of antibiotic treatment. Bacterial microbiome mediated resistance mechanisms probably play a major role in limiting fungal colonization of the lungs, and may therefore prevent humans from contracting Aspergillus-related diseases. In this perspective, we review this emerging area of research and discuss the role of the microbiome in aspergillosis, role of Aspergillus in the microbiome, and the influence of the microbiome on anti-Aspergillus host defense and its role in preventing aspergillosis.

  10. Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary endothelial cell dysfunction.

    PubMed

    Panwar, Hariom; Jain, Deepika; Khan, Saba; Pathak, Neelam; Raghuram, Gorantla V; Bhargava, Arpit; Banerjee, Smita; Mishra, Pradyumna K

    2013-01-01

    Mechanistic investigations coupled with epidemiology, case-control, cohort and observational studies have increasingly linked isocyanate exposure (both chronic and acute) with pulmonary morbidity and mortality. Though ascribed for impairment in endothelial cell function, molecular mechanisms of these significant adverse pulmonary outcomes remains poorly understood. As preliminary studies conducted in past have failed to demonstrate a cause-effect relationship between isocyanate toxicity and compromised pulmonary endothelial cell function, we hypothesized that direct exposure to isocyanate may disrupt endothelial structural lining, resulting in cellular damage. Based on this premise, we comprehensively evaluated the molecular repercussions of methyl isocyanate (MIC) exposure on human pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA damage response and apoptotic index. Our results demonstrate that exposure to MIC, augment mitochondrial reactive oxygen species production, depletion in antioxidant defense enzymes, elevated pro-inflammatory cytokine response and induced endothelial cell apoptosis via affecting the balance of mitochondrial-nuclear cross talk. We herein delineate the first and direct molecular cascade of isocyanate-induced pulmonary endothelial cell dysfunction. The results of our study might portray a connective link between associated respiratory morbidities with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype relationship in observed deficits of pulmonary endothelial cell function. Further, understanding of inter- and intra-cellular signaling pathways involved in isocyanate-induced endothelial damage would not only aid in biomarker identification but also provide potential new avenues to target specific therapeutic interventions.

  11. [Pathophysiology and classification of pulmonary hypertension].

    PubMed

    Sládková, H; Jansa, P; Susa, Z; Aschermann, M

    2004-09-01

    Pulmonary hypertension is present when the mean pulmonary pressure is increased above 25 mm Hg in a rest or above 30 mm Hg during exercise. It is possible to divide it from different point of view. Well known is pathophysiologic classification and Venice classification suggested by WHO symposium 2003. The rise of arterial pulmonary pressure is caused by three essential abnormalities, these are elevated pulmonary vascular resistance, blood flow and pulmonary artery wedge pressure. Vasoconstriction, remodeling of vessels and in situ trombosis are pathogenetic mechanism which contribute to rise of pulmonary hypertension.

  12. Single Exposure to near Roadway Particulate Matter Leads to Confined Inflammatory and Defense Responses: Possible Role of Metals.

    PubMed

    Pardo, Michal; Shafer, Martin M; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2015-07-21

    Inhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single ("subclinical response") exposure to water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-α), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage.

  13. Peripheral mechanisms II: the pharmacology of peripherally active antitussive drugs.

    PubMed

    Spina, D; McFadzean, I; Bertram, F K R; Page, C P

    2009-01-01

    Cough is an indispensable defensive reflex. Although generally beneficial, it is also a common symptom of diseases such as asthma, chronic obstructive pulmonary disease, upper respiratory tract infections, idiopathic pulmonary fibrosis and lung cancer. Cough remains a major unmet medical need and although the centrally acting opioids have remained the antitussive of choice for decades, they have many unwanted side effects. However, new research into the behaviour of airway sensory nerves has provided greater insight into the mechanisms of cough and new avenues for the discovery of novel non-opioid antitussive drugs. In this review, the pathophysiological mechanisms of cough and the development of novel antitussive drugs are reviewed.

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

    PubMed

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

    2016-09-01

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

  15. Molecular cloning of the tomato Hairless gene implicates actin dynamics in trichome-mediated defense and mechanical properties of stem tissue

    PubMed Central

    Kang, Jin-Ho; Campos, Marcelo L.; Zemelis-Durfee, Starla; Al-Haddad, Jameel M.; Jones, A. Daniel; Telewski, Frank W.; Brandizzi, Federica; Howe, Gregg A.

    2016-01-01

    Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta. Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290. The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1. PMID:27481446

  16. Molecular cloning of the tomato Hairless gene implicates actin dynamics in trichome-mediated defense and mechanical properties of stem tissue.

    PubMed

    Kang, Jin-Ho; Campos, Marcelo L; Zemelis-Durfee, Starla; Al-Haddad, Jameel M; Jones, A Daniel; Telewski, Frank W; Brandizzi, Federica; Howe, Gregg A

    2016-10-01

    Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290 The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1.

  17. Incidences of Deep Vein Thrombosis and Pulmonary Embolism after Total Knee Arthroplasty Using a Mechanical Compression Device with and without Low-Molecular-Weight Heparin

    PubMed Central

    Park, Sin Hyung; Ahn, Joong Hyeon; Park, Yong Bok; Lee, Sun Geun

    2016-01-01

    Purpose To investigate the incidence of thromboembolic events and complications related to bleeding after total knee arthroplasty (TKA) with a mechanical compression device alone or in combination with low-molecular-weight heparin (LMWH). Materials and Methods A total of 489 TKA patients (776 knees) were retrospectively reviewed for the incidence of thromboembolic events and complications related to bleeding. While 233 patients (354 knees) were treated with a mechanical compressive device without LMWH, 256 patients (422 knees) were treated with the mechanical compressive device along with LMWH. Results The incidences of deep vein thrombosis (DVT) and pulmonary embolism (PE) were 15 of 375 knees (4.0%) and 5 of 375 knees (1.3%), respectively, in the group that used only a mechanical compressive device, and 14 of 401 knees (3.4%) and 5 of 401 knees (1.2%), respectively, in the group that used the mechanical compressive device with LMWH. There was no significant difference between the two groups (p=0.125 and p=0.146, respectively). The postoperative hemovac drainage amount was 635±57 mL in the group with a mechanical compressive device only and 813±84 mL in the group with the device and LMWH; therefore, the amount of drainage was significantly greater in the latter group (p=0.013). Conclusions Mechanical compression alone for prophylaxis against DVT and PE after TKA can be an attractive option in Korean patients. PMID:27595075

  18. Pulmonary Embolism

    MedlinePlus

    ... for the Public » Health Topics » Pulmonary Embolism Explore Pulmonary Embolism What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia Deep Vein Thrombosis Lung VQ Scan Overweight and Obesity Send a ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Qiu, Wenping; Feechan, Angela; Dry, Ian

    2015-01-01

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

  1. Effect of delta-9-tetrahydrocannabinol on altered antioxidative enzyme defense mechanisms and lipid peroxidation in mice testes.

    PubMed

    Mandal, Tapas Kumar; Das, Niladri Sekhar

    2009-04-01

    The present study examined the adverse effects of delta-9-tetrahydrocannabinol (i.p injection in albino mice) on free radical damage of testicular lipids (lipid peroxidation) at low doses and the role of antioxidant enzymes defense system at high dose and particularly at the withdrawal of the drug after applying higher dose (recovery dose). At lower doses (total doses ranging from 6 mg to 28 mg), there was a significant increase of lipid peroxidation and decrease in testicular lipid content. But the effects were slightly lowered at high dose (total dose 70 mg) and at the withdrawal of the drug (recovery dose). Similarly, marked decrease of antioxidant enzyme systems (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione content were noticed at low doses. But the effects were slightly higher at high dose and at the withdrawal of the drug. Similarly, low-dose treatments caused significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis resulting in lowered plasma testosterone and pituitary gonadotropins (follicular stimulating and luteinizing hormone levels. But at high dose and particularly at withdrawal of the drug, regression of seminiferous tubules and recovery of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins were observed.

  2. Disentangling detoxification: gene expression analysis of feeding mountain pine beetle illuminates molecular-level host chemical defense detoxification mechanisms.

    PubMed

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

    2013-01-01

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

  3. Pulmonary blastomycosis.

    PubMed

    Bariola, J Ryan; Vyas, Keyur S

    2011-12-01

    Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.

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

    SciTech Connect

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

    2012-07-01

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

  5. Negative-Pressure Pulmonary Edema.

    PubMed

    Bhattacharya, Mallar; Kallet, Richard H; Ware, Lorraine B; Matthay, Michael A

    2016-10-01

    Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema.

  6. Sensory irritation and pulmonary irritation of cumene and n-propanol: mechanisms of receptor activation and desensitization.

    PubMed

    Kristiansen, U; Hansen, L; Nielsen, G D; Holst, E

    1986-07-01

    Cumene and n-propanol, model substances for alcohols and alkylbenzenes, were investigated for sensory irritation in mice. The concentrations within the first 2 min. depressing the respiratory rate by 50% due to the effect in the upper respiratory tract were 2,058 p.p.m. and 22,080 p.p.m., respectively. Activation of the sensory irritant receptor followed the dynamics of reversible bimolecular reactions. The extrapolated maximum response and the apparent dissociation constant were 114.3% and 2,723 p.p.m. for cumene and 68.4% and 8,178 p.p.m. for propanol, respectively. Later on desensitization was observed. The effect was weak for cumene but conspicuous for propanol. For cumene desensitization had the origin in the rise of a threshold. No change in the dissociation constant or the maximum response was found. For propanol a decrease in the maximum response, which may be explained by an allosteric effect, was observed. The pulmonary irritation response was weak for cumene but was for propanol more important than sensory irritation at high concentrations. The following hypotheses are put forward: the effect of pulmonary irritation on the tidal volume is mediated via the stretch receptors while the effect on the respiratory frequency is mediated via the J-receptors.

  7. Effect of miR-23a on anoxia-induced phenotypic transformation of smooth muscle cells of rat pulmonary arteries and regulatory mechanism

    PubMed Central

    Yan, Li; Gao, Haixiang; Li, Chunzhi; Han, Xiaowen; Qi, Xiaoyong

    2017-01-01

    We investigated the possible implication of miR-23a in anoxia-induced phenotypic transformation of the pulmonary arterial smooth muscle and studied the mechanism of upregulation of miR-23a expression in anoxia. The collagenase digestion method was used for preparing rat primary pulmonary artery smooth muscle cell (PASMC) culture. SM-MHC, SM-α-actin, calponin-1 and SM22α protein expression levels were evaluated using western blot analysis after the ASMCs were subjected to anoxia treatment (3% O2). Transfection with miR-23a mimics were conducted when PASMCs were under normoxia and anoxia conditions. EdU staining was used to detect the proliferative activity of PASMCs. Cells were transfected with HIF-1α specific siRNA under anoxia condition. RT-qPCR was used to detect miR-23a expression in PASMCs. Chromatin immunoprecipitation method was employed to verify the binding sites of HIF-1α. The dual-luciferase reporter gene was used to study the role of HIF-1 and its binding sites. Rat hypoxic pulmonary hypertension models were established to study the expression of miR-23a using RT-qPCR method and to verify the expression of miR-23a in the arteriole of the rat pulmonary. Our results showed that compared with normoxia condition, under anoxia condition (3% O2), the expression levels of the contractile phenotype marker proteins decreased significantly after 24 and 48 h. The positive rate of the EdU staining increased significantly and the expression of miR-23a increased. Transfection with miR-23a-mimic downregulated the expression of contractile marker proteins and improved the positive rate of the EdU staining under normoxia. Anoxia and transfection with HIF-1α enhanced the activity of the wild-type Luc-miR-23a-1 (WT) reporter gene. We concluded that miR-23a participated in the anoxia-induced phenotypic transformation of PASMCs. Increased expression of miR-23a under anoxia may primarily be due to miR-23a-1 and miR-23a-3 upregulation. The anoxia-induced upregulation of

  8. Evaluation of hydroxyapatite-bioglass and hydroxyapatite-ethyl vinyl acetate composite extracts on antioxidant defense mechanism and genotoxicity: an in vitro study.

    PubMed

    Arun, M; Silja, P K; Mohanan, P V

    2011-09-01

    Hydroxyapatite-bioglass (HA BG) and hydroxyapatite-ethyl vinyl acetate (HA EVA) are two composite materials that have been developed for bone substitution. Their activity on antioxidant defense mechanism and genotoxicity has not been investigated before. To further confirm its biocompatibility, the present study was undertaken to investigate the effect of HA BG and HA EVA on mice liver antioxidant mechanism along with chromosomal aberrations in human lymphocytes. Physiological saline extract of HA BG and HA EVA showed no adverse effect on liver antioxidant mechanism compared to the cyclophosphamide (CP)-induced toxicity on mice liver homogenate. The results were judged from the in vitro studies made on reduced glutathione, glutathione reductase and lipid peroxidation. These results were well supported by CP- and mytomycin C (MC)-induced genotoxicity studies on human lymphocytes in the presence and absence of a metabolic activator (S9). Hence, it was suggested that these tests could be considered for preliminary toxicological screening of materials intended for clinical applications ahead of in vivo animal model evaluation.

  9. Response and Defense Mechanisms of Taxus chinensis Leaves Under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses.

    PubMed

    Zheng, Wen; Komatsu, Setsuko; Zhu, Wei; Zhang, Lin; Li, Ximin; Cui, Lei; Tian, Jingkui

    2016-09-01

    Taxus chinensis var. mairei is a species endemic to south-eastern China and one of the natural sources for the anticancer medicine paclitaxel. To investigate the molecular response and defense mechanisms of T. chinensis leaves to enhanced ultraviolet-A (UV-A) radiation, gel-free/label-free and gel-based proteomics and gas chromatography-mass spectrometry (GC-MS) analyses were performed. The transmission electron microscopy results indicated damage to the chloroplast under UV-A radiation. Proteomics analyses in leaves and chloroplasts showed that photosynthesis-, glycolysis-, secondary metabolism-, stress-, and protein synthesis-, degradation- and activation-related systems were mainly changed under UV-A radiation. Forty-seven PSII proteins and six PSI proteins were identified as being changed in leaves and chloroplasts under UV-A treatment. This indicated that PSII was more sensitive to UV-A than PSI as the target of UV-A light. Enhanced glycolysis, with four glycolysis-related key enzymes increased, provided precursors for secondary metabolism. The 1-deoxy-d-xylulose-5-phosphate reductoisomerase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were identified as being significantly increased during UV-A radiation, which resulted in paclitaxel enhancement. Additionally, mRNA expression levels of genes involved in the paclitaxel biosynthetic pathway indicated a down-regulation under UV-A irradiation and up-regulation in dark incubation. These results reveal that a short-term high dose of UV-A radiation could stimulate the plant stress defense system and paclitaxel production.

  10. [Effect of methylphenidatum on inspiratory muscles function in patients with chronic obstructive pulmonary disease and its mechanism].

    PubMed

    Wang, Y; Luo, Y; Chen, W; Yuan, Y; He, T; Zeng, J

    1997-03-01

    To have a better understanding of the effect of methylphenidatum on inspiratory muscles function, we studied the respiratory force parameters of 70 patients with chronic obstructive pulmonary disease by intravenous infusion methylphenidatum in a randomized controlled clinical trial. The indices of respiratory force parameter included maximal inspiratory mouth pressure (MIP), maximal midinspiratory flow (MMIF), forced inspiratory capacity (FIC), maximal works of inspiration (Wimax) and airway occlusion pressure (P0.1), etc. Aminophylline and Nikethamidi were chosen as controls. The results showed that MIP, MMIF, FIC, Wimax, P0.1 and minute ventilation (Vr) were significantly increased after administration of methylphenidatum and aminophylline. There were no significant differences in MIP, MMIF, FIC and Wimax after administration of Nikethamidi, but P0.1 was significantly increased and the increase was higher than that after administration of methylphenidatum and aminophylline groups. We conclude that methylphenidatum can significantly improve the function of inspiratory muscles as aminophylline can do.

  11. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis The most common species of fungus that causes ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 7/31/2016 Updated by: Jatin ...

  12. Pulmonary atresia

    MedlinePlus

    ... blood flow from the right ventricle (right side pumping chamber) to the lungs. In pulmonary atresia, a ... Reconstructing the heart as a single ventricle (1 pumping chamber instead of 2) Heart transplant Outlook (Prognosis) ...

  13. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  14. Pulmonary Agenesis.

    PubMed

    Chawla, Rakesh K; Madan, Arun; Chawla, Aditya; Arora, Harsh Nandini; Chawla, Kiran

    2015-01-01

    Unilateral opaque lung with ipsilateral mediastinal shift is an uncommon cause of respiratory distress in newborn which can be found on simple radiograph of the chest. Pulmonary agenesis is a rare cause of unilateral opaque lung in the newborn. Nearly 50% cases of pulmonary agenesis are associated with other congenital defects including cardiovascular, skeletal, gastrointestinal or genitourinary systems. We report an infant with agenesis of the right lung associated with other congenital anomalies.

  15. Modelling pulmonary blood flow.

    PubMed

    Tawhai, Merryn H; Burrowes, Kelly S

    2008-11-30

    Computational model analysis has been used widely to understand and interpret complexity of interactions in the pulmonary system. Pulmonary blood transport is a multi-scale phenomenon that involves scale-dependent structure and function, therefore requiring different model assumptions for the microcirculation and the arterial or venous flows. The blood transport systems interact with the surrounding lung tissue, and are dependent on hydrostatic pressure gradients, control of vasoconstriction, and the topology and material composition of the vascular trees. This review focuses on computational models that have been developed to study the different mechanisms contributing to regional perfusion of the lung. Different models for the microcirculation and the pulmonary arteries are considered, including fractal approaches and anatomically-based methods. The studies that are reviewed illustrate the different complementary approaches that can be used to address the same physiological question of flow heterogeneity.

  16. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema.

    PubMed

    Chilosi, Marco; Carloni, Angelo; Rossi, Andrea; Poletti, Venerino

    2013-09-01

    Different anatomic and physiological changes occur in the lung of aging people that can affect pulmonary functions, and different pulmonary diseases, including deadly diseases such as chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF), can be related to an acceleration of the aging process. The individual genetic background, as well as exposure to a variety of toxic substances (cigarette smoke in primis) can contribute significantly to accelerating pulmonary senescence. Premature aging can impair lung function by different ways: by interfering specifically with tissue repair mechanisms after damage, thus perturbing the correct crosstalk between mesenchymal and epithelial components; by inducing systemic and/or local alteration of the immune system, thus impairing the complex mechanisms of lung defense against infections; and by stimulating a local and/or systemic inflammatory condition (inflammaging). According to recently proposed pathogenic models in COPD and IPF, premature cellular senescence likely affects distinct progenitors cells (mesenchymal stem cells in COPD, alveolar epithelial precursors in IPF), leading to stem cell exhaustion. In this review, the large amount of data supporting this pathogenic view are discussed, with emphasis on the possible molecular and cellular mechanisms leading to the severe parenchymal remodeling that characterizes, in different ways, these deadly diseases.

  17. Elucidation of the Mechanism by Which Catecholamine Stress Hormones Liberate Iron from the Innate Immune Defense Proteins Transferrin and Lactoferrin ▿

    PubMed Central

    Sandrini, Sara M.; Shergill, Raminder; Woodward, Jonathan; Muralikuttan, Remya; Haigh, Richard D.; Lyte, Mark; Freestone, Primrose P.

    2010-01-01

    The ability of catecholamine stress hormones and inotropes to stimulate the growth of infectious bacteria is now well established. A major element of the growth induction process has been shown to involve the catecholamines binding to the high-affinity ferric-iron-binding proteins transferrin (Tf) and lactoferrin, which then enables bacterial acquisition of normally inaccessible sequestered host iron. The nature of the mechanism(s) by which the stress hormones perturb iron binding of these key innate immune defense proteins has not been fully elucidated. The present study employed electron paramagnetic resonance spectroscopy and chemical iron-binding analyses to demonstrate that catecholamine stress hormones form direct complexes with the ferric iron within transferrin and lactoferrin. Moreover, these complexes were shown to result in the reduction of Fe(III) to Fe(II) and the loss of protein-complexed iron. The use of bacterial ferric iron uptake mutants further showed that both the Fe(II) and Fe(III) released from the Tf could be directly used as bacterial nutrient sources. We also analyzed the transferrin-catecholamine interactions in human serum and found that therapeutically relevant concentrations of stress hormones and inotropes could directly affect the iron binding of serum-transferrin so that the normally highly bacteriostatic tissue fluid became significantly more supportive of the growth of bacteria. The relevance of these catecholamine-transferrin/lactoferrin interactions to the infectious disease process is considered. PMID:19820086

  18. (1)H NMR and GC-MS Based Metabolomics Reveal Defense and Detoxification Mechanism of Cucumber Plant under Nano-Cu Stress.

    PubMed

    Zhao, Lijuan; Huang, Yuxiong; Hu, Jerry; Zhou, Hongjun; Adeleye, Adeyemi S; Keller, Arturo A

    2016-02-16

    Because copper nanoparticles are being increasingly used in agriculture as pesticides, it is important to assess their potential implications for agriculture. Concerns have been raised about the bioaccumulation of nano-Cu and their toxicity to crop plants. Here, the response of cucumber plants in hydroponic culture at early development stages to two concentrations of nano-Cu (10 and 20 mg/L) was evaluated by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and gas chromatography-mass spectrometry (GC-MS) based metabolomics. Changes in mineral nutrient metabolism induced by nano-Cu were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Results showed that nano-Cu at both concentrations interferes with the uptake of a number of micro- and macro-nutrients, such as Na, P, S, Mo, Zn, and Fe. Metabolomics data revealed that nano-Cu at both levels triggered significant metabolic changes in cucumber leaves and root exudates. The root exudate metabolic changes revealed an active defense mechanism against nano-Cu stress: up-regulation of amino acids to sequester/exclude Cu/nano-Cu; down-regulation of citric acid to reduce the mobilization of Cu ions; ascorbic acid up-regulation to combat reactive oxygen species; and up-regulation of phenolic compounds to improve antioxidant system. Thus, we demonstrate that nontargeted (1)H NMR and GC-MS based metabolomics can successfully identify physiological responses induced by nanoparticles. Root exudates metabolomics revealed important detoxification mechanisms.

  19. Diseases of Pulmonary Surfactant Homeostasis

    PubMed Central

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

  20. The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms.

    PubMed

    Athanasopoulos, Athanasios N; Economopoulou, Matina; Orlova, Valeria V; Sobke, Astrid; Schneider, Darius; Weber, Holger; Augustin, Hellmut G; Eming, Sabine A; Schubert, Uwe; Linn, Thomas; Nawroth, Peter P; Hussain, Muzaffar; Hammes, Hans-Peter; Herrmann, Mathias; Preissner, Klaus T; Chavakis, Triantafyllos

    2006-04-01

    Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus-infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presence of wild-type S aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alphav-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S aureus-infected wounds. Eap may also serve as a lead compound for new anti-inflammatory and antiangiogenic therapies in several pathologies.

  1. Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors.

    PubMed

    Walter, Robert Fred Henry; Vollbrecht, Claudia; Christoph, Daniel; Werner, Robert; Schmeller, Jan; Flom, Elena; Trakada, Georgia; Rapti, Aggeliki; Adamidis, Vasilis; Hohenforst-Schmidt, Wolfgang; Kollmeier, Jens; Mairinger, Thomas; Wohlschlaeger, Jeremias; Zarogoulidis, Paul; Porpodis, Konstantinos; Schmidt, Kurt Werner; Mairinger, Fabian Dominik

    2016-01-01

    Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.

  2. Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

    PubMed Central

    Walter, Robert Fred Henry; Vollbrecht, Claudia; Christoph, Daniel; Werner, Robert; Schmeller, Jan; Flom, Elena; Trakada, Georgia; Rapti, Aggeliki; Adamidis, Vasilis; Hohenforst-Schmidt, Wolfgang; Kollmeier, Jens; Mairinger, Thomas; Wohlschlaeger, Jeremias; Zarogoulidis, Paul; Porpodis, Konstantinos; Schmidt, Kurt Werner; Mairinger, Fabian Dominik

    2016-01-01

    Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors. PMID:27994651

  3. Pulmonary Vascular Impedance in Chronic Pulmonary Hypertension.

    DTIC Science & Technology

    PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA, PHYSIOLOGY.

  4. [Pulmonary infection by Geotrichum capitatum about a case and review of the literature].

    PubMed

    El-Hassani, I; Deham, H; Touaoussa, A; Er-Rami, M

    2014-12-01

    Pulmonary geotrichosis is a rare mycosis caused by an arthrospore filamentous fungi of the genus Geotrichum. It is an opportunistic infection that develops when underlying conditions are present, particularly immunosuppression including neutropenia. Pulmonary mycoses in non-neutropenic patients affect two main populations: the solid organ transplanted patients and patients whose local pulmonary defenses are altered by a chronic underlying lung pathology. We report a case of pulmonary infection Geotrichum capitatum in an old tuberculosis patient.

  5. Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

    PubMed

    Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

    2016-06-01

    Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response.

  6. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

    PubMed

    Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

    2015-09-01

    Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

  7. Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

    PubMed

    de Beer, F M; Aslami, H; Hoeksma, J; van Mierlo, G; Wouters, D; Zeerleder, S; Roelofs, J J T H; Juffermans, N P; Schultz, M J; Lagrand, W K

    2014-11-01

    Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.

  8. A Novel p38 Mitogen-activated Protein Kinase/Elk-1 Transcription Factor-dependent Molecular Mechanism Underlying Abnormal Endothelial Cell Proliferation in Plexogenic Pulmonary Arterial Hypertension*

    PubMed Central

    Patel, Monal; Predescu, Dan; Tandon, Rajive; Bardita, Cristina; Pogoriler, Jennifer; Bhorade, Sangeeta; Wang, Minhua; Comhair, Suzy; Ryan-Hemnes, Anna; Chen, Jiwang; Machado, Roberto; Husain, Aliya; Erzurum, Serpil; Predescu, Sanda

    2013-01-01

    Plexiform lesions (PLs), the hallmark of plexogenic pulmonary arterial hypertension (PAH), contain phenotypically altered, proliferative endothelial cells (ECs). The molecular mechanism that contributes to EC proliferation and formation of PLs is poorly understood. We now show that a decrease in intersectin-1s (ITSN-1s) expression due to granzyme B (GrB) cleavage during inflammation associated with PAH and the high p38/Erk1/2MAPK activity ratio caused by the GrB/ITSN cleavage products lead to EC proliferation and selection of a proliferative/plexiform EC phenotype. We used human pulmonary artery ECs of PAH subjects (ECPAH), paraffin-embedded and frozen human lung tissue, and animal models of PAH in conjunction with microscopy imaging, biochemical, and molecular biology approaches to demonstrate that GrB cleaves ITSN-1s, a prosurvival protein of lung ECs, and generates two biologically active fragments, an N-terminal fragment (GrB-EHITSN) with EC proliferative potential and a C-terminal product with dominant negative effects on Ras/Erk1/2. The proliferative potential of GrB-EHITSN is mediated via sustained phosphorylation of p38MAPK and Elk-1 transcription factor and abolished by chemical inhibition of p38MAPK. Moreover, lung tissue of PAH animal models and human specimens and ECPAH express lower levels of ITSN-1s compared with controls and the GrB-EHITSN cleavage product. Moreover, GrB immunoreactivity is associated with PLs in PAH lungs. The concurrent expression of the two cleavage products results in a high p38/Erk1/2MAPK activity ratio, which is critical for EC proliferation. Our findings identify a novel GrB-EHITSN-dependent pathogenic p38MAPK/Elk-1 signaling pathway involved in the poorly understood process of PL formation in severe PAH. PMID:23893408

  9. Effects of indacaterol versus tiotropium on respiratory mechanics assessed by the forced oscillation technique in patients with chronic obstructive pulmonary disease.

    PubMed

    Inui, Naoki; Matsushima, Sayomi; Kato, Shinpei; Yasui, Hideki; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Toyoshima, Mikio; Suda, Takafumi

    2015-01-01

    The forced oscillation technique (FOT) can measure respiratory mechanics and has attracted attention in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of only indacaterol and tiotropium monotherapies on airflow limitation and respiratory impedance. Pulmonary function tests, COPD assessment test (CAT), and multifrequency FOT with MostGraph-01 were performed at the beginning and after 8 weeks of treatment with indacaterol or tiotropium. The resistance index, resistance at 5 Hz (R5), resistance at 20 Hz (R20), reactance index, reactance at 5 Hz (X5), resonant frequency (Fres), and low-frequency reactance area (ALX) were determined at whole-breath, inspiratory, and expiratory phases. Eighty-two patients (mean age: 73 years; mean forced expiratory volume in 1 second (FEV1): 61.6%±19.0% predicted) were randomized to indacaterol or tiotropium treatment. Both bronchodilators improved airflow limitation, with mean trough improvements in FEV1 of 165 mL and 80 mL in the indacaterol and tiotropium groups, respectively. The CAT score decreased in the indacaterol group (P<0.001; 11.2±6.6 to 7.5±5.6). Compared with tiotropium, indacaterol significantly improved FEV1, percent predicted FEV1, and CAT score (P=0.042, P=0.008, and P=0.027, respectively). For respiratory impedance, indacaterol and tiotropium changed R5, X5, Fres, and ALX at whole-breath, inspiratory, and expiratory phases. In the indacaterol group, the changes in R5, R5-R20, X5, Fres, and ALX were significantly correlated with the changes in FEV1. The use of the FOT may enable the evaluation of the effects of bronchodilators in addition to FEV1-indicated therapeutic effects in COPD.

  10. A recessive resistance to rice yellow mottle virus is associated with a rice homolog of the CPR5 gene, a regulator of active defense mechanisms.

    PubMed

    Orjuela, Julie; Deless, E F Thiémélé; Kolade, Olufisayo; Chéron, Sophie; Ghesquière, Alain; Albar, Laurence

    2013-12-01

    RYMV2 is a major recessive resistance gene identified in cultivated African rice (Oryza glaberrima) which confers high resistance to the Rice yellow mottle virus (RYMV). We mapped RYMV2 in an approximately 30-kb interval in which four genes have been annotated. Sequencing of the candidate region in the resistant Tog7291 accession revealed a single mutation affecting a predicted gene, as compared with the RYMV-susceptible O. glaberrima CG14 reference sequence. This mutation was found to be a one-base deletion leading to a truncated and probably nonfunctional protein. It affected a gene homologous to the Arabidopsis thaliana CPR5 gene, known to be a defense mechanism regulator. Only seven O. glaberrima accessions showing this deletion were identified in a collection consisting of 417 accessions from three rice species. All seven accessions were resistant to RYMV, which is an additional argument in favor of the involvement of the deletion in resistance. In addition, fine mapping of a resistance quantitative trait locus in O. sativa advanced backcrossed lines pinpointed a 151-kb interval containing RYMV2, suggesting that allelic variants of the same gene may control both high and partial resistance.

  11. Lung epithelial MyD88 drives early pulmonary clearance of Pseudomonas aeruginosa by a flagellin dependent mechanism.

    PubMed

    Anas, Adam A; van Lieshout, Miriam H P; Claushuis, Theodora A M; de Vos, Alex F; Florquin, Sandrine; de Boer, Onno J; Hou, Baidong; Van't Veer, Cornelis; van der Poll, Tom

    2016-08-01

    Pseudomonas aeruginosa is a flagellated pathogen frequently causing pneumonia in hospitalized patients and sufferers of chronic lung disease. Here we investigated the role of the common Toll-like receptor (TLR) adaptor myeloid differentiation factor (MyD)88 in myeloid vs. lung epithelial cells in clearance of P. aeruginosa from the airways. Mice deficient for MyD88 in lung epithelial cells (Sftpccre-MyD88-lox mice) or myeloid cells (LysMcre-MyD88-lox mice) and bone marrow chimeric mice deficient for TLR5 (the receptor recognizing Pseudomonas flagellin) in either parenchymal or hematopoietic cells were infected with P. aeruginosa via the airways. Sftpccre-MyD88-lox mice demonstrated a reduced influx of neutrophils into the bronchoalveolar space and an impaired early antibacterial defense after infection with P. aeruginosa, whereas the response of LysMcre-MyD88-lox mice did not differ from control mice. The immune-enhancing role of epithelial MyD88 was dependent on recognition of pathogen-derived flagellin by epithelial TLR5, as demonstrated by an unaltered clearance of mutant P. aeruginosa lacking flagellin from the lungs of Sftpccre-MyD88-lox mice and an impaired bacterial clearance in bone marrow chimeric mice lacking TLR5 in parenchymal cells. These data indicate that early clearance of P. aeruginosa from the airways is dependent on flagellin-TLR5-MyD88-dependent signaling in respiratory epithelial cells.

  12. Secured network sensor-based defense system

    NASA Astrophysics Data System (ADS)

    Wei, Sixiao; Shen, Dan; Ge, Linqiang; Yu, Wei; Blasch, Erik P.; Pham, Khanh D.; Chen, Genshe

    2015-05-01

    Network sensor-based defense (NSD) systems have been widely used to defend against cyber threats. Nonetheless, if the adversary finds ways to identify the location of monitor sensors, the effectiveness of NSD systems can be reduced. In this paper, we propose both temporal and spatial perturbation based defense mechanisms to secure NSD systems and make the monitor sensor invisible to the adversary. The temporal-perturbation based defense manipulates the timing information of published data so that the probability of successfully recognizing monitor sensors can be reduced. The spatial-perturbation based defense dynamically redeploys monitor sensors in the network so that the adversary cannot obtain the complete information to recognize all of the monitor sensors. We carried out experiments using real-world traffic traces to evaluate the effectiveness of our proposed defense mechanisms. Our data shows that our proposed defense mechanisms can reduce the attack accuracy of recognizing detection sensors.

  13. Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study

    PubMed Central

    Xin, Xiaofeng; Dai, Wei; Wu, Jie; Fang, Liping; Zhao, Ming; Zhang, Pengpeng; Chen, Min

    2016-01-01

    The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens-1 (ZO-1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO-1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF-α, IFN-γ and IL-8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses. PMID:27588054

  14. Cardiovascular Function in Pulmonary Emphysema

    PubMed Central

    Visca, Dina; Aiello, Marina; Chetta, Alfredo

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function. PMID:24369007

  15. Cardiovascular function in pulmonary emphysema.

    PubMed

    Visca, Dina; Aiello, Marina; Chetta, Alfredo

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

  16. Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling.

    PubMed

    Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future.

  17. Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

    PubMed Central

    Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

  18. Characteristics and outcome of patients with difficult weaning from mechanical ventilation: an 18 years’ experience of a respiratory intermediate unit attached to a pulmonary department

    PubMed Central

    Tsara, V; Moisiadis, N; Antoniadou, M; Serasli, E

    2015-01-01

    Background: Respiratory dysfunction often persists in post intensive care unit (ICU) patients and intermediate care facilities have been established to ensure the continuous of appropriate care. Methods: The data of patients with difficult weaning from mechanical ventilation admitted to a respiratory intermediate unit (RIU) attached to a pulmonary department of a General Hospital, were retrospectively analyzed. Clinical characteristics, weaning from mechanical ventilation and tracheostomy, ICU readmission and RIU mortality were examined over a period of 18 years (1993- 2010) that was randomly divided into three six-year-periods. Results: A total of 548 patients (age 56.7±17.9 years) [mean ± standard deviation (SD)], of whom 80% with tracheostomy in place and 37.6% with pressure ulcers, were examined. The ICU stay was 30.1±24.7 days (mean ± SD) and increased over time (p<0.05). Patients’ baseline disorders were: chronic respiratory disease (41.3%), chronic cardiovascular diseases (10.6%), neuromuscular disease (22.8%) and miscellaneous (25.3%). The length of RIU stay (22.8±19.5 days) was constant over the examined periods but an increase in age and maintenance of tracheostomy were observed; 80% of patients were liberated from mechanical ventilation and 58.5% from tracheostomy, whereas the RIU mortality was 15%. Conclusion: In their vast majority patients with chronic respiratory failure, who were admitted to RIU,were weaned from mechanical ventilation, although in a substantial percentage the maintenance of tracheostomy was mandatory after discharge. Hippokratia 2015, 19 (1): 37-40. PMID:26435645

  19. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    PubMed Central

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  20. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

    PubMed

    Jiang, Chunling; Qian, Hong; Luo, Shuhua; Lin, Jing; Yu, Jerry; Li, Yajiao; An, Qi; Luo, Nanfu; Du, Lei

    2017-05-01

    Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

  1. Mechanisms of Attenuation of Pulmonary V’O2 Slow Component in Humans after Prolonged Endurance Training

    PubMed Central

    Zoladz, Jerzy A.; Majerczak, Joanna; Grassi, Bruno; Szkutnik, Zbigniew; Korostyński, Michał; Gołda, Sławomir; Grandys, Marcin; Jarmuszkiewicz, Wiesława; Kilarski, Wincenty; Karasinski, Janusz; Korzeniewski, Bernard

    2016-01-01

    In this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V’O2) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean±SD: age 22.33±1.44 years, V’O2peak 3198±458 mL ∙ min-1) performed an endurance training composed mainly of moderate-intensity cycling, lasting 20 weeks. Training resulted in a decrease (by ~5%, P = 0.027) in V’O2 during prior low-intensity exercise (20 W) and in shortening of τp of the V’O2 on-kinetics (30.1±5.9 s vs. 25.4±1.5 s, P = 0.007) during subsequent heavy-intensity cycling. This was accompanied by a decrease of the slow component of V’O2 on-kinetics by 49% (P = 0.001) and a decrease in the end-exercise V’O2 by ~5% (P = 0.005). An increase (P = 0.02) in the vascular endothelial growth factor receptor 2 mRNA level and a tendency (P = 0.06) to higher capillary-to-fiber ratio in the vastus lateralis muscle were found after training (n = 11). No significant effect of training on the V’O2peak was found (P = 0.12). However, the power output reached at the lactate threshold increased by 19% (P = 0.01). The power output obtained at the V’O2peak increased by 14% (P = 0.003) and the time of 1,500-m performance decreased by 5% (P = 0.001). Computer modeling of the skeletal muscle bioenergetic system suggests that the training-induced decrease in the slow component of V’O2 on-kinetics found in the present study is mainly caused by two factors: an intensification of the each-step activation (ESA) of oxidative phosphorylation (OXPHOS) complexes after training and decrease in the ‘‘additional” ATP usage rising gradually during heavy-intensity exercise. PMID:27104346

  2. PULMONARY TOXICOLOGY

    EPA Science Inventory

    Pulmonary disease and dysfunction exact a tremendous health burden on society. In a recent survey of lung disease published by the American Lung Association in 2012, upwards of 10 million Americans were diagnosed with chronic bronchitis while over 4 million Americans had emphysem...

  3. Defense Mechanisms of Conifers 1

    PubMed Central

    Lewinsohn, Efraim; Gijzen, Mark; Croteau, Rodney

    1991-01-01

    Levels of monoterpene cyclase activity were determined in extracts from wounded and unwounded saplings of 10 conifer species to assess whether oleoresin biosynthesis is induced by stem wounding. Species of Abies and Picea, with low to moderate levels of constitutive monoterpene cyclase activity, exhibited a five- to 15-fold increase in cyclase activity 7 days after wounding relative to unwounded controls. In contrast, species of genera such as Pinus, with high levels of constitutive cyclase activity, did not significantly respond to wounding by alteration in the level of cyclase activity. The highest fold increase in monoterpene cyclase activity was consistently observed in Abies grandis, and the time-course of induction of activity following stem wounding in this species demonstrated a threefold increase at 2 days relative to unwounded controls, rising to a maximum increase in the response at 9 days (greater than 10-fold) followed by an apparent decline. The wound response was localized, and both bark (phloem) and wood (xylem) tissues displayed increased cyclase activity at the wound site. The magnitude of the increase in cyclase activity was dependent on the severity of the wound. PMID:16668184

  4. Defense Mechanisms of Conifers 1

    PubMed Central

    Lewinsohn, Efraim; Gijzen, Mark; Savage, Thomas J.; Croteau, Rodney

    1991-01-01

    Cell-free extracts from Pinus ponderosa Lawson (ponderosa pine) and Pinus sylvestris L. (Scotch pine) wood exhibited high levels of monoterpene synthase (cyclase) activity, whereas bark extracts of these species contained no detectable activity, and they inhibited cyclase activity when added to extracts from wood, unless polyvinylpyrrolidone was included in the preparation. The molecular mass of the polyvinylpyrrolidone added was of little consequence; however, polyvinylpolypyrrolidone (a cross-linked insoluble form of the polymer) was ineffective in protecting enzyme activity. Based on these observations, methods were developed for the efficient extraction and assay of monoterpene cyclase activity from conifer stem (wood and bark) tissue. The level of monoterpene cyclase activity for a given conifer species was shown to correlate closely with the monoterpene content of the oleoresin and with the degree of anatomical complexity of the specialized resin-secreting structures. Cyclase activity and monoterpene content were lowest in the stems of species containing only isolated resin cells, such as western red cedar (Thuja plicata D. Don). Increasing levels of cyclase activity and oleoresin monoterpenes were observed in advancing from species with multicellular resin blisters (true firs [Abies]) to those with organized resin passages, such as western larch (Larix occidentalis Nutt.), Colorado blue spruce (Picea pungens Engelm.) and Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco). The highest levels of cyclase activity and oleoresin monoterpenes were noted in Pinus species that contain the most highly developed resin duct systems. The relationship between biosynthetic capacity, as measured by cyclase activity, monoterpene content, and the degree of organization of the secretory structures for a given species, may reflect the total number of specialized resin-producing cells per unit mass of stem tissue. PMID:16668182

  5. Regulation of the Arabidopsis defense transcriptome.

    PubMed

    Eulgem, Thomas

    2005-02-01

    Transcriptional re-programming is a key step of plant defense in response to pathogen recognition. Microarray analyses combined with genetic and biochemical approaches are now enabling us to study basic principles and details of regulatory mechanisms controlling the defense transcriptome in Arabidopsis. Recent results show that signaling pathways used by different defense systems converge and target overlapping gene sets. Furthermore, a quantitative mechanism common to multiple defense systems modulates transcript levels of these defense-associated genes. Most importantly, some transcription factors have been proven to play a pivotal role in disease resistance. Regulatory circuits linking signaling and gene regulation are emerging, suggesting that a complex interplay of transcriptional activators and repressors fine-tunes expression of the defense transcriptome.

  6. The Sweet Potato NAC-Domain Transcription Factor IbNAC1 Is Dynamically Coordinated by the Activator IbbHLH3 and the Repressor IbbHLH4 to Reprogram the Defense Mechanism against Wounding

    PubMed Central

    Chen, Shi-Peng; Kuo, Chih-Hsien; Lu, Hsueh-Han; Lo, Hui-Shan; Yeh, Kai-Wun

    2016-01-01

    IbNAC1 is known to activate the defense system by reprogramming a genetic network against herbivory in sweet potato. This regulatory activity elevates plant defense potential but relatively weakens plants by IbNAC1-mediated JA response. The mechanism controlling IbNAC1 expression to balance plant vitality and survival remains unclear. In this study, a wound-responsive G-box cis-element in the IbNAC1 promoter from -1484 to -1479 bp was identified. From a screen of wound-activated transcriptomic data, one transcriptional activator, IbbHLH3, and one repressor, IbbHLH4, were selected that bind to and activate or repress, respectively, the G-box motif in the IbNAC1 promoter to modulate the IbNAC1-mediated response. In the early wound response, the IbbHLH3-IbbHLH3 protein complex binds to the G-box motif to activate IbNAC1 expression. Thus, an elegant defense network is activated against wounding stress. Until the late stages of wounding, IbbHLH4 interacts with IbbHLH3, and the IbbHLH3-IbbHLH4 heterodimer competes with the IbbHLH3-IbbHLH3 complex to bind the G-box and suppress IbNAC1 expression and timely terminates the defense network. Moreover, the JAZs and IbEIL1 proteins interact with IbbHLH3 to repress the transactivation function of IbbHLH3 in non-wounded condition, but their transcription is immediately inhibited upon early wounding. Our work provides a genetic model that accurately switches the regulatory mechanism of IbNAC1 expression to adjust wounding physiology and represents a delicate defense regulatory network in plants. PMID:27780204

  7. Heart‐Specific Overexpression of Choline Acetyltransferase Gene Protects Murine Heart Against Ischemia Through Hypoxia‐Inducible Factor‐1α–Related Defense Mechanisms

    PubMed Central

    Kakinuma, Yoshihiko; Tsuda, Masayuki; Okazaki, Kayo; Akiyama, Tsuyoshi; Arikawa, Mikihiko; Noguchi, Tatsuya; Sato, Takayuki

    2013-01-01

    Background Murine and human ventricular cardiomyocytes rich in acetylcholine (Ach) receptors are poorly innervated by the vagus, compared with whole ventricular innervation by the adrenergic nerve. However, vagal nerve stimulation produces a favorable outcome even in the murine heart, despite relatively low ventricular cholinergic nerve density. Such a mismatch and missing link suggest the existence of a nonneuronal cholinergic system in ventricular myocardium. Methods and Results To examine the role of the nonneuronal cardiac cholinergic system, we generated choline acetyltransferase (ChAT)–expressing cells and heart‐specific ChAT transgenic (ChAT‐tg) mice. Compared with cardiomyocytes of wild‐type (WT) mice, those of the ChAT‐tg mice had high levels of ACh and hypoxia‐inducible factor (HIF)‐1α protein and augmented glucose uptake. These phenotypes were also reproduced by ChAT‐overexpressing cells, which utilized oxygen less. Before myocardial infarction (MI), the WT and ChAT‐tg mice showed similar hemodynamics; after MI, however, the ChAT‐tg mice had better survival than did the WT mice. In the ChAT‐tg hearts, accelerated angiogenesis at the ischemic area, and accentuated glucose utilization prevented post‐MI remodeling. The ChAT‐tg heart was more resistant to ischemia–reperfusion injury than was the WT heart. Conclusions These results suggest that the activated cardiac ACh‐HIF‐1α cascade improves survival after MI. We conclude that de novo synthesis of ACh in cardiomyocytes is a pivotal mechanism for self‐defense against ischemia. PMID:23525439

  8. The reproductive toxicity on the rotifer Brachionus plicatilis induced by BDE-47 and studies on the effective mechanism based on antioxidant defense system changes.

    PubMed

    Wang, Hong; Tang, Xuexi; Sha, Jingjing; Chen, Hongmei; Sun, Tianli; Wang, You

    2015-09-01

    2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a low-brominated Tetra-BDE that is widely distributed in the marine ecosystem, was selected to investigate the reproductive toxicity on the rotifer, Brachionus plicatilis, and the possible mechanism based on antioxidant defense system changes were studied. The results showed the following: (1) A low concentration of BDE-47 had a slight effect on the egg production of individual females and the egg production rate (EPR) of the population. In fact, BDE-47 exerted reproductive inhibition effects in a time- and concentration-dependent manner. The obtained life tables indicated that BDE-47 at a high concentration prolonged the generation time, whereas low and moderate concentrations of BDE-47 had the opposite effects. BDE-47 at a medium concentration significantly decreased the life expectancy and net reproductive rate (P<0.05). Additionally, a high concentration of BDE-47 markedly decreased the net reproductive rate and intrinsic increase rate (P<0.05). The ultra-structure of the ovary showed that BDE-47 severely damaged the ovary. (2) BDE-47 stress elevated the ROS level in B. plicatilis. The GST activity was induced significantly by the low concentration of BDE-47 and inhibited by the highest concentration tested. The GPx activity and GSH content were significant decreased in all the tested groups, and GR activity was induced. GST and GSH appeared to be sensitive to oxidative stress, and all of the glutathione-related enzymes were found to play an important role in maintaining the antioxidant/pro-oxidant balance based on Pearson's correlation analysis. The results indicated that BDE-47 causes reproductive toxicity in B. plicatilis and that the ROS-mediated pathway is responsible for the observed toxicity.

  9. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages

    SciTech Connect

    Skornik, W.A.; Brain, J.D.

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (/sup 198/Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC/sub 50/) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m/sup 3/), zinc sulfate (greater than or equal to 3.1 mg/m/sup 3/), ferric sulfate (greater than or equal to 7.8 mg/m/sup 3/), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m/sup 3/), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m/sup 3/ cupric sulfate or 9.8 mg/m/sup 3/ ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC/sub 50/ values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  10. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages.

    PubMed

    Skornik, W A; Brain, J D

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (198Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC50) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m3), zinc sulfate (greater than or equal to 3.1 mg/m3), ferric sulfate (greater than or equal to 7.8 mg/m3), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m3), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m3 cupric sulfate or 9.8 mg/m3 ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC50 values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  11. Mediator mechanisms involved in TRPV1, TRPA1 and P2X receptor-mediated sensory transduction of pulmonary ROS by vagal lung C-fibers in rats.

    PubMed

    Lin, Yu-Jung; Hsu, Hsao-Hsun; Ruan, Ting; Kou, Yu Ru

    2013-10-01

    We investigated the mediator mechanisms involved in the sensory transduction of pulmonary reactive oxygen species (ROS) by vagal lung C-fibers in anesthetized rats. Airway challenge of aerosolized H₂O₂ (0.4%) stimulated these afferent fibers. The H₂O₂-induced responses were reduced by a cyclooxygenase inhibitor or ATP scavengers and also attenuated by an antagonist of TRPV1, TRPA1 or P2X receptors. The suppressive effect of the cyclooxygenase inhibitor was not affected by a combined treatment with the TRPV1 or TRPA1 antagonist, but was amplified by a combined treatment with the P2X antagonists. The suppressive effect of ATP scavengers was not affected by a combined treatment with the P2X antagonist, but was amplified by a combined treatment with the TRPV1 or TRPA1 antagonist. Thus, the actions of cyclooxygenase metabolites are mediated through the functioning of the TRPV1 and TRPA1 receptors, whereas the action of ATP is mediated through the functioning of P2X receptors.

  12. Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM)

    PubMed Central

    Burrowes, K. S.; De Backer, J.; Smallwood, R.; Sterk, P. J.; Gut, I.; Wirix-Speetjens, R.; Siddiqui, S.; Owers-Bradley, J.; Wild, J.; Maier, D.; Brightling, C.

    2013-01-01

    The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium (Airway disease Predicting Outcomes through patient-specific computational Modelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD. PMID:24427517

  13. Pulmonary function in space

    NASA Technical Reports Server (NTRS)

    West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

    1997-01-01

    The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

  14. Pulmonary Hypertension: Types and Treatments

    PubMed Central

    Rose-Jones, Lisa J; Mclaughlin, Vallerie V

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmo-nary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario. PMID:24251459

  15. Non-invasive mechanical ventilation in the treatment of acute respiratory failure in chronic obstructive pulmonary disease.

    PubMed

    Ambrosino, N; Nava, S; Rubini, F

    1993-01-01

    Acute respiratory failure is usually managed by means of mechanical ventilation via an endotracheal tube or tracheostomy, when conservative treatment fails. Invasive mechanical ventilation is associated with several complications. The recent development of non-invasive methods of ventilation, has led to an attempt to avoid the complications of invasive mechanical ventilation during episodes of acute respiratory failure, ensuring at the same time a similar degree of efficacy. Both intermittent negative pressure ventilation and positive pressure ventilation by face or nasal mask have recently been used for this purpose. Negative pressure ventilation by means of iron lung, cuirass or poncho-wrap ventilators, has never been used in place of endotracheal intubation, and studies of this kind of ventilation are inconclusive: as a consequence, there is, at the moment, no indication for the generalized use of negative pressure ventilation in acute respiratory failure. Intermittent positive pressure ventilation by facial or nasal masks, has recently been used in the treatment of respiratory failure in place of endotracheal intubation. The results are promising, but remain controversial. It may be attempted in selected patients with obstructive respiratory disorders, but the procedure is very time-consuming for nurses.

  16. Inhibition of murine renal carcinoma pulmonary metastases by systemic administration of interferon gamma: mechanism of action and potential for combination with interleukin 4.

    PubMed

    Hillman, G G; Younes, E; Visscher, D; Hamzavi, F; Kim, S; Lam, J S; Montecillo, E J; Ali, E; Pontes, J E; Puri, R K; Haas, G P

    1997-10-01

    pulmonary metastases, probably due to different antitumor mechanisms induced by these two cytokines.

  17. Strategic defense initiative: critical issues

    SciTech Connect

    Nuckolls, J.H.

    1985-06-01

    The objectives of the Strategic Defense Initiative (SDI) as outlined by President Reagan are discussed. The principal objective for SDI is as a defense against ballistic missiles. Soviet objections and a summary of US-USSR dialogue on the subject are reviewed. Most US studies have been critical of SDI. Four critical issues are addressed in depth: are defense weapons technologically feasible which have high economic leverage relative to offensive ballistic missiles; would the defense feasibility and leverage be degraded or enhanced in the technological race between weapons innovation and countermeasures; could stability be achieved during and after the transition to the defense dominated world envisioned by SDI proponents; would the deployment of high leverage defensive weapons increase or decrease the security of NATO Europe, and the probability of major conventional or nuclear wars. The issue of SDI may lead to a paradox that contains the seeds of catastrophe. The author concludes by warning that nuclear disarmament may eliminate the highly successful deterrent mechanism for avoiding another major world war. In a world made safe for major conventional wars by the apparent ''elimination'' of nuclear weapons, the leaders in a conventional World War III - involving unimaginable suffering, hatred, terror, and death - would be strongly motivated to introduce nuclear weapons in the crucial decisive battles. Even if diplomacy could ''eliminate'' nuclear weapons, man's knowledge of nuclear weapons can never be eliminated. The paradox is the attempt to eliminate nuclear weapons may maximize the probability of their use. (DMC)

  18. Disease severity at the first hospitalization as a predictor for mechanical ventilation dependency in elderly patients with chronic obstructive pulmonary disease.

    PubMed

    Liao, Kuang-Ming; Lin, Wei-Chieh; Lin, Tzu-Chieh; Li, Chung-Yi; Yang, Yea-Huei Kao

    2014-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are predisposed to respiratory failure with ventilator dependency. This study aims to determine the risk of prolonged mechanical ventilation (PMV), defined as 22 days or more of mechanical ventilation dependency after the first day of hospital admission (index date) in patients diagnosed with COPD. A retrospective cohort was conducted using medical claim data of Taiwan's National Health Insurance Research Database. Eligible study subjects were those who had a diagnosis of COPD made between January 1, 2005 and December 31, 2009. Patients were then followed until being registered as a PMV case, death, or the end of the study. The comorbidities were measured from January 1, 1997 to the index date by the ICD-9 code. The study sample consisted of 6,341 patients with COPD with a mean age of 73.89 (± 12.01) years. Over a maximum of 6 years of follow-up, 654 patients developed PMV dependency, with an incidence density of 41.56 per 1,000 person-years. Patients aged 70 years and older were at significantly increased risk for PMV dependency, compared to those aged 40-49 years after adjusting for confounders. Expenses per visit and hospital visits per year, representing the severity of the COPD, were also associated with an elevated risk of PMV. Most patients developed PMV dependency within the first two years after the index date. Physicians should be aware that elderly patients with COPD have a high risk of PMV after first hospitalization, and these patients need to be closely monitored.

  19. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  20. Familial Pulmonary Fibrosis

    MedlinePlus

    ... Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  1. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  2. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-07-06

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  3. Pulmonary issues in the older adult.

    PubMed

    Frederick, Delia E

    2014-03-01

    This article elicits why critical care nurses need to become aware of the pulmonary issues of older adults. The population of older adults is increasing. Older adults undergo anatomic and physiologic changes of the protective mechanisms of the pulmonary system. These changes alter the rate and effort of breathing. Speech is slowed because of expiratory strength effort. Cognition changes may be the only indication of impaired oxygenation. Bedside nursing care provides protection from pulmonary complications. Health behaviors of smoking cessation, oral hygiene, and exercise promote pulmonary health even in older adults.

  4. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    PubMed

    Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen

    2016-10-01

    Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.

  5. Defense styles in Intermittent Explosive Disorder.

    PubMed

    Puhalla, Alexander A; McCloskey, Michael S; Brickman, Lauren J; Fauber, Robert; Coccaro, Emil F

    2016-04-30

    The overreliance on immature and/or neurotic defense mechanisms, as opposed to more mature defensive functioning has been linked to several psychiatric disorders. However, to date, the role of defense styles among individuals with Intermittent Explosive Disorder (IED) has not been examined. Given that individuals with IED display difficulties controlling their anger and aggression, one might expect these individuals to exhibit more immature and less mature defense styles. The current study compared participants with IED to a personality disorder (PD) comparison group, as well as to healthy volunteers (HV) on the Defense Style Questionnaire, a self-report measure that assesses the extent to which individuals endorse using mature, immature, and neurotic defense styles. Subjects with IED had significantly higher scores than both comparison groups on immature defense styles and exhibited lower scores on mature defense mechanisms. Hierarchical regression of significant defense style subscales showed that higher levels of acting out and lower levels of sublimation uniquely discriminated participants with IED from the PD and HV comparison groups.

  6. Effects of failure of the right side of the heart and increased pulmonary resistance on mechanical circulatory support with use of the miniaturized HIA-VAD displacement pump system.

    PubMed

    Waldenberger, F; Kim, Y I; Laycock, S; Meyns, B; Flameng, W

    1996-08-01

    support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the "low left ventricular assist device output syndrome," and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome.

  7. Pulmonary hypertension in dialysis patients.

    PubMed

    Kosmadakis, George; Aguilera, Didier; Carceles, Odette; Da Costa Correia, Enrique; Boletis, Ioannis

    2013-01-01

    Pulmonary hypertension in end-stage renal disease patients is associated with significantly increased morbidity and mortality. The prevalence of pulmonary hypertension in dialysis patients is relatively high and varies in different studies from 17% to 49.53% depending on the mode of dialysis and other selection factors, such as the presence of other cardiovascular comorbidities. The etiopathogenic mechanisms that have been studied in relatively small studies mainly include arteriovenous fistula-induced increased cardiac output, which cannot be accomodated by, the spacious under normal conditions pulmonary circulation. Additionally, pulmonary vessels show signs of endothelial dysfunction, dysregulation of vascular tone due to an imbalance in vasoactive substances, and local as well as systemic inflammation. It is also believed that microbubbles escaping from the dialysis circuit can trigger vasoconstriction and vascular sclerosis. The non-specific therapeutic options that proved to be beneficial in pulmonary artery pressure reduction are endothelin inhibitors, phosphodiesterase inhibitor sildenafil, and vasodilatory prostaglandins in various forms. The specific modes of treatment are renal transplantation, size reduction or closure of high-flow arteriovenous fistulas, and transfer from hemodialysis to peritoneal dialysis-a modality that is associated with a lesser prevalence of pulmonary hypertension.

  8. Chemical and mechanical defenses vary among maternal lines and leaf ages in Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist insect

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intra-specific variation in host-plant quality affects herbivore foraging decisions and, because of this, can feed back to shape plant fitness. In particular, among- and within plant variation in defense shapes herbivore behavior, and if genetically based, may respond to natural selection by herbivo...

  9. Pulmonary artery sarcoma mimicking pulmonary thromboembolism.

    PubMed

    Celik, Gökhan; Ciledağ, Aydin; Yüksel, Cabir; Yenigün, Bülent Mustafa; Kutlay, Hakan; Yazicıoğlu, Levent; Perçinel, Sibel; Kaya, Akin

    2011-01-01

    A 30 years old male patient was referred to our hospital with a diagnosis of pulmonary thromboembolism due to thorax-computerized tomography (CT) angiography, revealing a thrombus totally occluding left main pulmonary artery. The lesion was evaluated as tumoural mass. Positron emission tomography (PET)-CT revealed pathologic uptake at pulmonary artery mass. Due to localization of tumour, left pneumonectomy was performed. The pathological diagnosis revealed to be pulmonary artery sarcoma. The patient was presented because pulmonary artery sarcomas are very rare tumors and can mimick pulmonary thromboembolism. The true prevalence is underestimated as many pulmonary artery sarcomas are misdiagnosed as pulmonary thromboembolism. PET-CT may help to make a differential diagnosis.

  10. Treatment of Chronic Thromboembolic Pulmonary Hypertension: The Role of Medical Therapy and Balloon Pulmonary Angioplasty

    PubMed Central

    Fernandes, Timothy M.; Poch, David S.; Auger, William R.

    2016-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value. Previous unblinded cohort trials have assessed PH-targeted medical therapy in various subpopulations of CTEPH patients using epoprostenol, treprostinil, sildenafil, bosentan, and iloprost, each demonstrating measurable pulmonary hemodynamic effects. However, riociguat, a soluble guanylate cyclase stimulator, is the first FDA-approved therapy for inoperable CTEPH to demonstrate both an improvement in functional capabilities (6-minute walk time) as well as significant gains in secondary pulmonary hemodynamic end points in a large placebo-controlled trial. Balloon pulmonary angioplasty is an interventional procedure using telescoping catheters placed in the pulmonary arteries, through which wires and balloons are used to mechanically disrupt chronic clot material and relieve pulmonary vascular obstruction. Contemporary case series from multiple centers worldwide have demonstrated pulmonary hemodynamic improvement with this approach. As a result of these advances, patients with inoperable CTEPH who had few options as recently as 5 years ago now have alternatives with emerging evidence of therapeutic efficacy. PMID:28289495

  11. A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node.

    PubMed

    Ye, Wenduo; Wang, Jun; Song, Yingnan; Yu, Diankun; Sun, Cheng; Liu, Chao; Chen, Fading; Zhang, Yanding; Wang, Fen; Harvey, Richard P; Schrader, Laura; Martin, James F; Chen, YiPing

    2015-07-15

    In humans, atrial fibrillation is often triggered by ectopic pacemaking activity in the myocardium sleeves of the pulmonary vein (PV) and systemic venous return. The genetic programs that abnormally reinforce pacemaker properties at these sites and how this relates to normal sinoatrial node (SAN) development remain uncharacterized. It was noted previously that Nkx2-5, which is expressed in the PV myocardium and reinforces a chamber-like myocardial identity in the PV, is lacking in the SAN. Here we present evidence that in mice Shox2 antagonizes the transcriptional output of Nkx2-5 in the PV myocardium and in a functional Nkx2-5(+) domain within the SAN to determine cell fate. Shox2 deletion in the Nkx2-5(+) domain of the SAN caused sick sinus syndrome, associated with the loss of the pacemaker program. Explanted Shox2(+) cells from the embryonic PV myocardium exhibited pacemaker characteristics including node-like electrophysiological properties and the capability to pace surrounding Shox2(-) cells. Shox2 deletion led to Hcn4 ablation in the developing PV myocardium. Nkx2-5 hypomorphism rescued the requirement for Shox2 for the expression of genes essential for SAN development in Shox2 mutants. Similarly, the pacemaker-like phenotype induced in the PV myocardium in Nkx2-5 hypomorphs reverted back to a working myocardial phenotype when Shox2 was simultaneously deleted. A similar mechanism is also adopted in differentiated embryoid bodies. We found that Shox2 interacts with Nkx2-5 directly, and discovered a substantial genome-wide co-occupancy of Shox2, Nkx2-5 and Tbx5, further supporting a pivotal role for Shox2 in the core myogenic program orchestrating venous pole and pacemaker development.

  12. Pulmonary Vascular Stiffness: Measurement, Modeling, and Implications in Normal and Hypertensive Pulmonary Circulations

    PubMed Central

    Hunter, Kendall S.; Lammers, Steven R.; Shandas, Robin

    2014-01-01

    This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hypertension. It then progresses from the systems-level to the local level, discusses proposed methods by which upstream pulmonary vessels increase in stiffness, introduces concepts around vascular mechanics, and concludes by describing recent work incorporating advanced numerical methods to more thoroughly evaluate changes in local mechanical properties of pulmonary arteries. PMID:23733649

  13. Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

    PubMed

    Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

    2015-11-01

    Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations.

  14. [Idiopathic pulmonary hemosiderosis with dendriform pulmonary ossification].

    PubMed

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

    Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.

  15. RNase 7 in Cutaneous Defense

    PubMed Central

    Rademacher, Franziska; Simanski, Maren; Harder, Jürgen

    2016-01-01

    RNase 7 belongs to the RNase A superfamily and exhibits a broad spectrum of antimicrobial activity against various microorganisms. RNase 7 is expressed in human skin, and expression in keratinocytes can be induced by cytokines and microbes. These properties suggest that RNase 7 participates in innate cutaneous defense. In this review, we provide an overview about the role of RNase 7 in cutaneous defense with focus on the molecular mechanism of the antimicrobial activity of RNase 7, the regulation of RNase 7 expression, and the role of RNase 7 in skin diseases. PMID:27089327

  16. Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.

    PubMed

    Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos

    2016-03-01

    Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis.

  17. Pulmonary antioxidants

    SciTech Connect

    Massaro, E.J.; Grose, E.C.; Hatch, G.E.; Slade, R.

    1987-05-01

    One of the most vital of the cellular defenses against pollution is an antioxidant armanentarium which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate reductase, catalase, GSH synthetase, GSH peroxidase, GSH reductase, and GSH transferase) and appears to function in keeping oxidant forces under control. Pollutants can upset the oxidant/antioxidant balance of cells by inhibiting vital enzymes, by reacting with oxidant scavengers, or by forming free radical intermediates which initiate uncontrolled tissue reactions with molecular oxygen. The book chapter reviews possible interactions between pollutants and the oxidant/antioxidant balance.

  18. Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation

    PubMed Central

    Song, Rong-rong; Qiu, Yan-ping; Chen, Yong-ju; Ji, Yong

    2012-01-01

    BACKGROUND: Early withdrawal of invasive mechanical ventilation (IMV) followed by noninvasive MV (NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with acute respiratory failure (ARF). Using pulmonary infection control window (PIC window) as the switch point for transferring from invasive to noninvasive MV, the time for early extubation can be more accurately judged, and therapy efficacy can be improved. This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy (FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV. METHODS: Since July 2006 to January 2011, 106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization. Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used (group A, n=54) or not (group B, n=52) during sequential weaning from invasive to noninvasive MV. In group A, for sputum suction and bronchoalveolar lavage (BAL), a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube, which was accompanied with uninterrupted use of a ventilator. After achieving PIC window, patients of both groups changed to NIMV mode, and weaned from ventilation. The following listed indices were used to compare between the groups after treatment: 1) the occurrence time of PIC, the duration of MV, the length of ICU stay, the success rate of weaning from MV for the first time, the rate of reventilation and the occurrence rate of ventilator-associated pneumonia (VAP); 2) the convenience and safety of FOB manipulation. The results were compared using Student’s t test and the Chi-square test. RESULTS: The occurrence time of PIC was (5.01±1.49) d, (5.87±1.87) d in groups A and B, respectively (P<0.05); the duration of MV was (6.98±1.84) d, (8.69±2.41) d in groups A and B, respectively (P<0.01); the

  19. Management of pulmonary hypertension.

    PubMed

    Essop, M R; Galie, N; Badesch, D B; Lalloo, U; Mahomed, A G; Naidoo, D P; Ntsekhe, M; Williams, P G

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a potentially lethal disease mainly affecting young females. Although the precise mechanism of PAH is unknown, the past decade has seen the advent of many new classes of drugs with improvement in the overall prognosis of the disease. Unfortunately the therapeutic options for PAH in South Africa are severely limited. The Working Group on PAH is a joint effort by the South African Heart Association and the South African Thoracic Society tasked with improving the recognition and management of patients with PAH. This article provides a brief summary of the disease and the recommendations of the first meeting of the Working Group.

  20. Defense Spending and Reform

    DTIC Science & Technology

    2012-04-02

    Background paper on SIPRI military expenditure data Public Notice, “ Spending and Defending Defense spending has become a highly......Budget; Finance Reform; Military Spending ; Defense Spending ; Budget Cuts 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  1. Pulmonary drug delivery: a role for polymeric nanoparticles?

    PubMed

    d'Angelo, Ivana; Conte, Claudia; Miro, Agnese; Quaglia, Fabiana; Ungaro, Francesca

    2015-01-01

    Pulmonary drug delivery represents the best way of treating lung diseases, since it allows direct delivery of the drug to the site of action, with few systemic effects. Meanwhile, the lungs may be used as a portal of entry to the body, allowing systemic delivery of drugs via the airway surfaces into the bloodstream. In both cases, the therapeutic effect of the inhaled drug can be optimized by embedding it in appropriately engineered inhalable carriers, which can protect the drug against lung defense mechanisms and promote drug transport across the extracellular and cellular barriers. To this purpose, the attention has been very recently focused on polymeric nanoparticles (NPs). The aim of this review is to offer an overview on the recent advances in NPs for pulmonary drug delivery. After a description of the main challenges encountered in developing novel inhaled products, the design rules to engineer polymeric NPs for inhalation, and in so doing to overcome barriers imposed by the lungs anatomy and physiology, are described. Then, the state-of-art on inhalable biocompatible polymeric NPs based on enzymatically-degradable natural polymers and biodegradable poly(ester)s is presented, with a special focus on NP-based dry powders for inhalation. Finally, the in vitro/in vivo models useful to address the never-ending toxicological debate related to the use of NPs for inhalation are described.

  2. Genome defense against exogenous nucleic acids in eukaryotes by non-coding DNA occurs through CRISPR-like mechanisms in the cytosol and the bodyguard protection in the nucleus.

    PubMed

    Qiu, Guo-Hua

    2016-01-01

    In this review, the protective function of the abundant non-coding DNA in the eukaryotic genome is discussed from the perspective of genome defense against exogenous nucleic acids. Peripheral non-coding DNA has been proposed to act as a bodyguard that protects the genome and the central protein-coding sequences from ionizing radiation-induced DNA damage. In the proposed mechanism of protection, the radicals generated by water radiolysis in the cytosol and IR energy are absorbed, blocked and/or reduced by peripheral heterochromatin; then, the DNA damage sites in the heterochromatin are removed and expelled from the nucleus to the cytoplasm through nuclear pore complexes, most likely through the formation of extrachromosomal circular DNA. To strengthen this hypothesis, this review summarizes the experimental evidence supporting the protective function of non-coding DNA against exogenous nucleic acids. Based on these data, I hypothesize herein about the presence of an additional line of defense formed by small RNAs in the cytosol in addition to their bodyguard protection mechanism in the nucleus. Therefore, exogenous nucleic acids may be initially inactivated in the cytosol by small RNAs generated from non-coding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. Exogenous nucleic acids may enter the nucleus, where some are absorbed and/or blocked by heterochromatin and others integrate into chromosomes. The integrated fragments and the sites of DNA damage are removed by repetitive non-coding DNA elements in the heterochromatin and excluded from the nucleus. Therefore, the normal eukaryotic genome and the central protein-coding sequences are triply protected by non-coding DNA against invasion by exogenous nucleic acids. This review provides evidence supporting the protective role of non-coding DNA in genome defense.

  3. Pulmonary Vasculitis

    PubMed Central

    Brown, Kevin K.

    2006-01-01

    Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody–associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex–mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody–associated disorder, vasculitides. PMID:16493151

  4. Pulmonary fibrosis: pathogenesis, etiology and regulation

    PubMed Central

    Wilson, MS; Wynn, TA

    2009-01-01

    Pulmonary fibrosis and architectural remodeling of tissues can severely disrupt lung function, often with fatal consequences. The etiology of pulmonary fibrotic diseases is varied, with an array of triggers including allergens, chemicals, radiation and environmental particles. However, the cause of one of the most common pulmonary fibrotic conditions, idiopathic pulmonary fibrosis (IPF), is still unclear. This review examines common mechanisms of pulmonary wound-healing responses following lung injury, and highlights the pathogenesis of some of the most widespread pulmonary fibrotic diseases. A three phase model of wound repair is reviewed that includes; (1) injury; (2) inflammation; and (3) repair. In most pulmonary fibrotic conditions dysregulation at one or more of these phases has been reported. Chronic inflammation can lead to an imbalance in the production of chemokines, cytokines, growth factors, and disrupt cellular recruitment. These changes coupled with excessive pro-fibrotic IL-13 and/or TGFβ1 production can turn a well-controlled healing response into a pathogenic fibrotic response. Endogenous regulatory mechanisms are discussed including novel areas of therapeutic intervention. Restoring homeostasis to these dysregulated healing responses, or simply neutralizing the key pro-fibrotic mediators may prevent or slow the progression of pulmonary fibrosis. PMID:19129758

  5. Cross-Talk in Viral Defense Signaling in Plants

    PubMed Central

    Moon, Ju Y.; Park, Jeong M.

    2016-01-01

    Viruses are obligate intracellular parasites that have small genomes with limited coding capacity; therefore, they extensively use host intracellular machinery for their replication and infection in host cells. In recent years, it was elucidated that plants have evolved intricate defense mechanisms to prevent or limit damage from such pathogens. Plants employ two major strategies to counteract virus infections: resistance (R) gene-mediated and RNA silencing-based defenses. In this review, plant defenses and viral counter defenses are described, as are recent studies examining the cross-talk between different plant defense mechanisms. PMID:28066385

  6. LTB4 activates pulmonary artery adventitial fibroblasts in pulmonary hypertension

    PubMed Central

    Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.

    2015-01-01

    A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820

  7. Recognizing Plant Defense Priming.

    PubMed

    Martinez-Medina, Ainhoa; Flors, Victor; Heil, Martin; Mauch-Mani, Brigitte; Pieterse, Corné M J; Pozo, Maria J; Ton, Jurriaan; van Dam, Nicole M; Conrath, Uwe

    2016-10-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in plants.

  8. Radiological Defense. Textbook.

    ERIC Educational Resources Information Center

    Defense Civil Preparedness Agency (DOD), Washington, DC.

    This textbook has been prepared under the direction of the Defense Civil Preparedness Agency (DCPA) Staff College for use as a student reference manual in radiological defense (RADEF) courses. It provides much of the basic technical information necessary for a proper understanding of radiological defense and summarizes RADEF planning and expected…

  9. Real-time pulmonary graphics.

    PubMed

    Mammel, Mark C; Donn, Steven M

    2015-06-01

    Real-time pulmonary graphics now enable clinicians to view lung mechanics and patient-ventilator interactions on a breath-to-breath basis. Displays of pressure, volume, and flow waveforms, pressure-volume and flow-volume loops, and trend screens enable clinicians to customize ventilator settings based on the underlying pathophysiology and responses of the individual patient. This article reviews the basic concepts of pulmonary graphics and demonstrates how they contribute to our understanding of respiratory physiology and the management of neonatal respiratory failure.

  10. Immunosuppression of pulmonary natural killer activity by exposure to ozone

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.; Stutzman, J.D. )

    1989-01-01

    Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless involves several cell types and/or products of these cells. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, following 23.5 hours of exposure. NK activity is important for defense against viral, bacterial, and neoplastic disease. The depressed NK activity resulting from continuous ozone exposure could therefore result in a compromised ability to defend against pulmonary diseases.

  11. Diffuse interstitial pulmonary fibrosis: pulmonary fibrosis in mice induced by treatment with butylated hydroxytoluene and oxygen

    SciTech Connect

    Haschek, W.M.; Brody, A.R.; Klein-Szanto, A.J.P.; Witschi, H.

    1981-12-01

    It is proposed that the pulmonary fibrosis induced in mice by treatment with BHT and oxygen is a good experimental model for human pulmonary fibrosis. The mechanism of synergistic and additive effects of various agents on pulmonary injury and the epithelial mesenchymal interactions occurring during the early and late phases of lung repair could be studied. This model could be used for study of the effects of various concentrations of oxygen on diffusely damaged lung and assessment of the efficacy of drugs in preventing or resolving excessive collagen accumulation in lung. In addition, the relationship between pulmonary fibrosis and emphysema could be studied.

  12. Pulmonary pulse wave transit time is associated with right ventricular–pulmonary artery coupling in pulmonary arterial hypertension

    PubMed Central

    Weir, E. Kenneth; Archer, Stephen L.; Markowitz, Jeremy; Rose, Lauren; Pritzker, Marc; Madlon-Kay, Richard; Thenappan, Thenappan

    2016-01-01

    Abstract Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression. PMID:28090301

  13. DNA Damage and Pulmonary Hypertension

    PubMed Central

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  14. [Pulmonary hypertension in liver diseases].

    PubMed

    Savale, Laurent; Sattler, Caroline; Sitbon, Olivier

    2014-09-01

    Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH.

  15. Primitive defenses: cognitive aspects and therapeutic handling.

    PubMed

    Groh, L S

    In this paper the primitive defenses first described by Melanie Klein under the label of "schizoid mechanisms" are examined. The defenses considered are splitting the pathological uses of identification and projective identification, and the psychotic forms of denial. This examination is twofold: (1) the cognitive aspects of these defenses as described in terms of concepts developed by Jean Piaget; (2) concrete examples of the operation of these defenses during the treatment of schizophrenic patients are given and the effects of interventions based on the cognitive analysis are described. It is stressed that at times interventions, such as interpretation and confrontation, based on cognitive analysis, can temporarily and in some instances even permanently stop the operation of these defenses, allowing emotionally meaningful material to emerge which expedites the therapeutic process.

  16. Psychological defenses of Danish medical students.

    PubMed

    la Cour, Peter

    2002-01-01

    Patterns in the psychological defenses of medical students may have implications for the way they handle and respond to the pressures and developmental issues they encounter in medical school and beyond. Using the Defense Style Questionnaire (DSQ40) to assess psychological defenses, a sample of first-year Danish medical students was compared with a sample of students at a short-term boarding school for general education. The medical students scored significantly higher on items connected with pseudo-altruism, denial, and undoing. Trends in the data furthermore suggest a greater use of sublimation, rationalization, and dissociation among medical students. When defense mechanisms were labeled into mature, neurotic, and immature categories, there were no differences between the groups or in the total defense scores.

  17. [Congenital pulmonary capillary hemangiomatosis in a newborn].

    PubMed

    Sposito Cavallo, Sandra L; Macias Sobrino, Luciano A; Marenco Altamar, Luifer J; Mejía Alquichire, Andrés F

    2017-02-01

    Pulmonary capillary hemangiomatosis is a rare entity characterized by the proliferation of capillaries into alveolar walls, interlobular septa, pleura and pulmonary interstitium, without malignant characteristics, with almost constant association with pulmonary hypertension. Until now two cases of congenital presentation have been reported in the literature. This is the third case in a newborn; he has not followed the usual pattern associated with pulmonary hypertension as occurs in most patients with this pathology; the highest incidence is among 20-40 years old. We report a preterm newborn patient of 36 weeks of gestation with progressive respiratory distress requiring mechanical ventilation by constant desaturation during his clinical evolution without clinical, radiological or ultrasonographic signs of pulmonary hypertension.

  18. Potassium channels in pulmonary arterial hypertension.

    PubMed

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.

  19. Diffuse persistent interstitial pulmonary emphysema treated by lobectomy.

    PubMed

    Matta, Reva; Matta, Judy; Hage, Pierre; Nassif, Yolla; Mansour, Nabil; Diab, Nabil

    2011-10-01

    Persistent interstitial pulmonary emphysema is a rare condition that occurs in preterm infants on mechanical ventilation, characterized by abnormal accumulation of air in the pulmonary interstitium, due to disruption of the basement membrane. Diffuse persistent interstitial pulmonary emphysema is observed when small cysts are noted in all lobes of the lung. The management of infants suffering from diffuse persistent interstitial pulmonary emphysema varies according to severity and stability of the patient, being either conservative treatment or aggressive surgical treatment by pneumonectomy. We report a case of an unstable patient with diffuse persistent interstitial pulmonary emphysema successfully treated by lobectomy as a form of conservative surgical approach.

  20. Pulmonary Hypertension in Sarcoidosis.

    PubMed

    Baughman, Robert P; Engel, Peter J; Nathan, Steven

    2015-12-01

    Pulmonary hypertension is a complication of sarcoidosis leading to dyspnea and associated with increased morbidity and mortality. Sarcoidosis-associated pulmonary hypertension (SAPH) can be due to several factors, including vascular involvement by the granulomatous inflammation, compression of the pulmonary arteries by adenopathy, fibrotic changes within the lung, and left ventricular diastolic dysfunction. Several case series have suggested that some patients with SAPH benefit from specific therapy for pulmonary hypertension. A randomized, placebo-controlled trial found 16 weeks' bosentan therapy to be associated with significant improvement in pulmonary artery pressure. Future studies may better define who would respond to treatment of pulmonary hypertension.

  1. [Pulmonary alveolar microlithiasis. Study of pulmonary circulation].

    PubMed

    Orea Tejeda, A; Atencio, C; Sandoval, J; Lupi Herrera, E

    1982-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown etiology which consists of alveolar deposit of calcium microspheres. We report the procedures for the diagnosis of this disease, as well as the hemodynamic features of the pulmonary circulation. Pulmonary arterial hypertension (PAH), and cor pulmonale were documented. The active and passive factors involved in PAH are analyzed. We conclude that alveolar hypoxia and estructural vascular changes play a major role in the genesis of PAH.

  2. Hyponatremia in pulmonary TB: evidence of ectopic antidiuretic hormone production.

    PubMed

    Lee, Paul; Ho, Ken K Y

    2010-01-01

    Hyponatremia is among the most common biochemical abnormalities in hospital inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of several causes of hyponatremia, particularly in patients with pulmonary diseases. The mechanism of SIADH associated with pulmonary infection is, however, poorly understood. We report an unusual case of hyponatremia in a man with pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic antidiuretic hormone production as a possible mechanism causing hyponatremia.

  3. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

  4. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension.

    PubMed

    Perros, F; Dorfmüller, P; Souza, R; Durand-Gasselin, I; Godot, V; Capel, F; Adnot, S; Eddahibi, S; Mazmanian, M; Fadel, E; Hervé, P; Simonneau, G; Emilie, D; Humbert, M

    2007-05-01

    Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension. The aim of the study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular remodelling of a monocrotaline-induced pulmonary hypertension model. The expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription PCR on laser-captured microdissected pulmonary arteries. It was demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells. In conclusion, the current authors proposed that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodelling.

  5. Pulmonary function in microgravity

    NASA Technical Reports Server (NTRS)

    Guy, H. J.; Prisk, G. K.; West, J. B.

    1992-01-01

    We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non-gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS).

  6. Chronic obstructive pulmonary disease.

    PubMed

    Vijayan, V K

    2013-02-01

    The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines

  7. Pulmonary Hypertension: Diagnosis and Management

    PubMed Central

    McGoon, Michael D.; Kane, Garvan C.

    2009-01-01

    Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies. PMID:19181654

  8. Pulmonary hypertension - at home

    MedlinePlus

    Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right side ... Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, Mason ... Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: ...

  9. Pulmonary Fibrosis Foundation

    MedlinePlus

    ... for a friend. Ways to Give Announcements CHICAGO BEAR JORDAN HOWARD BRINGS HIS FIGHT TO PULMONARY FIBROSIS ... 22-year-old lead rusher for the Chicago Bears, will announce his commitment to fight pulmonary fibrosis ( ...

  10. Living with Pulmonary Embolism

    MedlinePlus

    ... on Twitter. Living With Pulmonary Embolism Pulmonary embolism (PE) usually is treated in a hospital. After leaving ... you're taking medicine. Medicines used to treat PE can thin your blood too much. This can ...

  11. Who Needs Pulmonary Rehabilitation?

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... other symptoms. Examples of interstitial lung diseases include sarcoidosis and idiopathic pulmonary fibrosis . Cystic fibrosis (CF). CF ...

  12. Idiopathic Pulmonary Fibrosis

    MedlinePlus

    ... the NHLBI on Twitter. What Is Idiopathic Pulmonary Fibrosis? Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a ... time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, your lungs can' ...

  13. Types of Pulmonary Hypertension

    MedlinePlus

    ... Hypertension The World Health Organization divides pulmonary hypertension (PH) into five groups. These groups are organized based ... lungs. Group 2 Pulmonary Hypertension Group 2 includes PH with left heart disease. Conditions that affect the ...

  14. The Mechanism of the Osteoprotective Action of a Polyphenol-Rich Aronia melanocarpa Extract during Chronic Exposure to Cadmium is Mediated by the Oxidative Defense System.

    PubMed

    Brzóska, Malgorzata M; Rogalska, Joanna; Roszczenko, Alicja; Galazyn-Sidorczuk, Malgorzata; Tomczyk, Michal

    2016-05-01

    Recently, we demonstrated in a rat model that consumption of a polyphenol-rich extract obtained from the berries of Aronia melanocarpa could protect from cadmium-induced disorders in bone turnover and changes in bone mineral status. The aim of this study was to investigate whether the osteoprotective effect of this extract is mediated by the oxidative defense system. Enzymatic and nonenzymatic antioxidants, total antioxidative and oxidative status, hydrogen peroxide, and markers of oxidative protein, lipid, and DNA damage were determined in bone tissue at the distal femoral epiphysis of female Wistar rats receiving 0.1 % aqueous A. melanocarpa extract (prepared from the lyophilized commercial extract containing 65.74 % of polyphenols) as the only drinking fluid and/or cadmium in the diet (1 and 5 mg/kg) for 3, 10, 17, and 24 months. The total oxidative and antioxidative status of the serum was also evaluated. The administration of A. melanocarpa extract provided significant protection from cadmium-induced oxidative stress in the bone and serum, and from lipid peroxidation and oxidative damage to the protein and DNA in the bone tissue. Numerous correlations were noted between indices of the oxidative/antioxidative bone status and markers of bone metabolism previously assayed in the animals receiving A. melanocarpa extract. The results allow the conclusion that the ability of A. melanocarpa extract to mediate the oxidative defense system and prevent oxidative modifications of protein, lipid, and DNA in the bone tissue plays an important role in its osteoprotective action under exposure to cadmium. The findings provide further evidence supporting our suggestion that chokeberry may be a promising natural agent for protection against the toxic action of cadmium in women chronically exposed to this metal.

  15. Quadrennial Defense Review Report

    DTIC Science & Technology

    2010-02-01

    Roles of Military Power 9  U.S. Defense Objectives 11  REBALANCING THE FORCE 17  Defend the United States and Support Civil Authorities at Home 18...the need to plan for the broadest possible range of operations—from homeland defense and defense support to civil authorities, to deterrence and...Defend the United States and support civil authorities at home: The rapid proliferation of destructive technologies, combined with potent

  16. [Pulmonary artery intimal sarcoma].

    PubMed

    Bourry, N; Chabrot, P; Jeannin, G; Filaire, M; Charpy, C; Bay, J O; Kemeny, J L; Caillaud, D; Escande, G; Boyer, L

    2008-02-01

    Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.

  17. Differential pulmonary and cardiac effects of pulmonary exposure to a panel of PM-associated metals

    EPA Science Inventory

    Biological mechanisms underlying the epidemiological association between exposure to particulate matter (PM) and increased risk of cardiovascular health effects are under investigation. Water soluble metals reaching systemic circulation following pulmonary exposure are likely exe...

  18. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  19. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  20. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  1. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  2. 22 CFR 130.4 - Defense articles and defense services.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and...

  3. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    PubMed

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  4. Dynamic defense workshop :

    SciTech Connect

    Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.

    2013-02-01

    On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-art work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.

  5. Technologies for Distributed Defense

    SciTech Connect

    Seiders, Barbara AB; Rybka, Anthony J.

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of "citizen soldiers," with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  6. Technologies for distributed defense

    NASA Astrophysics Data System (ADS)

    Seiders, Barbara; Rybka, Anthony

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of 'citizen soldiers', with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  7. Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension.

    PubMed

    Hetzel, M; Kochs, M; Marx, N; Woehrle, H; Mobarak, I; Hombach, V; Hetzel, J

    2003-01-01

    The association between nocturnal apneas and transient pulmonary hypertension (PHT) has been well documented. However, there is controversy over the frequency and pathophysiological mechanisms of daytime pulmonary hypertension in patients with obstructive sleep apnea (OSAS). The present study sought to evaluate frequency and mechanisms of pulmonary hypertension in patients with OSAS. It included 49 consecutive patients with polysomnographically proven OSAS without pathological lung function testing. All patients performed daytime measurements of pulmonary hemodynamics at rest and during exercise (50-75W). Six patients (12%) had resting PHT mean pulmonary of artery pressure (PAPM) of >20 mmHg), whereas 39 patients (80%) showed PHT during exercise (PAPM >30 mmHg). Multiple regression analysis revealed 3 independent contributing factors for mean pulmonary artery pressure during exercise (PAPMmax): body mass index, age and total lung capacity % of predicted. Twenty-five of the 39 patients with pathologically high PAPMmax (64%) showed elevated pulmonary capillary wedge pressures (PCWPmax > 20 mmHg), whereas no patient had elevated pulmonary vascular resistance (PVRmax > 120 dynes x s x cm(-5)). In conclusion, daytime PHT during exercise is frequently seen in patients with OSAS and normal lung function testing and is mainly caused by abnormally high PCWP, whereas PVR seems to play a minor role.

  8. Sex differences in the pulmonary circulation: implications for pulmonary hypertension

    PubMed Central

    Martin, Yvette N.

    2014-01-01

    Pulmonary arterial hypertension (PAH), a form of pulmonary hypertension, is a complex disease of multifactorial origin. While new developments regarding pathophysiological features and therapeutic options in PAH are being reported, one important fact has emerged over the years: there is a sex difference in the incidence of this disease such that while there is a higher incidence in females, disease outcomes are much worse in males. Accordingly, recent attention has been focused on understanding the features of sex differences in the pulmonary circulation and the contributory mechanisms, particularly sex hormones and their role in the pathological and pathophysiological features of PAH. However, to date, there is no clear consensus whether sex hormones (particularly female sex steroids) are beneficial or detrimental in PAH. In this review, we highlight some of the most recent evidence regarding the influence of sex hormones (estrogen, testosterone, progesterone, dehydroepiandrosterone) and estrogen metabolites on key pathophysiological features of PAH such as proliferation, vascular remodeling, vasodilation/constriction, and inflammation, thus setting the stage for research avenues to identify novel therapeutic target for PAH as well as potentially other forms of pulmonary hypertension. PMID:24610923

  9. Deception used for Cyber Defense of Control Systems

    SciTech Connect

    Wayne F. Boyer; Miles A. McQueen

    2009-05-01

    Control system cyber security defense mechanisms may employ deception to make it more difficult for attackers to plan and execute successful attacks. These deceptive defense mechanisms are organized and initially explored according to a specific deception taxonomy and the seven abstract dimensions of security previously proposed as a framework for the cyber security of control systems.

  10. Pulmonary Artery Sarcoma

    PubMed Central

    Shomaf, Maha; Obeidat, Nathir; Najjar, Saleh

    2014-01-01

    Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation. PMID:26425600

  11. Primary pulmonary artery sarcoma.

    PubMed

    Jin, Tao; Zhang, Chong; Feng, Zhiying; Ni, Yiming

    2008-08-01

    Primary pulmonary artery sarcoma is an uncommon tumor. We report a case of a 73-year-old male patient with a two-week history of palpitations and shortness of breath, aggravated for two days and was believed to be pulmonary hypertension. Emergency heart ultrasound after admission presented a massive pulmonary embolism in the pulmonary artery. The patient's condition was successfully managed with urgent pulmonary artery embolectomy. The patient demonstrated improvement in hemodynamics after the operation. Histologic and immunohistochemical assays were performed and a diagnosis was made as primary pulmonary artery sarcoma arising from the left pulmonary artery. Resection of the tumor is recommended for the treatment of this rare malignant tumor. The corresponding chemotherapy, follow-up and prognosis are described as well in this case report.

  12. [Pulmonary manifestations of antisynthetase syndrome].

    PubMed

    Jouneau, S; Hervier, B; Jutant, E-M; Decaux, O; Kambouchner, M; Humbert, M; Delaval, P; Montani, D

    2015-06-01

    Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians' knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.

  13. Hematological disorders and pulmonary hypertension

    PubMed Central

    Mathew, Rajamma; Huang, Jing; Wu, Joseph M; Fallon, John T; Gewitz, Michael H

    2016-01-01

    Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH. PMID:28070238

  14. Defense Science Board Task Force Report on Cyber Defense Management

    DTIC Science & Technology

    2016-09-01

    DSB Task Force Report on Cyber Defense Management September 2016 (U) This page intentionally blank REPORT OF THE DEFENSE SCIENCE BOARD STUDY ON Cyber...U) This report is a product of the Defense Science Board (DSB). (U) The DSB is a Federal Advisory Committee established to provide independent...position of the Department of Defense (DoD). The Defense Science Board Study on Cyber Defense completed its information-gathering in November 2015. The

  15. Schools and Civil Defense.

    ERIC Educational Resources Information Center

    Office of Civil Defense (DOD), Washington, DC.

    Civil defense is a planned, coordinated action to protect the population during any emergency whether arising from thermonuclear attack or natural disaster. The Federal Government has assumed four responsibilities--(1) to keep track of the nature of the threat which the civil defense program must meet, (2) to prepare and disseminate information…

  16. Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling

    PubMed Central

    Ni, Shirong; Wang, Dexuan; Qiu, Xiaoxiao; Pang, Lingxia; Song, Zhangjuan; Guo, Kunyuan

    2015-01-01

    Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of NAD(P)H: quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis. PMID:26339340

  17. Intra--and Intercellular Calcium Handling in Pulmonary Arterial Hypertension.

    PubMed

    Mouratoglou, Sophia-Anastasia; Giannakoulas, George; Deftereos, Spyridon; Giannopoulos, Georgios; Angelidis, Christos; Cleman, Michael W; Vassilikos, Vassilios P

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.

  18. Irradiation influence on the phenoloxidase pathway and an anti-oxidant defense mechanism in Spodoptera litura (Lepidoptera: Noctuidae) and its implication in radio-genetic 'F 1 sterility' and biorational pest suppression tactics.

    PubMed

    Sachdev, B; Khan, Z; Zarin, M; Malhotra, P; Seth, R K; Bhatnagar, R K

    2017-01-31

    The present study was conducted to appraise the ontogenic radio-sensitivity of a serious tropical pest, Spodoptera litura (Fabr.). The molecular responses pertaining to the phenoloxidase (PO) pathway and an anti-oxidant defense mechanism were evaluated in order to understand its implication in pest control at pre-harvest and post-harvest intervals. Irradiation exhibited an inverse relationship with age with respect to impact on developmental and transcriptional responses. Transcript abundance of PO cascade enzymes, prophenoloxidase (slppo-2), its activating enzyme (slppae-1) and free-radical scavenging enzymes, superoxide dismutase (slsod) and catalase (slcat) was evaluated upon gamma irradiation alone and the dual-stress of radiation plus microbial challenge. The slppo-2, slppae-1, slsod and slcat transcripts were significantly up-regulated in F 1 L6 larvae (6th-instar) resulting from 100 Gy sub-sterilized male adults and unirradiated female moths. The extent of upregulation was relatively higher in comparison with L6 survivors (6th-instar larvae) developed from irradiated neonates (L1) treated with 100 Gy. Upon Photorhabdus challenge, the transcripts were down-regulated in irradiated L1 suggesting increased larval susceptibility to bacterial infections. Radioresistance increased with the age of the insect, and molecular responses (transcript abundance) of insect defense mechanism were less influenced when older age (F 1 progeny) were irradiated. These findings will help to optimize the gamma dose to be employed in inherited sterility technique for (pre-harvest) pest suppression and (post-harvest) phytosanitation and quarantine, and suggest compatible integration of biorational tactics including nuclear technology.

  19. [Signaling of granulocyte macrophage colony stimulating factor and its clinical application: host-defense and organ protection].

    PubMed

    Uchida, Kanji

    2013-03-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine with multipotent properties. It has not only an activity to generate both granulocyte and macrophage lineages in the bone marrow, but also is capable of inducing terminal maturation of alveolar macrophages that is central for pulmonary host defense and pulmonary surfactant homeostasis. GM-CSF can stimulate mature myeloid cells (i.e. neutrophils and monocytes) with a known mechanism called "priming" to efficiently eliminate invading pathogens. Several clinical trials to evaluate therapeutic efficacy of GM-CSF in patients with diseases related to functional impairment of mature myeloid cells were reported. Inhalation of GM-CSF improved clinical severity of pulmonary alveolar proteionosis. Administration of GM-CSF for patients with immune compromised situation such as sepsis showed marginal benefits so far. Several animal experiments indicated neuroprotective effect of GM-CSE In the clinical setting, establishing reliable biomarkers to distinguish patients who will have benefit by administering GM-CSF may maximize its clinical efficacy.

  20. Kinetics and selectivity of mechanism-based inhibition of guinea pig hepatic and pulmonary cytochrome P450 by N-benzyl-1-aminobenzotriazole and N-alpha-methylbenzyl-1-aminobenzotriazole.

    PubMed

    Sinal, C J; Bend, J R

    1996-09-01

    The time dependence for mechanism-based inactivation of cytochrome P450 (P450)-dependent 7-pentoxyresorufin O-depentylation (PROD), 7-ethoxyresorufin O-deethylation (EROD), and 7-methoxyresorufin O-demethylation (MROD) activities by N-benzyl-1-aminobenzotriazole (BBT) and N-alpha-methylbenzyl-1-aminobenzotriazole (alpha MB) was investigated in hepatic and pulmonary microsomes from phenobarbital-treated guinea pigs. In the presence of NADPH, both compounds inhibited P450-dependent catalytic activity in a time- and concentration-dependent manner. Inactivation of hepatic PROD activity was more rapid (t1/2 = 13.2 vs. 155 min) for 0.1 microM alpha MB when compared with equimolar BBT. On the other hand, hepatic EROD inactivation was more rapid (t1/2 = 8.1 vs. 11 min) with 0.1 microM BBT, compared with equimolar alpha MB. Inactivation of pulmonary PROD activity was the most rapid and potent, with an apparent half-life for inactivation of t1/2 = 0.94 and 32.2 min for 0.025 microM alpha MB and BBT, respectively. Incubation of hepatic microsomes for 45 min in the presence of NADPH and 10 microM BBT or alpha MB resulted in > 90% inhibition of PROD, EROD, and MROD activities. After washing by repeated sedimentation and resuspension, inhibition of PROD (78%; 93% for BBT and alpha MB, respectively), EROD (80% and 50%), and MROD (15% and 3%) activities was reversed to varying degrees. We conclude that BBT and alpha MB are rapidly metabolized to products that inhibit individual P450 isozymes by both mechanism-based (P4502B and P4501A1) and reversible (P4501A2) mechanisms. Of the two inhibitors, alpha MB is relatively more potent and selective for guinea pig lung P4502B isozyme(s).

  1. Protective effects of moderate exercise with dietary vitamin C and E on blood antioxidative defense mechanism in rats with streptozotocin-induced diabetes.

    PubMed

    Naziroğlu, Mustafa; Butterworth, Peter J

    2005-04-01

    Daily moderate exercise and supplementation of vitamins C and E (VCE) can be beneficial in diabetes by ameliorating the effects of free radical production. The present study sought to analyze the effect of moderate exercise accompanying VCE supplementation on lipid peroxidation (LP) and antioxidative systems in the blood of streptozotocin-induced diabetic rats. Forty female Wistar rats were randomly divided 4 groups. The 1st and 2nd groups served as the control and diabetic groups, respectively. The 3rd group was the diabetic-exercise group. The 4th group, also diabetic-exercise rats, received VCE-supplemented feed. Animals in the exercised groups were moderately exercised on a treadmill 5 days a week for 3 weeks. Diabetes was induced on Day 0 of the exercise. Plasma and red blood cell (RBC) samples were taken from all animals on Day 20. Glutathione peroxidase, catalase, and reduced glutathione levels in plasma and RBCs, and vitamins A, E, and beta-carotene in plasma were lower in diabetic rats than in control animals, whereas there was a significant increase in platelet counts in both plasma and RBC LP levels. The decreased antioxidant enzymes and vitamins, and the increased LP levels and WBC counts, did improve through exercise only, although their levels were mostly increased by exercise + VCE supplementation. There were no significant changes in the hemoglobin and hematocrit values in the 4 groups. In conclusion, these data demonstrate an increase in LP in the blood of diabetic animals whereas there was a decrease in the antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system by decreasing reactive oxygen species.

  2. Pulmonary artery sarcoma mimicking a pulmonary embolism.

    PubMed

    Sandhu, A; Yates, T J; Kuriakose, P

    2008-01-01

    Sarcomas involving the lung are a rare occurrence, often a result of metastatic disease from primary malignancies involving the skin, liver, breast or heart. Primary pulmonary artery sarcomas are rarer still, with limited cases reported world-wide and consequently data regarding treatment modalities are sparse and largely experimental. These tumors are often mistaken for a pulmonary embolism and seemingly supported by radiological findings. Patients will often present without symptom resolution despite therapeutic anticoagulation. The following case illustrates how a soft tissue sarcoma of the pulmonary artery can mimic a pulmonary embolism, thus, resulting in both a diagnostic and therapeutic dilemma. A positron emission tomography scan was an invaluable tool in this case, showing increased radiotracer uptake and placing neoplasm at the top of the differential diagnosis. This ultimately led to a biopsy that was vimentin positive, cytokeratin negative and CD117 negative, thus consistent with soft tissue sarcoma.

  3. Pulmonary manifestations of sickle cell disease

    PubMed Central

    Siddiqui, A; Ahmed, S

    2003-01-01

    Pulmonary complications account for significant morbidity and mortality in patients with sickle cell disease. Clinical lung involvement manifests in two major forms: the acute chest syndrome and sickle cell chronic lung disease. Acute chest syndrome is characterised by fever, chest pain, and appearance of a new infiltrate on chest radiograph. Sickle cell chronic lung disease, on the other hand, manifests as radiographic interstitial abnormalities, impaired pulmonary function, and, in its most severe form, by the evidence of pulmonary hypertension. Progress has been made in understanding the pathophysiology and management of these complications. In this review the current knowledge of the mechanism, diagnosis, and treatment of pulmonary complications of sickle cell disease are discussed. PMID:12897216

  4. Strategies to reduce pulmonary complications after esophagectomy

    PubMed Central

    Weijs, Teus J; Ruurda, Jelle P; Nieuwenhuijzen, Grard AP; van Hillegersberg, Richard; Luyer, Misha DP

    2013-01-01

    Esophagectomy, the surgical removal of all or part of the esophagus, is a surgical procedure that is associated with high morbidity and mortality. Pulmonary complications are an especially important postoperative problem. Therefore, many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice. Here, we review these strategies, including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years. Furthermore, interventions such as methylprednisolone, neutrophil elastase inhibitor and epidural analgesia, which have been shown to reduce pulmonary complications, are discussed. Benefits of the commonly applied routine nasogastric decompression, delay of oral intake and prophylactic mechanical ventilation are unclear, and many of these strategies are also evaluated here. Finally, we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy. PMID:24151374

  5. Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases.

    PubMed

    Shlobin, Oksana A; Brown, A Whitney; Nathan, Steven D

    2017-01-01

    Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exac