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Sample records for model lung surfactant

  1. Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

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    Mikolka, P; Kopincová, J; Košútová, P; Čierny, D; Čalkovská, A; Mokrá, D

    2016-12-22

    Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

  2. Size influences the effect of hydrophobic nanoparticles on lung surfactant model systems.

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    Dwivedi, Mridula V; Harishchandra, Rakesh Kumar; Koshkina, Olga; Maskos, Michael; Galla, Hans-Joachim

    2014-01-07

    The alveolar lung surfactant (LS) is a complex lipid protein mixture that forms an interfacial monolayer reducing the surface tension to near zero values and thus preventing the lungs from collapse. Due to the expanding field of nanotechnology and the corresponding unavoidable exposure of human beings from the air, it is crucial to study the potential effects of nanoparticles (NPs) on the structural organization of the lung surfactant system. In the present study, we investigated both, the domain structure in pure DPPC monolayers as well as in lung surfactant model systems. In the pure lipid system we found that two different sized hydrophobic polymeric nanoparticles with diameter of ~12 nm and ~136 nm have contrasting effect on the functional and structural behavior. The small nanoparticles inserted into fluid domains at the LE-LC phase transition are not visibly disturbing the phase transition but disrupting the domain morphology of the LE phase. The large nanoparticles led to an expanded isotherm and to a significant decrease in the line tension and thus to a drastic disruption of the domain structures at a much lower number of nanoparticles with respect to the lipid. The surface activity of the model LS films again showed drastic variations due to presence of different sized NPs illustrated by the film balance isotherms and the atomic force microscopy. AFM revealed laterally profuse multilayer protrusion formation on compression but only in the presence of 136 nm sized nanoparticles. Moreover we investigated the vesicle insertion process into a preformed monolayer. A severe inhibition was observed only in the presence of ~136 nm NPs compared to minor effects in the presence of ~12 nm NPs. Our study clearly shows that the size of the nanoparticles made of the same material determines the interaction with biological membranes. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

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    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  4. Surfactant Delivery into the Lung

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    Grotberg, James; Filoche, Marcel

    2014-11-01

    We have developed a multiscale, compartmentalized model of surfactant and liquid delivery into the lung. Assuming liquid plug propagation, the airway compartment accounts for the plug's volume deposition (coating) on the airway wall, while the bifurcation compartment accounts for plug splitting from the parent airway to the two daughter airways. Generally the split is unequal due to gravity and geometry effects. Both the deposition ratio RD (deposition volume/airway volume), and the splitting ratio, RS, of the daughters volumes are solved independently from one another. Then they are used in a 3D airway network geometry to achieve the distribution of delivery into the lung. The airway geometry is selected for neonatal as well as adult applications, and can be advanced from symmetric, to stochastically asymmetric, to personalized. RD depends primarily on the capillary number, Ca, while RS depends on Ca, the Reynolds number, Re, the Bond number, Bo, the dose volume, VD, and the branch angles. The model predicts the distribution of coating on the airway walls and the remaining plug volume delivered to the alveolar region at the end of the tree. Using this model, we are able to simulate and test various delivery protocols, in order to optimize delivery and improve the respiratory function.

  5. Radiation Mitigating Properties of Intranasally Administered KL4Surfactant in a Murine Model of Radiation-Induced Lung Damage.

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    Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Koumenis, Constantinos; Segal, Robert

    2017-11-01

    The threat of exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions is a significant public health concern. The lung is particularly susceptible to radiation-induced injury from external sources or inhalation of radioactive particles from radioactive fallout. Radiation-induced lung disease can manifest with an acute radiation pneumonitis and/or delayed effects leading to pulmonary fibrosis. As prior warning of radiation exposure is unlikely, medical countermeasures (MCMs) to mitigate radiation-induced lung disease that can be given in mass-casualty situations many hours or days postirradiation are needed to prevent both early and late lung damage. In this study, KL 4 surfactant (lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage. Here, 120 mg/kg total phospholipid of KL 4 surfactant was administered twice daily intranasally, (enabling intrapulmonary inhalation of drug) to C57BL/6 mice 24 h after a single 13.5 Gy dose of thoracic irradiation (LD 50 dose). Both early and chronic phase (2 and 4 weeks and 18 weeks postirradiation, respectively) assessments were performed. Mice were evaluated for evidence of reduced arterial blood oxygenation and early and chronic lung and systemic inflammation, lung fibrosis and oxidative stress. Analysis was done by performing lung function/respiration dynamics and measuring cellular protein content of bronchoalveolar lavage fluid (BALF), and levels of cytokines, 8-iso-prostaglandin F2α, hydroxyproline in lung and plasma, along with evaluating lung histology. The results of this study showed that intranasal delivery of KL 4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF

  6. Surfactant gene polymorphisms and interstitial lung diseases

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    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  7. Pulmonary surfactant and lung transplantation

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    Erasmus, Michiel Elardus

    1997-01-01

    Pulmonary surfactant lowers the surface tension at the air-water interface inside the alveolus. This is achieved by adsorption of surfactant phospholipids at the air-water interface, a process controlled by surfactant-associated proteins, such as SP-A. In this way, surfactant prevents collapse of

  8. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

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    Richter Joachim

    2008-01-01

    Full Text Available Abstract Background Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. Methods Rats were randomly assigned to a control, Celsior (CE or Celsior + surfactant (CE+S group (n = 5 each. In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups or immediately after sacrifice (Control, the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. Results Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation: CE: 160 mm3 (0.61 vs. CE+S: 4 mm3 (0.75; p 3 (0.90 vs. CE+S: 0 mm3; p 3 (0.39 vs. CE+S: 268 mm3 (0.43; p 3(0.10 and CE+S (481 μm3(0.10 compared with controls (323 μm3(0.07; p Conclusion Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of

  9. Surfactant nebulisation : lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1997-01-01

    Objective: Surfactant nebulisation is a promising alternative to surfactant instillation in newborns with the respiratory distress syndrome. Although less surfactant is deposited in the lung, it improves gas exchange, probably due to a superior distribution. We hypothesize that a more uniform

  10. Lung Surfactant - The Indispensable Component of Respiratory ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 8. Lung Surfactant - The Indispensable Component of Respiratory Mechanics. Shweta Saxena. Research News Volume 10 Issue 8 August 2005 pp 91-96. Fulltext. Click here to view fulltext PDF. Permanent link:

  11. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part I

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    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 1 of the review gives information on the composition and properties of a pulmonary surfactant and quantitative and qual itative impairments in the pulmonary surfactant system in different neonatal and adult abnormalities and describes the composition of commercial synthetic and natural surfactants. The results of surfactant therapy for respiratory distress syndrome and other lung diseases with secondary surfactant deficiency in the newborns are analyzed.

  12. Lung Surfactant and Its Use in Lung Diseases

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    O. A. Rosenberg

    2007-01-01

    Full Text Available The review considers the present views of lung surfactant (LS functions with emphasis on its protective and barrier properties and ability to maintain local and adaptive immunity. The composition of commercial LS formulations is analyzed. Data on qualitative and quantitative LS abnormalities are presented in various diseases in neonates and adults. The results of clinical trials of different LS formulations in the treatment of acute respiratory distress syndrome in adults are analyzed in detail. Recent data on the results of and prospects for surfactant therapy for bronchial asthma, chronic obstructive pulmonary disease and pulmonary tuberculosis are given. 

  13. Lung surfactants and different contributions to thin film stability.

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    Hermans, Eline; Bhamla, M Saad; Kao, Peter; Fuller, Gerald G; Vermant, Jan

    2015-11-07

    The surfactant lining the walls of the alveoli in the lungs increases pulmonary compliance and prevents collapse of the lung at the end of expiration. In premature born infants, surfactant deficiency causes problems, and lung surfactant replacements are instilled to facilitate breathing. These pulmonary surfactants, which form complex structured fluid-fluid interfaces, need to spread with great efficiency and once in the alveolus they have to form a thin stable film. In the present work, we investigate the mechanisms affecting the stability of surfactant-laden thin films during spreading, using drainage flows from a hemispherical dome. Three commercial lung surfactant replacements Survanta, Curosurf and Infasurf, along with the phospholipid dipalmitoylphosphatidylcholine (DPPC), are used. The surface of the dome can be covered with human alveolar epithelial cells and experiments are conducted at the physiological temperature. Drainage is slowed down due to the presence of all the different lung surfactant replacements and therefore the thin films show enhanced stability. However, a scaling analysis combined with visualization experiments demonstrates that different mechanisms are involved. For Curosurf and Infasurf, Marangoni stresses are essential to impart stability and interfacial shear rheology does not play a role, in agreement with what is observed for simple surfactants. Survanta, which was historically the first natural surfactant used, is rheologically active. For DPPC the dilatational properties play a role. Understanding these different modes of stabilization for natural surfactants can benefit the design of effective synthetic surfactant replacements for treating infant and adult respiratory disorders.

  14. Electronic cigarette vapor alters the lateral structure but not tensiometric properties of calf lung surfactant.

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    Przybyla, Rebecca J; Wright, Jason; Parthiban, Rajan; Nazemidashtarjandi, Saeed; Kaya, Savas; Farnoud, Amir M

    2017-11-17

    Despite their growing popularity, the potential respiratory toxicity of electronic cigarettes (e-cigarettes) remains largely unknown. One potential aspect of e-cigarette toxicity is the effect of e-cigarette vapor on lung surfactant function. Lung surfactant is a mixture of lipids and proteins that lines the alveolar region. The surfactant layer reduces the surface tension of the alveolar fluid, thereby playing a crucial role in lung stability. Due to their small size, particulates in e-cigarette vapor can penetrate the deep lungs and come into contact with the lung surfactant. The current study sought to examine the potential adverse effects of e-cigarette vapor and conventional cigarette smoke on lung surfactant interfacial properties. Infasurf ® , a clinically used and commercially available calf lung surfactant extract, was used as lung surfactant model. Infasurf ® films were spread on top of an aqueous subphase in a Langmuir trough with smoke particulates from conventional cigarettes or vapor from different flavors of e-cigarettes dispersed in the subphase. Surfactant interfacial properties were measured in real-time upon surface compression while surfactant lateral structure after exposure to smoke or vapor was examined using atomic force microscopy (AFM). E-cigarette vapor regardless of the dose and flavoring of the e-liquid did not affect surfactant interfacial properties. In contrast, smoke from conventional cigarettes had a drastic, dose-dependent effect on Infasurf ® interfacial properties reducing the maximum surface pressure from 65.1 ± 0.2 mN/m to 46.1 ± 1.3 mN/m at the highest dose. Cigarette smoke and e-cigarette vapor both altered surfactant microstructure resulting in an increase in the area of lipid multilayers. Studies with individual smoke components revealed that tar was the smoke component most disruptive to surfactant function. While both e-cigarette vapor and conventional cigarette smoke affect surfactant lateral structure

  15. Lung preservation in experimental ischemia/reperfusion injury and lung transplantation: a comparison of natural and synthetic surfactants.

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    Knudsen, Lars; Boxler, Laura; Mühlfeld, Christian; Schaefer, Inga-Marie; Becker, Laura; Bussinger, Christine; von Stietencron, Immanuel; Madershahian, Navid; Richter, Joachim; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2012-01-01

    Surfactant inactivation results from ischemia/reperfusion injury and plays a major role in the pathogenesis of primary graft dysfunction after clinical lung transplantation. Thus, prophylactic administration of exogenous surfactant preparations before the onset of ischemia/reperfusion has proven to be effective in preserving pulmonary structure and function. Various natural and synthetic surfactant preparations exhibit differences regarding the biochemical composition and biophysical properties. In this study we compared the efficacy of preservation of pulmonary structure and function of the natural surfactant preparations Curosurf and Survanta to that of a synthetic surfactant containing an analog of surfactant protein C (SPC-33) in a rat model of ischemia/reperfusion injury. The oxygenation capacity and peak inspiratory pressure during the reperfusion period were recorded. By applying design-based stereology at the light- and electron-microscopic level, pathologic alterations, including alveolar edema, injury of the blood-air barrier and the intra-alveolar as well as intracellular surfactant pools, were quantified. The best oxygenation and preservation of lung structure was achieved with Curosurf. Survanta treatment was associated with the most severe injury of the blood-air barrier, and SPC-33 demonstrated signs of microatelectasis. The intra-alveolar surfactant pool after Curosurf and SPC-33 was dominated by active surfactant subtypes, whereas Survanta was associated with the highest fraction of inactive surfactant. The intracellular surfactant pool did not show any differences between the treatment groups. Taken together, Curosurf achieved the best structural and functional lung preservation, whereas Survanta was inferior to both Curosurf and SPC-33. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  16. Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

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    Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

    2014-07-01

    Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part II

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    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 2 of the review considers the problem of surfactant therapy for acute respiratory distress syndrome (ARDS in adults and young and old children. It gives information on the results of surfactant therapy and prevention of ARDS in patients with severe concurrent trauma, inhalation injuries, complications due to complex expanded chest surgery, or severe pneumonias, including bilateral pneumonia in the presence of A/H1N1 influenza. There are data on the use of a surfactant in obstetric care and prevention of primary graft dysfunction during lung transplantation. The results of longterm use of surfactant therapy in Russia, suggesting that death rates from ARDS may be substantially reduced (to 20% are discussed. Examples of surfactant therapy for other noncritical lung diseases, such as permanent athelectasis, chronic obstructive pulmonary diseases, and asthma, as well tuberculosis, are also considered.

  18. Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.

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    Mikolka, P; Kopincova, J; Tomcikova Mikusiakova, L; Kosutova, P; Antosova, M; Calkovska, A; Mokra, D

    2016-02-01

    Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free

  19. Surfactant Proteins in Smoking-Related Lung Disease.

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    Papaioannou, Andriana I; Papiris, Spyridon; Papadaki, Georgia; Manali, Effrosyni D; Roussou, Aneza; Spathis, Aris; Karakitsos, Petros; Kostikas, Konstantinos

    2016-01-01

    Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted in the alveoli by type II epithelial cells and is found in the fluid lining the alveolar surface. The protein part of surfactant constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and SP-C), which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Several studies have shown that cigarette smoke seems to affect, in several ways, both surfactant homeostasis and function. The alterations in surfactants' biophysical properties caused by cigarette smoking, contribute to the development of several smoking related lung diseases. In this review we provide information on biochemical and physiological aspects of the pulmonary surfactant and on its possible association with the development of two major chronic diseases of the lung known to be related to smoking, i.e. chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Additional information on the possible role of surfactant protein alterations and/or dysfunction in the combination of these two conditions, recently described as combined pulmonary fibrosis and emphysema (CPFE) are also provided.

  20. Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D.

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    Taku Fukuzawa

    Full Text Available Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known about how the surfactant pool is monitored and regulated. Here we show, by an analysis of gene-targeted mice exhibiting massive accumulation of surfactant, that Ig-Hepta/GPR116, an orphan receptor, is expressed on the type II cell and sensing the amount of surfactant by monitoring one of its protein components, surfactant protein D, and its deletion results in a pulmonary alveolar proteinosis and emphysema-like pathology. By a coexpression experiment with Sp-D and the extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation, we identified Sp-D as the ligand of Ig-Hepta/GPR116. Analyses of surfactant metabolism in Ig-Hepta(+/+ and Ig-Hepta(-/- mice by using radioactive tracers indicated that the Ig-Hepta/GPR116 signaling system exerts attenuating effects on (i balanced synthesis of surfactant lipids and proteins and (ii surfactant secretion, and (iii a stimulating effect on recycling (uptake in response to elevated levels of Sp-D in alveolar space.

  1. Budesonide added to modified porcine surfactant Curosurf may additionally improve the lung functions in meconium aspiration syndrome.

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    Mikolka, P; Mokrá, D; Kopincová, J; Tomčíková-Mikušiaková, L; Calkovská, A

    2013-01-01

    Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and inflammation increased from budesonide-only and surfactant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer-lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improved the effects of exogenous surfactant in experimental MAS.

  2. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was

  3. The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

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    Scott J Elliott

    2004-03-01

    Full Text Available Abstract Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS, termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung

  4. Poloxamer-Decorated Polymer Nanoparticles for Lung Surfactant Compatibility

    DEFF Research Database (Denmark)

    Beck-Broichsitter, Moritz; Bohr, Adam; Ruge, Christian A

    2017-01-01

    (styrene) and poly(lactide) nanoparticle-induced lung surfactant inhibition could be related to the type and content of the applied poloxamer. Escalations of the adsorbed coating layer thickness (>3 nm) as well as concentration (brush- rather than mushroom-like conformation of poly(ethylene glycol), chain...

  5. Lung Surfactant-The Indispensable Component of Respiratory ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 8. Lung Surfactant - The Indispensable Component of Respiratory Mechanics. Shweta Saxena. Research News Volume 10 Issue 8 August 2005 pp 91-96. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Porcine lung surfactant protein B gene (SFTPB)

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    Cirera Salicio, Susanna; Fredholm, Merete

    2008-01-01

    The porcine surfactant protein B (SFTPB) is a single copy gene on chromosome 3. Three different cDNAs for the SFTPB have been isolated and sequenced. Nucleotide sequence comparison revealed six nonsynonymous single nucleotide polymorphisms (SNPs), four synonymous SNPs and an in-frame deletion of 69...

  7. Design of Surfactant Protein B Peptide Mimics Based on the Saposin Fold for Synthetic Lung Surfactants.

    Science.gov (United States)

    Walther, Frans J; Gordon, Larry M; Waring, Alan J

    2016-01-01

    Surfactant protein (SP)-B is a 79-residue polypeptide crucial for the biophysical and physiological function of endogenous lung surfactant. SP-B is a member of the Saposin or Saposin-like proteins (SAPLIP) family of proteins that share an overall three-dimensional folding pattern based on secondary structures and disulfide connectivity and exhibit a wide diversity of biological functions. Here we review the synthesis, molecular biophysics and activity of synthetic analogs of Saposin proteins designed to mimic those interactions of the parent proteins with lipids that enhance interfacial activity. Saposin proteins generally interact with target lipids as either monomers or multimers via well-defined amphipathic helices, flexible hinge domains, and insertion sequences. Based on the known 3D-structural motif for the Saposin family, we show how bioengineering techniques may be used to develop minimal peptide constructs that maintain desirable structural properties and activities in biomedical applications. One important application is the molecular design, synthesis and activity of Saposin mimics based on the SP-B structure. Synthetic lung surfactants containing active SP-B analogs may be potentially useful in treating diseases of surfactant deficiency or dysfunction including the neonatal respiratory distress syndrome and acute lung injury/acute respiratory distress syndrome.

  8. SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung.

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    Sato, Atsuyasu; Ikegami, Machiko

    2012-01-01

    Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco(2) was maintained at 55 mmHg with 24 cmH(2)O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period.

  9. SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung.

    Directory of Open Access Journals (Sweden)

    Atsuyasu Sato

    Full Text Available Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633 containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco(2 was maintained at 55 mmHg with 24 cmH(2O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period.

  10. The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

    OpenAIRE

    Scott, J Elliott

    2004-01-01

    Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the...

  11. Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation – a stereological study

    Science.gov (United States)

    Herrmann, Gudrun; Knudsen, Lars; Madershahian, Navid; Mühlfeld, Christian; Frank, Konrad; Rahmanian, Parwis; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2014-01-01

    The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed

  12. Activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing Super-Mini-B DATK peptide

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    Robert H. Notter

    2016-01-01

    Full Text Available Background/objectives. This study examines the surface activity, resistance to biophysical inhibition, and pulmonary efficacy of a synthetic lung surfactant containing glycerophospholipids combined with Super Mini-B (S-MB DATK, a novel and stable molecular mimic of lung surfactant protein (SP-B. The objective of the work is to test whether S-MB DATK synthetic surfactant has favorable biophysical and physiological activity for future use in treating surfactant deficiency or dysfunction in lung disease or injury.Methods. The structure of S-MB DATK peptide was analyzed by homology modeling and by FTIR spectroscopy. The in vitro surface activity and inhibition resistance of synthetic S-MB DATK surfactant was assessed in the presence and absence of albumin, lysophosphatidylcholine (lyso-PC, and free fatty acids (palmitoleic and oleic acid. Adsorption and dynamic surface tension lowering were measured with a stirred subphase dish apparatus and a pulsating bubble surfactometer (20 cycles/min, 50% area compression, 37 °C. In vivo pulmonary activity of S-MB DATK surfactant was measured in ventilated rabbits with surfactant deficiency/dysfunction induced by repeated lung lavages that resulted in arterial PO2 values <100 mmHg.Results. S-MB DATK surfactant had very high surface activity in all assessments. The preparation adsorbed rapidly to surface pressures of 46–48 mN/m at 37 °C (low equilibrium surface tensions of 22–24 mN/m, and reduced surface tension to <1 mN/m under dynamic compression on the pulsating bubble surfactometer. S-MB DATK surfactant showed a significant ability to resist inhibition by serum albumin, C16:0 lyso-PC, and free fatty acids, but surfactant inhibition was mitigated by increasing surfactant concentration. S-MB DATK synthetic surfactant quickly improved arterial oxygenation and lung compliance after intratracheal instillation to ventilated rabbits with severe surfactant deficiency.Conclusions. S-MB DATK is an active mimic

  13. Spontaneous breathing or mechanical ventilation alters lung compliance and tissue association of exogenous surfactant in preterm newborn rabbits.

    Science.gov (United States)

    Bohlin, Kajsa; Bouhafs, Rabea K L; Jarstrand, Connie; Curstedt, Tore; Blennow, Mats; Robertson, Bengt

    2005-05-01

    In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant (14C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 +/- 10% (mean +/- SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml x cm H2O(-1) x kg(-1), respectively; p mechanically ventilated animals (p mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation.

  14. Surfactant treatment before first breath for respiratory distress syndrome in preterm lambs: comparison of a peptide-containing synthetic lung surfactant with porcine-derived surfactant

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    van Zyl JM

    2013-08-01

    Full Text Available Johann M van Zyl,1 Johan Smith2 1Division of Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; 2Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa Background: In a recent study utilizing a saline-lavaged adult rabbit model, we described a significant improvement in systemic oxygenation and pulmonary shunt after the instillation of a novel synthetic peptide-containing surfactant, Synsurf. Respiratory distress syndrome in the preterm lamb more closely resembles that of the human infant, as their blood gas, pH values, and lung mechanics deteriorate dramatically from birth despite ventilator support. Moreover, premature lambs have lungs which are mechanically unstable, with the advantage of being able to measure multiple variables over extended periods. Our objective in this study was to investigate if Synsurf leads to improved systemic oxygenation, lung mechanics, and histology in comparison to the commercially available porcine-derived lung surfactant Curosurf® when administered before first breath in a preterm lamb model. Materials and methods: A Cesarean section was performed under general anesthesia on 18 time-dated pregnant Dohne Merino ewes at 129–130 days gestation. The premature lambs were delivered and ventilated with an expiratory tidal volume of 6–8 mL/kg for the first 30 minutes and thereafter at 8–10 mL/kg. In a randomized controlled trial, the two surfactants tested were Synsurf and Curosurf®, both at a dose of 100 mg/kg phospholipids (1,2-dipalmitoyl-L-α-phosphatidylcholine; 90% in Synsurf, 40% in Curosurf®. A control group of animals was treated with normal saline. Measurements of physiological variables, blood gases, and lung mechanics were made before and after surfactant and saline replacement and at 15, 30, 45, 60, 90, 120, 180

  15. Surfactant Protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Lock Johansson, Sofie; Tan, Qihua; Holst, Rene

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  16. Micropipette Technique Study of Natural and Synthetic Lung Surfactants at the Air–Water Interface

    DEFF Research Database (Denmark)

    Ortiz, Elisa Parra; Kinoshita, K.; Needham, D.

    2016-01-01

    The present study is a microscopic interfacial characterization of a series of lung surfactant materials performed with the micropipette technique. The advantages of this technique include the measurement of equilibrium and dynamic surface tensions while acquiring structural and dynamic information...... at microscopic air-water interfaces in real time and upon compression. Here, we characterized a series of animal-derived and synthetic lung surfactant formulations, including native surfactant obtained from porcine lungs (NS); the commercial Curosurf, Infasurf, and Survanta; and a synthetic Super Mini-B (SMB...... but neither in the other clinical surfactants nor in protein-free preparations. Finally, the connection between this data and the observations from the lung surfactant literature concerning the widely reported "near-zero surface tension" for lung surfactant films and intact alveolar surfaces is also discussed...

  17. Acute Pathophysiological Effects of Intratracheal Instillation of Budesonide and Exogenous Surfactant in a Neonatal Surfactant-depleted Piglet Model

    Directory of Open Access Journals (Sweden)

    Chia-Feng Yang

    2010-08-01

    Conclusions: Intratracheal instillation of surfactant or surfactant plus budesonide can improve oxygenation and pulmonary histologic outcome in neonatal surfactant-depleted lungs. The additional use of budesonide does not disturb the function of the exogenous surfactant. Intratracheal administration of a corticosteroid combined with surfactant may be an effective method for alleviating local pulmonary inflammation in severe RDS.

  18. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

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    Frans J. Walther

    2014-05-01

    Full Text Available Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB, a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight, the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary

  19. Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116

    Directory of Open Access Journals (Sweden)

    Mi Young Yang

    2013-05-01

    Full Text Available GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders.

  20. SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Batenburg, JJ; Haagsman, HP; Oetomo, SB; Prop, J

    2002-01-01

    Background. The function of pulmonary surfactant is affected by lung transplantation, contributing to impaired lung transplant function. A decreased amount of surfactant protein-A (SP-A) after reperfusion is believed to contribute to the impaired surfactant function. Surfactant treatment has been

  1. Lung Lavage and Surfactant Replacement During Ex Vivo Lung Perfusion for Treatment of Gastric Acid Aspiration-Induced Donor Lung Injury.

    Science.gov (United States)

    Nakajima, Daisuke; Liu, Mingyao; Ohsumi, Akihiro; Kalaf, Ricardo; Iskender, Ilker; Hsin, Michael; Kanou, Takashi; Chen, Manyin; Baer, Brandon; Coutinho, Rafael; Maahs, Lucas; Behrens, Paula; Azad, Sassan; Martinu, Tereza; Waddell, Thomas K; Lewis, James F; Post, Martin; Veldhuizen, Ruud A W; Cypel, Marcelo; Keshavjee, Shaf

    2017-05-01

    Ex vivo lung perfusion (EVLP) provides opportunities to treat injured donor lungs before transplantation. We investigated whether lung lavage, to eliminate inflammatory inhibitory components, followed by exogenous surfactant replacement, could aid lung recovery and improve post-transplant lung function after gastric aspiration injury. Gastric acid aspiration was induced in donor pigs, which were ventilated for 6 hours to develop lung injury. After retrieval and 10 hours of cold preservation, EVLP was performed for 6 hours. The lungs were randomly divided into 4 groups (n = 5, each): (1) no treatment (control), (2) lung lavage, (3) surfactant administration, and (4) lung lavage, followed by surfactant administration. After another 2-hour period of cold preservation, the left lung was transplanted and reperfused for 4 hours. Physiologic lung function significantly improved after surfactant administration during EVLP. The EVLP perfusate from the lavage + surfactant group showed significantly lower levels of interleukin (IL)-1β, IL-6, IL-8, and secretory phospholipase A 2 . Total phosphatidylcholine was increased, and minimum surface tension was recovered to normal levels (≤5 mN/m) in the bronchioalveolar fluid after surfactant administration. Lysophosphatidylcholine in bronchioalveolar fluid was significantly lower in the lavage + surfactant group than in the surfactant group. Post-transplant lung function was significantly better in the lavage + surfactant group compared with all other groups. Lung lavage, followed by surfactant replacement during EVLP, reduced inflammatory mediators and prevented hydrolysis of phosphatidylcholine, which contributed to the superior post-transplant function in donor lungs with aspiration injury. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  2. The influence of lung surfactant liquid crystalline nanostructures on respiratory drug delivery.

    Science.gov (United States)

    Das, Shyamal C; Stewart, Peter J

    2016-12-05

    The respiratory route increasingly has been used for both local and systemic drug delivery. Although drug is absorbed rapidly after respiratory delivery, the role of lung surfactant in drug delivery is not well understood. The human lung contains only around 15mL of surface lining fluid spread over ∼100m 2 surface. The fluid contains lung surfactant at a concentration of 8-24mg/kg/body weight; the lung surfactant which is lipo-protein in nature can form different liquid crystalline nanostructures. After a brief overview of the anatomy of respiratory system, the review has focused on the current understanding of lung surface lining fluid, lung surfactants and their composition and possible self-assembled nanostructures. The role of lung surfactant in drug delivery and drug dissolution has been briefly considered. Lung surfactant may form different liquid crystalline phases which can have an active role in drug delivery. The hypotheses developed in this review focuses on the potential roles of surface epithelial fluid containing liquid crystalline nanostructures in defining the dissolution mechanism and rate. The hypotheses also focus an understanding how liquid crystalline nanostructures can be used to control dissolution rate and how the nanostructures might be changed to influence delivery and induce toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. [Clinical abservations of pulmonary surfactant' s autologous transfusion in massive lung lavage].

    Science.gov (United States)

    Xiao, X Y; Zhang, X P; Chen, G; Yuan, Y; Ma, G X; Duan, J Y; Sun, Z Q; Huang, J H; Cao, X; Zhang, J

    2017-01-20

    Objective: Investigate the pulmonary surfactant autotransfusion effect on the recovery of respiratory function in patients with whole lung lavage, to provide theoretical basis for the clinical application. Methods: We taken 30 patients of pneumoconiosis treated by whole lung lavage as the subjects. We extracted the pulmonary surfactant from lavage fluid, after single postoperative lung lavage for the first time; after one weeks when the second times of lung lavage were performed to the other side of the lung of patients, we put PS into the right side. We taken the patients the second times of lung lavage who were put PS into the right side as returning group, the first times of lung lavage who were not put PS into as on returning group. We observed indi-cators, such as expiratory resistance, respiratory work, lung compliance, airway pressure, PO(2), the pulmonary function recovery time and other indicators, comparing with the changes of pulmonary function before lung la-vage for the first time and at 0、60、90、120 min after the pulmonary surfactant autotransfusion. Results: Com-pared with the no returning group, the expiratory resistance of the returning group decreased significantly at 90 min、120 min after the pulmonary surfactant autotransfusion; the respiratory work and airway pressure of the re-turning group decreased significantly at 60、90、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups ( P surfactant autotransfusion, there was statistically significant in the difference between different groups ( P surfactant autotransfusion.There was no ad-verse reactions such as pulmonary infection, pulmonary infection and so on. Conclusion: The pulmonary surfac-tant autotransfusion may reduce expiratory resistance, work of breathing, airway pressure; improve lung compliance, alveolar ventilation function; increase oxygen partial pressure and decrease the surgery recovery time

  4. Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Holmskov, Uffe; Schiøtz, Peter Oluf

    2010-01-01

    BACKGROUND: Cystic fibrosis (CF) affects the lungs causing infections and inflammation. Surfactant protein D (SP-D) is an innate defense lectin primarily secreted in the lungs. We investigated the influence of the SP-D Met11Thr polymorphism on CF lung function; and serum SP-D as a marker for CF...

  5. Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

    NARCIS (Netherlands)

    K.L. So; E. de Buijzer; D.A.M.P.J. Gommers (Diederik); U. Kaisers; P.J.J. van Genderen (Perry); B.F. Lachmann (Burkhard)

    1998-01-01

    textabstractParaquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the

  6. Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage

    International Nuclear Information System (INIS)

    Lachmann, B.; Hallman, M.; Bergmann, K.C.

    1987-01-01

    Within 2 minutes intravenous anti-lung serum (ALS) into guinea pig induces a respiratory failure that is fatal within 30 min. The relationship between surfactant, alveolar-capillary permeability and respiratory failure was studied. Within two minutes ALS induced a leak in the alveolar-capillary barrier. Within 30 minutes 28.3% (controls, given normal rabbit serum: 0.7%) of iv 131 I-albumin, and 0.5% (controls 0.02%) of iv surfactant phospholipid tracer were recovered in bronchoalveolar lavage. Furthermore, 57% (controls 32%) of the endotracheally administered surfactant phospholipid became associated with lung tissue and only less than 0.5% left the lung. The distribution of proteins and phospholipids between the in vivo small volume bronchoalveolar lavages and the ex vivo bronchoalveolar lavages were dissimilar: 84% (controls 20%) of intravenously injected, lavageable 131 I-albumin and 23% (controls 18%) of total lavageable phospholipid were recovered in the in vivo small volume bronchoalveolar lavages. ALS also decreased lavageable surfactant phospholipid by 41%. After ALS the minimum surface tension increased. The supernatant of the lavage increased the minimum surface tension of normal surfactant. In addition, the sediment fraction of the lavage had slow surface adsorption, and a marked reduction in 35,000 and 10,000 MW peptides. Exogenous surfactant ameliorated the ALS-induced respiratory failure. We propose that inhibition, altered intrapulmonary distribution, and dissociation of protein and phospholipid components of surfactant are important in early pathogenesis of acute respiratory failure

  7. Normalisation of surfactant protein -A and -B expression in the lungs of low birth weight lambs by 21 days old.

    Directory of Open Access Journals (Sweden)

    Jia Yin Soo

    Full Text Available Intrauterine growth restriction (IUGR induced by placental restriction (PR in the sheep negatively impacts lung and pulmonary surfactant development during fetal life. Using a sheep model of low birth weight (LBW, we found that there was an increase in mRNA expression of surfactant protein (SP-A, -B and -C in the lung of LBW lambs but no difference in the protein expression of SP-A or -B. LBW also resulted in increased lysosome-associated membrane glycoprotein (LAMP-3 mRNA expression, which may indicate an increase in either the density of type II Alveolar epithelial cells (AEC or maturity of type II AECs. Although there was an increase in glucocorticoid receptor (GR and 11β-hydroxysteroid dehydrogenase (11βHSD-1 mRNA expression in the lung of LBW lambs, we found no change in the protein expression of these factors, suggesting that the increase in SP mRNA expression is not mediated by increased GC signalling in the lung. The increase in SP mRNA expression may, in part, be mediated by persistent alterations in hypoxia signalling as there was an increase in lung HIF-2α mRNA expression in the LBW lamb. The changes in the hypoxia signalling pathway that persist within the lung after birth may be involved in maintaining SP production in the LBW lamb.

  8. Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

    Science.gov (United States)

    Häfner, Dietrich; Germann, Paul-Georg; Hauschke, Dieter

    1998-01-01

    In a previous paper we showed that an SP-C containing surfactant preparation has similar activity as bovine-derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment). Four protein containing surfactants (rSP-C surfactant, bLES, Infasurf and Survanta) were compared with three protein-free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP-C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg−1 body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period. Tracheotomized rats (8–12 per dose and surfactant) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min−1, inspiration expiration ratio of 1 : 2, peak inspiratory pressure of 28 cmH2O at positive endexpiratory pressure (PEEP) of 8 cmH2O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed. Partial arterial oxygen pressures (PaO2, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose-dependent increase of the reduced PaO2 values at 30 min after treatment. The protein-free surfactants showed only weak dose-dependent increase in PaO2 values at this time. This difference between the

  9. Cellular uptake and processing of surfactant lipids and apoprotein SP-A by rat lung

    International Nuclear Information System (INIS)

    Young, S.L.; Wright, J.R.; Clements, J.A.

    1989-01-01

    The intracellular pathways and the kinetics of metabolism of surfactant apoprotein and lipid, which may be recycled from the alveolar space, are largely unknown. We used a lipid-apoprotein complex made from liposomes of pure lipids in a ratio found in mammalian pulmonary surfactant plus surfactant apoprotein (SP-A, Mr = 26,000-36,000) to test some possible relationships in the recycling of these major surfactant components between intrapulmonary compartments. After intratracheal instillation of 80 microliters of an apoprotein-liposome mixture with separate radiolabels in the lipid and the apoprotein, rats were killed at times from 8 min to 4 h later. The lungs were lavaged with saline, and subcellular fractions were isolated on discontinuous sucrose density gradients. Both the [ 14 C]lipid radiolabel and the 125 I-apoprotein radiolabel demonstrated a time-dependent increase in radioactivity recovered in a lamellar body-enriched fraction. Uptake of the radiolabels into other subcellular fractions did not exhibit a clear-cut time dependence; more of the protein than the lipid radiolabel was found in the Golgi-rich and microsomal fractions. We conclude that both the lipid and apoprotein portions of lung surfactant are taken up by lung cells and are incorporated into secretory granules of the cells

  10. Inhaled Surfactant Therapy in Newborns in Artificial Lung Ventilation

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency of inhaled surfactant therapy in neonatal infants with respiratory failure.Subjects and methods. The trial enrolled 13 premature neonatal infants; their mean gestational age was 31.8±2.8 weeks and the birth weight was 1825±600.9 g. They had a oneminute Apgar score of 4.3±1.4. All the neonates needed mechanical ventilation (MV atbirth because the leading clinical sign was respiratory failure caused by acute intranatal hypoxia, neonatal amniotic fluid aspiration, respiratory distress syndrome (RDS, and cerebral ischemia. Curosurf was injected in a dose of 174.7±21 mg/kg in the infants with neonatal RDS at 35 minutes of life. All the babies included in the study were noted to have severe disease and prolonged MV. After stabilization of their status, the neonates received combination therapy involving surfactantBL inhalation to reduce the duration of MV. The dose of the agent was 75 mg. Results. After surfactantBL inhalation, effective spontaneous respiration occurred in 69.2% of the newborn infants; successful extubation was carried out. The median duration ofMV after surfactant BL inhalation was 22 hours (4—68 hours. There were no reintubated cases after inhalation therapy. Following surfactantBL inhalation, 4 (30.8% patients remained to be on MV as a control regimen; 3 of them had highfre quency MV. SurfactantBL inhalation made it possible to change the respiratory support regimen and to reduce MV parame ters in these babies. 

  11. The influence of temperature, phylogeny, and lung structure on the lipid composition of reptilian pulmonary surfactant.

    Science.gov (United States)

    Daniels, C B; Orgeig, S; Smits, A W; Miller, J D

    1996-01-01

    The lungs of all air-breathing vertebrates contain a form of pulmonary surfactant that lines the alveolar air-water interface where it modifies the interfacial surface tension. These pulmonary surfactants all consist of varying amounts of phospholipids (saturated and unsaturated) and cholesterol. The extent of variation between vertebrate groups and between species within a vertebrate group has been attributed to differences in factors such as phylogeny, body temperature, habitat, and lung structure. The influence of these factors on amphibian surfactant composition and function has been studied, but the reptiles, which comprise a polyphyletic group of vertebrates, have never been critically examined. The surfactant lipid composition from species belonging to the three groups of reptiles, the Archosauria (crocodiles), Lepidosauria (snakes and lizards), and Anapsida (turtles), has been determined. New data is presented in conjunction with already published data to create an evolutionary framework that concentrates particularly on the influence of phylogeny, body temperature, and lung structure on the composition of the surfactant lipids. Large amounts of pulmonary surfactant were found in all species of reptiles. All species lavaged at 23 degrees C (except C. atrox) demonstrated DSP/PL ratios of 23-33%. Animals with multicameral lungs exhibited an elevated CHOL/DSP ratio compared with species with unicameral lungs. In all groups, phosphatidylcholine (PC) was the dominant (60-80%) phospholipid. Phosphatidylserine and phosphatidylinositol (PS/PI) and sphingomyelin (S) represented the other phospholipids, while phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) were occasionally observed. In two species of lizards (C. nuchalis and P. vitticeps), the saturated fatty acid, palmitic acid (16:0), was the dominant tail group on the phospholipids. Oleic acid (18:1) was the dominant monounsaturated fatty acid, whereas polyunsaturates

  12. Response to exogenous surfactant is different during open lung and conventional ventilation

    NARCIS (Netherlands)

    van Kaam, Anton H.; Haitsma, Jack J.; Dik, Willem A.; Naber, Birgitta A.; Alblas, Elise H.; de Jaegere, Anne; Kok, Joke H.; Lachmann, Burkhard

    2004-01-01

    Objective: Previous studies have shown that the efficacy of exogenous surfactant is dose-dependent during conventional positive pressure ventilation (PPVCON). The present study aimed to determine whether this dose-dependent relationship is also present during open lung (OLC) ventilation. We also

  13. Dynamic strength of the interaction between lung surfactant protein D (SP-D) and saccharide ligands

    DEFF Research Database (Denmark)

    Thormann, Esben; Dreyer, Jakob K; Simonsen, Adam C

    2007-01-01

    In order to investigate the dynamic strength of the interaction between lung surfactant protein D (SP-D) and different sugars, maltose, mannose, glucose, and galactose, we have used an atomic force microscope to monitor the interaction on a single molecule scale. The experiment is performed...

  14. Effect of Minimally Invasive Surfactant Therapy on Lung Volume and Ventilation in Preterm Infants

    NARCIS (Netherlands)

    van der Burg, Pauline S.; de Jongh, Frans H.; Miedema, Martijn; Frerichs, Inez; van Kaam, Anton H.

    2016-01-01

    To assess the changes in (regional) lung volume and gas exchange during minimally invasive surfactant therapy (MIST) in preterm infants with respiratory distress syndrome. In this prospective observational study, infants requiring a fraction of inspired oxygen (FiO2) ≥ 0.30 during nasal continuous

  15. Lessons from the biophysics of interfaces: Lung surfactant and tear fluid

    DEFF Research Database (Denmark)

    Rantamaki, A.; Telenius, J.; Koivuniemi, A.

    2011-01-01

    to the epithelium and an anterior lipid layer at the air-water interface. The aqueous layers contain soluble proteins and metabolites, and they are responsible for the host defence system and nutrition of the organ. However, many proteins also interact with the lipid layer and are important for the surface...... proportion and the spectrum of different polar and non-polar lipids seem to be more extensive in tear fluid than in lung surfactant. The differing lipid compositions generate distinctive lipid layer structures. Despite the structural differences, these lipid layers decrease the surface tension of the air......-water interface. The structure of the tear film lipid layer also minimises the evaporation of the tear fluid. In lung surfactant surface activity is crucial for the function of the organ, as the lipid layer prevents the collapse of the lung alveoli during the compression-expansion cycle of breathing. Similarly...

  16. Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

    Science.gov (United States)

    Abdullah, Mahdi; Goldmann, Torsten

    2012-11-20

    Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

  17. A comparison of conventional surfactant treatment and partial liquid ventilation on the lung volume of injured ventilated small lungs

    International Nuclear Information System (INIS)

    Proquitté, Hans; Hartenstein, Sebastian; Wauer, Roland R; Schmalisch, Gerd; Koelsch, Uwe; Rüdiger, Mario

    2013-01-01

    As an alternative to surfactant therapy (ST), partial liquid ventilation (PLV) with perfluorocarbons (PFC) has been considered as a treatment for acute lung injury (ALI) in newborns. The instilled PFC is much heavier than the instilled surfactant and the aim of this study was to investigate whether PLV, compared to ST, increases the end-expiratory volume of the lung (V L ). Fifteen newborn piglets (age <12 h, mean weight 678 g) underwent saline lung lavage to achieve a surfactant depletion. Thereafter animals were randomized to PLV (n = 8), receiving PFC PF5080 (3M, Germany) at 30 mL kg −1 , and ST (n = 7) receiving 120 mg Curosurf®. Blood gases, hemodynamics and static compliance were measured initially (baseline), immediately after ALI, and after 240 min mechanical ventilation with either technique. Subsequently all piglets were killed; the lungs were removed in toto and frozen in liquid N 2 . After freeze-drying the lungs were cut into lung cubes (LCs) with edge lengths of 0.7 cm, to calculate V L . All LCs were weighed and the density of the dried lung tissue was calculated. No statistically significant differences between treatment groups PLV and ST (means ± SD) were noted in body weight (676 ± 16 g versus 679 ± 17 g; P = 0.974) or lung dry weight (1.64 ± 0.29 g versus 1.79 ± 0.48 g; P = 0.48). Oxygenation index and ventilatory efficacy index did not differ significantly between both groups at any time. V L (34.28 ± 6.13 mL versus 26.22 ± 8.1 mL; P < 0.05) and the density of the dried lung tissue (48.07 ± 5.02 mg mL −1 versus 69.07 ± 5.30 mg mL −1 ; P < 0.001), however, differed significantly between the PLV and ST groups. A 4 h PLV treatment of injured ventilated small lungs increased V L by 30% and decreased lung density by 31% compared to ST treatment, indicating greater lung distension after PLV compared to ST. (paper)

  18. Bronchoalveolar lavage with pulmonary surfactant/dextran mixture improves meconium clearance and lung functions in experimental meconium aspiration syndrome.

    Science.gov (United States)

    Calkovska, Andrea; Mokra, Daniela; Drgova, Anna; Zila, Ivan; Javorka, Kamil

    2008-08-01

    Surfactant lung lavage is a promising approach in the treatment of meconium aspiration syndrome (MAS). We hypothesise that the enrichment of modified natural surfactant with dextran will enhance meconium clearance from the airspaces during lung lavage and improve lung function in experimental MAS. Human meconium (30 mg/ml; 4 ml/kg) was instilled into the tracheal cannula of anaesthetised and paralysed adult rabbits to induce respiratory failure. The animals were then lavaged with saline (Sal), surfactant without (Surf) and with dextran (Surf+dex). Lung lavage (10 ml/kg in three portions) was performed with diluted surfactant (Curosurf, 10 mg/ml, 100 mg/kg) without or with dextran (3 mg/mg of surfactant phospholipids) or saline and the animals were conventionally ventilated with 100% O(2) for an additional hour. Lung functions were measured prior to and after meconium instillation, and 10, 30 and 60 min after lavage. The recovery of meconium in bronchoalveolar lavage (BAL) fluid was quantified. More meconium solids was recovered in the surfactant-lavaged than in the saline-lavaged groups (Surf: 12.4 +/- 3.9% and Surf+dex: 17.5 +/- 3.5% vs. Sal: 4.8 +/- 1.0%; both P meconium solids was obtained by Curosurf/dextran than by Curosurf-only lavage (P meconium clearance and lung functions in surfactant-lavaged rabbits with meconium aspiration.

  19. Surfactant administration for neonatal respiratory distress does not improve lung interstitial fluid clearance: echographic and experimental evidence.

    Science.gov (United States)

    Cattarossi, Luigi; Copetti, Roberto; Poskurica, Besa; Miserocchi, Giuseppe

    2010-09-01

    Recent ultrasonographic studies suggest that the administration of surfactant to preterm infants with respiratory distress syndrome (RDS) does not affect lung water clearance. The purpose of the study was also to look at clearance of lung water in preterm rabbits receiving surfactant. Lung ultrasound was performed in 73 neonates at different gestational ages (range 23-34 weeks) with radiological and clinical signs of RDS, before and after surfactant administration. In premature rabbits (28-29 days' gestational age), either receiving or not receiving surfactant, we followed the time course of lung water balance considering the wet weight/dry weight ratio, the morphology and compliance of alveoli and pulmonary interstitial pressure. In all RDS infants lung ultrasound images consistently showed a generalized increase in extravascular lung fluid which remained unchanged after surfactant administration and did not affect the rate of fluid clearance. Surfactant administration in premature rabbits did not improve the time course of lung fluid clearance. Data from ultrasound in preterm babies are confirmed by animal experiments.

  20. Dosimetric lung models

    International Nuclear Information System (INIS)

    James, A.C.; Roy, M.

    1986-01-01

    The anatomical and physiological factors that vary with age and influence the deposition of airborne radionuclides in the lung are reviewed. The efficiency with which aerosols deposit in the lung for a given exposure at various ages from birth to adulthood is evaluated. Deposition within the lung is considered in relation to the clearance mechanisms acting in different regions or compartments. The procedure for evaluating dose to sensitive tissues in lung and transfer to other organs that is being considered by the Task Group established by ICRP to review the Lung Model is outlined. Examples of the application of this modelling procedure to evaluate lung dose as a function of age are given, for exposure to radon daughters in dwellings, and for exposure to an insoluble 239 Pu aerosol. The former represents exposure to short-lived radionuclides that deliver relatively high doses to bronchial tissue. In this case, dose rates are marginally higher in children than in adults. Plutonium exposure represents the case where dose is predominantly delivered to respiratory tissue and lymph nodes. In this case, the life-time doses tend to be lower for exposure in childhood. Some of the uncertainties in this modelling procedure are noted

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

    Science.gov (United States)

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

    2017-12-01

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

  2. Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

    Directory of Open Access Journals (Sweden)

    Rizzi Sabina

    2011-03-01

    Full Text Available Abstract Background Patients with Adult Respiratory Distress Syndrome (ARDS and Acute Lung Injury (ALI have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover. Objectives To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls. Methods 2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured. Results 1 Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2 In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p Conclusions 1 Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2 In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.

  3. The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

    OpenAIRE

    Scott, J Elliott

    2004-01-01

    Abstract Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactan...

  4. Diseases of Pulmonary Surfactant Homeostasis

    Science.gov (United States)

    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

  5. Biophysical mimicry of lung surfactant protein B by random nylon-3 copolymers.

    Science.gov (United States)

    Dohm, Michelle T; Mowery, Brendan P; Czyzewski, Ann M; Stahl, Shannon S; Gellman, Samuel H; Barron, Annelise E

    2010-06-16

    Non-natural oligomers have recently shown promise as functional analogues of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Here we present an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of beta-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B. Attachment of an N-terminal octadecanoyl unit to the nylon-3 copolymers, inspired by the post-translational modifications found in SP-C, affords further improvements by reducing the percent surface area compression to reach low minimum surface tension. Cytotoxic effects of the copolymers are diminished relative to that of an SP-B-derived peptide and a peptoid-based mimic. The current study provides evidence that sequence-random copolymers can mimic the in vitro surface-active behavior of lung surfactant proteins in a mixed lipid film. These findings raise the possibility that random copolymers might be useful for developing a lung surfactant replacement, which is an attractive prospect given that such polymers are easier to prepare than are sequence-specific oligomers.

  6. Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

    Science.gov (United States)

    Mishra, Amarjit; Chintagari, Narendranath Reddy; Guo, Yujie; Weng, Tingting; Su, Lijing; Liu, Lin

    2011-01-01

    Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X7 receptor (P2X7R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X7R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X7R) increased surfactant secretion, which was blocked by the P2X7R antagonist Brilliant Blue G. This effect was observed in AEC II co-cultured with human embryonic kidney HEK-293 cells stably expressing rat P2X7R, but not when co-cultured with AEC I in which P2X7R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X7R−/− mice. BzATP-mediated secretion involved P2Y2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X7R cells than with ATP alone. P2X7R−/− mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X7R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X7R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y2 receptors in AEC II. PMID:21266468

  7. Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

    Directory of Open Access Journals (Sweden)

    Julie G Ledford

    Full Text Available Surfactant protein-A (SP-A has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT and SP-A(-/- allergic mice challenged with the model antigen ovalbumin (Ova that were concurrently infected with Mp (Ova+Mp to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO, which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/- mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation

  8. Low Concentration Ozone Reacts with Plasmalogen Glycerophosphoethanolamine Lipids in Lung Surfactant

    Science.gov (United States)

    Wynalda, Kelly M.; Murphy, Robert C.

    2009-01-01

    Ozone is a common environmental toxicant to which individuals are exposed to on a daily basis. While biochemical endpoints such as increased mortality, decrements in pulmonary function and initiation of inflammatory processes are known, little is actually understood regarding the chemical mechanisms underlying changes in pulmonary health, especially for low concentrations of ozone. This study was undertaken to investigate ozone induced oxidation of endogenous lipids that are potentially exposed to environmental ozone within lung, specifically focusing on plasmalogen glycerophospholipids present in pulmonary surfactant. Sensitive liquid chromatography-mass spectrometry methods were developed to follow oxidation of diacyl and plasmalogen phosphatidylethanolamine (PE) phospholipids, and to identify and quantitate products generated by ozonolysis. Using a unilamellar vesicle system containing a 1:1 molar mixture of 1-O-octadec-1’-enyl-2-octadecenoyl-PE and 1,2-dihexadecanoyl-PC, these studies revealed the vinyl ether bond of plasmalogens was oxidized preferentially at low concentrations of ozone (100 ppb), when compared to olefinic bond oxidation on ω-9 of the fatty acyl chain in the same phospholipids. Major phospholipid products generated were identified as 1-formyl-2-octadecenoyl-PE and 1-hydroxy-2-octadecenoyl-PE. Heptadecanal and heptadecanoic acid production was also quantitated using gas chromatography-mass spectrometry and production was consistent with oxidation of the vinyl ether, at low concentrations of ozone. Analysis of murine lung surfactant from C57Bl/6 mice revealed several plasmalogen PE lipid species, encompassing ~38% of total PE species. Upon exposure of ozone (0 ppb, 100 ppb) to murine surfactant, plasmalogen PE molecular species preferentially reacted, as compared to diacyl PE molecular species. Lysophospholipids, pentadecanal, and nonanal were found to be the primary products of surfactant ozone oxidation. PMID:19916514

  9. A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

    Directory of Open Access Journals (Sweden)

    Wang SM

    2015-04-01

    Full Text Available Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 2School of Medicine, Suzhou University, SuZhou, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 4Department of Chest Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5CSIRO (Commonwealth Scientific and Industrial Research Materials Science and Engineering, Clayton, 6CSIRO Materials Science and Engineering, Parkville, Melbourne, VIC, Australia; 7Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA *These authors contributed equally to this work Abstract: Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high

  10. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.

    2013-01-01

    in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP...... injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically....... The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation....

  11. Dynamic modeling of surfactant flooding in low permeable argillaceous reservoirs

    Science.gov (United States)

    Kuznetsova, A. N.; Gunkin, A. S.; Rogachev, M. К

    2017-10-01

    This article reveals the current state and problems of the Russian oil production sector. Physicochemical enhanced oil recovery methods are proposed as a solution. The investigation of surfactant treatment efficiency and their integrated effect on oil and reservoir rock is conducted as well as its applicability analysis for low permeable poly-mineral reservoir. The results of dynamic modeling of oil displacement by the developed surfactant composition in a low permeable reservoir are presented.

  12. Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids

    Directory of Open Access Journals (Sweden)

    Robert H. Notter

    2016-10-01

    Full Text Available Background This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC and palmitoyl-oleoyl phosphatidylglycerol (POPG, while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight. The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Methods Surface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2 to <100 mmHg, consistent with clinical acute respiratory distress syndrome (ARDS. Results Synthetic surfactants containing 5:3:2 DPPC:POPC:POPG or 9:1 DEPN-8:PG-1 combined with 3% (by wt of S-MB DATK, 3% SP-Css ion-lock 1, or 1.5% each of both peptides all adsorbed rapidly to low equilibrium surface tensions and also reduced surface tension to ≤1 mN/m under dynamic compression at 37 °C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with

  13. Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids.

    Science.gov (United States)

    Notter, Robert H; Gupta, Rohun; Schwan, Adrian L; Wang, Zhengdong; Shkoor, Mohanad Gh; Walther, Frans J

    2016-01-01

    This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Surface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO 2 to surfactants containing 5:3:2 DPPC:POPC:POPG or 9:1 DEPN-8:PG-1 combined with 3% (by wt) of S-MB DATK, 3% SP-Css ion-lock 1, or 1.5% each of both peptides all adsorbed rapidly to low equilibrium surface tensions and also reduced surface tension to ≤1 mN/m under dynamic compression at 37 °C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with 9:1 DEPN-8:PG-1 or 5:3:2 DPPC:POPC:POPG had the greatest in vivo activity in improving arterial oxygenation and dynamic lung

  14. Developmental regulation of chicken surfactant protein A and its localization in lung

    DEFF Research Database (Denmark)

    Zhang, Weidong; Cuperus, Tryntsje; van Dijk, Albert

    2016-01-01

    in the lung lining fluid covering the parabronchial epithelia. Specific cSP-A producing epithelial cells, resembling mammalian type II cells, were identified in the parabronchi. Gene expression of cSP-A markedly increased from embryonic day 14 onwards until the time of hatch, comparable to the SP-A homologue......Surfactant Protein A (SP-A) is a collagenous C-type lectin (collectin) that plays an important role in the early stage of the host immune response. In chicken, SP-A (cSP-A) is expressed as a 26 kDa glycosylated protein in the lung. Using immunohistochemistry, cSP-A protein was detected mainly...... chicken lung lectin, while mannan binding lectin and collectins CL-L1 and CL-K1 only showed slightly changed expression during development. cSP-A protein could be detected as early as ED 18 in lung tissue using Western blotting, and expression increased steadily until day 28 post-hatch. Our observations...

  15. Mathematical Modelling of Surfactant Self-assembly at Interfaces

    KAUST Repository

    Morgan, C. E.

    2015-01-01

    © 2015 Society for Industrial and Applied Mathematics. We present a mathematical model to describe the distribution of surfactant pairs in a multilayer structure beneath an adsorbed monolayer. A mesoscopic model comprising a set of ordinary differential equations that couple the rearrangement of surfactant within the multilayer to the surface adsorption kinetics is first derived. This model is then extended to the macroscopic scale by taking the continuum limit that exploits the typically large number of surfactant layers, which results in a novel third-order partial differential equation. The model is generalized to allow for the presence of two adsorbing boundaries, which results in an implicit free-boundary problem. The system predicts physically observed features in multilayer systems such as the initial formation of smaller lamellar structures and the typical number of layers that form in equilibrium.

  16. The origin and evolution of the surfactant system in fish: insights into the evolution of lungs and swim bladders.

    Science.gov (United States)

    Daniels, Christopher B; Orgeig, Sandra; Sullivan, Lucy C; Ling, Nicholas; Bennett, Michael B; Schürch, Samuel; Val, Adalberto Luis; Brauner, Colin J

    2004-01-01

    Several times throughout their radiation fish have evolved either lungs or swim bladders as gas-holding structures. Lungs and swim bladders have different ontogenetic origins and can be used either for buoyancy or as an accessory respiratory organ. Therefore, the presence of air-filled bladders or lungs in different groups of fishes is an example of convergent evolution. We propose that air breathing could not occur without the presence of a surfactant system and suggest that this system may have originated in epithelial cells lining the pharynx. Here we present new data on the surfactant system in swim bladders of three teleost fish (the air-breathing pirarucu Arapaima gigas and tarpon Megalops cyprinoides and the non-air-breathing New Zealand snapper Pagrus auratus). We determined the presence of surfactant using biochemical, biophysical, and morphological analyses and determined homology using immunohistochemical analysis of the surfactant proteins (SPs). We relate the presence and structure of the surfactant system to those previously described in the swim bladders of another teleost, the goldfish, and those of the air-breathing organs of the other members of the Osteichthyes, the more primitive air-breathing Actinopterygii and the Sarcopterygii. Snapper and tarpon swim bladders are lined with squamous and cuboidal epithelial cells, respectively, containing membrane-bound lamellar bodies. Phosphatidylcholine dominates the phospholipid (PL) profile of lavage material from all fish analyzed to date. The presence of the characteristic surfactant lipids in pirarucu and tarpon, lamellar bodies in tarpon and snapper, SP-B in tarpon and pirarucu lavage, and SPs (A, B, and D) in swim bladder tissue of the tarpon provide strong evidence that the surfactant system of teleosts is homologous with that of other fish and of tetrapods. This study is the first demonstration of the presence of SP-D in the air-breathing organs of nonmammalian species and SP-B in actinopterygian

  17. Statistical lung model for microdosimetry

    International Nuclear Information System (INIS)

    Fisher, D.R.; Hadley, R.T.

    1984-03-01

    To calculate the microdosimetry of plutonium in the lung, a mathematical description is needed of lung tissue microstructure that defines source-site parameters. Beagle lungs were expanded using a glutaraldehyde fixative at 30 cm water pressure. Tissue specimens, five microns thick, were stained with hematoxylin and eosin then studied using an image analyzer. Measurements were made along horizontal lines through the magnified tissue image. The distribution of air space and tissue chord lengths and locations of epithelial cell nuclei were recorded from about 10,000 line scans. The distribution parameters constituted a model of lung microstructure for predicting the paths of random alpha particle tracks in the lung and the probability of traversing biologically sensitive sites. This lung model may be used in conjunction with established deposition and retention models for determining the microdosimetry in the pulmonary lung for a wide variety of inhaled radioactive materials

  18. [Lung ultrasound as a tool to guide the administration of surfactant in premature neonates].

    Science.gov (United States)

    Rodríguez-Fanjul, J; Balcells Esponera, C; Moreno Hernando, J; Sarquella-Brugada, G

    2016-05-01

    The aim of this study is to assess the usefulness of lung ultrasound (LUS) to estimate the endotracheal tube (ETT) depth position during the Intubation-Surfactant-Extubation (INSURE) procedure. The ETT insertion depth was estimated using the weight (insertion depth (cm)=weight (kg)+5.5). After intubation two independent neonatologists using bilateral auscultation or LUS checked the ETT depth. Twelve newborns with respiratory distress syndrome were included. In two cases LUS helped to correctly replace the ETT. All the patients progressed well, with normal x-ray and LUS before discharge. LUS appears to be a safe and non-invasive technique and is useful in clinical situations were x-ray is not routinely performed, as it is fast and radiation free. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. Alterations of alveolar type II cells and intraalveolar surfactant after bronchoalveolar lavage and perfluorocarbon ventilation. An electron microscopical and stereological study in the rat lung

    Directory of Open Access Journals (Sweden)

    Burkhardt Wolfram

    2007-06-01

    Full Text Available Abstract Background Repeated bronchoalveolar lavage (BAL has been used in animals to induce surfactant depletion and to study therapeutical interventions of subsequent respiratory insufficiency. Intratracheal administration of surface active agents such as perfluorocarbons (PFC can prevent the alveolar collapse in surfactant depleted lungs. However, it is not known how BAL or subsequent PFC administration affect the intracellular and intraalveolar surfactant pool. Methods Male wistar rats were surfactant depleted by BAL and treated for 1 hour by conventional mechanical ventilation (Lavaged-Gas, n = 5 or partial liquid ventilation with PF 5080 (Lavaged-PF5080, n = 5. For control, 10 healthy animals with gas (Healthy-Gas, n = 5 or PF5080 filled lungs (Healthy-PF5080, n = 5 were studied. A design-based stereological approach was used for quantification of lung parenchyma and the intracellular and intraalveolar surfactant pool at the light and electron microscopic level. Results Compared to Healthy-lungs, Lavaged-animals had more type II cells with lamellar bodies in the process of secretion and freshly secreted lamellar body-like surfactant forms in the alveoli. The fraction of alveolar epithelial surface area covered with surfactant and total intraalveolar surfactant content were significantly smaller in Lavaged-animals. Compared with Gas-filled lungs, both PF5080-groups had a significantly higher total lung volume, but no other differences. Conclusion After BAL-induced alveolar surfactant depletion the amount of intracellularly stored surfactant is about half as high as in healthy animals. In lavaged animals short time liquid ventilation with PF5080 did not alter intra- or extracellular surfactant content or subtype composition.

  20. Interindividual variability in the expression of surfactant protein A and B in the human lung during development

    Directory of Open Access Journals (Sweden)

    F. Cau

    2016-09-01

    Full Text Available The surfactant complex, thanks to its multiple actions including decrease of surface- tension and antimicrobial activity, plays a fundamental role in newborn survival, lowering the risk of respiratory distress syndrome. The aim of this work was to determine if the synthesis of two surfactant proteins (SP, SPA and pro-SPB, shows some inter-individual variability during lung development in the intrauterine life. Immunoreactivity for SPA and pro-SPB was investigated in the lungs of  40 subjects, including 15 fetuses, ranging from 14 to 22 weeks of gestation, and 25 neonates, from 24 to 41 weeks. Lung samples were formalin fixed, paraffin-embedded and routinely processed. SPA and pro-SPB were detected utilizing commercial antibodies.  A semi-quantitative grading system (1 to 4 was applied, based on the number of reactive cells and the intensity of immunostaining. Surfactant protein immunostaining was found in  three compartments: bronchi, bronchioles and alveoli, starting from 14 weeks of gestation in the bronchial epithelium and from the 21st week in the alveolar spaces. Differences were found regarding SPA and pro-SPB expression in the vast majority of subjects: in some lungs, SPA was more expressed whereas in others pro-SPB showed an higher degree of immunoreactivity. The expression of both surfactant proteins was not strictly correlated with gestational age. Whereas the highest levels of reactivity were detected in at term neonates, on the other hand one case with grade 3 was detected at 22 weeks and one negative case for both proteins was observed at 31 weeks. Our data clearly show a marked inter-individual variability regarding the production of SPA and pro-SPB and suggest the existence of other epigenetic factors, acting during gestation, that might influence surfactant production and, consequently, the survival potential of  neonates at birth. 

  1. Impact of model perfumes on surfactant and mixed surfactant self-assembly.

    Science.gov (United States)

    Penfold, J; Tucker, I; Green, A; Grainger, D; Jones, C; Ford, G; Roberts, C; Hubbard, J; Petkov, J; Thomas, R K; Grillo, I

    2008-11-04

    The impact of some model perfumes on surfactant self-assembly has been investigated, using small-angle neutron scattering. A range of different model perfumes, with differing degrees of hydrophilicity/hydrophobicity, have been explored, and in order of increasing hydrophobicity include phenyl ethanol (PE), rose oxide (RO), limonene (LM), linalool (LL), and dihydrogen mercenol (DHM). The effect of their solubilization on the nonionic surfactant micelles of dodecaethylene monododecyl ether (C12EO12) and on the mixed surfactant aggregates of C12EO12 and the cationic dialkyl chain surfactant dihexadecyl dimethyl ammonium bromide (DHDAB) has been quantified. For PE and LL the effect of their solubilization on the micelle, mixed micelle/lamellar and lamellar regimes of the C12EO12/DHDAB mixtures, has also been determined. For the C12EO12 and mixed DHDAB/C12EO12 micelles PE is solubilized predominantly at the hydrophilic/hydrophobic interface, whereas the more hydrophobic perfumes, from RO to DHM, are solubilized predominantly in the hydrophobic core of the micelles. For the C12EO12 micelles, with increasing perfume concentration, the more hydrophobic perfumes (RO to DHM) promote micellar growth. Relatively modest growth is observed for RO and LM, whereas substantial growth is observed for LL and DHM. In contrast, for the addition of PE the C12EO12 micelles remain as relatively small globular micelles, with no significant growth. For the C12EO12/DHDAB mixed micelles, the pattern of behavior with the addition of perfume is broadly similar, except that the micellar growth with increasing perfume concentration for the more hydrophobic perfumes is less pronounced. In the Lbeta (Lv) region of the DHDAB-rich C12EO12/DHDAB phase diagram, the addition of PE results in a less structured (less rigid) lamellar phase, and ultimately a shift toward a structure more consistent with a sponge or bicontinuous phase. In the mixed L1/Lbeta region of the phase diagram PE induces a slight

  2. Computational multiscale toxicodynamic modeling of silver and carbon nanoparticle effects on mouse lung function.

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    Full Text Available A computational, multiscale toxicodynamic model has been developed to quantify and predict pulmonary effects due to uptake of engineered nanomaterials (ENMs in mice. The model consists of a collection of coupled toxicodynamic modules, that were independently developed and tested using information obtained from the literature. The modules were developed to describe the dynamics of tissue with explicit focus on the cells and the surfactant chemicals that regulate the process of breathing, as well as the response of the pulmonary system to xenobiotics. Alveolar type I and type II cells, and alveolar macrophages were included in the model, along with surfactant phospholipids and surfactant proteins, to account for processes occurring at multiple biological scales, coupling cellular and surfactant dynamics affected by nanoparticle exposure, and linking the effects to tissue-level lung function changes. Nanoparticle properties such as size, surface chemistry, and zeta potential were explicitly considered in modeling the interactions of these particles with biological media. The model predictions were compared with in vivo lung function response measurements in mice and analysis of mice lung lavage fluid following exposures to silver and carbon nanoparticles. The predictions were found to follow the trends of observed changes in mouse surfactant composition over 7 days post dosing, and are in good agreement with the observed changes in mouse lung function over the same period of time.

  3. X-Ray Diffraction and Reflectivity Validation of the Depletion Attraction in the Competitive Adsorption of Lung Surfactant and Albumin

    DEFF Research Database (Denmark)

    Stenger, Patric C.; Wu, Guohui; Miller, Chad E.

    2009-01-01

    Lung surfactant (LS) and albumin compete for the air-water interface when both are present in solution. Equilibrium favors LS because it has a lower equilibrium surface pressure, but the smaller albumin is kinetically favored by faster diffusion. Albumin at the interface creates an energy barrier...... and the interface that enhances LS adsorption without substantially altering the structure or properties of the LS monolayer....

  4. The nanoparticle corona in the deep lung : pulmonary surfactant adsorption and its role in nano-bio interactions

    OpenAIRE

    Räsch, Simon Sebastian

    2016-01-01

    Nanoparticles (NPs) for drug delivery to the respiratory tract are of considerable interest, for the treatment of chronic and acute pulmonary and systemic disorders, promising the potential for sustained release and targeted delivery. Although the targets for these formulations are usually cells, the NPs, once inhaled, first encounter a non-cellular barrier in the deep lung: the pulmonary surfactant (PS). This is a lipid-protein mixture which covers the alveoli and enables gas exchange as a r...

  5. Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

    Directory of Open Access Journals (Sweden)

    Cogo Paola E

    2007-02-01

    Full Text Available Abstract Background In patients with acute respiratory distress syndrome (ARDS, it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes. Methods We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of 13C-dipalmitoyl-phosphatidylcholine, we measured the 13C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds. Results In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08. Conclusion In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered.

  6. Genetics Home Reference: surfactant dysfunction

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Surfactant dysfunction Surfactant dysfunction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Surfactant dysfunction is a lung disorder that causes breathing ...

  7. Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies

    Directory of Open Access Journals (Sweden)

    Mercer Robert R

    2010-10-01

    Full Text Available Abstract Background Accumulating evidence indicate that the degree of dispersion of nanoparticles has a strong influence on their biological activities. The aims of this study were to develop a simple and rapid method of nanoparticle dispersion using a natural lung surfactant and to evaluate the effect of dispersion status of SWCNT on cytotoxicity and fibrogenicity in vitro and in vivo. Results The natural lung surfactant Survanta® was used to disperse single-walled carbon nanotubes (SWCNT in a biological medium. At physiologically relevant concentrations, Survanta® produced well dispersed SWCNT without causing a cytotoxic or fibrogenic effect. In vitro studies show that Survanta®-dispersed SWCNT (SD-SWCNT stimulated proliferation of lung epithelial cells at low doses (0.04-0.12 μg/ml or 0.02-0.06 μg/cm2 exposed surface area but had a suppressive effect at high doses. Non-dispersed SWCNT (ND-SWCNT did not exhibit these effects, suggesting the importance of dispersion status of SWCNT on bioactivities. Studies using cultured human lung fibroblasts show that SD-SWCNT stimulated collagen production of the cells. This result is supported by a similar observation using Acetone/sonication dispersed SWCNT (AD-SWCNT, suggesting that Survanta® did not mask the bioactivity of SWCNT. Likewise, in vivo studies show that both SD-SWCNT and AD-SWCNT induced lung fibrosis in mice, whereas the dispersing agent Survanta® alone or Survanta®-dispersed control ultrafine carbon black had no effect. Conclusions The results indicate that Survanta® was effective in dispersing SWCNT in biological media without causing cytotoxic effects at the test concentrations used in this study. SD-SWCNT stimulated collagen production of lung fibroblasts in vitro and induced lung fibrosis in vivo. Similar results were observed with AD-SWCNT, supporting the conclusion that Survanta® did not mask the bioactivities of SWCNT and thus can be used as an effective dispersing agent

  8. Effects of simulated microgravity on surfactant and water balance of lung in animals with different resistance to stress

    Science.gov (United States)

    Bryndina, Irina; Vasilieva, Natalia

    Weightlessness is accompanied by redistribution of blood flow in lung, changes of lung volumes and gas exchange (Prisk et al., 2002; Grigoriev, Baranov, 2003). On the other hand, it is known that microgravity is considered as a kind of moderate stress (Grigoriev et al., 2004). Stress response may differ in animals resistant or vulnerable to stress (Sudakov, 2007). To study the effects of simulated microgravity upon lung, we used 20 male albino rats tested for behavior in the "open field" and than divided into active (stress resistant - SR ) and passive (stress vulnerable - CV) groups. Two mouse lines were used with similar goal - C57Bl/6 and BALB/c mice (n=16). According to data obtained earlier, BALB/c mice referred as more stress vulnerable, in contrast to C57BL/6 mice, which are considered to be relatively stress resistant (Flint et al., 2007). We have previously shown that changes in lung surfactant system after psychosocial stress or long-term immobilization are less pronounced in stress resistant rats (Vasilieva, Bryndina, 2012). The aim of this work is to study the properties and biochemical composition of pulmonary surfactant and lung water balance in rats and mice with different stress resistance in antiorthostatic suspension (AOS) of short and long duration. Simulated microgravity was reproduced according to procedure of Ilyin-Novikov in modification of Morey-Holton. The duration of exposure was 10 days for rats and 30 days for mice. The properties of pulmonary surfactant were assessed by the evaluation of surface activity (surface tension - ST), the content of total phospholipids (PL) and their fractions. Simultaneously we calculated the gravimetric water balance indices: lung coefficient, "dry residue" and wet-to-dry ratio. Total and extravascular lung fluid and pulmonary blood supply were estimated as well. The experiments demonstrated that there was a decrease of surface tension of surfactant films after 10-day AOS in both groups of rats (to a greater

  9. Delivery and performance of surfactant replacement therapies to treat pulmonary disorders

    Science.gov (United States)

    El-Gendy, Nashwa; Kaviratna, Anubhav; Berkland, Cory; Dhar, Prajnaparamita

    2013-01-01

    Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed. PMID:23919474

  10. Surfactant Phosphatidylcholine Metabolism in Severe Neonatal Lung Disease: Studied with Stable Isotopes

    NARCIS (Netherlands)

    D.J.M.T. Janssen (Daphne)

    2003-01-01

    markdownabstract__Abstract__ Avery and Mead showed in 1959 that pulmonary surfactant deficiency is a major factor in the pathophysiology of respiratory distress syndrome (RDS). In 1980 Fujiwara et al. administered exogenous surfactant for the first time successfully to preterm infants with RDS

  11. The interaction of a model active pharmaceutical with cationic surfactant and the subsequent design of drug based ionic liquid surfactants.

    Science.gov (United States)

    Qamar, Sara; Brown, Paul; Ferguson, Steven; Khan, Rafaqat Ali; Ismail, Bushra; Khan, Abdur Rahman; Sayed, Murtaza; Khan, Asad Muhammad

    2016-11-01

    Interactions of active pharmaceutical ingredients (API) with surfactants remain an important research area due to the need to improve drug delivery systems. In this study, UV-Visible spectrophotometry was used to investigate the interactions between a model low molecular weight hydrophilic drug sodium valproate (SV) and cationic surfactant cetyltrimethylammonium bromide (CTAB). Changes in the spectra of SV were observed in pre- and post-micellar concentrations of CTAB. The binding constant (Kb) values and the number of drug molecules encapsulated per micelle were calculated, which posed the possibility of mixed micelle formation and strong complexation between SV and CTAB. These results were compared to those of a novel room temperature surface active ionic liquid, which was synthesized by the removal of inorganic counterions from a 1:1 mixture of CTAB and SV. In this new compound the drug now constitutes a building block of the carrier and, as such, has considerably different surfactant properties to its building blocks. In addition, enhanced solubility in a range of solvents, including simulated gastric fluid, was observed. The study provides valuable experimental evidence concerning the performance of drug based surfactant ionic liquids and how their chemical manipulation, without altering the architecture of the API, leads to control of surfactant behavior and physicochemical properties. In turn, this should feed through to improved and controlled drug release rates and delivery mechanisms, and the prevention of precipitation or formation of polymorphs typical of crystalline form APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Surfactant with and without bronchoalveolar lavage in an experimental model of meconium aspiration syndrome.

    Science.gov (United States)

    Henn, Roseli; Fiori, Renato Machado; Fiori, Humberto Holmer; Pereira, Manuel Ruttkay; Colvero, Maurício Obal; Ramos Garcia, Pedro Celiny; Padoim, Priscila; Stivanin, Jaqueline Basso

    2016-08-01

    To assess the effect of surfactant administration, preceded or not by bronchoalveolar lavage (BAL) with dilute surfactant, on pulmonary function in experimental severe meconium aspiration syndrome. Twenty-one newborn pigs received 20% meconium in saline intratracheally and were randomly allocated to one of three groups: I, control; II, surfactant only (poractant alfa, 200 mg/kg); or III, dilute surfactant BAL followed by 125 mg/kg surfactant. Arterial blood gases (ABGs), lung compliance, and resistance were assessed. Thirty minutes after treatment, mean PaO2 (mm Hg) increased to 72 in group I, to 106 in group II and to 172 in group III (P=0.01). After 3 h, mean PaO2 (mm Hg) was 70 in group I, 95 in group II and 198 in group III (P<0.01). After 6 h, it was 79 in group I, 110 in group II, and 217 in group III (P=0.01). From the 30-min point onward, there were significant differences among treatment groups in all other parameters and at every point of assessment, except for compliance and resistance 3 h after treatment. BAL with dilute surfactant, followed by an additional dose of surfactant, produced significant improvements in ABGs and pulmonary mechanics as compared with a single dose of surfactant.

  13. Models for enzyme superactivity in aqueous solutions of surfactants.

    OpenAIRE

    Viparelli, P; Alfani, F; Cantarella, M

    1999-01-01

    Theoretical models are developed here for enzymic activity in the presence of direct micellar aggregates. An approach similar to that of Bru et al. [Bru, Sánchez-Ferrer and Garcia-Carmona (1989) Biochem. J. 259, 355-361] for reverse micelles has been adopted. The system is considered to consist of three pseudo-phases: free water, bound water and surfactant tails. The substrate concentration in each pseudo-phase is related to the total substrate concentration in the reaction medium. In the abs...

  14. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Contrast media inhibit exogenous surfactant therapy in rats with acute respiratory distress syndrome

    NARCIS (Netherlands)

    Kesecioglu, Jozef; Haitsma, Jack J.; Schultz, Marcus J.; den Heeten, Gerard J.; Lachmann, Burkhard

    2006-01-01

    AIM: To test the effects of various contrast media on the pulmonary surfactant system. MATERIAL AND METHODS: In a rat model of acute respiratory distress syndrome (ARDS) induced by lung lavage, the effects of surfactant suspended in saline were compared with surfactant suspended in the contrast

  16. Efficiency of Combined Use of a Surfactant and the «Lung Opening» Maneuver in the Treatment of Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    A. V. Vlasenko

    2007-01-01

    Full Text Available The paper discusses whether the «lung opening» maneuver in combination with the endobronchial administration of a pulmonary surfactant can be used in the treatment of patients with acute respiratory distress syndrome (ARDS of various genesis. The authors outline data of their studies of the separate use of both methods and present the results of successful treatment in a patient with severe concomitant injury and posttraumatic ARDS in the combined use of the «lung opening» maneuver and Surfactant-BL. With intensive care, the combined use of these methods is a more effective way of improving gas exchange as compared with their use alone. Key words: acute respiratory distress syndrome, surfactant-BL, «lung opening» maneuver, combined use of both methods.

  17. Surfactant micelles: model systems for flow instabilities of complex fluids.

    Science.gov (United States)

    Perge, Christophe; Fardin, Marc-Antoine; Manneville, Sébastien

    2014-04-01

    Complex fluids such as emulsions, colloidal gels, polymer or surfactant solutions are all characterized by the existence of a "microstructure" which may couple to an external flow on time scales that are easily probed in experiments. Such a coupling between flow and microstructure usually leads to instabilities under relatively weak shear flows that correspond to vanishingly small Reynolds numbers. Wormlike micellar surfactant solutions appear as model systems to study two examples of such instabilities, namely shear banding and elastic instabilities. Focusing on a semidilute sample we show that two-dimensional ultrafast ultrasonic imaging allows for a thorough investigation of unstable shear-banded micellar flows. In steady state, radial and azimuthal velocity components are recovered and unveil the original structure of the vortical flow within an elastically unstable high shear rate band. Furthermore thanks to an unprecedented frame rate of up to 20,000 fps, transients and fast dynamics can be resolved, which paves the way for a better understanding of elastic turbulence.

  18. Intra-amniotic administration of exogenous pulmonary surfactant for improving in lung maturity of fetal rabbits with intrauterine infection caused by premature rupture of membranes

    Directory of Open Access Journals (Sweden)

    Jing Liu

    2011-05-01

    Full Text Available This study was to investigate the effect of intra-amniotic administration of pulmonary surfactant (PS on lung maturation in conditions of experimentally induced premature rupture of membranes (PROM and intrauterine infection of rabbits. To establish animal (rabbit models of intrauterine infection caused by PROM, E. coli was intrauterinely injected in 24-and 26-day pregnant animals. Twenty healthy pregnancy adult Japanese white rabbits were divided into three groups: the infection group (8 rabbits, infection group with intra-amniotic PS administration (8 rabbits and healthy controls (4 rabbits. Ultrastructure changes in the lung were observed under an electron microscope 19.5 hours after intervention. The results showed that the lung infection levels of fetal rabbits in the infection group and the infection group with PS had no significant difference. Bacillus bodies and infiltrated inflammatory cells can be occasionally seen in the alveoli, bronchial lumen, and cytoplasm. The type II alveolar epithelial cells (AT-II were decreased in the infection group than that in control group. Lamellar bodies showed vacuolation changes and different levels of apoptosis. In the infection group with PS, the count of AT-II did not show an obvious decrease. Lamellar bodies increased, and different secretion forms appeared. Also, there was little apoptosis and no obvious collagen fiber hyperplasia in antenatal administration of PS group. We believe that once PROM has happened, intrauterine infection and inflammation stimulated a cascade reaction on the fetal lung, leading to abnormal changes in the alveolar ultrastructure. Intra-amniotic administration of PS can improve the fetal lung ultrastructure and its maturity.

  19. Minimization of Ventilator-Induced Lung Injury in ARDS Patients – Part I: Complex Model of Mechanically Ventilated ARDS Lungs

    Directory of Open Access Journals (Sweden)

    Glapiński Jarosław

    2017-12-01

    Full Text Available A complex model of mechanically ventilated ARDS lungs is proposed in the paper. This analogue is based on a combination of four components that describe breathing mechanics: morphology, mechanical properties of surfactant, tissue and chest wall characteristics. Physical-mathematical formulas attained from experimental data have been translated into their electrical equivalents and implemented in MultiSim software. To examine the adequacy of the forward model to the properties and behaviour of mechanically ventilated lungs in patients with ARDS symptoms, several computer simulations have been performed and reported in the paper. Inhomogeneous characteristics observed in the physical properties of ARDS lungs were mapped in a multi-lobe model and the measured outputs were compared with the data from physiological reports. In this way clinicians and scientists can obtain the knowledge on the moment of airway zone reopening/closure expressed as a function of pressure, volume or even time. In the paper, these trends were assessed for inhomogeneous distributions (proper for ARDS of surfactant properties and airway geometry in consecutive lung lobes. The proposed model enables monitoring of temporal alveolar dynamics in successive lobes as well as those occurring at a higher level of lung structure organization, i.e. in a point P0 which can be used for collection of respiratory data during indirect management of recruitment/de-recruitment processes in ARDS lungs. The complex model and synthetic data generated for various parametrization scenarios make possible prospective studies on designing an indirect mode of alveolar zone management, i.e. with

  20. A liquid CO2-compatible hydrocarbon surfactant: experiment and modelling

    NARCIS (Netherlands)

    Banerjee, S.; Kleijn, J.M.; Cohen Stuart, M.A.; Leermakers, F.A.M.

    2013-01-01

    Surfactants soluble in liquid CO2 are rare and knowledge on interfacial and self-assembly behaviour is fragmented. We found that polyoxyethylene (5) isooctylphenyl ether is interfacially active at the water–liquid CO2 interface. Water–liquid CO2 interfacial tension was measured at various surfactant

  1. Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken design.

    Science.gov (United States)

    Kaur, Prabhjot; Garg, Tarun; Rath, Goutam; Murthy, R S Rayasa; Goyal, Amit K

    2016-07-01

    In the present study, nanostructured lipid carriers (NLCs) along with various surfactants loaded with paclitaxel (PTX) were prepared by an emulsification technique using a Box-Behnken design. The Box-Behnken design indicated that the most effective factors on the size and PDI were at high surfactant concentration (1.5%), low lipids ratio (6:4) and medium homogenization speed (6000 rpm). Among all the formulations, Tween 20-loaded NLCs show least particle size compared to Tween 80 and Tween 60. Entrapment efficiency of Tween 20, Tween 80 and Tween 60-loaded formulations were 82.40, 85.60 and 79.78%, respectively. Drug release of Tween 80, Tween 20 and Tween 60-loaded NLCs is 64.9, 62.3 and 59.7%, respectively (within 72 h). Maximum cellular uptake was observed with Tween 20 formulation on Caco-2 cell lines. Furthermore, spray drying of resultant NLCs was showed good flow properties and was selected for drug delivery to deeper airways. In-vivo studies demonstrated the better localization of drug within the lungs using different surfactant-based pulmonary delivery systems. From this study, we have concluded that delivering drugs through pulmonary route is advantageous for local action in lungs as maximum amount of drug concentration was observed in lungs. The surfactants could prove to be beneficial in treating drug resistance lung cancer by inhibiting P-gp efflux in the form of nano lipidic carriers.

  2. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates. A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition. This protein exists both...

  3. A model of flow and surfactant transport in an oscillatory alveolus partially filled with liquid

    Science.gov (United States)

    Wei, Hsien-Hung; Fujioka, Hideki; Hirschl, Ronald B.; Grotberg, James B.

    2005-03-01

    The flow and transport in an alveolus are of fundamental importance to partial liquid ventilation, surfactant transport, pulmonary drug administration, cell-cell signaling pathways, and gene therapy. We model the system in which an alveolus is partially filled with liquid in the presence of surfactants. By assuming a circular interface due to sufficiently strong surface tension and small surfactant activity, we combine semianalytical and numerical techniques to solve the Stokes flow and the surfactant transport equations. In the absence of surfactants, there is no steady streaming because of reversibility of Stokes flow. The presence of surfactants, however, induces a nontrivial cycle-averaged surfactant concentration gradient along the interface that generates steady streaming. The steady streaming patterns (e.g., number of vortices) particularly depend on the ratio of inspiration to expiration periods (I :E ratio) and the sorption parameter K. For an insoluble surfactant, a single vortex is formed when the I :E ratio is either smaller or larger than 1:1, but the recirculations have opposite directions in the two cases. A soluble surfactant can lead to more complex flow patterns such as three vortices or saddle-point flow structures. The estimated unsteady velocity is 10-3cm/s, and the corresponding Péclet number for transporting respiratory gas is O(1). For a cell-cell signaling molecule such as surfactant-associated protein-A for regulating surfactant secretion, the Péclet number could be O(10) or higher. Convection is either comparable to or more dominant than diffusion in these processes. The estimated steady velocity ranges from 10-6to10-4cm /s, depending on I :E and K, and the corresponding steady Péclet number is between 10-8/Dm and 10-6/Dm (Dm is the molecular diffusivity with units of cm2/s). Therefore, for Dm⩽10-8cm2/s, the convective transport dominates.

  4. Vitamin A is systemically bioavailable after intratracheal administration with surfactant in an animal model of newborn respiratory distress.

    Science.gov (United States)

    Singh, Avash J; Bronshtein, Vadim; Khashu, Minesh; Lee, Kyle; Potts, James E; Friel, James; Chessex, Philippe

    2010-06-01

    Chronic lung disease (CLD) is a major cause of long-term morbidity in extremely LBW infants with respiratory distress syndrome. Parenteral vitamin A administration decreases the risk of CLD. We tested the hypothesis that intratracheal vitamin A administration with surfactant is systemically bioavailable without interfering with the functional properties of exogenous surfactant. Newborn piglets were ventilated with 100% FiO2 and sequential saline lavage induced respiratory distress syndrome. During lung injury induction, ventilator changes were allowed, but none were made following treatment allocation. Animals were assigned by chance in a blinded control trial to three groups: I=control; II=surfactant; III=surfactant+vitamin A. Hemodynamics, lung mechanics, and blood gases were measured following instrumentation, pre- and posttreatment for 4 h, at which time the liver was sampled for retinol determination. All parameters improved in animals receiving surfactant. A significant interaction existed between time and group for PaO2 and alveolar-arterial oxygen difference (A-aDO2). Hepatic levels of retinol were higher (p<0.001) in animals receiving retinyl acetate. Intratracheal administration of surfactant+vitamin A did not alter the beneficial effects of surfactant on lung compliance and gas exchange. Intratracheal Vitamin A was associated with rapid hepatic uptake. Further studies are warranted.

  5. Surfactant protein D (SP-D) deficiency is attenuated in humanised mice expressing the Met(11)Thr short nucleotide polymorphism of SP-D: implications for surfactant metabolism in the lung

    Science.gov (United States)

    Knudsen, Lars; Ochs, Katharina; Boxler, Laura; Tornoe, Ida; Lykke-Sorensen, Grith; Mackay, Rose-Marie; Clark, Howard W; Holmskov, Uffe; Ochs, Matthias; Madsen, Jens

    2013-01-01

    Surfactant protein D (SP-D) is part of the innate immune system involved in lung homeostasis. SP-D knockout mice show accumulations of foamy alveolar macrophages, alveolar lipoproteinosis and pulmonary emphysema. Three single nucleotide polymorphisms (SNPs) have been described in the coding sequence of the human SP-D gene SFTPD. Clinical studies showed that the SNP SFTPD with a nucleotide change from A to C resulting in a Met to Thr substitution at position 11 in the protein (Met(11)Thr), is relevant. This study set out to create a humanised mouse model of the Met(11)Thr SNP. Transgenic mice lines expressing either Met(11) or Thr(11) SP-D under the control of the ubiquitously expressed pROSA26 promoter in C57Bl/6 SP-D deficient mice (DKO) was created. Both Met(11) (142 ± 52 ng mL−1) and Thr(11) (228 ± 76 ng mL−1) mice lines expressed human SP-D at almost similar levels. According to the literature this was within the range of SP-D levels found in wildtype (WT) mice (253 ± 22 ng mL−1). Met(11) or Thr(11) SP-D in serum from transgenic mice bound maltose in a calcium-dependent manner, and binding was inhibited in the presence of EDTA or maltose. Bronchoalveolar lavage showed for both transgenic mice lines complementation of the DKO phenotype by restoring cell counts, phospholipid levels and protein content back to WT levels. Cytospins of BAL pellet cells showed a resemblance to WT but both mice lines showed some foamy alveolar macrophages. The stereological analysis showed for none of the mice lines a complete abrogation of emphysematous alterations. However, both Met(11) and Thr(11) mice lines were partially reverted back to a WT phenotype when compared with DKO mice, indicating important effects on surfactant metabolism in vivo. PMID:24111992

  6. Influence of Natural Lung Surfactant Inhalations on Clinical Symptoms and Pulmonary Function Parameters in Patients with Bronchial Asthma. Communication 1

    Directory of Open Access Journals (Sweden)

    O.V. Stepanova

    2016-12-01

    Full Text Available Background: Damage to lung surfactant (LS enabling the lung local immunity may contribute to the development of bronchial inflammation in patients with bronchial asthma. Methods and Results: A 40-day course of 16 LS (Surfactant-BL inhalations at the dose of 25mg was added to inhaled corticosteroids (ICS and short/long-acting bronchodilators or combined inhalers in 14 patients with bronchial asthma. After 7 inhalations, patients demonstrated a significant decrease in shortness of breath and bronchospasm attacks, double reduction of ICS dose (p=0.01, and improvement of pulmonary function. Forced vital capacity (FVC increases during treatment in a linear fashion (y=62.9+5.60•x; p<0.05, reaching the normal level (80% after 9 inhalations (Day 15. Forced expiratory volume (FEV1 increases in a linear fashion (y=50.7+4.15•x; p<0.05 without reaching the normal level (80% after 16 inhalations (Day 41. The FEV1/FVC ratio does not change significantly in the time period between Day 1 to Day 15. By Day 41 the value decreases significantly to 67.4±4.66% (p<0.05. The peak expiratory flow (PEF parameter increases in a linear fashion (y=53.9+5.00•x; p<0.01 from 57.7±6.33% to 76.2±9.33% of the predicted value. Conclusion: LS inhalations improve the condition of patients with BA, allow ICS dose reduction by 2 times, and improve pulmonary function parameters.

  7. Self-consistent field modeling of adsorption from polymer/surfactant mixtures.

    Science.gov (United States)

    Postmus, Bart R; Leermakers, Frans A M; Cohen Stuart, Martien A

    2008-06-01

    We report on the development of a self-consistent field model that describes the competitive adsorption of nonionic alkyl-(ethylene oxide) surfactants and nonionic polymer poly(ethylene oxide) (PEO) from aqueous solutions onto silica. The model explicitly describes the response to the pH and the ionic strength. On an inorganic oxide surface such as silica, the dissociation of the surface depends on the pH. However, salt ions can screen charges on the surface, and hence, the number of dissociated groups also depends on the ionic strength. Furthermore, the solvent quality for the EO groups is a function of the ionic strength. Using our model, we can compute bulk parameters such as the average size of the polymer coil and the surfactant CMC. We can make predictions on the adsorption behavior of either polymers or surfactants, and we have made adsorption isotherms, i.e., calculated the relationship between the surface excess and its corresponding bulk concentration. When we add both polymer and surfactant to our mixture, we can find a surfactant concentration (or, more precisely, a surfactant chemical potential) below which only the polymer will adsorb and above which only the surfactant will adsorb. The corresponding surfactant concentration is called the CSAC. In a first-order approximation, the surfactant chemical potential has the CMC as its upper bound. We can find conditions for which CMC model is to understand the experimental data from one of our previous articles. We managed to explain most, but unfortunately not all, of the experimental trends. At the end of the article we discuss the possibilities for improving the model.

  8. Measurement of cytotoxicity and irritancy potential of sugar-based surfactants on skin-related 3D models.

    Science.gov (United States)

    Lu, Biao; Miao, Yong; Vigneron, Pascale; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Pezron, Isabelle; Egles, Christophe; Vayssade, Muriel

    2017-04-01

    Sugar-based surfactants present surface-active properties and relatively low cytotoxicity. They are often considered as safe alternatives to currently used surfactants in cosmetic industries. In this study, four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or a maltose headgroup through an amide linkage, were synthesized and compared to two standard surfactants. The cytotoxic and irritant effects of surfactants were evaluated using two biologically relevant models: 3D dermal model (mouse fibroblasts embedded in collagen gel) and reconstituted human epidermis (RHE, multi-layered human keratinocytes). Results show that three synthesized surfactants possess lower cytotoxicity compared to standard surfactants as demonstrated in the 3D dermal model. Moreover, the IC50s of surfactants against the 3D dermal model are higher than IC50s obtained with the 2D dermal model (monolayer mouse fibroblasts). Both synthesized and standard surfactants show no irritant effects after 48h of topical application on RHE. Throughout the study, we demonstrate the difficulty to link the physico-chemical properties of surfactants and their cytotoxicity in complex models. More importantly, our data suggest that, prior to in vivo tests, a complete understanding of surfactant cytotoxicity or irritancy potential requires a combination of cellular and tissue models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Specific cleavage of the lung surfactant protein A by human cathepsin S may impair its antibacterial properties.

    Science.gov (United States)

    Lecaille, Fabien; Naudin, Clément; Sage, Juliette; Joulin-Giet, Alix; Courty, Agnès; Andrault, Pierre-Marie; Veldhuizen, Ruud A W; Possmayer, Fred; Lalmanach, Gilles

    2013-08-01

    Human cysteine cathepsins (Cats) are implicated in lung injuries and tissue remodeling and have recently emerged as important players in pulmonary inflammations. The proteolytic activities of Cat B, L, K, S and H are dramatically increased in the sputum of patients with cystic fibrosis (CF), suggesting a possible involvement in the CF pathophysiology. We found that pulmonary surfactant protein A (SP-A) that participates to innate host defense is extensively degraded in CF expectorations. Breakdown of SP-A was markedly decreased in CF sputum by E-64 and Mu-Leu-Hph-VSPh, a Cat S inhibitor. Cat S cleaved efficiently and specifically SP-A within critical residues of the solvent-exposed loop of its carbohydrate recognition (C-type lectin) domain that allows binding to pathogens. Cat S decreased aggregation properties of SP-A (self-aggregation, aggregation of phospholipid vesicles and rough LPS). Moreover cleavage of SP-A by Cat S reduced binding to yeast mannan and impaired agglutination of Escherichia coli and Pseudomonas aeruginosa, a foremost detrimental pathogen colonizing the lungs of CF patients. Besides human neutrophil serine proteases and bacterial proteases, we propose that Cat S may participate in the pathophysiology of CF by weakening the antibacterial activity of SP-A. More broadly, present results provide further indication that Cat S, along with Cats B and L, could display immuno-modulatory functions by inactivating key proteins involved in the innate immunity defense. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. [Exogenous surfactant therapy: new synthetic surfactants].

    Science.gov (United States)

    Lacaze-Masmonteil, Th

    2008-06-01

    There are numerous pulmonary conditions in which qualitative or quantitative anomalies of the surfactant system have been demonstrated. In premature newborns with immature lungs, a functional deficit in surfactant is the main physiopathologic mechanism of the neonatal respiratory distress syndrome (RDS). Since the landmark pilot study of Fujiwara, published more than 20 years ago, the efficacy of exogenous surfactant for the treatment of neonatal RDS has been established by numerous controlled studies and meta-analyses. Enlightened by a growing insight into both the structure and function of the different surfactant components, a new generation of synthetic surfactants has been developed. Various complementary approaches have confirmed the fundamental role of the two hydrophobic proteins, SP-B and SP-C, in the surfactant system, thus opening the way to the design of analogues, either by chemical synthesis or expression in a prokaryotic system. An example of these peptide-containing synthetic surfactant preparations, lucinactant (Surfaxin), has been recently tested in comparison to a synthetic surfactant that does not contain protein as well as to animal derived surfactant preparations. Major clinical outcomes between lucinactant and animal-derived surfactant preparations were fund similar in two randomized controlled trials, opening the way to a new generation of synthetic surfactants in the near future.

  11. Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Pérez-Gil, Jesús

    2014-06-01

    Pulmonary surfactant is an essential lipid-protein complex to maintain an operative respiratory surface at the mammalian lungs. It reduces surface tension at the alveolar air-liquid interface to stabilise the lungs against physical forces operating along the compression-expansion breathing cycles. At the same time, surfactant integrates elements establishing a primary barrier against the entry of pathogens. Lack or deficiencies of the surfactant system are associated with respiratory pathologies, which treatment often includes supplementation with exogenous materials. The present review summarises current models on the molecular mechanisms of surfactant function, with particular emphasis in its biophysical properties to stabilise the lungs and the molecular alterations connecting impaired surfactant with diseased organs. It also provides a perspective on the current surfactant-based strategies to treat respiratory pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The impact of alkyl sulfate surfactant geometry and electrolyte on the co-adsorption of anionic surfactants with model perfumes at the air-solution interface.

    Science.gov (United States)

    Bradbury, Robert; Penfold, Jeffrey; Thomas, Robert K; Tucker, Ian M; Petkov, Jordan T; Jones, Craig

    2013-08-01

    The impact of surfactant geometry and electrolyte on the co-adsorption of anionic surfactants and model perfumes at the air-solution interface has been studied by neutron reflectivity. The more hydrophobic perfume linalool, competes more favourably for the surface with sodium dodecylsulfate than was previously reported for the anionic surfactant, sodium dodecyl 6-benzenesulfonate. Due to an increase in surface activity of the sodium dodecylsulfate, the addition of electrolyte results in a reduction in the linalool adsorption. Changing the alkyl chain length affects the relative adsorption of linalool and surfactant at the interface. Similar measurements for the different alkyl sulfates and with electrolyte with the more hydrophilic perfume phenyl ethanol, reveal broadly similar trends. Although the relative adsorption of phenyl ethanol with sodium dodecylsulfate is substantially enhanced compared to sodium dodecyl-6-benzenesulfonate the effects are not as significant as was observed with linalool. The variations with alkyl chain geometry show the importance of the hydrophobic interaction between the perfume and surfactant and changes in the packing constraints on the relative adsorption. The results highlight the importance of the specific interaction between the surfactant and perfume, and the surfactant and perfume geometries on the relative adsorption at the interface. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Djo Hasan

    2018-04-01

    Full Text Available Stretching the alveolar epithelial type I (AT I cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP (purinergic signaling. Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.

  14. Micromechanical model of lung parenchyma hyperelasticity

    Science.gov (United States)

    Concha, Felipe; Sarabia-Vallejos, Mauricio; Hurtado, Daniel E.

    2018-03-01

    Mechanics plays a key role in respiratory physiology, as lung tissue cyclically deforms to bring air in and out the lung, a life-long process necessary for respiration. The study of regional mechanisms of deformation in lung parenchyma has received great attention to date due to its clinical relevance, as local overstretching and stress concentration in lung tissue is currently associated to pathological conditions such as lung injury during mechanical ventilation therapy. This mechanical approach to lung physiology has motivated the development of constitutive models to better understand the relation between stress and deformation in the lung. While material models proposed to date have been key in the development of whole-lung simulations, either they do not directly relate microstructural properties of alveolar tissue with coarse-scale behavior, or they require a high computational effort when based on real alveolar geometries. Furthermore, most models proposed to date have not been thoroughly validated for anisotropic deformation states, which are commonly found in normal lungs in-vivo. In this work, we develop a novel micromechanical model of lung parenchyma hyperelasticity using the framework of finite-deformation homogenization. To this end, we consider a tetrakaidecahedron unit cell with incompressible Neo-Hookean structural elements that account for the alveolar wall tissue responsible for the elastic response, and derive expressions for its effective coarse-scale behavior that directly depend on the alveolar wall elasticity, reference porosity, and two other geometrical coefficients. To validate the proposed model, we simulate the non-linear elastic response of twelve representative volume elements (RVEs) of lung parenchyma with micrometric dimensions, whose geometry is obtained from micrometric computed-tomography reconstructions of murine lungs. We show that the proposed micromechanical model accurately captures the RVEs response not only for isotropic

  15. The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Zhong, Fei; Chow, Vincent T K

    2007-01-01

    The severe acute respiratory syndrome coronavirus (SARS-CoV) infects host cells with its surface glycosylated spike-protein (S-protein). Here we expressed the SARS-CoV S-protein to investigate its interactions with innate immune mechanisms in the lung. The purified S-protein was detected as a 210 k...

  16. The Effects of Periodic Wall Stretch on Surfactant and Liquid Transport

    Science.gov (United States)

    Bull, Joseph; Halpern, David; Grotberg, James

    1999-11-01

    The cycle-mean transport of soluble surfactant and airway surface liquid is examined using a mathematical model of Marangoni flows which accounts for airway branching and for time-periodic radial and axial airway stretch. The transport of surfactant and liquid is fundamental to surfactant replacement therapy as well as liquid and surfactant clearance from healthy lungs. The majority of surfactant and liquid transport occurs in the cycle-mean spreading which follows the very brief initial transient spreading phase. We consider either delivery of surfactants into the lung, by setting the proximal boundary condition to a higher concentration compared to the distal boundary condition, or removal from the lung by switching these end conditions. Starting with a steady-state, non-cycled, non-uniform, surfactant distribution we find that transport of surfactant into the lung is enhanced for larger strain amplitudes and frequency, though frequency is less important. For surfactant clearance from the lung we find, as in the case of delivery, that larger strain amplitude enhances transport. But, cycling frequency has the opposite effect with larger frequencies leading to reduced transport. Liquid clearance is enhanced by larger strain amplitudes and slower frequencies. This work supported by NIH grant HL-41126 and NSF grant CTS-9412523.

  17. High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C

    OpenAIRE

    Willander, Hanna; Askarieh, Glareh; Landreh, Michael; Westermark, Per; Nordling, Kerstin; Keränen, Henrik; Hermansson, Erik; Hamvas, Aaron; Nogee, Lawrence M.; Bergman, Tomas; Saenz, Alejandra; Casals, Cristina; Åqvist, Johan; Jörnvall, Hans; Berglund, Helena

    2012-01-01

    BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 Å crystal structure of the human proSP-C BRICHOS domain, which, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry, reveals how BRICHOS ...

  18. Diffuse interface model of surfactant adsorption onto flat and droplet interfaces

    NARCIS (Netherlands)

    Sman, van der R.G.M.; Graaf, van der S.

    2006-01-01

    For applications where droplet breakup and surfactant adsorption are strongly coupled, a diffuse interface model is developed. The model is based on a free energy functional, partly adapted from the sharp interface model of [Diamant and Andelman 34(8):575-580, (1996)]. The model is implemented as a

  19. Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study.

    Science.gov (United States)

    Nakamura, Kota; Kato, Motoyasu; Shukuya, Takehito; Mori, Keita; Sekimoto, Yasuhito; Ihara, Hiroaki; Kanemaru, Ryota; Ko, Ryo; Shibayama, Rina; Tajima, Ken; Koyama, Ryo; Shimada, Naoko; Nagashima, Osamu; Takahashi, Fumiyuki; Sasaki, Shinichi; Takahashi, Kazuhisa

    2017-05-02

    Interstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA. Between April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA. Thirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA. This is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to

  20. Understanding the Impact of Model Surfactants on Cloud Condensation Nuclei Activity of Sea Spray Aerosols

    Science.gov (United States)

    Forestieri, S.; Cappa, C. D.; Ruehl, C. R.; Bertram, T. H.; Staudt, S.; Kuborn, T.

    2017-12-01

    Aerosol impacts on cloud properties, also known as indirect effects, remain a major source of uncertainty in modeling global radiative forcing. Reducing this uncertainty necessitates better understanding of how aerosol chemical composition impacts the cloud-forming ability of aerosols. The presence of surfactants in aerosols can decrease the surface tension of activating droplets relative to water and lead to more efficient activation. The importance of this effect has been debated, but recent surface tension measurements of microscopic droplets indicate that surface tension is substantially depressed relative to water for lab-generated particles consisting of salt and a single organic species and for complex mixtures of organic matter. However, little work has been done on understanding how chemical complexity (i.e. interaction between different surfactant species) impacts surface tension for particles containing mixtures of surfactants. In this work, we quantified the surface tension of lab-generated aerosols containing surfactants that are commonly found in nascent sea spray aerosol (SSA) at humidities close to activation using a continuous flow stream-wise thermal gradient chamber (CFSTGC). Surface tension was quantified for particles containing single surfactant species and mixtures of these surfactants to investigate the role of chemical complexity on surface tension and molecular packing at the air-water interface. For all surfactants tested in this study, substantial surface tension depression (20-40 mN/m) relative to water was observed for particles containing large fractions of organic matter at humidities just below activation. However, the presence of these surfactants only weakly depressed surface tension at activation. Kinetic limitations were observed for particles coated with just palmitic acid, since palmitic acid molecules inhibit water uptake through their ability to pack tightly at the surface. However, these kinetic limitations disappeared when

  1. Surfactant Therapy of ALI and ARDS

    OpenAIRE

    Raghavendran, K; Willson, D; Notter, RH

    2011-01-01

    This article examines exogenous lung surfactant replacement therapy and its utility in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Biophysical research has documented that lung surfactant dysfunction can be reversed or mitigated by increasing surfactant concentration, and multiple studies in animals with ALI/ARDS have shown that respiratory function and pulmonary mechanics in vivo can be improved by exogenous surfactant administration. Exoge...

  2. Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome.

    Science.gov (United States)

    Milesi, Ilaria; Tingay, David G; Zannin, Emanuela; Bianco, Federico; Tagliabue, Paolo; Mosca, Fabio; Lavizzari, Anna; Ventura, Maria Luisa; Zonneveld, C Elroy; Perkins, Elizabeth J; Black, Don; Sourial, Magdy; Dellacá, Raffaele L

    2016-07-01

    Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome. Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis. Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBFConclusion:In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted.

  3. Bronchoalveolar lavage plus surfactant in a piglet model of meconium aspiration syndrome.

    Science.gov (United States)

    Colvero, Mauricio Obal; Fiori, Humberto Holmer; Fiori, Renato Machado; Luz, Jorge Hecker; de Paula, Davi; Oppermann, Christina; Pitrez, Paulo Márcio; da Silva, Vinícius Duval; Colvero, Aline Pieruccini

    2008-01-01

    Meconium aspiration produces airway obstruction and surfactant inhibition. Bronchoalveolar lavage (BAL) and surfactant replacement have been proposed as treatments for the syndrome. To evaluate the effect of BAL with normal saline followed by a supplementary dose of surfactant in a piglet model of meconium aspiration syndrome. 15 newborn piglets were used in the study. The animals were ventilated with fixed settings. After inhalation of 4 ml/kg of diluted meconium, the piglets were randomized into three groups: group I (n = 5) - tracheal aspiration without BAL; group II (n = 5) - BAL with normal saline (15 ml/kg), and group III (n = 5) - BAL with normal saline (15 ml/kg) followed by a supplementary dose of surfactant (Curosurf(R) 100 mg/kg). Arterial blood gas samples were obtained 30 min and 6 h after the inhalation of meconium. A significant increase of PaO(2 )values at 6 h after treatment was only observed in group III (from 51 +/- 13 to 189 +/- 115 mm Hg; p = 0.04). At this time, PaO(2) in group III was significantly higher compared to group II (189 +/- 115 and 37 +/- 11 mm Hg, respectively; p = 0.023) and showed a borderline significance when compared to group I (p = 0.066). BAL with normal saline followed by a supplementary dose of surfactant may improve oxygenation in an experimental piglet model of meconium aspiration syndrome. Copyright (c) 2007 S. Karger AG, Basel.

  4. Self-consistent field modeling of adsorption from polymer/surfactant mixtures

    NARCIS (Netherlands)

    Postmus, B.R.; Leermakers, F.A.M.; Cohen Stuart, M.A.

    2008-01-01

    We report on the development of a self-consistent field model that describes the competitive adsorption of nonionic alkyl-(ethylene oxide) surfactants and nonionic polymer poly(ethylene oxide) (PEO) from aqueous solutions onto silica. The model explicitly describes the response to the pH and the

  5. Risk considerations related to lung modeling

    International Nuclear Information System (INIS)

    Masse, R.; Cross, F.T.

    1989-01-01

    Improved lung models provide a more accurate assessment of dose from inhalation exposures and, therefore, more accurate dose-response relationships for risk evaluation and exposure limitation. Epidemiological data for externally irradiated persons indicate that the numbers of excess respiratory tract carcinomas differ in the upper airways, bronchi, and distal lung. Neither their histogenesis and anatomical location nor their progenitor cells are known with sufficient accuracy for accurate assessment of the microdosimetry. The nuclei of sensitive cells generally can be assumed to be distributed at random in the epithelium, beneath the mucus and tips of the beating cilia and cells. In stratified epithelia, basal cells may be considered the only cells at risk. Upper-airway tumors have been observed in both therapeutically irradiated patients and in Hiroshima-Nagasaki survivors. The current International Commission on Radiological Protection Lung-Model Task Group proposes that the upper airways and lung have a similar relative risk coefficient for cancer induction. The partition of the risk weighting factor, therefore, will be proportional to the spontaneous death rate from tumors, and 80% of the weighting factor for the respiratory tract should be attributed to the lung. For Weibel lung-model branching generations 0 to 16 and 17 to 23, the Task Group proposes an 80/20 partition of the risk, i.e., 64% and 16%, respectively, of the total risk. Regarding risk in animals, recent data in rats indicate a significantly lower effectiveness for lung-cancer induction at low doses from insoluble long-lived alpha-emitters than from Rn daughters. These findings are due, in part, to the fact that different regions of the lung are irradiated. Tumors in the lymph nodes are rare in people and animals exposed to radiation.44 references

  6. X-ray diffraction and reflectivity validation of the depletion attraction in the competitive adsorption of lung surfactant and albumin.

    Science.gov (United States)

    Stenger, Patrick C; Wu, Guohui; Miller, Chad E; Chi, Eva Y; Frey, Shelli L; Lee, Ka Yee C; Majewski, Jaroslaw; Kjaer, Kristian; Zasadzinski, Joseph A

    2009-08-05

    Lung surfactant (LS) and albumin compete for the air-water interface when both are present in solution. Equilibrium favors LS because it has a lower equilibrium surface pressure, but the smaller albumin is kinetically favored by faster diffusion. Albumin at the interface creates an energy barrier to subsequent LS adsorption that can be overcome by the depletion attraction induced by polyethylene glycol (PEG) in solution. A combination of grazing incidence x-ray diffraction (GIXD), x-ray reflectivity (XR), and pressure-area isotherms provides molecular-resolution information on the location and configuration of LS, albumin, and polymer. XR shows an average electron density similar to that of albumin at low surface pressures, whereas GIXD shows a heterogeneous interface with coexisting LS and albumin domains at higher surface pressures. Albumin induces a slightly larger lattice spacing and greater molecular tilt, similar in effect to a small decrease in the surface pressure. XR shows that adding PEG to the LS-albumin subphase restores the characteristic LS electron density profile at the interface, and confirms that PEG is depleted near the interface. GIXD shows the same LS Bragg peaks and Bragg rods as on a pristine interface, but with a more compact lattice corresponding to a small increase in the surface pressure. These results confirm that albumin adsorption creates a physical barrier that inhibits LS adsorption, and that PEG in the subphase generates a depletion attraction between the LS aggregates and the interface that enhances LS adsorption without substantially altering the structure or properties of the LS monolayer.

  7. High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies.

    Science.gov (United States)

    Meenach, Samantha A; Anderson, Kimberly W; Hilt, J Zach; McGarry, Ronald C; Mansour, Heidi M

    2014-12-01

    Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 μm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions.

  8. Polymers and surfactants in solution and at interfaces : a model study on detergency

    NARCIS (Netherlands)

    Torn, B.

    2000-01-01

    This thesis deals with detergency-related adsorption phenomena of (mixtures of) polymers and surfactants. Both types of molecules play an important role in the removal and subsequent stabilization of soil from a substrate. Starting with a model detergency system consisting of polymers,

  9. Surfactant nebulization versus instillation during high frequency ventilation in surfactant-deficient rabbits

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1998-01-01

    Surfactant nebulization improves lung function at low alveolar doses of surfactant. However, efficiency of nebulization is low, and lung deposition seems to depend on lung aeration. High frequency ventilation (HFV) has been shown to improve lung aeration. We hypothesize that the combination of HFV

  10. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice

    DEFF Research Database (Denmark)

    Viby, Niels-Erik; Isidor, Marie Sophie; Buggeskov, Katrine B

    2013-01-01

    pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with measurement of enhanced...... pause (Penh) in a whole body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Penh increased...... dramatically at day 17 in all control mice but the increase was significantly less in the groups of GLP-1R agonist treated mice (p...

  11. A mean-density model of ionic surfactants for the dispersion of carbon nanotubes in aqueous solutions

    Science.gov (United States)

    Joung, Young Soo

    2018-05-01

    We propose a new analytical model of ionic surfactants used for the dispersion of carbon nanotubes (CNTs) in aqueous solutions. Although ionic surfactants are commonly used to facilitate the dispersion of CNTs in aqueous solutions, understanding the dispersion process is challenging and time-consuming owing to its complexity and nonlinearity. In this work, we develop a mean-density model of ionic surfactants to simplify the calculation of interaction forces between CNTs stabilized by ionic surfactants. Using this model, we can evaluate various interaction forces between the CNTs and ionic surfactants under different conditions. The dispersion mechanism is investigated by estimating the potential of mean force (PMF) as a function of van der Waals forces, electrostatic forces, interfacial tension, and osmotic pressure. To verify the proposed model, we compare the PMFs derived using our method with those derived from molecular dynamics simulations using comparable CNTs and ionic surfactants. Notably, for stable dispersions, the osmotic pressure and interfacial energy are important for long-range and short-range interactions, respectively, in comparison with the effect of electrostatic forces. Our model effectively prescribes specific surfactants and their concentrations to achieve stable aqueous suspensions of CNTs.

  12. Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs

    International Nuclear Information System (INIS)

    Jobe, A.H.; Ikegami, M.; Seidner, S.R.; Pettenazzo, A.; Ruffini, L.

    1989-01-01

    Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs

  13. Chain architecture and micellization: A mean-field coarse-grained model for poly(ethylene oxide) alkyl ether surfactants

    Energy Technology Data Exchange (ETDEWEB)

    García Daza, Fabián A.; Mackie, Allan D., E-mail: allan.mackie@urv.cat [Department d’Enginyeria Química, ETSEQ, Universitat Rovira i Virgili, Avinguda dels Països Catalans 26, 43007 Tarragona (Spain); Colville, Alexander J. [Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115-5000 (United States)

    2015-03-21

    Microscopic modeling of surfactant systems is expected to be an important tool to describe, understand, and take full advantage of the micellization process for different molecular architectures. Here, we implement a single chain mean field theory to study the relevant equilibrium properties such as the critical micelle concentration (CMC) and aggregation number for three sets of surfactants with different geometries maintaining constant the number of hydrophobic and hydrophilic monomers. The results demonstrate the direct effect of the block organization for the surfactants under study by means of an analysis of the excess energy and entropy which can be accurately determined from the mean-field scheme. Our analysis reveals that the CMC values are sensitive to branching in the hydrophilic head part of the surfactant and can be observed in the entropy-enthalpy balance, while aggregation numbers are also affected by splitting the hydrophobic tail of the surfactant and are manifested by slight changes in the packing entropy.

  14. Chain architecture and micellization: A mean-field coarse-grained model for poly(ethylene oxide) alkyl ether surfactants

    Science.gov (United States)

    García Daza, Fabián A.; Colville, Alexander J.; Mackie, Allan D.

    2015-03-01

    Microscopic modeling of surfactant systems is expected to be an important tool to describe, understand, and take full advantage of the micellization process for different molecular architectures. Here, we implement a single chain mean field theory to study the relevant equilibrium properties such as the critical micelle concentration (CMC) and aggregation number for three sets of surfactants with different geometries maintaining constant the number of hydrophobic and hydrophilic monomers. The results demonstrate the direct effect of the block organization for the surfactants under study by means of an analysis of the excess energy and entropy which can be accurately determined from the mean-field scheme. Our analysis reveals that the CMC values are sensitive to branching in the hydrophilic head part of the surfactant and can be observed in the entropy-enthalpy balance, while aggregation numbers are also affected by splitting the hydrophobic tail of the surfactant and are manifested by slight changes in the packing entropy.

  15. Surfactants and the Mechanics of Respiration

    Science.gov (United States)

    Jbaily, Abdulrahman; Szeri, Andrew J.

    2016-11-01

    Alveoli are small sacs found at the end of terminal bronchioles in human lungs with a mean diameter of 200 μm. A thin layer of fluid (hypophase) coats the inner face of an alveolus and is in contact with the air in the lungs. The thickness of this layer varies among alveoli, but is in the range of 0.1 to 0.5 μm for many portions of the alveolar network. The interfacial tension σ at the air-hypophase interface tends to favor collapse of the alveolus, and resists its expansion during inhalation. Type II alveolar cells synthesize and secrete a mixture of phospholipids and proteins called pulmonary surfactant. These surfactant molecules adsorb to the interface causing σ of water at body temperature is 70 mN/m and falls to an equilibrium value of 25 mN/m when surfactants are present. Also, in a dynamic sense, it is known that σ is reduced to near 0 during exhalation when the surfactant film compresses. In this work, the authors develop a mechanical and transport model of the alveolus to study the effect of surfactants on various aspects of respiration. The model is composed of three principal parts: (i) air movement into and out of the alveolus; (ii) a balance of linear momentum across the two-layered membrane of the alveolus (hypophase and elastic wall); and (iii) a pulmonary surfactant transport problem in the hypophase. The goal is to evaluate the influence of pulmonary surfactant on respiratory mechanics.

  16. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  17. Development of a Guinea Pig Lung Deposition Model

    Science.gov (United States)

    2016-01-01

    lung airways are not feasible due to the large number of airways, complexity of the lung geometry, and lack of data on pleural pressure distribution...modeling each airway as a cylindrical tube and the lung as a dichotomous branching network of airways, representative, typical-path, dichotomous and...pressure between the atmosphere and pleural pressure in the lung cavity during inhalation. While inhalation is initiated by the expansion of the lung

  18. Altered expression of cyclooxygenase-2, 12-lipoxygenase, inducible nitric oxide synthase-2 and surfactant protein D in lungs of patients with pulmonary injury caused by sulfur mustard.

    Science.gov (United States)

    Tahmasbpour, Eisa; Ghanei, Mostafa; Khor, Abolfazl; Panahi, Yunes

    2018-03-14

    Sulfur mustard (SM) is a strong alkylating toxicant that targets different organs, particularly human lung tissue. Change in genes expression is one of the molecular mechanisms of SM toxicity in damaged tissue. The purpose of this investigation is to characterize the expression of cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LO), inducible nitric oxide synthase 2 (iNOS2), and surfactant protein D (SFTPD) in lungs of patients who exposed to SM. Lung biopsies were provided from SM-exposed patients (n = 6) and controls (n = 5). Total RNA were extracted from all specimens and then cDNA was synthesized for each sample. Changes in gene expression were measured using RT 2 Profiler ™PCR Array. Pulmonary function tests revealed more obstructive and restrictive spirometric patterns among patients compared to the control group. Expression of COX-2 and 12-LO in the lung of patients was increased by 6.2555 (p = 0.004) and 6.2379-folds (p = 0.002), respectively. In contrast, expression of SF-D and iNOS genes was reduced by 8.5869-fold (p = 0.005) and 2.4466-folds (p = 0.011), respectively. Mustard lungs were associated with overexpression of COX-2 and 12-LO, which are responsible for inflammation, overproduction of free radicals and oxidative stress. Downregulation of iNOS2 and SF-D are probably the reason for lung disease and dysfunction among these patients. Therefore, the expression of these genes could be an important, routine part of the management of such patients.

  19. Evaluation of the interaction of surfactants with stratum corneum model membrane from Bothrops jararaca by DSC.

    Science.gov (United States)

    Baby, André Rolim; Lacerda, Aurea Cristina Lemos; Velasco, Maria Valéria Robles; Lopes, Patrícia Santos; Kawano, Yoshio; Kaneko, Telma Mary

    2006-07-06

    The interaction of surfactants sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium chloride (CTAC) and lauryl alcohol ethoxylated (12 mol ethylene oxide) (LAE-12OE) was evaluated on the stratum corneum (SC) of shed snake skins from Bothrops jararaca, used as model membrane, and thermal characterized by differential scanning calorimetry (DSC). Surfactant solutions were employed above of the critical micellar concentration (CMC) with treatment time of 8h. The SDS interaction with the SC model membrane has increased the characteristic transition temperature of 130 degrees C in approximately 10 degrees C for the water loss and keratin denaturation, indicating an augmentation of the water content. Samples treated with CTAC have a decrease of the water loss temperature, while, for the LAE-12OE treated samples, changes on the transition temperature have not been observed.

  20. Modeling of the Critical Micelle Concentration (CMC) of Nonionic Surfactants with an Extended Group-Contribution Method

    DEFF Research Database (Denmark)

    Mattei, Michele; Kontogeorgis, Georgios; Gani, Rafiqul

    2013-01-01

    A group-contribution (GC) property prediction model for estimating the critical micelle concentration (CMC) of nonionic surfactants in water at 25 °C is presented. The model is based on the Marrero and Gani GC method. A systematic analysis of the model performance against experimental data...... is carried out using data for a wide range of nonionic surfactants covering a wide range of molecular structures. As a result of this procedure, new third order groups based on the characteristic structures of nonionic surfactants are defined and are included in the Marrero and Gani GC model. In this way...... of 150 experimental measurements covering a large variety of nonionic surfactants including linear, branched, and phenyl alkyl ethoxylates; alkanediols; alkyl mono- and disaccharide ethers and esters; ethoxylated alkyl amines and amides; fluorinated linear ethoxylates and amides; polyglycerol esters...

  1. CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D

    DEFF Research Database (Denmark)

    Madsen, Jens; Tornøe, Ida; Nielsen, Ole

    2003-01-01

    CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report ...

  2. Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage.

    Science.gov (United States)

    Menk, Mario; Graw, Jan Adriaan; Steinkraus, Henrik; Haefen, Clarissa von; Sifringer, Marco; Spies, Claudia D; Lachmann, Burkhard; Schwaiberger, David

    2015-01-01

    Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1β, TNF-α, and IL-6 mRNA and protein expression of IL-1β and TNF-α was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI.

  3. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.

    Science.gov (United States)

    Viby, Niels-Erik; Isidor, Marie S; Buggeskov, Katrine B; Poulsen, Steen S; Hansen, Jacob B; Kissow, Hannelouise

    2013-12-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P agonist-treated mice (P agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

  4. Effects of Surfactant on the Transport of Toxoplasma gondii in Saturated Sandy Porous Media: Experimental Tests and Modeling

    Science.gov (United States)

    Darnault, C. J. G.; Mutty, T.; L'Ollivier, C.; Dubey, J. P.; Aurélien, D.; Pullano, C. P.

    2017-12-01

    Understanding the transport of pathogens in the subsurface environment is essential for the risk assessment of groundwater contamination and the potential threat to human health. Currently, there is a lack of research in particular concerning the fate and transport of Toxoplasma gondii in porous media. The purpose of this research will be to characterize and model the transport and retention of Toxoplasma gondii in saturated silica-sand porous media in the presence of surfactant. Surfactants are chemicals commonly used as detergents and soaps, however they are able to impact flow properties in porous media and the interactions between surfaces, such as oocysts walls with sand grains. Therefore, we chose to characterize the changes that two surfactants have on the transport and fate of T. gondii. A total of 14 Column experiments were conducted including replicates as follows: 6 columns with an anionic-surfactant solution, 6 with a nonionic-surfactant solution, and 2 columns without surfactant to act as controls. All of the columns contained fine sand as the dominant grain size and each was run with a specified saturated flow rate in order to analyze the change with surfactant and disregard change as a result of a variation in the pore velocity. We chose to determine the retention and flow using the classic clean-bed colloid filtration model, and implemented sources for both adsorption and desorption of the particles which is known to happen on other biocolloids including oocysts. We implemented both Linear alkylbenzene sulphonic acid and Alkylphenol ethoxylate as our surfactants since they are the anionic and nonionic surfactants most commonly found in wastewater. Three different Critical Micelle Concentrations (CMC's) were run through the columns prior to the T. gondii oocysts injection followed by sequential injection of surfactant only and then deionized water only. The study compares the breakthrough of T. gondii with surfactant, without surfactant, as well as a

  5. Surfactant protein A (SP-A) and angiotensin converting enzyme (ACE) as early biomarkers for pulmonary edema formation in ventilated human lung lobes.

    Science.gov (United States)

    Gnadt, Mirjam; Kardziev, Boris; Schmidt, Michael; Högger, Petra

    2012-08-01

    Ex vivo perfused and ventilated lung lobes frequently develop pulmonary edema. We were looking for a suitable and early detectable biomarker in the perfusion fluid indicating lung cell damage and loss of tissue integrity in ventilated human lung lobes. Therefore, we elucidated whether surfactant protein A (SP-A) and angiotensin-converting enzyme (ACE) were measurable in the perfusion fluid and whether they were suitable indicators for edema formation occurring within the experimental time frame of 1-2 h. Patients (n = 39) undergoing a lobectomy, bilobectomy or pneumonectomy due to primary bronchial cell carcinoma were included in the studies. Lung lobes were extracorporally ventilated and perfused for up to 2 h. Two different perfusion fluids were used, plain perfusion buffer and perfusion buffer containing packed erythrocytes or buffy coats. Perfusion fluid samples were analyzed for SP-A and ACE using immunoassays served as perfusion fluids. SP-A and ACE concentrations were analyzed in fluid sample sets of 39 and 33 perfusion experiments, respectively. Degrees of edema formation were arbitrarily classified into three groups (≤ 29, 30-59, ≥ 60 % weight gain). The maximum increase of SP-A and ACE concentrations in the perfusate was significantly higher for more pronounced edemas in case of perfusions using a mixture of blood components and buffer. Interestingly, the time courses of ACE and SP-A were highly similar. We suggest that SP-A and ACE are promising early biochemical markers for the development for pulmonary edema formation in the ex vivo lung lobe perfusion.

  6. Magnetic surfactants

    OpenAIRE

    Brown, P.; Alan Hatton, T.; Eastoe, J.

    2015-01-01

    Surfactants are ubiquitous, being important commodity chemicals with wide industrial applications, and essential components of living organisms. With stimuli-responsive surfactants, self-assembly and physicochemical properties of a wide variety of materials may be readily manipulated, both reversibly and irreversibly. Until recently, magnetically responsive surfactants had not been reported. This review reports the recent progress in magnetoresponsive surfactants, covering control of interfac...

  7. [Clinical effects of different ways of mechanical ventilation combined with pulmonary surfactant in treatment of acute lung injury/acute respiratory distress syndrome in neonates: a comparative analysis].

    Science.gov (United States)

    Chang, Ming; Lu, Hong-Yan; Xiang, Hong; Lan, Hou-Ping

    2016-11-01

    To compare the therapeutic effects of high-frequency oscillatory ventilation+pulmonary surfactant (HFOV+PS), conventional mechanical ventilation+pulmonary surfactant (CMV+PS), and conventional mechanical ventilation (CMV) alone for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in neonates. A total of 136 neonates with ALI/ARDS were enrolled, among whom 73 had ALI and 63 had ARDS. They were divided into HFOV+PS group (n=45), CMV+PS group (n=53), and CMV group (n=38). The neonates in the first two groups were given PS at a dose of 70-100 mg/kg. The partial pressure of oxygen (PaO 2 ), partial pressure of carbon dioxide (PaCO 2 ), PaO 2 /fraction of inspired oxygen (FiO 2 ), oxygenation index (OI), and respiratory index (RI) were measured at 0, 12, 24, 48, and 72 hours of mechanical ventilation. At 12, 24, and 48 hours of mechanical ventilation, the HFOV+PS group had higher PaO 2 and lower PaCO 2 than the CMV+PS and CMV groups (Pmechanical ventilation, the HFOV+PS group had higher PaO 2 /FiO 2 and lower OI and RI than the CMV+PS and CMV groups (Pmechanical ventilation and oxygen use than the CMV+PS and CMV groups (Pmechanical ventilation and oxygen use compared with CMV+PS and CMV alone. It does not increase the incidence of complications.

  8. Effects of surfactants and thermodynamic activity of model active ingredient on transport over plant leaf cuticle.

    Science.gov (United States)

    Fagerström, Anton; Kocherbitov, Vitaly; Ruzgas, Tautgirdas; Westbye, Peter; Bergström, Karin; Engblom, Johan

    2013-03-01

    The main objective of this study was to investigate the mechanism of molecular transport across the cuticle of Clivia leaves. In vitro diffusion methodology was used to investigate the transport of a systemic fungicide, tebuconazole, over a model silicone membrane, enzymatically isolated cuticle membranes, and dermatomed leaves. It was shown that dermatomed leaves may replace enzymatically isolated cuticles. Furthermore, the effects of two surfactants, C(10)EO(7) and C(8)G(1.6), on the fungicide transport were investigated. Tebuconazole cuticle permeation was described using Fick's first law of diffusion, expressed by the thermodynamic activity of the solute in the membrane. A new method for calculation of diffusion coefficients in the membrane is proposed. To access the thermodynamic activity of the fungicide in the membranes, sorption isotherms of tebuconazole in the membrane materials studied were recorded. The thermodynamic activity of the fungicide in aqueous solutions was calculated from solubility data. For that purpose, the effect of surfactants on tebuconazole solubility was studied. The results show that addition of surfactants allows for higher concentrations of tebuconazole available for penetration. Nonetheless, at a fixed fungicide thermodynamic activity, all formulations produced the same flux over the silicone membrane independently on the fungicide concentration. This shows that the driving force across non-responding membranes is the gradient of thermodynamic activity, rather than the gradient of the fungicide concentration. In case of leaves, surfactants induced the same quantitative increase in both flux and diffusion coefficient of solute in the cuticle, while the cuticle-water partition coefficient was unaffected. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Linking surfactant protein SP-D and IL-13

    DEFF Research Database (Denmark)

    Qaseem, Asif S; Sonar, Sanchaita; Mahajan, Lakshna

    2012-01-01

    Surfactant protein D (SP-D) is an innate immune molecule that plays a protective role against lung infection, allergy, asthma and inflammation. In vivo experiments with murine models have shown that SP-D can protect against allergic challenge via a range of mechanisms including inhibition...

  10. Respiratory Mechanics and Gas Exchange: The Effect of Surfactants

    Science.gov (United States)

    Jbaily, Abdulrahman; Szeri, Andrew J.

    2017-11-01

    The purpose of the lung is to exchange gases, primarily oxygen and carbon dioxide, between the atmosphere and the circulatory system. To enable this exchange, the airways in the lungs terminate in some 300 million alveoli that provide adequate surface area for transport. During breathing, work must be done to stretch various tissues to accommodate a greater volume of gas. Considerable work must also be done to expand the liquid lining (hypophase) that coats the interior surfaces of the alveoli. This is enabled by a surface active lipo-protein complex, known as pulmonary surfactant, that modifies the surface tension at the hypophase-air interface. Surfactants also serve as physical barriers that modify the rate of gas transfer across interfaces. We develop a mathematical model to study the action of pulmonary surfactant and its determinative contributions to breathing. The model is used to explore the influence of surfactants on alveolar mechanics and on gas exchange: it relates the work of respiration at the level of the alveolus to the gas exchange rate through the changing influence of pulmonary surfactant over the breathing cycle. This work is motivated by a need to develop improved surfactant replacement therapies to treat serious medical conditions.

  11. Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    E.C. Scheffers; H. IJsselstijn (Hanneke); R. Tenbrinck (Robert); B.F. Lachmann (Burkhard); J.C. de Jongste (Johan); J.C. Molenaar; D. Tibboel (Dick)

    1994-01-01

    textabstractPatients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research

  12. Dynamic modeling of lung tumor motion during respiration

    Energy Technology Data Exchange (ETDEWEB)

    Kyriakou, E; McKenzie, D R, E-mail: e.kyriakou@physics.usyd.edu.au, E-mail: d.mckenzie@physics.usyd.edu.au [School of Physics, University of Sydney, NSW 2006 (Australia)

    2011-05-21

    A dynamic finite element model of the lung that incorporates a simplified geometry with realistic lung material properties has been developed. Observations of lung motion from respiratory-gated computed tomography were used to provide a database against which the predictions of the model are assessed. Data from six patients presenting with lung tumors were processed to give sagittal sections of the lung containing the tumor as a function of the breathing phase. Statistical shape modeling was used to outline the diaphragm, the tumor volume and the thoracic wall at each breathing phase. The motion of the tumor in the superior-inferior direction was plotted against the diaphragm displacement. The finite element model employed a simplified geometry in which the lung material fills a rectangular volume enabling two-dimensional coordinates to be used. The diaphragm is represented as a piston, driving the motion. Plots of lung displacement against diaphragm displacement form hysteresis loops that are a sensitive indicator of the characteristics of the motion. The key parameters of lung material that determine the motion are the density and elastic properties of lung material and the airway permeability. The model predictions of the hysteresis behavior agreed well with observation only when lung material is modeled as viscoelastic. The key material parameters are suggested for use as prognostic indicators of the progression of disease and of changes arising from the response of the lung to radiation treatment.

  13. Irreversible electroporation in a Swine lung model.

    Science.gov (United States)

    Dupuy, Damian E; Aswad, Bassam; Ng, Thomas

    2011-04-01

    This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.

  14. Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

    Science.gov (United States)

    Wilhelm, K P; Freitag, G; Wolff, H H

    1994-06-01

    Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

  15. Impact of model perfume molecules on the self-assembly of anionic surfactant sodium dodecyl 6-benzene sulfonate.

    Science.gov (United States)

    Bradbury, Robert; Penfold, Jeffrey; Thomas, Robert K; Tucker, Ian M; Petkov, Jordan T; Jones, Craig; Grillo, Isabelle

    2013-03-12

    The impact of two model perfumes with differing degrees of hydrophobicity/hydrophilicity, linalool (LL) and phenylethanol (PE), on the solution structure of anionic surfactant sodium dodecyl 6-benzene sulfonate, LAS-6, has been studied by small angle neutron scattering, SANS. For both types of perfume molecules, complex phase behavior is observed. The phase behavior depends upon the concentration, surfactant/perfume composition, and type of perfume. The more hydrophilic perfume PE promotes the formation of more highly curved structures. At relatively low surfactant concentrations, small globular micelles, L1, are formed. These become perfume droplets, L(sm), stabilized by the surfactant at much higher perfume solution compositions. At higher surfactant concentrations, the tendency of LAS-6 to form more planar structures is evident. The more hydrophobic linalool promotes the formation of more planar structures. Combined with the greater tendency of LAS-6 to form planar structures, this results in the planar structures dominating the phase behavior for the LAS-6/linalool mixtures. For the LAS-6/linalool mixture, the self-assembly is in the form of micelles only at the lowest surfactant and perfume concentrations. Over most of the concentration-composition space explored, the structures are predominantly lamellar, L(α), or vesicle, L(v), or in the form of a lamellar/micellar coexistence. At low and intermediate amounts of LL, a significantly different structure is observed, and the aggregates are in the form of small, relatively monodisperse vesicles (i.e., nanovesicles), L(sv).

  16. Influence of pulmonary surfactant on in vitro bactericidal activities of amoxicillin, ceftazidime, and tobramycin

    NARCIS (Netherlands)

    A. van 't Veen (Annemarie); J.W. Mouton (Johan); D.A.M.P.J. Gommers (Diederik); J.A.J.W. Kluytmans (Jan); P. Dekkers; B.F. Lachmann (Burkhard)

    1995-01-01

    textabstractThe influence of a natural pulmonary surfactant on antibiotic activity was investigated to assess the possible use of exogenous surfactant as a vehicle for antibiotic delivery to the lung. The influence of surfactant on the bactericidal activity of

  17. Persurf, a new method to improve surfactant delivery: a study in surfactant depleted rats.

    Directory of Open Access Journals (Sweden)

    Wolfram Burkhardt

    Full Text Available PURPOSE: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf and to test in surfactant depleted Wistar rats whether Persurf achieves I. a more homogenous pulmonary distribution and II. a more homogenous recruitment of alveoli when compared with surfactant or PFC alone. METHODS: Three different PFC were mixed with surfactant and phospholipid concentration in the emulsion was measured. After surfactant depletion, animals either received 30 ml/kg of PF5080, 100 mg/kg of stained (green dye Curosurf™ or 30 ml/kg of Persurf. Lungs were fixated after 1 hour of ventilation and alveolar aeration and surfactant distribution was estimated by a stereological approach. RESULTS: Persurf contained 3 mg/ml phospholipids and was stable for more than 48 hours. Persurf-administration improved oxygenation. Histological evaluation revealed a more homogenous surfactant distribution and alveolar inflation when compared with surfactant treated animals. CONCLUSIONS: In surfactant depleted rats administration of PFC-in-surfactant emulsion leads to a more homogenous distribution and aeration of the lung than surfactant alone.

  18. Computational modeling of a forward lunge

    DEFF Research Database (Denmark)

    Alkjær, Tine; Wieland, Maja Rose; Andersen, Michael Skipper

    2012-01-01

    This study investigated the function of the cruciate ligaments during a forward lunge movement. The mechanical roles of the anterior and posterior cruciate ligament (ACL, PCL) during sagittal plane movements, such as forward lunging, are unclear. A forward lunge movement contains a knee joint fle...

  19. A discrete element model for the influence of surfactants on sedimentation characteristics of magnetorheological fluids

    Science.gov (United States)

    Son, Kwon Joong

    2018-02-01

    Hindering particle agglomeration and re-dispersion processes, gravitational sedimentation of suspended particles in magnetorheological (MR) fluids causes inferior performance and controllability of MR fluids in response to a user-specified magnetic field. Thus, suspension stability is one of the principal factors to be considered in synthesizing MR fluids. However, only a few computational studies have been reported so far on the sedimentation characteristics of suspended particles under gravity. In this paper, the settling dynamics of paramagnetic particles suspended in MR fluids was investigated via discrete element method (DEM) simulations. This work focuses particularly on developing accurate fluid-particle and particle-particle interaction models which can account for the influence of stabilizing surfactants on the MR fluid sedimentation. Effect of the stabilizing surfactants on interparticle interactions was incorporated into the derivation of a reliable contact-impact model for DEM computation. Also, the influence of the stabilizing additives on fluid-particle interactions was considered by incorporating Stokes drag with shape and wall correction factors into DEM formulation. The results of simulations performed for model validation purposes showed a good agreement with the published sedimentation measurement data in terms of an initial sedimentation velocity and a final sedimentation ratio.

  20. Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

    Science.gov (United States)

    Wilhelm, K P; Freitag, G; Wolff, H H

    1994-12-01

    Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of

  1. Effect of Surfactants on the Deformation and Detachment of Oil Droplets in a Model Laminar Flow Cell

    Directory of Open Access Journals (Sweden)

    Fréville V.

    2013-10-01

    Full Text Available Sugar-based surfactants are increasingly present in the development of eco-friendly detergents due to current regulations and consumer demand. In order to assess the degreasing performance of these new surfactants, the behavior of model oil droplets subjected to the action of a flow of surfactant solutions of different concentrations was studied in a laminar flow cell and related to the physico-chemical properties measured at the liquid/liquid (interfacial tension and solid/liquid/liquid interfaces (contact angle. With the surfactant solutions and the model oils employed in this study, three main behaviors were observed when a critical flow rate was reached: elongation, fragmentation or spontaneous detachment of the droplet. The analysis of the results leads to a correlation between the droplet behavior and the balance of the forces applied on the droplet in its initial position, in particular the gravity force Fg, which tends to move the oil droplet upwards (given the density difference, and the capillary force Fc, which tends to keep the droplet spherical. A state diagram could be established, based on the dimensionless Bond number (Fg/Fc and cosθ, θ being the initial contact angle of the drop on the surface before the establishment of the flow. One can thus predict the droplet behavior as a function of the system initial characteristics. The results allowed the comparison of degreasing performance of the different surfactants used and illustrated the potential of AlkylPolyPentosides (APP for detergent formulations.

  2. Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340

    DEFF Research Database (Denmark)

    Ligtenberg, T J; Bikker, F J; Groenink, J

    2001-01-01

    by quadrupole time-of-flight (Q-TOF) tandem MS. The sequence showed 100% identity with part of the scavenger receptor cysteine-rich ('SRCR') domain found in gp-340/DMBT1 (deleted in malignant brain tumours-1). The mass spectrum revealed 11 peaks with an identical mass as a computer-simulated trypsin digest....../PAGE and the amino acid composition of agglutinin, was found to be nearly identical with that of gp-340. It was shown by Western blotting that monoclonal antibodies against gp-340 reacted with salivary agglutinin, and monoclonals against agglutinin reacted with gp-340. It was demonstrated that gp-340 and agglutinin...... bound in a similar way to Streptococcus mutans and surfactant protein-D. Histochemically, the distribution of gp-340 in the submandibular salivary glands was identical with the agglutinin distribution, as shown in a previous paper [Takano, Bogert, Malamud, Lally and Hand (1991) Anat. Rec. 230, 307...

  3. Improvement of lung mechanics by exogenous surfactant: effect of prior application of high positive end-expiratory pressure

    NARCIS (Netherlands)

    A. Hartog (Anneke); D.A.M.P.J. Gommers (Diederik); J.J. Haitsma (Jack); B.F. Lachmann (Burkhard)

    2000-01-01

    textabstractThe use of a ventilation strategy with high positive end-expiratory pressure (PEEP) that is intended to recruit collapsed alveoli and to prevent recurrent collapse can reduce alveolar protein influx in experimental acute lung injury (ALI). This could affect

  4. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.

    2006-01-01

    from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340...... has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition...

  5. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.

    2006-01-01

    from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340...... has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition...... domain of SP-D as compared with the binding of lung gp-340. These findings may relate to inter-individual variations in innate defence against highly pathogenic IAV and to effects of aspiration of oral contents on SP-D-mediated lung functions....

  6. Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion.

    Science.gov (United States)

    Soluri-Martins, André; Moraes, Lillian; Santos, Raquel S; Santos, Cintia L; Huhle, Robert; Capelozzi, Vera L; Pelosi, Paolo; Silva, Pedro L; de Abreu, Marcelo Gama; Rocco, Patricia R M

    2017-01-01

    Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV ( n = 6/group) [tidal volume (V T ) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH 2 O, fraction of inspired oxygen (FiO 2 ) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V T values ( n = 1200; mean V T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH 2 0/ml and 2.0 ± 0.8 cmH 2 0/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and

  7. Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits.

    Science.gov (United States)

    Almlén, Andreas; Walther, Frans J; Waring, Alan J; Robertson, Bengt; Johansson, Jan; Curstedt, Tore

    2010-06-01

    Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8-9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3-4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15-17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.

  8. Computer modeling of lung cancer diagnosis-to-treatment process.

    Science.gov (United States)

    Ju, Feng; Lee, Hyo Kyung; Osarogiagbon, Raymond U; Yu, Xinhua; Faris, Nick; Li, Jingshan

    2015-08-01

    We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed.

  9. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

    Directory of Open Access Journals (Sweden)

    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  10. Human autoantibodies against Clq: lack of cross reactivity with the collectins mannan-binding protein, lung surfactant protein A and bovine conglutinin.

    Science.gov (United States)

    Mårtensson, U; Thiel, S; Jensenius, J C; Sjöholm, A G

    1996-03-01

    The collectins, a group of humoral C-type lectins, have globular and collagen-like regions and share structural features with the complement protein C1q. The question was asked if autoantibodies to the collagen-like region of C1q (anti-C1qCLR) might cross-react with collectins, such as mannan-binding protein (MBP), lung surfactant protein A (SP-A) and bovine conglutinin (BK). Anti-C1qCLR antibodies of the systemic lupus erythematosus (SLE) type and anti-C1qCLR antibodies of the hypocomplementemic urticarial vasculitis syndrome (HUVS) type were investigated. Cross-absorption and elution experiments combined with antibody detection by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis gave no evidence of cross-reactive anti-C1qCLR antibodies. However, one serum with HUVS type anti-C1qCLR antibodies contained anti-MBP antibodies that were cross-reactive with SP-A. Judging from results of ELISA inhibition experiments and immunoblot analysis, four SLE sera contained antibodies to native BK, while two sera with HUVS type anti-C1qCLR antibodies contained antibodies to epitopes of denatured BK. This might imply that autoimmunity to collagen-like structures is not restricted to C1qCLR in HUVS and HUVS/SLE overlap syndromes.

  11. Prophylactic administration of porcine-derived lung surfactant is a significant factor in reducing the odds for peri-intraventricular haemorrhage in premature infants.

    Science.gov (United States)

    Walti, Hervé; Paris-Llado, Josefa; Egberts, Johannes; Brand, Roland; Bevilacqua, Giulio; Gardini, Fabrizio; Bréart, Gérard

    2002-01-01

    We hypothesized that prophylactic treatment with a porcine-modified lung surfactant (PLS) reduces the rate of peri-intraventricular haemorrhage (PIVH) more than rescue treatment. We performed a meta-analysis of three prophylactic versus rescue trials conducted with PLS in four countries using individual data. Overall (grades 1-4) or severe (grades 3 and 4) PIVH of 671 newborns was the outcome. A logistic regression analysis was performed. Prophylactic exposure to PLS was a significant independent factor in reducing the incidence of overall (OR 0.65; 95% CI 0.47-0.90) and severe (OR 0.56; 95% CI 0.35-0.89) PIVH. Moreover, for severe PIVH, the adjusted OR for outborn babies exposed to prophylactic treatment with PLS was highly significant (OR 0.11; 95% CI 0.02-to 0.49). The results we obtained show that prophylactic treatment with PLS reduces the rate of PIVH more than rescue treatment. Copyright 2002 S. Karger AG, Basel

  12. Anti-IL-8 antibody potentiates the effect of exogenous surfactant in respiratory failure caused by meconium aspiration.

    Science.gov (United States)

    Mikolka, Pavol; Kopincova, Jana; Kosutova, Petra; Kolomaznik, Maros; Calkovska, Andrea; Mokra, Daniela

    2018-02-01

    Meconium aspiration syndrome (MAS) is life-threatening respiratory failure of newborns which can be treated by exogenous surfactant. In response to meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil infiltration of the lungs. Local accumulation and activation of neutrophils, on-going inflammation, lung edema, and oxidative damage contribute to inactivation of endogenous and therapeutically given surfactants. Therefore, we have hypothesized that addition of monoclonal anti-IL-8 antibody into exogenous surfactant can mitigate the neutrophil-induced local injury and the secondary surfactant inactivation and may finally result in improvement of respiratory functions. New Zealand rabbits with intratracheal meconium-induced respiratory failure (meconium 25 mg/ml, 4 ml/kg) were divided into three groups: untreated (M), surfactant-treated (M + S), and treated with combination of surfactant and anti-IL-8 antibody (M + S + anti-IL-8). Surfactant therapy consisted of two lung lavages with diluted porcine surfactant Curosurf (10 ml/kg, 5 mg phospholipids (PL)/ml) followed by undiluted Curosurf (100 mg PL/kg) delivered by means of asymmetric high-frequency jet ventilation (f. 300/min, Ti 20%). In M + S + anti-IL-8 group, anti-IL-8 antibody (100 µg/kg) was added directly to Curosurf dose. Animals were oxygen-ventilated for additional 5 h, respiratory parameters were measured regularly. Subsequently, cell counts in bronchoalveolar lavage fluid (BAL), lung edema formation, oxidative damage, levels of interleukins (IL)-1β and IL-6 in the lung homogenate were evaluated. Surfactant instillation significantly improved lung function. Addition of anti-IL-8 to surfactant further improved gas exchange and ventilation efficiency and had longer-lasting effect than surfactant-only therapy. Combined treatment showed the trend to reduce neutrophil count in BAL fluid, local oxidative damage, and levels of IL-1β and IL-6 more effectively than surfactant

  13. Self-consistent field modeling of non-ionic surfactants at the silica-water interface: Incorporating molecular detail

    NARCIS (Netherlands)

    Postmus, B.R.; Leermakers, F.A.M.; Cohen Stuart, M.A.

    2008-01-01

    We have constructed a model to predict the properties of non-ionic (alkyl-ethylene oxide) (C(n)E(m)) surfactants, both in aqueous solutions and near a silica surface, based upon the self-consistent field theory using the Scheutjens-Fleer discretisation scheme. The system has the pH and the ionic

  14. A lung segmental model of chronic Pseudomonas infection in sheep.

    Directory of Open Access Journals (Sweden)

    David Collie

    Full Text Available Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4 cfu/g.The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  15. A lung segmental model of chronic Pseudomonas infection in sheep.

    Science.gov (United States)

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

  16. Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells.

    Science.gov (United States)

    Bai, Ru; Guan, Longfei; Zhang, Wei; Xu, Jinxia; Rui, Wei; Zhang, Fang; Ding, Wenjun

    2016-12-01

    There is a strong link between smaller air pollution particles and a range of serious health conditions. Thus, there is a need for understanding the impacts of airborne fine particulate matter (PM) with an aerodynamic diameter of PM1) on lung alveolar epithelial cells. In the present study, mouse lung epithelial type II cell MLE-12 cells were used to examine the intracellular oxidative responses and the surfactant protein expressions after exposure to various concentrations of PM1 collected from an urban site and a steel-factory site (referred as uPM1 and sPM1 hereafter, respectively). Physicochemical characterization of PM1 was performed by using scanning electron microscopy and transmission electron microscopy. Cytotoxicity and autophagy induced by PM1 were assessed by using comprehensive approaches after MLE-12 cells were exposed to different concentrations of PM1 for various times. Expression of surfactant proteins B and C in MLE-12 cells was determined by Western blotting. All of the tested PM1 induced cytotoxicity evidenced by significant decrease of cell viability and increase of lactate dehydrogenase (LDH) release in a time- and concentration-dependent manner in the exposed cells compared with the unexposed cells. A similar pattern of increase of intercellular reactive oxygen species (ROS) generation and decrease of superoxide dismutase (SOD) and catalase (CAT) activities was also observed. PM1-induced autophagy was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and increased levels of beclin1. Data from Western blotting showed significant decrease of surfactant protein B and C expressions. Relatively high concentrations of transition metals, including Fe, Cu and Mn, may be responsible for the higher toxicity of sPM1 compared with uPM1. Moreover, pretreatment with N-acetylcysteine (NAC) or Chelex (a metal chelating agent, which removes a large suite of metals from PM1) prevented the increase of

  17. On a PCA-based lung motion model.

    Science.gov (United States)

    Li, Ruijiang; Lewis, John H; Jia, Xun; Zhao, Tianyu; Liu, Weifeng; Wuenschel, Sara; Lamb, James; Yang, Deshan; Low, Daniel A; Jiang, Steve B

    2011-09-21

    Respiration-induced organ motion is one of the major uncertainties in lung cancer radiotherapy and is crucial to be able to accurately model the lung motion. Most work so far has focused on the study of the motion of a single point (usually the tumor center of mass), and much less work has been done to model the motion of the entire lung. Inspired by the work of Zhang et al (2007 Med. Phys. 34 4772-81), we believe that the spatiotemporal relationship of the entire lung motion can be accurately modeled based on principle component analysis (PCA) and then a sparse subset of the entire lung, such as an implanted marker, can be used to drive the motion of the entire lung (including the tumor). The goal of this work is twofold. First, we aim to understand the underlying reason why PCA is effective for modeling lung motion and find the optimal number of PCA coefficients for accurate lung motion modeling. We attempt to address the above important problems both in a theoretical framework and in the context of real clinical data. Second, we propose a new method to derive the entire lung motion using a single internal marker based on the PCA model. The main results of this work are as follows. We derived an important property which reveals the implicit regularization imposed by the PCA model. We then studied the model using two mathematical respiratory phantoms and 11 clinical 4DCT scans for eight lung cancer patients. For the mathematical phantoms with cosine and an even power (2n) of cosine motion, we proved that 2 and 2n PCA coefficients and eigenvectors will completely represent the lung motion, respectively. Moreover, for the cosine phantom, we derived the equivalence conditions for the PCA motion model and the physiological 5D lung motion model (Low et al 2005 Int. J. Radiat. Oncol. Biol. Phys. 63 921-9). For the clinical 4DCT data, we demonstrated the modeling power and generalization performance of the PCA model. The average 3D modeling error using PCA was within 1

  18. Surfactant -- Where Are We in 2003?

    Directory of Open Access Journals (Sweden)

    JF Lewis

    2004-01-01

    Full Text Available Surfactant research has progressed over the past several years to the extent that exogenous surfactant administration in patients with the acute respiratory distress syndrome (ARDS is now being evaluated. Unfortunately, clinical responses have been variable, and we now need to take a look at how surfactant is altered in this disease so that more effective treatment strategies can be developed. This review briefly discusses the biophysical and host defense properties of surfactant, the impact of mechanical ventilation (MV on the endogenous surfactant system and the most recent clinical data involving exogenous surfactant administration in patients with ARDS. Discussions regarding future directions of surfactant research both in ARDS and diseases other than acute lung injury are included.

  19. Modeling of the Critical Micelle Concentration (CMC) of Nonionic Surfactants with an Extended Group-Contribution Method

    DEFF Research Database (Denmark)

    Mattei, Michele; Kontogeorgis, Georgios; Gani, Rafiqul

    2013-01-01

    of 150 experimental measurements covering a large variety of nonionic surfactants including linear, branched, and phenyl alkyl ethoxylates; alkanediols; alkyl mono- and disaccharide ethers and esters; ethoxylated alkyl amines and amides; fluorinated linear ethoxylates and amides; polyglycerol esters...... concentration, and in particular, the quantitative structure−property relationship models, the developed GC model provides an accurate correlation and allows for an easier and faster application in computer-aided molecular design techniques facilitating chemical process and product design....

  20. Chapter 7: Description of miscan-lung, the erasmus mc lung cancer microsimulation model for evaluating cancer control interventions

    NARCIS (Netherlands)

    F.W. Schultz (Frank); R. Boer (Rob); H.J. de Koning (Harry)

    2012-01-01

    textabstractThe MISCAN-lung model was designed to simulate population trends in lung cancer (LC) for comprehensive surveillance of the disease, to relate past exposure to risk factors to (observed) LC incidence and mortality, and to estimate the impact of cancer-control interventions. MISCAN-lung

  1. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel

    2005-01-01

    Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have...... overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach...

  2. Pulmonary clearance of {sup 99m}Tc-DTPA in experimental surfactant dysfunction treated with surfactant installation

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, K.; John, J.; Lachmann, B.; Robertson, B.; Wollmer, P.

    1997-02-01

    Background: Breakdown of the alveolo-capillary barrier is a characteristic feature of respiratory distress syndrome. Restoration of alveolo-capillary barrier function may be an important aspect of surfactant replacement therapy. We examined the effect of surfactant installation on alveolo-capillary barrier function in an experimental model of surfactant dysfunction by measuring pulmonary clearance of {sup 99m}Tc-DTPA. Methods: Nineteen rabbits were tracheotomized and mechanically ventilated. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Detergent was given to 13 rabbits; seven rabbits were then treated with installation of natural surfactant, whereas six rabbits received saline. Six rabbits were used as untreated controls. An aerosol of {sup 99m}Tc-DTPA was administered to all animals and the pulmonary clearance was measured with a gamma camera. Results: {sup 99m}Tc-DTPA cleared from the lungs with a half-life of 71{+-}22 min in the control animals, 21.4{+-}7.4 min in the surfactant-treated animals and 5.8{+-}1.5 min in the saline-treated animals. The difference in half-life between groups was highly significant (P<0.001). There was no change in arterial oxygenation or compliance in controls or in animals treated with saline. In animals treated with surfactant, a small transient reduction in arterial oxygen tension and a more long-standing reduction in compliance were observed. Conclusion: Surfactant treatment thus significantly attenuated the effect of detergent treatment but did not restore alveolo-capillary transfer of {sup 99m}Tc-DTPA to normal. (AU) 26 refs.

  3. CFD analysis and flow model reduction for surfactant production in helix reactor

    Directory of Open Access Journals (Sweden)

    Nikačević N.M.

    2015-01-01

    Full Text Available Flow pattern analysis in a spiral Helix reactor is conducted, for the application in the commercial surfactant production. Step change response curves (SCR were obtained from numerical tracer experiments by three-dimensional computational fluid dynamics (CFD simulations. Non-reactive flow is simulated, though viscosity is treated as variable in the direction of flow, as it increases during the reaction. The design and operating parameters (reactor diameter, number of coils and inlet velocity are varied in CFD simulations, in order to examine the effects on the flow pattern. Given that 3D simulations are not practical for fast computations needed for optimization, scale-up and control, CFD flow model is reduced to one-dimensional axial dispersion (AD model with spatially variable dispersion coefficient. Dimensionless dispersion coefficient (Pe is estimated under different conditions and results are analyzed. Finally, correlation which relates Pe number with Reynolds number and number of coils from the reactor entrance is proposed for the particular reactor application and conditions.

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

    Directory of Open Access Journals (Sweden)

    Menk M

    2018-05-01

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

  5. Variables used to set PEEP in the lung lavage model are poorly related.

    Science.gov (United States)

    Lichtwarck-Aschoff, M; Hedlund, A J; Nordgren, K A; Wegenius, G A; Markström, A M; Guttmann, J; Sjöstrand, U H

    1999-12-01

    Setting an appropriate positive end-expiratory pressure (PEEP) value is determined by respiratory mechanics, gas exchange and oxygen transport. As these variables may be optimal at different PEEP values, a unique PEEP value may not exist which satisfies both the demands of minimizing mechanical stress and optimizing oxygen transport. In 15 surfactant-deficient piglets, PEEP was increased progressively. Arterial oxygenation and functional residual capacity (FRC) increased, while specific compliance of the respiratory system decreased. Static compliance increased up to a threshold value of PEEP of 8 cm H2O, after which it decreased. This threshold PEEP did not coincide with the lower inflection point of the inspiratory limb of the pressure-volume (PV) loop. Oxygen transport did not correlate with respiratory mechanics or FRC. In the lavage model, the lower inflection point of the PV curve may reflect opening pressure rather than the pressure required to keep the recruited lung open. Recruitment takes place together with a change in the elastic properties of the already open parts of the lung. No single PEEP level is optimal for both oxygen transport and reduction of mechanical stress.

  6. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    OpenAIRE

    Gilliss, Brian M.; Looney, Mark R.

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approache...

  7. On the predictions and limitations of the Becker–Döring model for reaction kinetics in micellar surfactant solutions

    KAUST Repository

    Griffiths, I.M.

    2011-08-01

    We investigate the breakdown of a system of micellar aggregates in a surfactant solution following an order-one dilution. We derive a mathematical model based on the Becker-Döring system of equations, using realistic expressions for the reaction constants fit to results from Molecular Dynamics simulations. We exploit the largeness of typical aggregation numbers to derive a continuum model, substituting a large system of ordinary differential equations for a partial differential equation in two independent variables: time and aggregate size. Numerical solutions demonstrate that re-equilibration occurs in two distinct stages over well-separated timescales, in agreement with experiment and with previous theories. We conclude by exposing a limitation in the Becker-Döring theory for re-equilibration of surfactant solutions. © 2011 Elsevier Inc.

  8. Adsorption of model perfumes at the air-solution interface by coadsorption with an anionic surfactant.

    Science.gov (United States)

    Bradbury, Robert; Penfold, Jeffrey; Thomas, Robert K; Tucker, Ian M; Petkov, Jordan T; Jones, Craig

    2013-03-12

    The adsorption of the model perfumes phenyl ethanol, PE, and linalool, LL, at the air-solution interface by coadsorption with the anionic surfactant sodium dodecyl 6-benezene sulfonate, LAS-6, has been studied primarily by neutron reflectivity, NR. The variation in the mixed surface adsorption with solution composition is highly nonideal, and the more hydrophobic LL is more surface active. At a LAS-6 concentration of 0.5 mM the adsorption of PE and LL is broadly similar but with the LL systematically more surface active, and at 2 mM the LL completes more effectively for the surface than the PE. The variation in surface composition with solution composition and concentration reflect the greater hydrophobicity and hence surface activity of LL, and the greater solubility of PE in aqueous solution. Changing the geometry of the LAS isomer, from the symmetrical LAS-6 geometry to the more asymmetrical LAS-4, results in the LL competing more effectively for the surface due to changes in the packing constraints associated with the hydrophobic region. The results provide insights into the factors that affect coadsorption that can be more broadly applied to the surface delivery of a wide range of molecules other than perfumes.

  9. Surfactant nebulisation prevents the adverse effects of surfactant therapy on blood pressure and cerebral blood flow in rabbits with severe respiratory failure

    NARCIS (Netherlands)

    Dijk, Peter H.; Heikamp, A; Bambang Oetomo, Sidarto

    1997-01-01

    Objective: Surfactant replacement therapy for the neonatal respiratory distress syndrome has shown beneficial effects on lung function and survival. Recently, rapid fluctuations of haemodynamics and cerebral perfusion following surfactant instillation have beer, described and an association with the

  10. Numerical approximation of a binary fluid-surfactant phase field model of two-phase incompressible flow

    KAUST Repository

    Zhu, Guangpu

    2018-04-17

    In this paper, we consider the numerical approximation of a binary fluid-surfactant phase field model of two-phase incompressible flow. The nonlinearly coupled model consists of two Cahn-Hilliard type equations and incompressible Navier-Stokes equations. Using the Invariant Energy Quadratization (IEQ) approach, the governing system is transformed into an equivalent form, which allows the nonlinear potentials to be treated efficiently and semi-explicitly. we construct a first and a second-order time marching schemes, which are extremely efficient and easy-to-implement, for the transformed governing system. At each time step, the schemes involve solving a sequence of linear elliptic equations, and computations of phase variables, velocity and pressure are totally decoupled. We further establish a rigorous proof of unconditional energy stability for the semi-implicit schemes. Numerical results in both two and three dimensions are obtained, which demonstrate that the proposed schemes are accurate, efficient and unconditionally energy stable. Using our schemes, we investigate the effect of surfactants on droplet deformation and collision under a shear flow. The increase of surfactant concentration can enhance droplet deformation and inhibit droplet coalescence.

  11. Regional differences in prediction models of lung function in Germany

    Directory of Open Access Journals (Sweden)

    Schäper Christoph

    2010-04-01

    Full Text Available Abstract Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

  12. Development of Mouse Lung Deposition Models

    Science.gov (United States)

    2015-07-01

    J. K. Dunnick, M. R. Elwell, J. M. Benson, C. H. Hobbs , F. F. Hahn, P. J. Haly, Y. S. Cheng, and A. F. Eidson, “Lung toxicity after 13-week...Hahn, P. J. Haley, R. L. Hanson, C. H. Hobbs , J. A. Pickrell, and J. K. Dunnick, “Comparative inhalation toxicity of nickel subsulfide to F344/N...ATTN: MR. THOMAS WOLFINGER /J9CBI DEFENSE THREAT REDUCTION AGENCY 8725 JOHN J. KINGMAN ROAD FT. BELVOIR, VA 22060-6201 ATTN: DR. ERIN REICHERT

  13. Biomimicry of surfactant protein C.

    Science.gov (United States)

    Brown, Nathan J; Johansson, Jan; Barron, Annelise E

    2008-10-01

    Since the widespread use of exogenous lung surfactant to treat neonatal respiratory distress syndrome, premature infant survival and respiratory morbidity have dramatically improved. Despite the effectiveness of the animal-derived surfactant preparations, there still remain some concerns and difficulties associated with their use. This has prompted investigation into the creation of synthetic surfactant preparations. However, to date, no clinically used synthetic formulation is as effective as the natural material. This is largely because the previous synthetic formulations lacked analogues of the hydrophobic proteins of the lung surfactant system, SP-B and SP-C, which are critical functional constituents. As a result, recent investigation has turned toward the development of a new generation of synthetic, biomimetic surfactants that contain synthetic phospholipids along with a mimic of the hydrophobic protein portion of lung surfactant. In this Account, we detail our efforts in creating accurate mimics of SP-C for use in a synthetic surfactant replacement therapy. Despite SP-C's seemingly simple structure, the predominantly helical protein is extraordinarily challenging to work with given its extreme hydrophobicity and structural instability, which greatly complicates the creation of an effective SP-C analogue. Drawing inspiration from Nature, two promising biomimetic approaches have led to the creation of rationally designed biopolymers that recapitulate many of SP-C's molecular features. The first approach utilizes detailed SP-C structure-activity relationships and amino acid folding propensities to create a peptide-based analogue, SP-C33. In SP-C33, the problematic and metastable polyvaline helix is replaced with a structurally stable polyleucine helix and includes a well-placed positive charge to prevent aggregation. SP-C33 is structurally stable and eliminates the association propensity of the native protein. The second approach follows the same design

  14. Novel swine model of transfusion-related acute lung injury.

    Science.gov (United States)

    Okazaki, Hitoshi; Ishikawa, Osamu; Iijima, Takehiko; Kohira, Takahiro; Teranishi, Mai; Kawasaki, Shin; Saito, Akira; Mikami, Yu; Sugiura, Asuka; Hashimoto, Shiho; Shimada, Eiko; Uchikawa, Makoto; Matsuhashi, Mika; Tsuno, Nelson H; Tanaka, Minoru; Kiyokawa, Nobutaka; Fujimoto, Junichiro; Nagase, Takahide; Tadokoro, Kenji; Takahashi, Koki

    2014-12-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. Antibodies against human leukocyte antigens in donors' plasma are the major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been developed, large-animal models of antibody-mediated TRALI are not yet available. To develop a swine model of TRALI, male Clawn strain miniature pigs were used. A monoclonal antibody (MoAb) against swine leukocyte antigens (SLAs) Class I (4G8, 0.3 or 1.0 mg/kg body weight [BW]) and a control antibody (1.0 mg/kg BW) were injected into the peripheral vein after priming with or without 1 μg/kg BW lipopolysaccharide (LPS; n = 3 each). Lung injury was assessed using PaO2 /FiO2 (P/F) ratio and by chest X-ray imaging. Histopathologic analysis was also conducted. Lung injury could be induced by injecting 4G8 at an amount of 1.0 mg/kg BW, after LPS. The P/F ratio 90 minutes after the administration of 4G8 significantly decreased (p Lung injury was confirmed by histopathologic analysis. Lung injury in pigs was successfully induced by anti-SLA MoAb. Priming with LPS is a prerequisite for inducing lung injury and the amount of the antibody is a critical condition. © 2014 AABB.

  15. Different effects of surfactant proteins B and C - implications for development of synthetic surfactants.

    Science.gov (United States)

    Curstedt, Tore; Johansson, Jan

    2010-06-01

    Treatment of premature newborn rabbits with synthetic surfactants containing a surfactant protein C analogue in a simple phospholipid mixture gives similar tidal volumes as treatment with poractant alfa (Curosurf(R)) but ventilation with a positive end-expiratory pressure (PEEP) is needed for this synthetic surfactant to stabilize the alveoli at end-expiration. The effect on lung gas volumes seems to depend on the structure of the peptide since treatment with a synthetic surfactant containing the 21-residue peptide (LysLeu(4))(4)Lys (KL(4)) gives low lung gas volumes in experiments also performed with PEEP. Surfactant preparations containing both surfactant proteins B and C or their analogues prevent alveolar collapse at end-expiration even if ventilated without PEEP. Treatment of premature newborn rabbits with different natural surfactants indicates that both the lipid composition and the proteins are important in order to stabilize the alveoli at end-expiration. Synthetic surfactants containing two peptides may be able to replace natural surfactants within the near future but more trials need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants. Copyright 2010 S. Karger AG, Basel.

  16. Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model.

    Science.gov (United States)

    Romero, A; Moreno, A; García, J; Sánchez, C; Santos, M; García, J

    2016-01-01

    Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Effect of SP-C on surface potential distribution in pulmonary surfactant: Atomic force microscopy and Kelvin probe force microscopy study

    International Nuclear Information System (INIS)

    Hane, Francis; Moores, Brad; Amrein, Matthias; Leonenko, Zoya

    2009-01-01

    The air-lung interface is covered by a molecular film of pulmonary surfactant (PS). The major function of the film is to reduce the surface tension of the lung's air-liquid interface, providing stability to the alveolar structure and reducing the work of breathing. Earlier we have shown that function of bovine lipid extract surfactant (BLES) is related to the specific molecular architecture of surfactant films. Defined molecular arrangement of the lipids and proteins of the surfactant film also give rise to a local highly variable electrical surface potential of the interface. In this work we investigated a simple model of artificial lung surfactant consisting of DPPC, eggPG, and surfactant protein C (SP-C). Effects of surface compression and the presence of SP-C on the monolayer structure and surface potential distribution were investigated using atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM). We show that topography and locally variable surface potential of DPPC-eggPG lipid mixture are similar to those of pulmonary surfactant BLES in the presence of SP-C and differ in surface potential when SP-C is absent.

  18. Material model of lung parenchyma based on living precision-cut lung slice testing.

    Science.gov (United States)

    Rausch, S M K; Martin, C; Bornemann, P B; Uhlig, S; Wall, W A

    2011-05-01

    We describe a novel constitutive model of lung parenchyma, which can be used for continuum mechanics based predictive simulations. To develop this model, we experimentally determined the nonlinear material behavior of rat lung parenchyma. This was achieved via uni-axial tension tests on living precision-cut rat lung slices. The resulting force-displacement curves were then used as inputs for an inverse analysis. The Levenberg-Marquardt algorithm was utilized to optimize the material parameters of combinations and recombinations of established strain-energy density functions (SEFs). Comparing the best-fits of the tested SEFs we found Wpar = 4.1 kPa(I1-3)2 + 20.7 kPa(I1 - 3)3 + 4.1 kPa(-2 ln J + J2 - 1) to be the optimal constitutive model. This SEF consists of three summands: the first can be interpreted as the contribution of the elastin fibers and the ground substance, the second as the contribution of the collagen fibers while the third controls the volumetric change. The presented approach will help to model the behavior of the pulmonary parenchyma and to quantify the strains and stresses during ventilation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Bayesian Age-Period-Cohort Model of Lung Cancer Mortality

    Directory of Open Access Journals (Sweden)

    Bhikhari P. Tharu

    2015-09-01

    Full Text Available Background The objective of this study was to analyze the time trend for lung cancer mortality in the population of the USA by 5 years based on most recent available data namely to 2010. The knowledge of the mortality rates in the temporal trends is necessary to understand cancer burden.Methods Bayesian Age-Period-Cohort model was fitted using Poisson regression with histogram smoothing prior to decompose mortality rates based on age at death, period at death, and birth-cohort.Results Mortality rates from lung cancer increased more rapidly from age 52 years. It ended up to 325 deaths annually for 82 years on average. The mortality of younger cohorts was lower than older cohorts. The risk of lung cancer was lowered from period 1993 to recent periods.Conclusions The fitted Bayesian Age-Period-Cohort model with histogram smoothing prior is capable of explaining mortality rate of lung cancer. The reduction in carcinogens in cigarettes and increase in smoking cessation from around 1960 might led to decreasing trend of lung cancer mortality after calendar period 1993.

  20. Surfactant softening of plant leaf cuticle model wax--a Differential Scanning Calorimetry (DSC) and Quartz Crystal Microbalance with Dissipation (QCM-D) study.

    Science.gov (United States)

    Fagerström, Anton; Kocherbitov, Vitaly; Westbye, Peter; Bergström, Karin; Arnebrant, Thomas; Engblom, Johan

    2014-07-15

    The aim was to quantify the softening effect that two surfactants (C10EO7 and C8G1.6) have on a plant leaf cuticle model wax. Effects on the thermotropic phase behavior and fluidity of the wax (C22H45OH/C32H66/H2O) were determined. The model wax is crystalline at ambient conditions, yet it is clearly softened by the surfactants. Both surfactants decreased the transition temperatures in the wax and the G″/G' ratio of the wax film increased in irreversible steps following surfactant exposure. C10EO7 has a stronger fluidizing effect than C8G1.6 due to stronger interaction with the hydrophobic waxes. Intracuticular waxes (IW) comprise both crystalline and amorphous domains and it has previously been proposed that the fluidizing effects of surfactants are due to interactions with the amorphous parts. New data suggests that this may be a simplification. Surfactants may also absorb in crevices between crystalline domains. This causes an irreversible effect and a softer cuticle wax. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome.

    Directory of Open Access Journals (Sweden)

    Hans Fuchs

    Full Text Available BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8-10 ml/kg/PaCO(2 = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2 = 80 mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2 = 120 mm Hg; Group 4: tidal volume = 2-3 ml/kg/PaCO(2 = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO(2 were found in all low tidal volume/hypercapnia groups (group 2, 3, 4 as compared to the group with conventional tidal volume/normocapnia (group 1. The reduction of the tidal volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.

  2. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs.

    Directory of Open Access Journals (Sweden)

    Matthias Seehase

    Full Text Available BACKGROUND: Respiratory distress syndrome in preterm babies is caused by a pulmonary surfactant deficiency, but also by its inactivation due to various conditions, including plasma protein leakage. Surfactant replacement therapy is well established, but clinical observations and in vitro experiments suggested that its efficacy may be impaired by inactivation. A new synthetic surfactant (CHF 5633, containing synthetic surfactant protein B and C analogs, has shown comparable effects on oxygenation in ventilated preterm rabbits versus Poractant alfa, but superior resistance against inactivation in vitro. We hypothesized that CHF 5633 is also resistant to inactivation by serum albumin in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Nineteen preterm lambs of 127 days gestational age (term = 150 days received CHF 5633 or Poractant alfa and were ventilated for 48 hours. Ninety minutes after birth, the animals received albumin with CHF 5633 or Poractant alfa. Animals received additional surfactant if P(aO(2 dropped below 100 mmHg. A pressure volume curve was done post mortem and markers of pulmonary inflammation, surfactant content and biophysiology, and lung histology were assessed. CHF 5633 treatment resulted in improved arterial pH, oxygenation and ventilation efficiency index. The survival rate was significantly higher after CHF 5633 treatment (5/7 than after Poractant alfa (1/8 after 48 hours of ventilation. Biophysical examination of the surfactant recovered from bronchoalveolar lavages revealed that films formed by CHF 5633-treated animals reached low surface tensions in a wider range of compression rates than films from Poractant alfa-treated animals. CONCLUSIONS: For the first time a synthetic surfactant containing both surfactant protein B and C analogs showed significant benefit over animal derived surfactant in an in vivo model of surfactant inactivation in premature lambs.

  3. Enterobacter agglomerans lipopolysaccharide-induced changes in pulmonary surfactant as a factor in the pathogenesis of byssinosis.

    Science.gov (United States)

    DeLucca, A J; Brogden, K A; Engen, R

    1988-04-01

    Lipopolysaccharide (LPS) from Enterobacter agglomerans and pulmonary surfactant mixtures were centrifuged in discontinuous sucrose gradients to determine whether LPS bound to surfactant and examined in a Langmuir trough with a Wilhelmy balance to determine whether LPS altered the surface activity of surfactant. The LPS was found to bind to the surfactant and altered its surface tension properties. The binding of LPS to surfactant in the lung may change the physiological properties of surfactant and be a possible mechanism for the pathogenesis of byssinosis.

  4. Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits.

    Science.gov (United States)

    Calkovska, Andrea; Linderholm, Bim; Haegerstrand-Björkman, Marie; Pioselli, Barbara; Pelizzi, Nicola; Johansson, Jan; Curstedt, Tore

    2016-01-01

    The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. Treatment with Curosurf or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (VT) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small VT, but after addition of both analogues VT was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on VT and LGV as Curosurf. Phospholipid composition is important for VT while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding VT and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure. © 2016 S. Karger AG, Basel.

  5. Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B.

    Science.gov (United States)

    Danhaive, Olivier; Chapin, Cheryl; Horneman, Hart; Cogo, Paola E; Ballard, Philip L

    2015-02-01

    Pulmonary surfactant provides an alveolar surface-active film that is critical for normal lung function. Our objective was to determine in vitro film formation properties of therapeutic and infant surfactants and the influence of surfactant protein (SP)-B content. We used a multiwell fluorescent assay measuring maximum phospholipid surface accumulation (Max), phospholipid concentration required for half-maximal film formation (½Max), and time for maximal accumulation (tMax). Among five therapeutic surfactants, calfactant (highest SP-B content) had film formation values similar to natural surfactant, and addition of SP-B to beractant (lowest SP-B) normalized its Max value. Addition of budesonide to calfactant did not adversely affect film formation. In tracheal aspirates of preterm infants with evolving chronic lung disease, SP-B content correlated with ½Max and tMax values, and SP-B supplementation of SP-B-deficient infant surfactant restored normal film formation. Reconstitution of normal surfactant indicated a role for both SP-B and SP-C in film formation. Film formation in vitro differs among therapeutic surfactants and is highly dependent on SP-B content in infant surfactant. The results support a critical role of SP-B for promoting surface film formation.

  6. Sex and smoking sensitive model of radon induced lung cancer

    International Nuclear Information System (INIS)

    Zhukovsky, M.; Yarmoshenko, I.

    2006-01-01

    Radon and radon progeny inhalation exposure are recognized to cause lung cancer. Only strong evidence of radon exposure health effects was results of epidemiological studies among underground miners. Any single epidemiological study among population failed to find reliable lung cancer risk due to indoor radon exposure. Indoor radon induced lung cancer risk models were developed exclusively basing on extrapolation of miners data. Meta analyses of indoor radon and lung cancer case control studies allowed only little improvements in approaches to radon induced lung cancer risk projections. Valuable data on characteristics of indoor radon health effects could be obtained after systematic analysis of pooled data from single residential radon studies. Two such analyses are recently published. Available new and previous data of epidemiological studies of workers and general population exposed to radon and other sources of ionizing radiation allow filling gaps in knowledge of lung cancer association with indoor radon exposure. The model of lung cancer induced by indoor radon exposure is suggested. The key point of this model is the assumption that excess relative risk depends on both sex and smoking habits of individual. This assumption based on data on occupational exposure by radon and plutonium and also on the data on external radiation exposure in Hiroshima and Nagasaki and the data on external exposure in Mayak nuclear facility. For non-corrected data of pooled European and North American studies the increased sensitivity of females to radon exposure is observed. The mean value of ks for non-corrected data obtained from independent source is in very good agreement with the L.S.S. study and Mayak plutonium workers data. Analysis of corrected data of pooled studies showed little influence of sex on E.R.R. value. The most probable cause of such effect is the change of men/women and smokers/nonsmokers ratios in corrected data sets in North American study. More correct

  7. The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis

    Directory of Open Access Journals (Sweden)

    Rothenberg Marc E

    2010-06-01

    Full Text Available Abstract Background Arginine is an amino acid that serves as a substrate for the enzymes nitric oxide synthase (NOS and arginase, leading to synthesis of NO and ornithine, respectively. As such, arginine has the potential to influence diverse fundamental processes in the lung. Methods We used mice deficient in cationic amino acid transporter (CAT 2 in models of allergic airway inflammation and pulmonary fibrosis. Results We report that the arginine transport protein CAT2 was over-expressed in the lung during the induction of allergic airway inflammation. Furthermore, CAT2 mRNA was strongly induced by transgenically over-expressed IL-4, and allergen-induced expression was dependent upon signal-transducer-and-activator-of-transcription (STAT 6. In situ mRNA hybridization demonstrated marked staining of CAT2, predominantly in scattered mononuclear cells. Analysis of allergic airway inflammation and bleomycin-induced inflammation in CAT2-deficient mice revealed that while inflammation was independent of CAT2 expression, bleomycin-induced fibrosis was dependent upon CAT2. Mechanistic analysis revealed that arginase activity in macrophages was partly dependent on CAT2. Conclusion Taken together, these results identify CAT2 as a regulator of fibrotic responses in the lung.

  8. Experimental models of transfusion-related acute lung injury.

    Science.gov (United States)

    Gilliss, Brian M; Looney, Mark R

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    Science.gov (United States)

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

  10. The protective effect of different airway humidification liquids to lung after tracheotomy in traumatic brain injury: The role of pulmonary surfactant protein-A (SP-A).

    Science.gov (United States)

    Su, Xinyang; Li, Zefu; Wang, Meilin; Li, Zhenzhu; Wang, Qingbo; Lu, Wenxian; Li, Xiaoli; Zhou, Youfei; Xu, Hongmei

    2016-02-10

    The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used. Brain tissue samples were taken to determine water content, while lung tissue samples were taken to determine wet/dry weight ratio (W/D), histological changes and expression levels of SP-A mRNA and SP-A protein. 30 patients with brain injury and tracheotomy were selected and divided into two groups based on the airway humidification liquid instilled in the trachea tube, 0.45% NaCl and 0.9% NaCl+ambroxol. Blood was then extracted from the patients to measure the levels of SP-A, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The difference between group C and other groups in lung W/D and expression levels of SP-A mRNA and SP-A protein was significant (Phumidification liquid. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Automatic lung segmentation in functional SPECT images using active shape models trained on reference lung shapes from CT.

    Science.gov (United States)

    Cheimariotis, Grigorios-Aris; Al-Mashat, Mariam; Haris, Kostas; Aletras, Anthony H; Jögi, Jonas; Bajc, Marika; Maglaveras, Nicolaos; Heiberg, Einar

    2018-02-01

    Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes. A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images. The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p automatic quantification of wide range of measurements.

  12. Experimental Study of Aerosol Deposition in a Realistic Lung Model

    Directory of Open Access Journals (Sweden)

    František LÍZAL

    2010-12-01

    Full Text Available The inhalation route for administration of medicaments is becoming more and more popular in recent years. The reason is non-invasiveness of the method and instantaneous absorption of drugs to the blood circulation. It is necessary to deliver exact amount of drug to the specific segment because of occurrence of diverse diseases in different segments of lungs. The aim of our work is to contribute to better understanding of transport and deposition of aerosolized drugs in lungs and hence to more effective treatment of respiratory diseases due to the targeted drug delivery. We provided measurements of aerosol deposition in segmented realistic model of lungs without a mouth cavity. Monodisperse particles marked with fluorescein were supplied to the model. The model was then disassembled to segments and each segment was rinsed with isopropanol, whereby fluorescent samples were created. Each sample was analysed by fluorometer and an amount of aerosol deposited in the segment was calculated. Experiences obtained by this study were used for creation of a new model with the mouth cavity. This model will be used for future studies with porous and fiber aerosols.

  13. Water Repellent Soils: The use of electrical resistivity tomography in a small scale catchment model to evaluate the effectiveness of surfactants.

    Science.gov (United States)

    Lowe, Mary-Anne; Mathes, Falko; McGrath, Gavan; Leopold, Matthias

    2017-04-01

    Soil water repellence effects large areas of land in Western Australia causing large forfeits in agricultural profit. Surfactants are a potential management tool, however, in field trials they have had varied success and their impact on water movement is poorly understood. This study employs a novel approach to determine the effectiveness of surfactants at modifying infiltration into water repellent soils. Using a physical catchment model (0.6 m × 0.6 m) with soils arranged in a ridge and furrow topography, irrigation and runoff were quantified. Electrical resistivity tomography (ERT) was used to measure changes in soil moisture patterns in two dimensions. Two sandy soils with contrasting severity of water repellence, as measured by the Molarity of Ethanol Droplet (MED) test, were assessed. The impact of two surfactants, at an equivalent rate of 1 L ha-1, and an untreated control were monitored over 5 wetting events. With surfactant application the very severely water repellent soil (MED 4.2 M) showed an increase in infiltration of up to 31%, which was concentrated under the area of surfactant application in the furrow. Volumetric water contents beneath the furrow increased up to 40% below 20 mm depth. Water infiltration into the untreated soil with low water repellence (MED 1.0 M) was 98%, and this did not significantly change with surfactant application. This physical catchment model, combined with hydrological and geophysical monitoring provides a useful tool to assess the effectiveness of surfactants in increasing water infiltration and subsurface soil moisture in water repellent soils. The work is part of the Australian CRC for Polymer project.

  14. Theoretical model to investigate the alkyl chain and anion dependent interactions of gemini surfactant with bovine serum albumin.

    Science.gov (United States)

    Vishvakarma, Vijay K; Kumari, Kamlesh; Patel, Rajan; Dixit, V S; Singh, Prashant; Mehrotra, Gopal K; Chandra, Ramesh; Chakrawarty, Anand Kumar

    2015-05-15

    Surfactants are used to prevent the irreversible aggregation of partially refolded proteins and they also assist in protein refolding. We have reported the design and screening of gemini surfactant to stabilize bovine serum albumin (BSA) with the help of computational tool (iGEMDOCK). A series of gemini surfactant has been designed based on bis-N-alkyl nicotinate dianion via varying the alkyl group and anion. On changing the alkyl group and anion of the surfactant, the value of Log P changes means polarity of surfactant can be tuned. Further, the virtual screening of the gemini surfactant has been carried out based on generic evolutionary method. Herein, thermodynamic data was studied to determine the potential of gemini surfactant as BSA stabilizer. Computational tools help to find out the efficient gemini surfactant to stabilize the BSA rather than to use the surfactant randomly and directionless for the stabilization. It can be confirmed through the experimental techniques. Previously, researcher synthesized one of the designed and used gemini surfactant to stabilize the BSA and their interactions were confirmed through various techniques and computational docking. But herein, the authors find the most competent gemini surfactant to stabilize BSA using computational tools on the basis of energy score. Different from the single chain surfactant, the gemini surfactants exhibit much stronger electrostatic and hydrophobic interactions with the protein and are thus effective at much lower concentrations. Based on the present study, it is expected that gemini surfactants may prove useful in the protein stabilization operations and may thus be effectively employed to circumvent the problem of misfolding and aggregation. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A moving boundary problem and orthogonal collocation in solving a dynamic liquid surfactant membrane model including osmosis and breakage

    Directory of Open Access Journals (Sweden)

    E.C. Biscaia Junior

    2001-06-01

    Full Text Available A dynamic kinetic-diffusive model for the extraction of metallic ions from aqueous liquors using liquid surfactant membranes is proposed. The model incorporates undesirable intrinsic phenomena such as swelling and breakage of the emulsion globules that have to be controlled during process operation. These phenomena change the spatial location of the chemical reaction during the course of extraction, resulting in a transient moving boundary problem. The orthogonal collocation method was used to transform the partial differential equations into an ordinary differential equation set that was solved by an implicit numerical routine. The model was found to be numerically stable and reliable in predicting the behaviour of zinc extraction with acidic extractant for long residence times.

  16. "SP-G", a putative new surfactant protein--tissue localization and 3D structure.

    Directory of Open Access Journals (Sweden)

    Felix Rausch

    Full Text Available Surfactant proteins (SP are well known from human lung. These proteins assist the formation of a monolayer of surface-active phospholipids at the liquid-air interface of the alveolar lining, play a major role in lowering the surface tension of interfaces, and have functions in innate and adaptive immune defense. During recent years it became obvious that SPs are also part of other tissues and fluids such as tear fluid, gingiva, saliva, the nasolacrimal system, and kidney. Recently, a putative new surfactant protein (SFTA2 or SP-G was identified, which has no sequence or structural identity to the already know surfactant proteins. In this work, computational chemistry and molecular-biological methods were combined to localize and characterize SP-G. With the help of a protein structure model, specific antibodies were obtained which allowed the detection of SP-G not only on mRNA but also on protein level. The localization of this protein in different human tissues, sequence based prediction tools for posttranslational modifications and molecular dynamic simulations reveal that SP-G has physicochemical properties similar to the already known surfactant proteins B and C. This includes also the possibility of interactions with lipid systems and with that, a potential surface-regulatory feature of SP-G. In conclusion, the results indicate SP-G as a new surfactant protein which represents an until now unknown surfactant protein class.

  17. Colloid and surfactant

    International Nuclear Information System (INIS)

    Kuk, Yun Hwan; Lee, Jeong Jung; Cho, Sun Chae; Ryeo, Su Dong

    1995-08-01

    This book consists of two parts about colloid and surfactant. The first parts has explanations colloid and surface science, which deal with creation and properties of colloidal particles, surfactant and micelle colloid, property of surfactant, membranes, absorption of surface science, electrokinetic phenomenon, emulsion, foam and rheology. The second part mentions surfactant on anionic surfactant with five types, amphoteric surface active agent, non-ionic surface active agent and use of surfactant.

  18. Antimicrobial and biophysical properties of surfactant supplemented with an antimicrobial peptide for treatment of bacterial pneumonia.

    Science.gov (United States)

    Banaschewski, Brandon J H; Veldhuizen, Edwin J A; Keating, Eleonora; Haagsman, Henk P; Zuo, Yi Y; Yamashita, Cory M; Veldhuizen, Ruud A W

    2015-01-01

    Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

    Science.gov (United States)

    Veldhuizen, Edwin J. A.; Keating, Eleonora; Haagsman, Henk P.; Zuo, Yi Y.; Yamashita, Cory M.; Veldhuizen, Ruud A. W.

    2015-01-01

    Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a “perfect storm” for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia. PMID:25753641

  20. Lung-derived growth factors: possible paracrine effectors of fetal lung development

    International Nuclear Information System (INIS)

    Montes, A.M.

    1985-01-01

    A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

  1. The Role of Surfactant in Respiratory Distress Syndrome

    OpenAIRE

    Ma, Christopher Cheng-Hwa; Ma, Sze

    2012-01-01

    The key feature of respiratory distress syndrome (RDS) is the insufficient production of surfactant in the lungs of preterm infants. As a result, researchers have looked into the possibility of surfactant replacement therapy as a means of preventing and treating RDS. We sought to identify the role of surfactant in the prevention and management of RDS, comparing the various types, doses, and modes of administration, and the recent development. A PubMed search was carried out up to March 2012 u...

  2. A conservative SPH method for surfactant dynamics

    Science.gov (United States)

    Adami, S.; Hu, X. Y.; Adams, N. A.

    2010-03-01

    In this paper, a Lagrangian particle method is proposed for the simulation of multiphase flows with surfactant. The model is based on the multiphase smoothed particle hydrodynamics (SPH) framework of Hu and Adams (2006) [1]. Surface-active agents (surfactants) are incorporated into our method by a scalar quantity describing the local concentration of molecules in the bulk phase and on the interface. The surfactant dynamics are written in conservative form, thus global mass of surfactant is conserved exactly. The transport model of the surfactant accounts for advection and diffusion. Within our method, we can simulate insoluble surfactant on an arbitrary interface geometry as well as interfacial transport such as adsorption or desorption. The flow-field dynamics and the surfactant dynamics are coupled through a constitutive equation, which relates the local surfactant concentration to the local surface-tension coefficient. Hence, the surface-tension model includes capillary and Marangoni-forces. The present numerical method is validated by comparison with analytic solutions for diffusion and for surfactant dynamics. More complex simulations of an oscillating bubble, the bubble deformation in a shear flow, and of a Marangoni-force driven bubble show the capabilities of our method to simulate interfacial flows with surfactants.

  3. Quantification of Lung Metastases from In Vivo Mouse Models

    DEFF Research Database (Denmark)

    Chang, Joan; Erler, Janine T

    2016-01-01

    Cancer research has made significant progress in terms of understanding and targeting primary tumors; however, the challenge remains for the successful treatment of metastatic cancers. This highlights the importance to use in vivo models to study the metastatic process, as well as for preclinical...... testing of compounds that could inhibit metastasis. As a result, proper quantification of metastases from in vivo models is of the utmost significance. Here, we provide a detailed protocol for collecting and handling lung tissues from mice, and guidance for subsequent analysis of metastases, as well...

  4. Deformable object model and simulation. Application to lung cancer treatment

    International Nuclear Information System (INIS)

    Baudet, V.

    2006-06-01

    Ionising treatment against cancers such as conformal radiotherapy and hadron therapy are set with error margins that take into account statistics of tumour motions, for instance. We are looking for reducing these margins by searching deformable models that would simulate displacements occurring in lungs during a treatment. It must be personalized with the geometry obtained from CT scans of the patient and also it must be parameterized with physiological measures of the patient. In this Ph. D. thesis, we decided to use a mass-spring system to model lungs because of its fast and physically realist deformations obtained in animation. As a starting point, we chose the model proposed by Van Gelder in order to parameterize a mass-spring system with rheological characteristics of an homogeneous, linear elastic isotropic material in two dimensions (2D). However, we tested this model and proved it was false. Hence we did a Lagrangian study in order to obtain a parametric model with rectangular in 2D (cubic in 3D) elements. We also determined the robustness by testing with stretching, inflating, shearing and bending experiments and also by comparing results with other infinite element method. Thus, in this Ph.D. thesis, we explain how to obtain this parametric model, and how it will be linked to physiological data and how accurate it will be. (author)

  5. Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

    Science.gov (United States)

    Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

    2016-01-01

    The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

  6. Microfibril-associated Protein 4 Binds to Surfactant Protein A (SP-A) and Colocalizes with SP-A in the Extracellular Matrix of the Lung

    DEFF Research Database (Denmark)

    Schlosser, Anders; Thomsen, Theresa H.; Shipley, J. Michael

    2006-01-01

    Pulmonary surfactant protein A (SP-A) is an oligomeric collectin that recognizes lipid and carbohydrate moieties present on broad range of micro-organisms, and mediates microbial lysis and clearance. SP-A also modulates multiple immune-related functions including cytokine production and chemotaxis......-A composed of the neck region and carbohydrate recognition domain of SP-A indicating that the interaction between MFAP4 and SP-A is mediated via the collagen domain of SP-A. Monoclonal antibodies directed against MFAP4 and SP-A were used for immunohistochemical analysis, which demonstrates that the two...

  7. Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

    Full Text Available Abstract In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1 TNF-α production in pleural exudates and in the lung tissues, (2 the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity, (3 the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry and (4 apoptosis (TUNEL staining, Bax, Bcl-2 expression. Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.

  8. Development of the Stochastic Lung Model for Asthma

    International Nuclear Information System (INIS)

    Dobos, E.; Borbely-Kiss, I.; Kertesz, Zs.; Balashazy, I.

    2005-01-01

    Complete text of publication follows. The Stochastic Lung Model is a state-of-the-art tool for the investigation of the health impact of atmospheric aerosols. This model has already been tested and applied to calculate the deposition fractions of aerosols in different regions of the human respiratory tract. The health effects of inhaled aerosols may strongly depend on the distribution of deposition within the respiratory tract. In the current study three Asthma Models have been incorporated into the Stochastic Lung Deposition Code. A common new feature of these models is that the breathing cycle may be asymmetric. It means that the inspiration time, the expiration time and the two breath hold times are independent. And the code can simulate the mucus blockage, too. The main characteristics of the models are the followings: a) ASTHMA MODEL I: One input bronchial asthma factor is applied for the whole tracheobronchial region. The code multiplies all tracheobroncial diameters with this single value. b) ASTHMA MODEL II: Bronchial asthma factors have to be given for each bronchial generation as input data (21 values). The program multiplies the diameter of bronchi with these factors. c) ASTHMA MODEL III: Here, only the range of bronchial asthma factors are presented as input data and the code selects randomly the exact factors in pre-described airway generations. In this case the stochastic character appears in the Asthma Model, as well. As an example, Figure 1 shows the deposition fractions in the tracheobronchial and acinar regions of the human lung in the case of healthy and asthmatic adults at sitting breathing conditions as a function of particle size computed by Asthma Model I where the bronchial asthma factor was 30%. These models have been tested and compared for different types of asthma at various breathing conditions and in a wide range of particle sizes. The distribution of deposition in the characteristic regions of the respiratory tract have been computed

  9. DISTRIBUTION OF A 2ND DOSE OF EXOGENOUS SURFACTANT IN RABBITS WITH SEVERE RESPIRATORY-FAILURE

    NARCIS (Netherlands)

    PLOTZ, FB; STEVENS, H; HEIKAMP, A; OETOMO, SB

    Newborn infants with respiratory distress who fail to respond to surfactant treatment receive a second dose of surfactant. The effect of this strategy on the distribution of surfactant to the lung is unknown. We therefore investigated the distribution of the first (100 mg/kg body weight) and second

  10. Prenatal development of the pulmonary surfactant system and the influence of hypoxia.

    Science.gov (United States)

    Orgeig, Sandra; Morrison, Janna L; Daniels, Christopher B

    2011-08-31

    Pulmonary surfactant fulfils diverse functions at the lung air-liquid interface of all air-breathing vertebrates. Neurohormonal regulation of surfactant synthesis and secretion is highly conserved among non-mammalian amniotes. Although the pattern of surfactant lipid maturation is similar among species, the onset and completion differ dramatically. These differences are apparently not determined by phylogeny, but may relate to the timing of development of relative hypoxia as an embryo develops, which is related to birthing strategy. We have proposed that hypoxia is an evolutionary drive for differential surfactant development among species. In mammalian and non-mammalian models, hypoxia induces fetal growth restriction. Depending on the timing of the insult, this may be associated with an acceleration or deceleration of surfactant development. The hypoxic effect may be mediated via hormonal and growth factors, such as glucocorticoids and VEGF. However, the multifactorial nature of mammalian growth restriction models complicates the mechanistic interpretations. Hence, less complex oviparous animal models are required, in which hypoxia can be isolated from maternal influences. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Preparation and tumor cell model based biobehavioral evaluation of the nanocarrier system using partially reduced graphene oxide functionalized by surfactant

    Directory of Open Access Journals (Sweden)

    Wang Y

    2015-07-01

    lysosomes in 2 hours through endocytosis, then the drug is released in the cytoplasm in 8 hours, and ultimately EPI is delivered into cell nucleus to exhibit medicinal effects in 1 day.Conclusion: The comprehensive exploration of the biological uptake mechanism of functional graphene-mediated tumor cell targeting model provides a typical protocol for evaluation of drug delivery system and will benefit the discovery of new surfactant-modified nanocarriers in nanomedicine. Keywords: biocompatibility, cytotoxicity, drug delivery, controlled release, fluorescence colocalization, epirubicin

  12. Study of adjuvant effect of model surfactants from the groups of alkyl sulfates, alkylbenzene sulfonates, alcohol ethoxylates and soaps

    DEFF Research Database (Denmark)

    Clausen, S K; Sobhani, S; Poulsen, O M

    2000-01-01

    The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice. The surfact......The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice...... showed a statistically significant increase in OVA specific IgE levels. After two boosters, a statistically significant suppression in OVA-specific IgE production occurred with SDS (1000 mg/l), SDBS (1000 and 100 mg/l), coconut soap (1000 mg/l) and the alcohol ethoxylate (10 mg/l). This study suggests...

  13. Study of adjuvant effect of model surfactants from the groups of alkyl sulfates, alkylbenzene sulfonates, alcohol ethoxylates and soaps

    DEFF Research Database (Denmark)

    Clausen, S K; Sobhani, S; Poulsen, O M

    2000-01-01

    The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice....... The surfactants were injected subcutaneously (sc) in concentrations of 1000, 100, 10 or 1 mg/l, respectively, together with 1 microg of ovalbumin (OVA). In addition, groups of mice received OVA in saline (control group) or in Al(OH)(3) (positive adjuvant control group). After the primary immunization the mice...... that a limited number of surfactants possess an adjuvant effect whereas all surfactants at certain levels can suppress specific IgE production....

  14. Experimental rat lung tumor model with intrabronchial tumor cell implantation.

    Science.gov (United States)

    Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

    2008-01-01

    The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

  15. Surfactant protein-B 121ins2 heterozygosity, reduced pulmonary function, and chronic obstructive pulmonary disease in smokers

    DEFF Research Database (Denmark)

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjaerg-Hansen, Anne

    2010-01-01

    Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant protein-B gen....... Individuals heterozygous for this mutation have partial absence of surfactant protein-B and could be at risk of lung disease when exposed to additional risk factors for impaired surfactant function such as tobacco smoking....

  16. History of surfactant up to 1980.

    Science.gov (United States)

    Obladen, Michael

    2005-01-01

    Remarkable insight into disturbed lung mechanics of preterm infants was gained in the 18th and 19th century by the founders of obstetrics and neonatology who not only observed respiratory failure but also designed devices to treat it. Surfactant research followed a splendid and largely logical growth curve. Pathological changes in the immature lung were characterized in Germany by Virchow in 1854 and by Hochheim in 1903. The Swiss physiologist von Neergard fully understood surfactant function in 1929, but his paper was ignored for 25 years. The physical properties of surfactant were recognized in the early 1950s from research on warfare chemicals by Pattle in Britain and by Radford and Clements in the United States. The causal relationship of respiratory distress syndrome (RDS) and surfactant deficiency was established in the USA by Avery and Mead in 1959. The Australian obstetrician Liggins induced lung maturity with glucocorticoids in 1972, but his discovery was not fully believed for another 20 years. A century of basic research was rewarded when Fujiwara introduced surfactant substitution in Japan in 1980 for treatment and prevention of RDS. Copyright 2005 S. Karger AG, Basel

  17. A model for predicting lung cancer response to therapy

    International Nuclear Information System (INIS)

    Seibert, Rebecca M.; Ramsey, Chester R.; Hines, J. Wesley; Kupelian, Patrick A.; Langen, Katja M.; Meeks, Sanford L.; Scaperoth, Daniel D.

    2007-01-01

    Purpose: Volumetric computed tomography (CT) images acquired by image-guided radiation therapy (IGRT) systems can be used to measure tumor response over the course of treatment. Predictive adaptive therapy is a novel treatment technique that uses volumetric IGRT data to actively predict the future tumor response to therapy during the first few weeks of IGRT treatment. The goal of this study was to develop and test a model for predicting lung tumor response during IGRT treatment using serial megavoltage CT (MVCT). Methods and Materials: Tumor responses were measured for 20 lung cancer lesions in 17 patients that were imaged and treated with helical tomotherapy with doses ranging from 2.0 to 2.5 Gy per fraction. Five patients were treated with concurrent chemotherapy, and 1 patient was treated with neoadjuvant chemotherapy. Tumor response to treatment was retrospectively measured by contouring 480 serial MVCT images acquired before treatment. A nonparametric, memory-based locally weight regression (LWR) model was developed for predicting tumor response using the retrospective tumor response data. This model predicts future tumor volumes and the associated confidence intervals based on limited observations during the first 2 weeks of treatment. The predictive accuracy of the model was tested using a leave-one-out cross-validation technique with the measured tumor responses. Results: The predictive algorithm was used to compare predicted verse-measured tumor volume response for all 20 lesions. The average error for the predictions of the final tumor volume was 12%, with the true volumes always bounded by the 95% confidence interval. The greatest model uncertainty occurred near the middle of the course of treatment, in which the tumor response relationships were more complex, the model has less information, and the predictors were more varied. The optimal days for measuring the tumor response on the MVCT images were on elapsed Days 1, 2, 5, 9, 11, 12, 17, and 18 during

  18. A systems approach to mapping transcriptional networks controlling surfactant homeostasis

    Directory of Open Access Journals (Sweden)

    Dave Vrushank

    2010-07-01

    Full Text Available Abstract Background Pulmonary surfactant is required for lung function at birth and throughout life. Lung lipid and surfactant homeostasis requires regulation among multi-tiered processes, coordinating the synthesis of surfactant proteins and lipids, their assembly, trafficking, and storage in type II cells of the lung. The mechanisms regulating these interrelated processes are largely unknown. Results We integrated mRNA microarray data with array independent knowledge using Gene Ontology (GO similarity analysis, promoter motif searching, protein interaction and literature mining to elucidate genetic networks regulating lipid related biological processes in lung. A Transcription factor (TF - target gene (TG similarity matrix was generated by integrating data from different analytic methods. A scoring function was built to rank the likely TF-TG pairs. Using this strategy, we identified and verified critical components of a transcriptional network directing lipogenesis, lipid trafficking and surfactant homeostasis in the mouse lung. Conclusions Within the transcriptional network, SREBP, CEBPA, FOXA2, ETSF, GATA6 and IRF1 were identified as regulatory hubs displaying high connectivity. SREBP, FOXA2 and CEBPA together form a common core regulatory module that controls surfactant lipid homeostasis. The core module cooperates with other factors to regulate lipid metabolism and transport, cell growth and development, cell death and cell mediated immune response. Coordinated interactions of the TFs influence surfactant homeostasis and regulate lung function at birth.

  19. Mucus Distribution Model in a Lung with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Sara Zarei

    2012-01-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disease in Caucasians with a reported incidence of 1 in every 3200 live births. Most strikingly, CF is associated with early mortality. Host in flammatory responses result in airway mucus plugging, airway wall edema, and eventual destruction of airway wall support structure. Despite aggressive treatment, the median age of survival is approximately 38 years. This work is the first attempt to parameterize the distributions of mucus in a CF lung as a function of time. By default, the model makes arbitrary choices at each stage of the construction process, whereby the simplest choice is made. The model is sophisticated enough to fit the average CF patients' spirometric data over time and to identify several interesting parameters: probability of colonization, mucus volume growth rate, and scarring rate. Extensions of the model appropriate for describing the dynamics of single patient MRI data are also discussed.

  20. Lung Cancer Pathological Image Analysis Using a Hidden Potts Model

    Directory of Open Access Journals (Sweden)

    Qianyun Li

    2017-06-01

    Full Text Available Nowadays, many biological data are acquired via images. In this article, we study the pathological images scanned from 205 patients with lung cancer with the goal to find out the relationship between the survival time and the spatial distribution of different types of cells, including lymphocyte, stroma, and tumor cells. Toward this goal, we model the spatial distribution of different types of cells using a modified Potts model for which the parameters represent interactions between different types of cells and estimate the parameters of the Potts model using the double Metropolis-Hastings algorithm. The double Metropolis-Hastings algorithm allows us to simulate samples approximately from a distribution with an intractable normalizing constant. Our numerical results indicate that the spatial interaction between the lymphocyte and tumor cells is significantly associated with the patient’s survival time, and it can be used together with the cell count information to predict the survival of the patients.

  1. Lung Cancer Pathological Image Analysis Using a Hidden Potts Model

    Science.gov (United States)

    Li, Qianyun; Yi, Faliu; Wang, Tao; Xiao, Guanghua; Liang, Faming

    2017-01-01

    Nowadays, many biological data are acquired via images. In this article, we study the pathological images scanned from 205 patients with lung cancer with the goal to find out the relationship between the survival time and the spatial distribution of different types of cells, including lymphocyte, stroma, and tumor cells. Toward this goal, we model the spatial distribution of different types of cells using a modified Potts model for which the parameters represent interactions between different types of cells and estimate the parameters of the Potts model using the double Metropolis-Hastings algorithm. The double Metropolis-Hastings algorithm allows us to simulate samples approximately from a distribution with an intractable normalizing constant. Our numerical results indicate that the spatial interaction between the lymphocyte and tumor cells is significantly associated with the patient’s survival time, and it can be used together with the cell count information to predict the survival of the patients. PMID:28615918

  2. Microbial volatile communication in human organotypic lung models.

    Science.gov (United States)

    Barkal, Layla J; Procknow, Clare L; Álvarez-García, Yasmín R; Niu, Mengyao; Jiménez-Torres, José A; Brockman-Schneider, Rebecca A; Gern, James E; Denlinger, Loren C; Theberge, Ashleigh B; Keller, Nancy P; Berthier, Erwin; Beebe, David J

    2017-11-24

    We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.

  3. Lung cancer, intracellular signaling pathways, and preclinical models

    International Nuclear Information System (INIS)

    Mordant, P.

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Activation of phosphatidylinositol-3-kinase (PI3K)-AKT and Kirsten rat sarcoma viral oncogene homologue (KRAS) can induce cellular immortalization, proliferation, and resistance to anticancer therapeutics such as epidermal growth factor receptor inhibitors or chemotherapy. This study assessed the consequences of inhibiting these two pathways in tumor cells with activation of KRAS, PI3K-AKT, or both. We investigated whether the combination of a novel RAF/vascular endothelial growth factor receptor inhibitor, RAF265, with a mammalian target of rapamycin (mTOR) inhibitor, RAD001 (everolimus), could lead to enhanced anti-tumoral effects in vitro and in vivo. To address this question, we used cell lines with different status regarding KRAS, PIK3CA, and BRAF mutations, using immunoblotting to evaluate the inhibitors, and MTT and clonogenic assays for effects on cell viability and proliferation. Subcutaneous xenografts were used to assess the activity of the combination in vivo. RAD001 inhibited mTOR downstream signaling in all cell lines, whereas RAF265 inhibited RAF downstream signaling only in BRAF mutant cells. In vitro, addition of RAF265 to RAD001 led to decreased AKT, S6, and Eukaryotic translation initiation factor 4E binding protein 1 phosphorylation in HCT116 cells. In vitro and in vivo, RAD001 addition enhanced the anti-tumoral effect of RAF265 in HCT116 and H460 cells (both KRAS mut, PIK3CA mut); in contrast, the combination of RAF265 and RAD001 yielded no additional activity in A549 and MDAMB231 cells. The combination of RAF and mTOR inhibitors is effective for enhancing anti-tumoral effects in cells with deregulation of both RAS-RAF and PI3K, possibly through the cross-inhibition of 4E binding protein 1 and S6 protein. We then focus on animal models. Preclinical models of NSCLC require better clinical relevance to study disease mechanisms and innovative

  4. Thermally cleavable surfactants

    Science.gov (United States)

    McElhanon, James R [Manteca, CA; Simmons, Blake A [San Francisco, CA; Zifer, Thomas [Manteca, CA; Jamison, Gregory M [Albuquerque, NM; Loy, Douglas A [Albuquerque, NM; Rahimian, Kamyar [Albuquerque, NM; Long, Timothy M [Urbana, IL; Wheeler, David R [Albuquerque, NM; Staiger, Chad L [Albuquerque, NM

    2006-04-04

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments and the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

  5. Thermally cleavable surfactants

    Science.gov (United States)

    McElhanon, James R [Manteca, CA; Simmons, Blake A [San Francisco, CA; Zifer, Thomas [Manteca, CA; Jamison, Gregory M [Albuquerque, NM; Loy, Douglas A [Albuquerque, NM; Rahimian, Kamyar [Albuquerque, NM; Long, Timothy M [Urbana, IL; Wheeler, David R [Albuquerque, NM; Staiger, Chad L [Albuquerque, NM

    2009-11-24

    Two new surfactant molecules are reported which contain thermally labile Diels-Alder adducts connecting the polar and non-polar sections of each molecule. The two surfactants possess identical non-polar dodecyl tail segments but exhibit different polar headgroups. The surfactants become soluble in water when anionic salts are formed through the deprotonation of the surfactant headgroups by the addition of potassium hydroxide. When either surfactant is exposed to temperature above about 60.degree. C., the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments or the aqueous solutions of the surfactants subsequently exhibit loss of all surface-active behavior.

  6. Pulmonary surfactant proteins and polymer combinations reduce surfactant inhibition by serum

    Science.gov (United States)

    Lu, Karen W.; Pérez-Gil, Jesús; Echaide, Mercedes; Taeusch, H. William

    2011-01-01

    Acute respiratory distress syndrome (ARDS) is an inflammatory condition that can be associated with capillary leak of serum into alveoli causing inactivation of surfactant. Resistance to inactivation is affected by types and concentrations of surfactant proteins, lipids, and polymers. Our aim was to investigate the effects of different combinations of these three components. A simple lipid mixture (DPPC/POPG) or a more complex lipid mixture (DPPC/POPC/POPG/cholesterol) was used. Native surfactant proteins SP-B and SP-C obtained from pig lung lavage were added either singly or combined at two concentrations. Also, non-ionic polymers polyethylene glycol and dextran and the anionic polymer hyaluronan were added either singly or in pairs with hyaluronan included. Non-ionic polymers work by different mechanisms than anionic polymers, thus the purpose of placing them together in the same surfactant mixture was to evaluate if the combination would show enhanced beneficial effects. The resulting surfactant mixtures were studied in the presence or absence of serum. A modified bubble surfactometer was used to evaluate surface activities. Mixtures that included both SP-B and SP-C plus hyaluronan and either dextran or polyethylene glycol were found to be the most resistant to inhibition by serum. These mixtures, as well as some with either SP-B or SP-C with combined polymers were as or more resistant to inactivation than native surfactant. These results suggest that improved formulations of lung surfactants are possible and may be useful in reducing some types of surfactant inactivation in treating lung injuries. PMID:21741354

  7. Experimental model to evaluate the effect of hydrothorax and lobar resection on lung compliance.

    Science.gov (United States)

    Salito, Caterina; Bovio, Dario; Mazzuca, Enrico; Rivolta, Ilaria; Brunelli, Alessandro; Aliverti, Andrea; Miserocchi, Giuseppe

    2014-03-01

    The objective of this study was to evaluate to what extent lung compliance is affected by the individual and combined action of lung resection and hydrothorax in an animal model. Anaesthetized and mechanically ventilated rabbits (weight range 2 ÷ 2.2 kg) were randomized in two groups: (i) experimental hydrothorax (from 2 to 8 ml) (n = 5) and (ii) right lower lobe lobectomy (n = 4) and right middle plus lower lobe resection (n = 2). To obtain lung compliance, we measured alveolar, oesophageal pressures and lung volume during slow inflation manoeuvres in control conditions and after hydrothorax or lung resection. Lung compliance was estimated as the change in lung volume divided by the change in transpulmonary pressure. Based on the changes in compliance of the whole lung, we calculated the corresponding changes in compliance of the right lung, which was directly exposed to unilateral hydrothorax and lobectomy. Average total lung compliance in the control was 3.3 ± 0.8 (SD) ml/cmH2O. Eight millilitres of hydrothorax significantly decreased (P < 0.001) lung compliance to 2.7 ± 0.7 ml/cmH2O and increased pleural liquid pressure at the bottom of the cavity from -1 cmH2O up to ∼ 2.5-3 cmH2O. Resection of the right lower lobe significantly decreased (P < 0.001) lung compliance to 1.75 ± 0.3 ml/cmH2O. Resection of the right middle plus lower lobes significantly decreased (P < 0.001) lung compliance to 1.52 ± 0.4 ml/cmH2O. Following hydrothorax, the decrease in right lung compliance (∼ 45%) was much greater than that expected based on the estimated decrease in right lung volume (20%). We attribute this difference to the fact that hydrothorax causes the lung to be exposed to positive, rather than sub-atmospheric, pressure, causing atelectasis. Following lobectomy, right lung compliance decreased by 62 and 80% for estimated decreases in lung volume of 30 and 60%. This difference could reflect inaccuracy in the estimate of lung volume reduction based on resected

  8. Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2014-09-01

    The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

  9. Biology Based Lung Cancer Model for Chronic Low Radon Exposures

    International Nuclear Information System (INIS)

    Truta-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

    2008-01-01

    Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival.To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates

  10. C-reactive protein increases membrane fluidity and distorts lipid lateral organization of pulmonary surfactant. Protective role of surfactant protein A

    DEFF Research Database (Denmark)

    Saenz, Alejandra; Lopez-Sanchez, Almudena; Mojica-Lazaro, Jonas

    2010-01-01

    intratracheal instillation of CRP into rat lungs. Insertion of CRP into surfactant membranes was investigated through monolayer techniques. The effect of CRP on membrane structure was studied through differential scanning calorimetry and fluorescence spectroscopy and microscopy using large and giant unilamellar......The purpose of this study was to investigate how surfactant membranes can be perturbed by C-reactive protein (CRP) and whether surfactant protein A (SP-A) might overcome CRP-induced surfactant membrane alterations. The effect of CRP on surfactant surface adsorption was evaluated in vivo after...... vesicles. Our results indicate that CRP inserts into surfactant membranes and drastically increases membrane fluidity, resulting in surfactant inactivation. At 10% CRP/phospholipid weight ratio, CRP causes disappearance of liquid-ordered/liquid-disordered phase coexistence distinctive of surfactant...

  11. Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity.

    Science.gov (United States)

    Patel, Apurva R; Doddapaneni, Ravi; Andey, Terrick; Wilson, Heather; Safe, Stephen; Singh, Mandip

    2015-09-10

    3, 3-Diindolylmethane-14 (DIM-14), a novel lipophilic derivative of DIM, has demonstrated anticancer activity in different types of cancers. However, poor solubility and low oral bioavailability of DIM-14 limit its translational benefits in vivo. This study was carried out to improve the oral bioavailability of DIM-14 via self-emulsifying drug (SED) delivery system in dogs and to evaluate pharmacodynamic characteristics of SED against H1650 stem cell tumor models. DIM-14 was incorporated into an oil, surfactant, and co-surfactant mixture using labrafil and tween-80 to obtain SED. SED were characterized by droplet size, polydispersitiy index (PDI), zeta potential, entrapment efficiency (EE), in vitro permeability and drug release (investigated with Caco-2 monolayers and dissolution apparatus respectively). Pharmacokinetic parameters in dogs were evaluated and analyzed using Winonlin. Anti-tumor activity was carried out in H1650 lung tumor model. Particle size of SED was between 230 and 246 nm and surface charge was negative and ranged from 26.50 to 28.69 mV. Entrapment efficiency of SED was 85%. Pharmacokinetic evaluation in dogs showed increased Cmax (39.18 ± 7.34 vs 21.68 ± 6.3 μg·dL-1), higher AUC0-t (34,481.34 ± 1125.46 vs 14,159.53 ± 702.20 μg·min·dL-1) and improved absorption with 3 times more bioavailability of SED compared to DIM-14 solution. SED showed ~30-59% tumor volume/weight reduction in H1650 tumor model compared to DIM-P solution. Our studies demonstrate the potential application of self-emulsifying drug delivery system (SEDDS), that enhances oral absorption of DIM-14 and increased anti-tumor activity against lung tumor models. Published by Elsevier B.V.

  12. How to overcome surfactant dysfunction in meconium aspiration syndrome?

    Science.gov (United States)

    Mokra, Daniela; Calkovska, Andrea

    2013-06-01

    Surfactant dysfunction in meconium aspiration syndrome (MAS) is caused by meconium components, by plasma proteins leaking through the injured alveolocapillary membrane and by substances originated in meconium-induced inflammation. Surfactant inactivation in MAS may be diminished by several ways. Firstly, aspirated meconium should be removed from the lungs to decrease concentrations of meconium inhibitors coming into the contact with surfactant in the alveolar compartment. Once the endogenous surfactant becomes inactivated, components of surfactant should be substituted by exogenous surfactant at a sufficient dose, and surfactant administration should be repeated, if oxygenation remains compromised. To delay the inactivation by inhibitors, exogenous surfactants may be enriched with surfactant proteins, phospholipids, or other substances such as polymers. Finally, to diminish an adverse action of products of meconium-induced inflammation on both endogenous and exogenously delivered surfactant, anti-inflammatory drugs may be administered. A combined therapeutic approach may result in better outcome in patients with MAS and in lower costs of treatment. Copyright © 2013. Published by Elsevier B.V.

  13. Musculoskeletal Modeling of a Forward Lunge Movement:Implications for ACL Loading

    DEFF Research Database (Denmark)

    Alkjaer, T; Wieland, MR; Andersen, MS

    2010-01-01

    Context: The forward lunge is widely used among athletes for training and rehabilitation purposes. The forward lunge movement has also been suggested as a model to study functional adaptation to ACL rupture. Previous investigations indicate that the absence of the ACL influences the movement...... pattern of many patients during a forward lunge, while direct measurements of ACL strain show that except for cases close to full extension, quadriceps activity does not seem to influence the ACL strain. The question is whether there are other external forces present in the lunge movement that may cause...... an anterior force on the tibia, requiring the ACL to be intact to stabilize the knee? Objective: To establish a musculoskeletal model of the forward lunge to computationally investigate the force equilibrium in the knee during forward lunge and answer the following questions: 1) Which structures in the knee...

  14. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    Science.gov (United States)

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

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

    Directory of Open Access Journals (Sweden)

    Shaw Geoffrey M

    2006-08-01

    Full Text Available Abstract 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.

  16. Destabilization, Propagation, and Generation of Surfactant-Stabilized Foam during Crude Oil Displacement in Heterogeneous Model Porous Media.

    Science.gov (United States)

    Xiao, Siyang; Zeng, Yongchao; Vavra, Eric D; He, Peng; Puerto, Maura; Hirasaki, George J; Biswal, Sibani L

    2018-01-23

    Foam flooding in porous media is of increasing interest due to its numerous applications such as enhanced oil recovery, aquifer remediation, and hydraulic fracturing. However, the mechanisms of oil-foam interactions have yet to be fully understood at the pore level. Here, we present three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam, and we describe a series of pore-level dynamics in these zones which were not observed in experiments involving paraffin oil. In the displacement front zone, foam coalesces upon initial contact with crude oil, which is known to destabilize the liquid lamellae of the foam. Directly upstream, a transition zone occurs where surface wettability is altered from oil-wet to water-wet. After this transition takes place, a strong foam bank zone exists where foam is generated within the porous media. We visualized each zone using a microfluidic platform, and we discuss the unique physicochemical phenomena that define each zone. In our analysis, we also provide an updated mechanistic understanding of the "smart rheology" of foam which builds upon simple "phase separation" observations in the literature.

  17. The Effect of Phospholipids (Surfactant on Adhesion and Biomechanical Properties of Tendon: A Rat Achilles Tendon Repair Model

    Directory of Open Access Journals (Sweden)

    T. Kursat Dabak

    2015-01-01

    Full Text Available Adhesion of the tendon is a major challenge for the orthopedic surgeon during tendon repair. Manipulation of biological environment is one of the concepts to prevent adhesion. Lots of biochemicals have been studied for this purpose. We aimed to determine the effect of phospholipids on adhesion and biomechanical properties of tendon in an animal tendon repair model. Seventy-two Wistar rats were divided into 4 groups. Achilles tendons of rats were cut and repaired. Phospholipids were applied at two different dosages. Tendon adhesion was determined histopathologically and biomechanical test was performed. At macroscopic evaluation of adhesion, there are statistically significant differences between multiple-dose phospholipid injection group and Control group and also hyaluronic acid group and Control group (p0.008. Ultimate strength was highest at hyaluronic acid injection group and lowest at multiple-dose phospholipid injection group. Single-dose phospholipids (surfactant application may have a beneficial effect on the tendon adhesion. Although multiple applications of phospholipids seem the most effective regime to reduce the tendon adhesion among groups, it deteriorated the biomechanical properties of tendon.

  18. Gemini (dimeric) Surfactants

    Indian Academy of Sciences (India)

    Gemini, surfactants, micelle. Figure 1. Schematic repre- sentation of the gemini sur- factant structure. B S Sekhon. A gemini surfactant (GS) consists of two conventional surfactant molecules chemically bonded together by a spacer. The two terminal hydrocarbon tails can be short or long; the two polar head groups can be ...

  19. [Deficiency of surfactant protein: Case report].

    Science.gov (United States)

    Milet, María Beatriz; Mena N, Patricia; Pérez, Héctor I; Espinoza, Tatiana

    Congenital surfactant deficiency is a condition infrequently diagnosed in newborns. A clinical case is presented of surfactant protein B deficiency. A review is performed on the study, treatment and differential diagnosis of surfactant protein deficiencies and infant chronic interstitial lung disease. The case is presented of a term newborn that developed respiratory distress, recurrent pulmonary opacification, and a transient response to the administration of surfactant. Immunohistochemical and genetic studies confirmed the diagnosis of surfactant protein B deficiency. Pulmonary congenital anomalies require a high index of suspicion. Surfactant protein B deficiency is clinically progressive and fatal in the majority of the cases, similar to that of ATP binding cassette subfamily A member 3 (ABCA3) deficiency. Protein C deficiency is insidious and may present with a radiological pulmonary interstitial pattern. Due to the similarity in the histological pattern, genetic studies help to achieve greater certainty in the prognosis and the possibility of providing adequate genetic counselling. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Inositol-trisphosphate reduces alveolar apoptosis and pulmonary edema in neonatal lung injury.

    Science.gov (United States)

    Preuss, Stefanie; Stadelmann, Sabrina; Omam, Friede D; Scheiermann, Julia; Winoto-Morbach, Supandi; von Bismarck, Philipp; Knerlich-Lukoschus, Friederike; Lex, Dennis; Adam-Klages, Sabine; Wesch, Daniela; Held-Feindt, Janka; Uhlig, Stefan; Schütze, Stefan; Krause, Martin F

    2012-08-01

    D-myo-inositol-1,2,6-trisphosphate (IP3) is an isomer of the naturally occurring second messenger D-myo-inositol-1,4,5-trisphosphate, and exerts anti-inflammatory and antiedematous effects in the lung. Myo-inositol (Inos) is a component of IP3, and is thought to play an important role in the prevention of neonatal pulmonary diseases such as bronchopulmonary dysplasia and neonatal acute lung injury (nALI). Inflammatory lung diseases are characterized by augmented acid sphingomyelinase (aSMase) activity leading to ceramide production, a pathway that promotes increased vascular permeability, apoptosis, and surfactant alterations. A novel, clinically relevant triple-hit model of nALI was developed, consisting of repeated airway lavage, injurious ventilation, and lipopolysaccharide instillation into the airways, every 24 hours. Thirty-five piglets were randomized to one of four treatment protocols: control (no intervention), surfactant alone, surfactant + Inos, and surfactant + IP3. After 72 hours of mechanical ventilation, lungs were excised from the thorax for subsequent analyses. Clinically, oxygenation and ventilation improved, and extravascular lung water decreased significantly with the S + IP3 intervention. In pulmonary tissue, we observed decreased aSMase activity and ceramide concentrations, decreased caspase-8 concentrations, reduced alveolar epithelial apoptosis, the reduced expression of interleukin-6, transforming growth factor-β1, and amphiregulin (an epithelial growth factor), reduced migration of blood-borne cells and particularly of CD14(+)/18(+) cells (macrophages) into the airspaces, and lower surfactant surface tensions in S + IP3-treated but not in S + Inos-treated piglets. We conclude that the admixture of IP3 to surfactant, but not of Inos, improves gas exchange and edema in our nALI model by the suppression of the governing enzyme aSMase, and that this treatment deserves clinical evaluation.

  1. Study of adjuvant effect of model surfactants from the groups of alkyl sulfates, alkylbenzene sulfonates, alcohol ethoxylates and soaps.

    Science.gov (United States)

    Clausen, S K; Sobhani, S; Poulsen, O M; Poulsen, L K; Nielsen, G D

    2000-11-01

    The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice. The surfactants were injected subcutaneously (sc) in concentrations of 1000, 100, 10 or 1 mg/l, respectively, together with 1 microg of ovalbumin (OVA). In addition, groups of mice received OVA in saline (control group) or in Al(OH)(3) (positive adjuvant control group). After the primary immunization the mice were boosted up to three times with OVA (0.1 microg sc) in saline. OVA-specific IgE antibodies were determined by the heterologous mouse rat passive cutaneous anaphylaxis test. The results were confirmed by a specific ELISA method. After the first booster, the Al(OH)(3) group and the 10 mg/l SDS group showed a statistically significant increase in OVA specific IgE levels. After two boosters, a statistically significant suppression in OVA-specific IgE production occurred with SDS (1000 mg/l), SDBS (1000 and 100 mg/l), coconut soap (1000 mg/l) and the alcohol ethoxylate (10 mg/l). This study suggests that a limited number of surfactants possess an adjuvant effect whereas all surfactants at certain levels can suppress specific IgE production.

  2. Modeling the lung: Design and development of tissue engineered macro- and micro-physiologic lung models for research use.

    Science.gov (United States)

    Nichols, Joan E; Niles, Jean A; Vega, Stephanie P; Argueta, Lissenya B; Eastaway, Adriene; Cortiella, Joaquin

    2014-09-01

    Respiratory tract specific cell populations, or tissue engineered in vitro grown human lung, have the potential to be used as research tools to mimic physiology, toxicology, pathology, as well as infectious diseases responses of cells or tissues. Studies related to respiratory tract pathogenesis or drug toxicity testing in the past made use of basic systems where single cell populations were exposed to test agents followed by evaluations of simple cellular responses. Although these simple single-cell-type systems provided good basic information related to cellular responses, much more can be learned from cells grown in fabricated microenvironments which mimic in vivo conditions in specialized microfabricated chambers or by human tissue engineered three-dimensional (3D) models which allow for more natural interactions between cells. Recent advances in microengineering technology, microfluidics, and tissue engineering have provided a new approach to the development of 2D and 3D cell culture models which enable production of more robust human in vitro respiratory tract models. Complex models containing multiple cell phenotypes also provide a more reasonable approximation of what occurs in vivo without the confounding elements in the dynamic in vivo environment. The goal of engineering good 3D human models is the formation of physiologically functional respiratory tissue surrogates which can be used as pathogenesis models or in the case of 2D screening systems for drug therapy evaluation as well as human toxicity testing. We hope that this manuscript will serve as a guide for development of future respiratory tract model systems as well as a review of conventional models. © 2014 by the Society for Experimental Biology and Medicine.

  3. Development of a metastatic fluorescent Lewis Lung carcinoma mouse model

    DEFF Research Database (Denmark)

    Rask, Lene; Fregil, Marianne; Høgdall, Estrid

    2013-01-01

    ) and spleen tyrosine kinase (SYK). A modest decrease in Drosha and Dicer mRNA levels was accompanied by significant downregulation of ten microRNAs, including miR-9 and miR-203, in the lung metastatic Lewis Lung carcinoma cell culture. Thus, a tool for cancer metastasis studies has been established...

  4. Murine model of BCG lung infection: Dynamics of lymphocyte ...

    Indian Academy of Sciences (India)

    Unknown

    pulmonary BCG infection. Few T cells in tracheal LN of BCG infected mice produce IFNγ, suggesting that maturational changes associated with migration to the lungs or residence in the lungs enhance the capability of some T cells to produce this cytokine. [Saxena R K, Weissman D, Simpson J and Lewis D M 2002 Murine ...

  5. Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.

    Science.gov (United States)

    Katki, Hormuzd A; Kovalchik, Stephanie A; Berg, Christine D; Cheung, Li C; Chaturvedi, Anil K

    2016-06-07

    The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations. Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST. Annual CT lung screening for 3 years beginning at age 50 years. For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death). Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US

  6. Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

    Science.gov (United States)

    Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

    2017-07-01

    Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion related acute lung injury

    NARCIS (Netherlands)

    Müller, Marcella C. A.; Tuinman, Pieter R.; van der Sluijs, Koenraad F.; Boon, Louis; Roelofs, Joris J.; Vroom, Margreeth B.; Juffermans, Nicole P.

    2014-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on

  8. A multiscale MDCT image-based breathing lung model with time-varying regional ventilation

    Science.gov (United States)

    Yin, Youbing; Choi, Jiwoong; Hoffman, Eric A.; Tawhai, Merryn H.; Lin, Ching-Long

    2013-07-01

    A novel algorithm is presented that links local structural variables (regional ventilation and deforming central airways) to global function (total lung volume) in the lung over three imaged lung volumes, to derive a breathing lung model for computational fluid dynamics simulation. The algorithm constitutes the core of an integrative, image-based computational framework for subject-specific simulation of the breathing lung. For the first time, the algorithm is applied to three multi-detector row computed tomography (MDCT) volumetric lung images of the same individual. A key technique in linking global and local variables over multiple images is an in-house mass-preserving image registration method. Throughout breathing cycles, cubic interpolation is employed to ensure C1 continuity in constructing time-varying regional ventilation at the whole lung level, flow rate fractions exiting the terminal airways, and airway deformation. The imaged exit airway flow rate fractions are derived from regional ventilation with the aid of a three-dimensional (3D) and one-dimensional (1D) coupled airway tree that connects the airways to the alveolar tissue. An in-house parallel large-eddy simulation (LES) technique is adopted to capture turbulent-transitional-laminar flows in both normal and deep breathing conditions. The results obtained by the proposed algorithm when using three lung volume images are compared with those using only one or two volume images. The three-volume-based lung model produces physiologically-consistent time-varying pressure and ventilation distribution. The one-volume-based lung model under-predicts pressure drop and yields un-physiological lobar ventilation. The two-volume-based model can account for airway deformation and non-uniform regional ventilation to some extent, but does not capture the non-linear features of the lung.

  9. Dry Lung as a Physical Model in Studies of Aerosol Deposition.

    Science.gov (United States)

    Morozov, Victor N; Kanev, Igor L

    2015-10-01

    A new physical model was developed to evaluate the deposition of micro- and nanoaerosol particles (NAPs) into the lungs as a function of size and charges. The model was manufactured of a dry, inflated swine lung produced by Nasco company (Fort Atkinson, WI). The dry lung was cut into two lobes and a conductive tube was glued into the bronchial tube. The upper 1-2-mm-thick layer of the lung lobe was removed with a razor blade to expose the alveoli. The lobe was further enclosed into a plastic bag and placed within a metalized plastic box. The probability of aerosol deposition was calculated by comparing the size distribution of NAPs passed through the lung with that of control, where aerosol passed through a box bypassing the lung. Using this new lung model, it was demonstrated that charged NAPs are deposited inside the lung substantially more efficiently than neutral ones. It was also demonstrated that deposition of neutral NAPs well fits prediction of the Multiple-Path Particle Dosimetry (MPPD) model developed by the Applied Research Associates, Inc. (ARA).

  10. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury

    NARCIS (Netherlands)

    Hofstra, Jorrit J; Vlaar, Alexander P; Cornet, Alexander D; Dixon, Barry; Roelofs, Joris J; Choi, Goda; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

    BACKGROUND: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury. METHODS: Male Sprague-Dawley rats were intravenously

  11. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    NARCIS (Netherlands)

    Wille, M.M.W.; Riel, S.J. van; Saghir, Z.; Dirksen, A.; Pedersen, J.H.; Jacobs, C.; Thomsen, L.H.u.; Scholten, E.T.; Skovgaard, L.T.; Ginneken, B. van

    2015-01-01

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models.From the DLCST database, 1,152

  12. Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation

    International Nuclear Information System (INIS)

    Benavides, T.; Mitjans, M.; Martinez, V.; Clapes, P.; Infante, M.R.; Clothier, R.H.; Vinardell, M.P.

    2004-01-01

    Extensive efforts have been made, recently, to find surfactants with lower irritation potential than those presently commercially available, for use in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of a novel family of dicationic arginine-diglyceride surfactant compounds, 1,2-diacyl,3-O-(L-arginyl)-rac-glycerol with alkyl chain lengths in the range from 8 to 14 carbon atoms, were compared to three commercial surfactants. The end-points used to assess toxicity were the red blood cell lysis assay and uptake of the vital dye neutral red 24 h after dosing (NRU), respectively. Two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, were used as in vitro models to predict the potential phototoxicity which could result in irritation, determined by resazurin reduction to resorufin and neutral red uptake (NRU). All tested surfactants had cytotoxicity effects as demonstrated by and decrease of NR uptake, which showed a clear concentration-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC 50 ) range from 1 μmol l -1 (hexadecyl trimethyl ammonium bromide) to 565 μmol l -1 (12,12-L-arginine). Erythrocyte haemolysis also showed a clear concentration-response relationship, the 50% of haemolysis ranged from 37 μmol l -1 (10,10-L-arginine) to 151 μmol l -1 (sodium lauryl sulphate). Phototoxicity was performed with 12,12-L-acetyl-arginine, the most stable chemical structure. The validated 3T3 NRU photoxicity assay was used and revealed a phototoxic potential

  13. Conformational alterations induced by novel green 16-E2-16 gemini surfactant in xanthine oxidase: Biophysical insights from tensiometry, spectroscopy, microscopy and molecular modeling.

    Science.gov (United States)

    Akram, Mohd; Bhat, Imtiyaz Ahmad; Bhat, Waseem Feeroze; Kabir-ud-Din

    2015-01-01

    Herein we report the interaction of a biodegradable gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) dichloride (16-E2-16) with bovine milk xanthine oxidase (XO), employing tensiometry, fluorescence spectroscopy, UV spectroscopy, far-UV circular dichroism spectroscopy (CD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and computational molecular modeling. Surface tension results depict substantial changes in the micellar as well as interfacial parameters (CMC, ΠCMC, γCMC, Γmax, Amin, ΔGmic° and ΔGads°) of 16-E2-16 gemini surfactant upon XO combination, deciphering the interaction of XO with the gemini surfactant. Fluorescence measurements reveal that 16-E2-16 gemini surfactant causes quenching in the xanthine oxidase (XO) fluorescence spectra via static procedure and the values of various evaluated binding parameters (KSV, Kb, kq, ΔGb° and n) describe that 16-E2-16 effectively binds to XO. Three dimensional fluorescence, 8-anilino-1-naphthalene sulfonic acid (ANS) binding, F1F3 ratio, UV, CD, FTIR, SEM and TEM results delineate changes in the secondary structure of xanthine oxidase. Molecular docking results provide complement to the steady-state fluorescence findings and support the view that quenching occurs due to non-polar environment experienced by aromatic residues of the enzyme. The results of this study can help scientists to tune the conformation of an enzyme (XO) with biocompatible amphiphilic microstructures, which will help to unfold further understanding in the treatment modes of various diseases like gout, hyperuricemia, liver and brain necrosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Meconium-induced inflammation and surfactant inactivation: specifics of molecular mechanisms.

    Science.gov (United States)

    Kopincova, Jana; Calkovska, Andrea

    2016-04-01

    This review summarizes neonatal meconium aspiration syndrome in light of meconium-induced inflammation and inflammatory surfactant inactivation, related to both endogenous and therapeutic exogenous surfactant. The wide effect of meconium on surfactant properties is divided into three points. Direct effect of meconium on surfactant properties refers mainly to fragmentation of dipalmitoylphosphatidylcholine and other surfactant phospholipids together with cleavage of surfactant proteins. Initiation of inflammatory response due to activation of receptors by yet unspecified compounds involves complement and Toll-like receptor activation. A possible role of lung collectins, surfactant proteins A and D, which can exert both pro- and anti-inflammatory reactions, is discussed. Initiation of inflammatory response by specified compounds in meconium reflects inflammatory functioning of cytokines, bile acids, and phospholipases contained in meconium. Unifying sketch of many interconnections in all these actions aims at providing integrated picture of inflammatory surfactant inactivation.

  15. Exploring the uncertainties of early detection results: model-based interpretation of mayo lung project

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    Berman Barbara

    2011-03-01

    Full Text Available Abstract Background The Mayo Lung Project (MLP, a randomized controlled clinical trial of lung cancer screening conducted between 1971 and 1986 among male smokers aged 45 or above, demonstrated an increase in lung cancer survival since the time of diagnosis, but no reduction in lung cancer mortality. Whether this result necessarily indicates a lack of mortality benefit for screening remains controversial. A number of hypotheses have been proposed to explain the observed outcome, including over-diagnosis, screening sensitivity, and population heterogeneity (initial difference in lung cancer risks between the two trial arms. This study is intended to provide model-based testing for some of these important arguments. Method Using a micro-simulation model, the MISCAN-lung model, we explore the possible influence of screening sensitivity, systematic error, over-diagnosis and population heterogeneity. Results Calibrating screening sensitivity, systematic error, or over-diagnosis does not noticeably improve the fit of the model, whereas calibrating population heterogeneity helps the model predict lung cancer incidence better. Conclusions Our conclusion is that the hypothesized imperfection in screening sensitivity, systematic error, and over-diagnosis do not in themselves explain the observed trial results. Model fit improvement achieved by accounting for population heterogeneity suggests a higher risk of cancer incidence in the intervention group as compared with the control group.

  16. Easy Applicable Model of Ischemia and Reperfusion on Lung Transplantation

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    Orhan Yücel

    2010-01-01

    Full Text Available Akciğer Transplantasyonun da Kolay Uygulanabilir İskemi ve Reperfüzyon Modeli Easy Applicable Model of Ischemia and Reperfusion on Lung transplantation Akciğer İskemi ve Reperfüzyon Modeli Lung Model of Ischemia and Reperfusion Türkçe özet Giriş:Akciğer transplantasyon (AT%u2019unda organ disfonksiyonunun en önemli nedenleri arasında yer alan iskemi reperfüzyon (İ/R hasarını önlemek için birçok klinik ve deneysel çalışma yapılmıştır. Çalışmamızda mikrocerrahi gerektirmeyen, kısa sürede uygulanabilecek, karmaşık prosedür içermeyen, ucuz, geliştirilebilir ve İ/R hasarının araştırılabileceği bir AT modeli oluşturulmasını amaçladık. Gereç ve Yöntem: Çalışmamızda Sprague Dawley ırkı, 200-225g ağırlığındaki 21 adet erkek rat kullanıldı. Her biri yedi rat içeren üç grup oluşturuldu. İlk grup kontrol grubu (KG, ikinci grup donör grubu (DG ve üçüncü grup İ/R grubu (İRG olarak adlandırıldı. KG%u2019daki deneklere herhangi bir ek işlem yapılmadan sol akciğer alt lobundan histopatolojik ve biyokimyasal inceleme için örnekleme yapıldı. DG%u2019daki deneklere sol üst lobektomi ile allograft sol alt lob çıkarılma işlemi uygulandı. İRG%u2019na sol üst lobektomi ve sol alt loba giden pulmoner arter ve ven dalı proksimal yönde kateterizasyon işlemi uygulandı. Pulmoner arter ve ven kateterizasyon işleminden sonra allogreft sol alt lob iki saat süreyle reperfüze ve reventile edildi. AAD%u2019dan histopatolojik ve biyokimyasal inceleme için örnekleme yapıldı ve istatistiksel olarak değerlendirildi. Bulgular: Histopatolojik incelemede kontrol grubuna göre İRG%u2019nda konjesyon, kanama, parankimal makrofaj ve PMN lökosit infiltrasyonu, amfizem, atelektazi, vakuolar dejenerasyon ve peribronşiyal lenfosit infiltrasyonu açısından istatistiksel olarak anlamlı sonuç elde edildi. MDA seviyesinde ve GPX aktivitesinde İRG grubunda ortalama artarken, SOD ve CAT

  17. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

    OpenAIRE

    Kamaruzaman, Nurfatin Asyikhin; Kardia, Egi; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

    2013-01-01

    No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, e...

  18. Modeling the effect of structural details of nonionic surfactant on micellization in solution and adsorption onto hydrophobic surfaces

    NARCIS (Netherlands)

    Jodar-Reyes, A.B.; Ortega-Vinuesa, J.L.; Martin-Rodriguez, A.; Leermakers, F.A.M.

    2002-01-01

    Applying the classical one-gradient self-consistent-field (SCF) theory for adsorption and/or association, we can show that the molecular architecture of nonionic surfactants influences strongly the micellization in solution and the adsorption on solid-liquid interfaces. This is illustrated by using

  19. Differential Effect of Soy Isoflavones in Enhancing High Intensity Radiotherapy and Protecting Lung Tissue in a Pre-Clinical Model of Lung Carcinoma

    Science.gov (United States)

    Hillman, Gilda G.; Singh-Gupta, Vinita; Hoogstra, David J.; Abernathy, Lisa; Rakowski, Joseph; Yunker, Christopher K.; Rothstein, Shoshana E.; Sarkar, Fazlul H.; Gadgeel, Shirish; Konski, Andre A.; Lonardo, Fulvio; Joiner, Michael C.

    2013-01-01

    Background Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model. Methods Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson’s Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls. Results Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels. Conclusions These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer. PMID:24021346

  20. Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity

    Directory of Open Access Journals (Sweden)

    Schaller Peter

    2006-03-01

    Full Text Available Abstract Background Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV. It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]. Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. Objective To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP early after surfactant instillation in relation to phrenic nerve activity (PNA and the activity of PSRs. Methods Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2–0.5 kPa before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. Results Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p Conclusion PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

  1. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

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    David Fecher

    Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

  2. Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants.

    Science.gov (United States)

    Singh, Neetu; Halliday, Henry L; Stevens, Timothy P; Suresh, Gautham; Soll, Roger; Rojas-Reyes, Maria Ximena

    2015-12-21

    Animal-derived surfactants have been shown to have several advantages over the first generation synthetic surfactants and are the most commonly used surfactant preparations. The animal-derived surfactants in clinical use are minced or lavaged and modified or purified from bovine or porcine lungs. It is unclear whether significant differences in clinical outcome exist among the available bovine (modified minced or lavage) and porcine (minced or lavage) surfactant extracts. To compare the effect of administration of different animal-derived surfactant extracts on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having respiratory distress syndrome (RDS). We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to July 31, 2015), EMBASE (1980 to July 31, 2015), and CINAHL (1982 to July 31, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Randomized or quasi-randomized controlled trials that compared the effect of animal-derived surfactant extract treatment administered to preterm infants at risk for or having RDS to prevent complications of prematurity and mortality. Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on gestational age, surfactant dosing and schedule, treatment severity and treatment strategy. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group. Sixteen randomized controlled trials were included in the analysis. Bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract: Seven treatment studies and two prevention studies compared bovine lung

  3. Surfactant uptake dynamics in mammalian cells elucidated with quantitative coherent anti-stokes Raman scattering microspectroscopy.

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    Masanari Okuno

    Full Text Available The mechanism of surfactant-induced cell lysis has been studied with quantitative coherent anti-Stokes Raman scattering (CARS microspectroscopy. The dynamics of surfactant molecules as well as intracellular biomolecules in living Chinese Hamster Lung (CHL cells has been examined for a low surfactant concentration (0.01 w%. By using an isotope labeled surfactant having CD bonds, surfactant uptake dynamics in living cells has been traced in detail. The simultaneous CARS imaging of the cell itself and the internalized surfactant has shown that the surfactant molecules is first accumulated inside a CHL cell followed by a sudden leak of cytosolic components such as proteins to the outside of the cell. This finding indicates that surfactant uptake occurs prior to the cell lysis, contrary to what has been believed: surface adsorption of surfactant molecules has been thought to occur first with subsequent disruption of cell membranes. Quantitative CARS microspectroscopy enables us to determine the molecular concentration of the surfactant molecules accumulated in a cell. We have also investigated the effect of a drug, nocodazole, on the surfactant uptake dynamics. As a result of the inhibition of tubulin polymerization by nocodazole, the surfactant uptake rate is significantly lowered. This fact suggests that intracellular membrane trafficking contributes to the surfactant uptake mechanism.

  4. Modelling Adsorption of Foam-Forming Surfactants Modélisation de l'adsorption des produits tensio-actifs moussants

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    Mannhardt K.

    2006-11-01

    Full Text Available There is considerable interest in the use of foam-forming surfactants for mobility control in gas flooding enhanced oil recovery processes. The success of any such process is strongly affected by the rate of propagation of the surfactant through the reservoir. A sound understanding of surfactant adsorption on rock surfaces at reservoir conditions is therefore essential. This paper describes a model for the evaluation of adsorption during flow of surfactant solutions through porous media. The adsorption term in the flow equation is expressed in terms of the surface excess which proves to be more generally applicable than, for example, the Langmuir adsorption isotherm. Adsorption isotherms of three types of commercially available foam-forming surfactants are determined from core flooding data at different temperatures and brine salinities. L'utilisation de produits tensio-actifs moussants pour le contrôle de mobilité dans les procédés de récupération assistée du pétrole par injection de gaz suscite actuellement un grand intérêt. Mais le succès d'un tel procédé dépend largement de la vitesse de propagation du tensioactif dans le réservoir. Il est donc indispensable d'avoir une bonne connaissance de l'adsorption du tensio-actif sur les surfaces de la roche, dans les conditions de réservoir. Cet article décrit un modèle qui permet d'évaluer l'adsorption pendant l'écoulement de solutions tensio-actives en milieu poreux. Le terme qui représente l'adsorption dans l'équation de l'écoulement est exprimé en fonction de l'excédent de surface, concept qui s'est révélé d'une application plus générale que, par exemple, l'isotherme d'adsorption de Langmuir. Les isothermes d'adsorption de trois types de tensio-actifs moussants disponibles sur le marché sont déterminées à partir de données obtenues lors d'essais de déplacement dans des carottes, à différentes températures et avec des saumures de différentes salinités.

  5. Surfactants in tribology

    CERN Document Server

    Biresaw, Girma

    2014-01-01

    Surface science and tribology play very critical roles in many industries. Manufacture and use of almost all consumer and industrial products rely on the application of advanced surface and tribological knowledge. The fourth in a series, Surfactants in Tribology, Volume 4 provides an update on research and development activities connecting surfactants and tribological phenomena. Written by renowned subject matter experts, the book demonstrates how improved design of surfactants can be harnessed to control tribological phenomena. Profusely illustrated and copiously referenced, the chapters also

  6. Lung Impedance Contributions to the Total Impedance based on a FDM Model and Lead Field Theory.

    Science.gov (United States)

    Patterson, Robert; Yang, Fei

    2005-01-01

    Predicting tissue resistivity is of significance in medical diagnosis due to the fact that disease induces related tissue resistivity change. Studies have shown that the lung and tissues tumors reflect significant impedance change with disease states. It is hypothesized that the impedance measurement with the largest contribution from the organ of interest will result in less error. In this paper, we determined the percentage contribution of the lung impedance to the total impedance for five different external electrode configurations using a high resolution finite difference model (FDM) of the thorax along with lead field theory. The electrode combinations showed a contribution by the lungs of approximately 20% of the total impedance. Many configurations showed contributions of 15%. The results also showed that each lung could be isolated from the opposite lung.

  7. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  8. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    Science.gov (United States)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  9. The let-7 microRNA reduces tumor growth in mouse models of lung cancer.

    Science.gov (United States)

    Esquela-Kerscher, Aurora; Trang, Phong; Wiggins, Jason F; Patrawala, Lubna; Cheng, Angie; Ford, Lance; Weidhaas, Joanne B; Brown, David; Bader, Andreas G; Slack, Frank J

    2008-03-15

    MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.

  10. Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs

    OpenAIRE

    Kusztrich, Ariane

    2012-01-01

    Objective: Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Design: Prospective laborato...

  11. Effect of surfactants, gastric emptying, and dosage form on supersaturation of dipyridamole in an in vitro model simulating the stomach and duodenum.

    Science.gov (United States)

    Mitra, A; Fadda, H M

    2014-08-04

    The purpose of this study was to investigate the influence of gastric emptying patterns, surfactants, and dosage form on the supersaturation of a poorly soluble weakly basic drug, dipyridamole, using an in vitro model mimicking the dynamic environment of the upper gastrointestinal tract, and, furthermore, to evaluate the usefulness of this model in establishing correlations to in vivo bioavailability for drugs with solubility/dissolution limited absorption. A simulated stomach duodenum model comprising four compartments was used to assess supersaturation and precipitation kinetics as a function of time. It integrates physiologically relevant fluid volumes, fluid transfer rates, and pH changes of the upper GI tract. Monoexponential gastric emptying patterns simulating the fasted state were compared to linear gastric emptying patterns simulating the fed state. The effect of different surfactants commonly used in oral preparations, specifically, sodium lauryl sulfate (SLS), poloxamer-188, and polysorbate-80, on dipyridamole supersaturation was investigated while maintaining surface tension of the simulated gastric fluids at physiological levels and without obtaining artificial micellar solubilization of the drug. The supersaturation behavior of different dose strengths of dipyridamole was explored. Significant levels of dipyridamole supersaturation were observed in the duodenal compartment under all the different in vivo relevant conditions explored. Dipyridamole supersaturation ratios of up to 11-fold have been observed, and supersaturation has been maintained for up to 120 min. Lower duodenal concentrations of dipyridamole were observed under linear gastric emptying patterns compared to mononexponential gastric emptying. The mean duodenal area under concentration-time curves (AUC60min) for the dipyridamole concentration profile in the duodenal compartment is significantly different for all the surfactants explored (P < 0.05). Our investigations with the different

  12. Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future.

    Science.gov (United States)

    Sardesai, Smeeta; Biniwale, Manoj; Wertheimer, Fiona; Garingo, Arlene; Ramanathan, Rangasamy

    2017-01-01

    Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants and has been shown to significantly decrease air leaks and neonatal and infant mortality. Synthetic and animal-derived surfactants from bovine as well as porcine origin have been evaluated in randomized controlled trials. Animal-derived surfactants generally result in faster weaning of respiratory support, shorter duration of invasive ventilation, and decreased mortality when compared to first- or second-generation of synthetic surfactants, but some of the second-generation synthetic surfactants are at least not inferior to the animal-derived surfactants. Using a higher initial dose of porcine derived surfactant may provide better outcomes when compared with using lower doses of bovine surfactants, likely, due to compositional difference and/or the dose. Third-generation synthetic surfactant containing peptide analogs of surfactant protein B and C are currently being studied. Less invasive intra-tracheal surfactant administration techniques in spontaneously breathing neonate receiving noninvasive ventilator support are also being evaluated. In the present era, prophylactic surfactant is not recommended as it may increase the risk of lung injury or death. In the future, surfactants may be used as vector to deliver steroids, or used in combination with molecules, such as, recombinant Club Cell Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant administration techniques, such as aerosolization or atomization of surfactant may play a greater role in the future.

  13. Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

    Science.gov (United States)

    Schwaiberger, David; Pickerodt, Philipp A; Pomprapa, Anake; Tjarks, Onno; Kork, Felix; Boemke, Willehad; Francis, Roland C E; Leonhardt, Steffen; Lachmann, Burkhard

    2017-06-26

    Adherence to low tidal volume (V T ) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low V T -ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.

  14. Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs

    Directory of Open Access Journals (Sweden)

    Erzsébet Bartolák-Suki

    2017-06-01

    Full Text Available Preterm infants often require mechanical ventilation due to lung immaturity including reduced or abnormal surfactant. Since cyclic stretch with cycle-by-cycle variability is known to augment surfactant release by epithelial cells, we hypothesized that such in vivo mechanotransduction improves surfactant maturation and hence lung physiology in preterm subjects. We thus tested whether breath-by-breath variability in tidal volume (VT in variable ventilation (VV can be tuned for optimal performance in a preterm lamb model. Preterm lambs were ventilated for 3 h with conventional ventilation (CV or two variants of VV that used a maximum VT of 1.5 (VV1 or 2.25 (VV2 times the mean VT. VT was adjusted during ventilation to a permissive pCO2 target range. Respiratory mechanics were monitored continuously using the forced oscillation technique, followed by postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV in blood gas parameters (pH, SaO2, cerebral O2 saturation. However, only VV2 lowered PaCO2 and had a higher specific respiratory compliance than CV. VV2 also increased surfactant protein (SP-B release compared to VV1 and stimulated its production compared to CV. The production and release of proSP-C however, was increased with CV compared to both VVs. There was more SP-A in both VVs than CV in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly increased in CV in both the lavage and lung. Compared to CV, the cytokines IL-1β, and TNFα decreased with both VVs with less inflammation during VV2. Additionally, VV2 lungs showed the most homogeneous alveolar structure and least inflammatory cell infiltration assessed by histology. CV lungs exhibited over-distension mixed with collapsed and interstitial edematous regions with occasional hemorrhage. Following VV1, some lambs had normal alveolar structure while others were similar to CV. The IgG serum proteins in the lavage, a marker of leakage, were the

  15. Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs.

    Science.gov (United States)

    Bartolák-Suki, Erzsébet; Noble, Peter B; Bou Jawde, Samer; Pillow, Jane J; Suki, Béla

    2017-01-01

    Preterm infants often require mechanical ventilation due to lung immaturity including reduced or abnormal surfactant. Since cyclic stretch with cycle-by-cycle variability is known to augment surfactant release by epithelial cells, we hypothesized that such in vivo mechanotransduction improves surfactant maturation and hence lung physiology in preterm subjects. We thus tested whether breath-by-breath variability in tidal volume (V T ) in variable ventilation (VV) can be tuned for optimal performance in a preterm lamb model. Preterm lambs were ventilated for 3 h with conventional ventilation (CV) or two variants of VV that used a maximum V T of 1.5 (VV1) or 2.25 (VV2) times the mean V T . V T was adjusted during ventilation to a permissive pCO 2 target range. Respiratory mechanics were monitored continuously using the forced oscillation technique, followed by postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV in blood gas parameters (pH, Sa O 2 , cerebral O 2 saturation). However, only VV2 lowered PaCO 2 and had a higher specific respiratory compliance than CV. VV2 also increased surfactant protein (SP)-B release compared to VV1 and stimulated its production compared to CV. The production and release of proSP-C however, was increased with CV compared to both VVs. There was more SP-A in both VVs than CV in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly increased in CV in both the lavage and lung. Compared to CV, the cytokines IL-1β, and TNFα decreased with both VVs with less inflammation during VV2. Additionally, VV2 lungs showed the most homogeneous alveolar structure and least inflammatory cell infiltration assessed by histology. CV lungs exhibited over-distension mixed with collapsed and interstitial edematous regions with occasional hemorrhage. Following VV1, some lambs had normal alveolar structure while others were similar to CV. The IgG serum proteins in the lavage, a marker of leakage, were the

  16. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    Science.gov (United States)

    1984-10-01

    intercellular attachments. After evaluation of a number of enzymes and enzyme mixtures including Protease I (Sigma), collagenase (Worthington), thermolysin ...in HPBS. At this time, the lung lobes are removed, minced and stirred with soybean trypsin inhibitor (1 mg/mL, Sigma) in the cold for an additional 30

  17. Modeling Lung Carcinogenesis in Radon-Exposed Miner

    NARCIS (Netherlands)

    Teun van Dillen; Irene Brüske; Fieke Dekkers; Harmen Bijwaard

    2015-01-01

    Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a

  18. The pathogenesis of lung emphysema: lessons learned from murine models

    NARCIS (Netherlands)

    Braber, S.

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is defined by the Global initiative in Obstructive Lung Disease (GOLD) as: “a disease state characterized by airflow limitation that is not fully reversible. The airflow

  19. Surfactant therapy in late preterm infants

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök

    2013-06-01

    Full Text Available Late preterm (LPT neonates are at a high risk for respiratory distress soon after birth due to respiratory distress syndrome (RDS, transient tachypnea of the newborn, persistent pulmonary hypertension, and pneumonia along with an increased need for surfactant replacement therapy, continuous positive airway pressure, and ventilator support when compared with the term neonates. In the past, studies on outcomes of infants with respiratory distress have primarily focused on extremely premature infants, leading to a gap in knowledge and understanding of the developmental biology and mechanism of pulmonary diseases in LPT neonates. Surfactant deficiency is the most frequent etiology of RDS in very preterm and moderately preterm infants, while cesarean section and lung infection play major roles in RDS development in LPT infants. The clinical presentation and the response to surfactant therapy in LPT infants may be different than that seen in very preterm infants. Incidence of pneumonia and occurrence of pneumothorax are significantly higher in LPT and term infants. High rates of pneumonia in these infants may result in direct injury to the type II alveolar cells of the lung with decreasing synthesis, release, and processing of surfactant. Increased permeability of the alveolar capillary membrane to both fluid and solutes is known to result in entry of plasma proteins into the alveolar hypophase, further inhibiting the surface properties of surfactant. However, the oxygenation index value do not change dramatically after ventilation or surfactant administration in LPT infants with RDS compared to very preterm infants. These finding may indicate a different pathogenesis of RDS in late preterm and term infants. In conclusion, surfactant therapy may be of significant benefit in LPT infants with serious respiratory failure secondary to a number of insults. However, optimal timing and dose of administration are not so clear in this group. Additional

  20. Development of a Three‐Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling

    Science.gov (United States)

    Wilkinson, Dan C.; Alva‐Ornelas, Jackelyn A.; Sucre, Jennifer M.S.; Vijayaraj, Preethi; Durra, Abdo; Richardson, Wade; Jonas, Steven J.; Paul, Manash K.; Karumbayaram, Saravanan; Dunn, Bruce

    2016-01-01

    Abstract Stem cell technologies, especially patient‐specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ‐level tissues. The generation of three‐dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology. This is specifically true of lung diseases where animal models often do not recapitulate human disease. Here, we present a method for the generation of self‐assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis (IPF). Tissue formation occurs because of the overlapping processes of cellular adhesion to multiple alveolar sac templates, bioreactor rotation, and cellular contraction. Addition of transforming growth factor‐β1 to single cell‐type mesenchymal organoids resulted in morphologic scarring typical of that seen in IPF but not in two‐dimensional IPF fibroblast cultures. Furthermore, this lung organoid may be modified to contain multiple lung cell types assembled into the correct anatomical location, thereby allowing cell‐cell contact and recapitulating the lung microenvironment. Our bottom‐up approach for synthesizing patient‐specific lung tissue in a scalable system allows for the development of relevant human lung disease models with the potential for high throughput drug screening to identify targeted therapies. Stem Cells Translational Medicine 2017;6:622–633 PMID:28191779

  1. Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling.

    Science.gov (United States)

    Wilkinson, Dan C; Alva-Ornelas, Jackelyn A; Sucre, Jennifer M S; Vijayaraj, Preethi; Durra, Abdo; Richardson, Wade; Jonas, Steven J; Paul, Manash K; Karumbayaram, Saravanan; Dunn, Bruce; Gomperts, Brigitte N

    2017-02-01

    Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology. This is specifically true of lung diseases where animal models often do not recapitulate human disease. Here, we present a method for the generation of self-assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis (IPF). Tissue formation occurs because of the overlapping processes of cellular adhesion to multiple alveolar sac templates, bioreactor rotation, and cellular contraction. Addition of transforming growth factor-β1 to single cell-type mesenchymal organoids resulted in morphologic scarring typical of that seen in IPF but not in two-dimensional IPF fibroblast cultures. Furthermore, this lung organoid may be modified to contain multiple lung cell types assembled into the correct anatomical location, thereby allowing cell-cell contact and recapitulating the lung microenvironment. Our bottom-up approach for synthesizing patient-specific lung tissue in a scalable system allows for the development of relevant human lung disease models with the potential for high throughput drug screening to identify targeted therapies. Stem Cells Translational Medicine 2017;6:622-633. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  2. Assessment of an infant whole-body plethysmograph using an infant lung function model.

    Science.gov (United States)

    Reinmann, B; Stocks, J; Frey, U

    2001-04-01

    In order to facilitate international multicentre studies and improve the quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society Task Force for infant lung function testing has recently developed specifications for standardized infant lung function equipment and software. A mechanical infant lung model analogue has been developed to assess whether infant lung function equipment is able to meet these requirements. However, the practical testing of infant lung function equipment using such models is highly complex because of the need to use very small pressure and flow changes, and the numerous potentially confounding factors associated with both the design of the device and the testing procedure. The aim of this study was to determine whether the infant lung model is capable of assessing the overall function of an whole-body infant- plethysmograph, using the only infant plethysmograph that was commercially available at the time as an example. The mechanical characteristics of the model such as vibrations or noise did not disturb the delicate plethysmographic measurements and thereby allowed a reliable assessment of the system. A series of tests revealed that the plethysmograph was able to measure airway resistance 1-3.5 kPa.L(-1).s with an accuracy of +/-2.5% and lung volumes 75-300 mL with an accuracy of +/-2.5% under in vitro conditions. To conclude, the infant lung model is a useful means of assessing the overall in vitro performance of infant whole-body plethysmographs, but thermal, mechanical and frequency response characteristics of such a device must be taken into account when interpreting the results of such assessments.

  3. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

    Directory of Open Access Journals (Sweden)

    Kevin Ten Haaf

    2017-04-01

    Full Text Available Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years. Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer.Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST participants (1,925 lung cancer cases and 884 lung cancer deaths and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths. Six-year lung cancer incidence and mortality risk predictions were assessed for (1 calibration (graphically by comparing the agreement between the predicted and the observed risks, (2 discrimination (area under the receiver operating characteristic curve [AUC] between individuals with and without lung cancer (death, and (3 clinical usefulness (net benefit in decision curve analysis by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81. The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a

  4. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

    Science.gov (United States)

    Ten Haaf, Kevin; Jeon, Jihyoun; Tammemägi, Martin C; Han, Summer S; Kong, Chung Yin; Plevritis, Sylvia K; Feuer, Eric J; de Koning, Harry J; Steyerberg, Ewout W; Meza, Rafael

    2017-04-01

    Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation) as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer. Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST) participants (1,925 lung cancer cases and 884 lung cancer deaths) and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths). Six-year lung cancer incidence and mortality risk predictions were assessed for (1) calibration (graphically) by comparing the agreement between the predicted and the observed risks, (2) discrimination (area under the receiver operating characteristic curve [AUC]) between individuals with and without lung cancer (death), and (3) clinical usefulness (net benefit in decision curve analysis) by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81). The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a slightly

  5. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  6. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    International Nuclear Information System (INIS)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-01-01

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

  7. Fundamentals of surfactant sputtering

    International Nuclear Information System (INIS)

    Hofsaess, Hans; Zhang Kun

    2009-01-01

    We introduce a new sputter technique, utilizing the steady-state coverage of a substrate surface with up to 10 16 cm -2 of foreign atoms simultaneously during sputter erosion by combined ion irradiation and atom deposition. These atoms strongly modify the substrate sputter yield on atomic to macroscopic length scales and therefore act as surfactant atoms (a blend of 'surface active agent'). Depending on the surfactant-substrate combination, the novel technique allows enhanced surface smoothing, generation of novel surface patterns, shaping of surfaces and formation of ultra-thin films. Sputter yield attenuation is demonstrated for sputtering of Si and Fe substrates and different surfactant species using 5 keV Xe ions at different incidence angles and fluences up to 10 17 cm -2 . Analytical approaches and Monte Carlo simulations are used to predict the sputtering yield attenuation as function of surfactant coverage. For sputtering of Si with Au surfactants we observe high sputter yields despite a steady-state surfactant coverage, which can be explained by strong ion-induced interdiffusion of substrate and surfactant atoms and the formation of a buried Au x Si surfactant layer in dynamic equilibrium.

  8. Dynamic covalent surfactants

    NARCIS (Netherlands)

    Minkenberg, C.B.

    2012-01-01

    In this thesis the development of surfactant aggregates with fast exchange dynamics between the aggregated and non-aggregated state is described. Dynamic surfactant exchange plays an important role in natural systems, for instance in cell signaling, cell division, and uptake and release of cargo.

  9. Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Xue-Yuan Chen

    Full Text Available OBJECTIVE: Acute lung injury (ALI, is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM-loaded immunoliposome (NLP functionalized with pulmonary surfactant protein A (SP-A antibody (SPA-DXM-NLP in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

  10. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Directory of Open Access Journals (Sweden)

    Christopher B Massa

    2017-08-01

    Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

  11. Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury.

    Science.gov (United States)

    Saddy, Felipe; Oliveira, Gisele P; Garcia, Cristiane S N B; Nardelli, Liliane M; Rzezinski, Andreia F; Ornellas, Debora S; Morales, Marcelo M; Capelozzi, Vera L; Pelosi, Paolo; Rocco, Patricia R M

    2010-08-01

    The goal of the study was to compare the effects of different assisted ventilation modes with pressure controlled ventilation (PCV) on lung histology, arterial blood gases, inflammatory and fibrogenic mediators in experimental acute lung injury (ALI). Paraquat-induced ALI rats were studied. At 24 h, animals were anaesthetised and further randomized as follows (n = 6/group): (1) pressure controlled ventilation mode (PCV) with tidal volume (V (T)) = 6 ml/kg and inspiratory to expiratory ratio (I:E) = 1:2; (2) three assisted ventilation modes: (a) assist-pressure controlled ventilation (APCV1:2) with I:E = 1:2, (b) APCV1:1 with I:E = 1:1; and (c) biphasic positive airway pressure and pressure support ventilation (BiVent + PSV), and (3) spontaneous breathing without PEEP in air. PCV, APCV1:1, and APCV1:2 were set with P (insp) = 10 cmH(2)O and PEEP = 5 cmH(2)O. BiVent + PSV was set with two levels of CPAP [inspiratory pressure (P (High) = 10 cmH(2)O) and positive end-expiratory pressure (P (Low) = 5 cmH(2)O)] and inspiratory/expiratory times: T (High) = 0.3 s and T (Low) = 0.3 s. PSV was set as follows: 2 cmH(2)O above P (High) and 7 cmH(2)O above P (Low). All rats were mechanically ventilated in air and PEEP = 5 cmH(2)O for 1 h. Assisted ventilation modes led to better functional improvement and less lung injury compared to PCV. APCV1:1 and BiVent + PSV presented similar oxygenation levels, which were higher than in APCV1:2. Bivent + PSV led to less alveolar epithelium injury and lower expression of tumour necrosis factor-alpha, interleukin-6, and type III procollagen. In this experimental ALI model, assisted ventilation modes presented greater beneficial effects on respiratory function and a reduction in lung injury compared to PCV. Among assisted ventilation modes, Bi-Vent + PSV demonstrated better functional results with less lung damage and expression of inflammatory mediators.

  12. Protective roles of Cordyceps on lung fibrosis in cellular and rat models.

    Science.gov (United States)

    Chen, Mengli; Cheung, Florence W K; Chan, Ming Hung; Hui, Pak Kwan; Ip, Siu-Po; Ling, Yick Hin; Che, Chun-Tao; Liu, Wing Keung

    2012-09-28

    Cordyceps sinensis is a fungus used in traditional Chinese medicine as a tonic to soothe the lung for the treatment of fatigue and respiratory diseases. Idiopathic pulmonary fibrosis is a chronic, irreversible and debilitating lung disease showing fibroblast/myofibroblast expansion and excessive deposition of extracellular matrix in the interstitium leading to breathing difficulty. Our previous observation revealed a partial relief of lung fibrosis in patients suffering from severe acute respiratory syndrome (SARS). We hypothesize that Cordyceps has beneficial effects on lung fibrosis and the objective of this study is to explore the target(s) of Cordyceps in the relief of lung fibrosis in animal and cell models and to gain insight into its underlying mechanisms. A rat model of bleomycin (BLM)-induced lung fibrosis and a fibrotic cell model with transforming growth factor beta-1 induction were employed in the studies. Reduction of infiltration of inflammatory cells, deposition of fibroblastic loci and collagen, formation of reactive oxygen species, and production of cytokines, as well as recovery from imbalance of MMP-9/TIMP-1, were observed in fibrotic rats after treatment with Cordyceps in preventive (from the day of BLM administration) and therapeutic (from 14 days after BLM) regimens. In a fibrotic cell model with transforming growth factor beta-1 induction, the human lung epithelial A549 acquired a mesenchymal phenotype and an increase of vimentin expression with a concomitant decrease of E-cadherin. This epithelial-mesenchymal transition could be partially reverted by cordycepin, a major component of Cordyceps. The findings provide an insight into the preventive and therapeutic potentials of Cordyceps for the treatment of lung fibrosis. Copyright © 2012. Published by Elsevier Ireland Ltd.

  13. Cytotoxicity assessment of lipid-based self-emulsifying drug delivery system with Caco-2 cell model: Cremophor EL as the surfactant.

    Science.gov (United States)

    Bu, Pengli; Narayanan, Silpa; Dalrymple, Damon; Cheng, Xingguo; Serajuddin, Abu T M

    2016-08-25

    Caco-2 cells are used extensively for in vitro prediction of intestinal drug absorption. However, toxicity of excipients and formulations used can artificially increase drug permeation by damaging cell monolayers, thus providing misleading results. The present study aimed to investigate cytotoxicity of common lipid-based excipients and formulations on Caco-2 cells. Medium-chain monoglycerides alone or in mixture with the surfactant Cremophor EL, with and without a medium-chain triglyceride, were prepared and incubated with Caco-2 cells from a series of culture stages with varying maturity. Cell viability was evaluated and cell membrane integrity assessed. Cytotoxicity of lipid-based formulations was influenced by the maturity of Caco-2 cells and formulation composition. One-day culture was most sensitive to lipids. When cultured for 5days, viability of Caco-2 cells was significantly improved. The 21-day Caco-2 monolayers maintained the highest survival rate. Microemulsion formulations exhibited significantly less cytotoxicity than neat lipids or surfactant at all stages of cell maturity, and microemulsions containing 1:1 mixtures of monoglyceride and triglyceride appeared to be best tolerated among all the formulations tested. Mechanistically, the observed cytotoxicity was partially due to lipid-induced rupture of cell membrane. Microemulsions of lipid-surfactant mixtures have less cytotoxicity than lipid alone. Maturity of Caco-2 cells renders significant resistance to cytotoxicity, and monolayers with 21-day maturity are more relevant to in vivo conditions and appear to be a more accurate in vitro model for cytotoxicity assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Establishment of A Clinical Prediction Model of Prolonged Air Leak 
after Anatomic Lung Resection].

    Science.gov (United States)

    Wu, Xianning; Xu, Shibin; Ke, Li; Fan, Jun; Wang, Jun; Xie, Mingran; Jiang, Xianliang; Xu, Meiqing

    2017-12-20

    Prolonged air leak (PAL) after anatomic lung resection is a common and challenging complication in thoracic surgery. No available clinical prediction model of PAL has been established in China. The aim of this study was to construct a model to identify patients at increased risk of PAL by using preoperative factors exclusively. We retrospectively reviewed clinical data and PAL occurrence of patients after anatomic lung resection, in department of thoracic surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, from January 2016 to October 2016. 359 patients were in group A, clinical data including age, body mass index (BMI), gender, smoking history, surgical methods, pulmonary function index, pleural adhesion, pathologic diagnosis, side and site of resected lung were analyzed. By using univariate and multivariate analysis, we found the independent predictors of PAL after anatomic lung resection and subsequently established a clinical prediction model. Then, another 112 patients (group B), who underwent anatomic lung resection in different time by different team, were chosen to verify the accuracy of the prediction model. Receiver-operating characteristic (ROC) curve was constructed using the prediction model. Multivariate Logistic regression analysis was used to identify six clinical characteristics [BMI, gender, smoking history, forced expiratory volume in one second to forced vital capacity ratio (FEV1%), pleural adhesion, site of resection] as independent predictors of PAL after anatomic lung resection. The area under the ROC curve for our model was 0.886 (95%CI: 0.835-0.937). The best predictive P value was 0.299 with sensitivity of 78.5% and specificity of 93.2%. Our prediction model could accurately identify occurrence risk of PAL in patients after anatomic lung resection, which might allow for more effective use of intraoperative prophylactic strategies.
.

  15. A randomised control study of partial liquid ventilation after airway lavage with exogenous surfactant in a meconium aspiration syndrome animal model

    Science.gov (United States)

    Nakamura, T.; Matsuzawa, S.; Sugiura, M.; Tamura, M.

    2000-01-01

    AIMS—To test the hypothesis that lavage with exogenous surfactant before partial liquid ventilation in meconium aspiration syndrome (MAS) would improve debris removal, and therefore the effectiveness of partial liquid ventilation.
METHODS—12 newborn piglets were randomised into 4 groups, partial liquid ventilation or gas ventilation, with and without surfactant lavage. Physiological and blood gas data were compared between groups by analysis of variance.
RESULTS—Arterial oxygen pressure (PaO2) was improved in the group treated with surfactant lavage when compared with the group not receiving surfactant. PaO2 in the group receiving surfactant lavage followed by partial liquid ventilation was further improved when compared with the group treated with surfactant lavage followed by gas ventilation and the group receiving partial liquid ventilation alone.
CONCLUSION—The effectiveness of partial liquid ventilation in MAS might be enhanced by pretreatment with exogenous surfactant bronchial lavage.

 PMID:10685992

  16. Molecular simulation of surfactant-assisted protein refolding

    Science.gov (United States)

    Lu, Diannan; Liu, Zheng; Liu, Zhixia; Zhang, Minlian; Ouyang, Pingkai

    2005-04-01

    Protein refolding to its native state in vitro is a challenging problem in biotechnology, i.e., in the biomedical, pharmaceutical, and food industry. Protein aggregation and misfolding usually inhibit the recovery of proteins with their native states. These problems can be partially solved by adding a surfactant into a suitable solution environment. However, the process of this surfactant-assisted protein refolding is not well understood. In this paper, we wish to report on the first-ever simulations of surfactant-assisted protein refolding. For these studies, we defined a simple model for the protein and the surfactant and investigated how a surfactant affected the folding behavior of a two-dimensional lattice protein molecule. The model protein and model surfactant were chosen such that we could capture the important features of the folding process and the interaction between the protein and the surfactant, namely, the hydrophobic interaction. It was shown that, in the absence of surfactants, a protein in an "energy trap" conformation, i.e., a local energy minima, could not fold into the native form, which was characterized by a global energy minimum. The addition of surfactants created folding pathways via the formation of protein-surfactant complexes and thus enabled the conformations that fell into energy trap states to escape from these traps and to form the native proteins. The simulation results also showed that it was necessary to match the hydrophobicity of surfactant to the concentration of denaturant, which was added to control the folding or unfolding of a protein. The surfactants with different hydrophobicity had their own concentration range on assisting protein refolding. All of these simulations agreed well with experimental results reported elsewhere, indicating both the validity of the simulations presented here and the potential application of the simulations for the design of a surfactant on assisting protein refolding.

  17. Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

    Science.gov (United States)

    Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

    2012-04-01

    To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

  18. Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

    Directory of Open Access Journals (Sweden)

    Yi-fan LIU

    2013-09-01

    Full Text Available Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

  19. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome.

    Science.gov (United States)

    Uriarte, Juan J; Meirelles, Thayna; Gorbenko Del Blanco, Darya; Nonaka, Paula N; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome.

  20. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome.

    Directory of Open Access Journals (Sweden)

    Juan J Uriarte

    Full Text Available Early morbidity and mortality in patients with Marfan syndrome (MFS -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM is affected in a well-characterized MFS mouse model (FBN1C1039G/+. The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome.

  1. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    Science.gov (United States)

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  2. Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Crimi Nunzio

    2006-11-01

    Full Text Available Abstract Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-α were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i loss of body weight, (ii mortality rate, (iii lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts, (iv lung edema, (v histological evidence of lung injury and collagen deposition, (vi lung myeloperoxidase, IL-1 and TNF-α staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.

  3. The effect of tracheal occlusion on lung branching in the rat nitrofen CDH model.

    Science.gov (United States)

    Baird, Robert; Khan, Nasir; Flageole, Helene; Anselmo, Mark; Puligandla, Pramod; Laberge, Jean-Martin

    2008-08-01

    Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia (CDH). TO increases lung size, but it is unclear whether TO stimulates mature lung growth or simply induces alveolarization without concomitant bronchial development. In this study, we characterize bronchial branch development in fetal rats with CDH with or without TO through conventional histological and morphometric analysis as well as lung casting. Rat dams were gavaged nitrofen at gestational day 9.5, and 3 to 4 fetuses per dam underwent fetal TO on gestational day 19 (term = 22 days). Fetuses were sacrificed on day 21, the presence of CDH was confirmed, and the lung weight to body weight ratio (LW/BW) was calculated. Lung casts of all research groups were created using liquid silicon and bronchial branches were quantified from lung periphery to carina. CDH fetuses had smaller LW/BW ratios and a lesser percentage (%) of airspace when compared to controls, and manifested less lung branching than controls. Fetuses treated by TO had a greater LW/BW ratio and % airspace, but did not have a different number of branch iterations. Fetuses with CDH and TO demonstrated a restoration in LW/BW ratio to control levels (P = 0.42), but the number of bronchial branch iterations remained less than control animals. The results of this study suggest that TO in this animal model at gestational day 19 promotes distal airway proliferation but does not reverse the underdevelopment of bronchial branching seen in lung hypoplasia due to CDH.

  4. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde M.; van Riel, Sarah J.; Saghir, Zaigham

    2015-01-01

    ; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. Conclusions: High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were......Objectives: Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. Methods: From...... used to evaluate risk discrimination. Results: AUCs of 0.826–0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer...

  5. Patient specific respiratory motion modeling using a limited number of 3D lung CT images.

    Science.gov (United States)

    Cui, Xueli; Gao, Xin; Xia, Wei; Liu, Yangchuan; Liang, Zhiyuan

    2014-01-01

    To build a patient specific respiratory motion model with a low dose, a novel method was proposed that uses a limited number of 3D lung CT volumes with an external respiratory signal. 4D lung CT volumes were acquired for patients with in vitro labeling on the upper abdominal surface. Meanwhile, 3D coordinates of in vitro labeling were measured as external respiratory signals. A sequential correspondence between the 4D lung CT and the external respiratory signal was built using the distance correlation method, and a 3D displacement for every registration control point in the CT volumes with respect to time can be obtained by the 4D lung CT deformable registration. A temporal fitting was performed for every registration control point displacements and an external respiratory signal in the anterior-posterior direction respectively to draw their fitting curves. Finally, a linear regression was used to fit the corresponding samples of the control point displacement fitting curves and the external respiratory signal fitting curve to finish the pulmonary respiration modeling. Compared to a B-spline-based method using the respiratory signal phase, the proposed method is highly advantageous as it offers comparable modeling accuracy and target modeling error (TME); while at the same time, the proposed method requires 70% less 3D lung CTs. When using a similar amount of 3D lung CT data, the mean of the proposed method's TME is smaller than the mean of the PCA (principle component analysis)-based methods' TMEs. The results indicate that the proposed method is successful in striking a balance between modeling accuracy and number of 3D lung CT volumes.

  6. Predicting the lung compliance of mechanically ventilated patients via statistical modeling

    International Nuclear Information System (INIS)

    Ganzert, Steven; Kramer, Stefan; Guttmann, Josef

    2012-01-01

    To avoid ventilator associated lung injury (VALI) during mechanical ventilation, the ventilator is adjusted with reference to the volume distensibility or ‘compliance’ of the lung. For lung-protective ventilation, the lung should be inflated at its maximum compliance, i.e. when during inspiration a maximal intrapulmonary volume change is achieved by a minimal change of pressure. To accomplish this, one of the main parameters is the adjusted positive end-expiratory pressure (PEEP). As changing the ventilator settings usually produces an effect on patient's lung mechanics with a considerable time delay, the prediction of the compliance change associated with a planned change of PEEP could assist the physician at the bedside. This study introduces a machine learning approach to predict the nonlinear lung compliance for the individual patient by Gaussian processes, a probabilistic modeling technique. Experiments are based on time series data obtained from patients suffering from acute respiratory distress syndrome (ARDS). With a high hit ratio of up to 93%, the learned models could predict whether an increase/decrease of PEEP would lead to an increase/decrease of the compliance. However, the prediction of the complete pressure–volume relation for an individual patient has to be improved. We conclude that the approach is well suitable for the given problem domain but that an individualized feature selection should be applied for a precise prediction of individual pressure–volume curves. (paper)

  7. 4D motion models over the respiratory cycle for use in lung cancer radiotherapy planning

    Science.gov (United States)

    McClelland, J. R.; Chandler, A. G.; Blackall, J. M.; Ahmad, S.; Landau, D. B.; Hawkes, D. J.

    2005-04-01

    Respiratory motion causes problems of tumour localisation in radiotherapy treatment planning for lung cancer patients. We have developed a novel method of building patient specific motion models, which model the movement and non-rigid deformation of a lung tumour and surrounding lung tissue over the respiratory cycle. Free-breathing (FB) CT scans are acquired in cine mode, using 3 couch positions to acquire contiguous 'slabs' of 16 slices covering the region of interest. For each slab, 20 FB volumes are acquired over approx 20s. A reference volume acquired at Breath Hold (BH) and covering the whole lung, is non-rigidly registered to each of the FB volumes. The FB volumes are assigned a position in the respiratory cycle (PRC) calculated from the displacement of the chest wall. A motion model is then constructed for each slab, by fitting functions that temporally interpolate the registration results over the respiratory cycle. This can produce a prediction of the lung and tumour within the slab at any arbitrary PRC. The predictions for each of the slabs are then combined to produce a volume covering the whole region of interest. Results indicate that the motion modelling method shows considerable promise, offering significant improvement over current clinical practice, and potential advantages over alternative 4D CT imaging techniques. Using this framework, we examined and evaluated several different functions for performing the temporal interpolation. We believe the results of these comparisons will aid future model building for this and other applications.

  8. Surfactants in the environment.

    Science.gov (United States)

    Ivanković, Tomislav; Hrenović, Jasna

    2010-03-01

    Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.

  9. Surfactant and perfluorocarbon aerosolization during different mechanical ventilation strategies by means of inhalation catheters: an in vitro study.

    Science.gov (United States)

    Murgia, Xabier; Gastiasoro, Elena; Mielgo, Victoria; Ruiz-Del-Yerro, Estibaliz; Alvarez-Diaz, Francisco José; Lafuente, Hector; Valls-I-Soler, Adolf; Gomez-Solaetxe, Miguel Angel; Rey-Santano, Carmen

    2012-02-01

    perfluorocarbon to the lung model. Changes in PIP and RR directly influence the percentage of surfactant and perfluorocarbon recovered.

  10. In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

    Science.gov (United States)

    Walters, Russel M; Gandolfi, Lisa; Mack, M Catherine; Fevola, Michael; Martin, Katharine; Hamilton, Mathew T; Hilberer, Allison; Barnes, Nicole; Wilt, Nathan; Nash, Jennifer R; Raabe, Hans A; Costin, Gertrude-Emilia

    2016-12-01

    The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing. 2016 FRAME.

  11. Cycle-Induced Flow and Surfactant Transport in an Alveolus

    Science.gov (United States)

    Wei, H. H.

    2002-11-01

    The flow and transport in an alveolus are of fundamental importance to partial liquid ventilation, surfactant transport, pulmonary drug administration, cell-cell signaling pathways and gene therapy. We model the system in which an alveolus is partially filled with liquid in the presence of surfactants. Assuming a circular interface due to sufficiently strong surface tension, we can apply two-dimensional bipolar coordinates to describe the system. We then combine analytical and numerical techniques to solve the Stokes flow and the surfactant concentration. In the absence of surfactants, there is no steady streaming because of reversibility of the Stokes flow. The presence of surfactants however induces a non-trivial cycle-averaged surfactant concentration gradient along the interface that generates steady streaming. The steady streaming patterns (e.g., number of vortices) depend on the parameters, especially on the ratio of inspiration to expiration periods (I:E ratio). Either smaller or larger I:E ratio exhibits two primary vortices but the direction of primary vortices for small I:E is opposite to large I:E. Extension to soluble surfactants is also discussed. For sufficiently high surfactant bulk concentration, the surfactant transport is sorption-controlled and soluble surfactants diminish the size of steady vortices near the alveolar opening. For the estimated steady velocity u 10-5 cm/s, the corresponding Peclet number is 10-7/ D_m. Therefore, for Dm <= 10-7 cm^2/s, the convective transport dominates.

  12. Tuning of nanoparticle-surfactant interactions in aqueous system

    Science.gov (United States)

    Kumar, Sugam; Aswal, V. K.

    2011-01-01

    The interaction of charged (anionic) silica nanoparticles with ionic and nonionic surfactants has been studied using small-angle neutron scattering (SANS). The surfactants used are anionic sodium dodecyl sulfate (SDS), cationic dodecyltrimethyl ammonium bromide (DTAB) and nonionic decaoxyethylene n-dodecylether (C12E10). The measurements are carried out at fixed concentration (1 wt%) of silica nanoparticles and with surfactant concentration varied in the range 0-2 wt%. It is found that there is no direct interaction between the nanoparticles and the surfactant (SDS) when they both are similarly charged. Both the silica nanoparticles and micelles coexist individually with no significant change in the structure of the micelles with respect to that in the pure surfactant solution. On the other hand, the presence of oppositely charged surfactant (DTAB) leads to the aggregation of silica nanoparticles even with very low surfactant concentration. The aggregation of silica nanoparticles is characterized by fractal structure and its fractal dimension remains constant with the increase in the surfactant concentration. In the case of nonionic surfactant, it interacts with the individual silica nanoparticles. The interaction is examined using two models: one that considers the surfactant layer coating on silica nanoparticles and a second one where the surface of the nanoparticles is decorated by the micelles. Contrast variation SANS measurements confirm the uniform decoration of nonionic micelles on the nanoparticles.

  13. Tuning of nanoparticle-surfactant interactions in aqueous system

    International Nuclear Information System (INIS)

    Kumar, Sugam; Aswal, V K

    2011-01-01

    The interaction of charged (anionic) silica nanoparticles with ionic and nonionic surfactants has been studied using small-angle neutron scattering (SANS). The surfactants used are anionic sodium dodecyl sulfate (SDS), cationic dodecyltrimethyl ammonium bromide (DTAB) and nonionic decaoxyethylene n-dodecylether (C 12 E 10 ). The measurements are carried out at fixed concentration (1 wt%) of silica nanoparticles and with surfactant concentration varied in the range 0-2 wt%. It is found that there is no direct interaction between the nanoparticles and the surfactant (SDS) when they both are similarly charged. Both the silica nanoparticles and micelles coexist individually with no significant change in the structure of the micelles with respect to that in the pure surfactant solution. On the other hand, the presence of oppositely charged surfactant (DTAB) leads to the aggregation of silica nanoparticles even with very low surfactant concentration. The aggregation of silica nanoparticles is characterized by fractal structure and its fractal dimension remains constant with the increase in the surfactant concentration. In the case of nonionic surfactant, it interacts with the individual silica nanoparticles. The interaction is examined using two models: one that considers the surfactant layer coating on silica nanoparticles and a second one where the surface of the nanoparticles is decorated by the micelles. Contrast variation SANS measurements confirm the uniform decoration of nonionic micelles on the nanoparticles.

  14. Development of diagnostic model of lung cancer based on multiple tumor markers and data mining.

    Science.gov (United States)

    Wang, Zhaoxian; Feng, Feifei; Zhou, Xiaoshan; Duan, Liju; Wang, Jing; Wu, Yongjun; Wang, Na

    2017-11-07

    To develop early intelligent discriminative model of lung cancer and evaluate the efficiency of diagnosis value. Based on the genetic polymorphism profile of CYP1A1-rs1048943, GSTM1, mEH-rs1051740, XRCC1-rs1799782 and XRCC1-rs25489 and the methylations of p16 and RASSF1A gene, and the length of telomere in the peripheral blood from 200 lung cancer patients and 200 health persons, the discriminative model was established through decision tree and ANN technique. ACU of the discriminative model based on multiple tumour markers increased by about 10%; The accuracy rate of decision tree model and ANN model for testing set were 93.00% and 89.62% respectively. The ROC analysis showed the decision tree model's AUC is 0.929 (0.894∼0.964), the ANN model's AUC is 0.894 (0.853∼0.935). However, the classify accuracy rate and AUC of Fisher discriminatory analysis model are all about 0.7. The early intelligent discriminative model of lung cancer based on multiple tumor markers and data mining techniques has a higher accuracy rate and might be useful for early diagnosis of lung cancer.

  15. Metathesis depolymerizable surfactants

    Science.gov (United States)

    Jamison, Gregory M [Albuquerque, NM; Wheeler, David R [Albuquerque, NM; Loy, Douglas A [Tucson, AZ; Simmons, Blake A [San Francisco, CA; Long, Timothy M [Evanston, IL; McElhanon, James R [Manteca, CA; Rahimian, Kamyar [Albuquerque, NM; Staiger, Chad L [Albuquerque, NM

    2008-04-15

    A class of surfactant molecules whose structure includes regularly spaced unsaturation in the tail group and thus, can be readily decomposed by ring-closing metathesis, and particularly by the action of a transition metal catalyst, to form small molecule products. These small molecules are designed to have increased volatility and/or enhanced solubility as compared to the original surfactant molecule and are thus easily removed by solvent extraction or vacuum extraction at low temperature. By producing easily removable decomposition products, the surfactant molecules become particularly desirable as template structures for preparing meso- and microstructural materials with tailored properties.

  16. Synthesis and characterization of gold graphene composite with dyes as model substrates for decolorization: A surfactant free laser ablation approach

    Science.gov (United States)

    Sai Siddhardha, R. S.; Lakshman Kumar, V.; Kaniyoor, Adarsh; Sai Muthukumar, V.; Ramaprabhu, S.; Podila, Ramakrishna; Rao, A. M.; Ramamurthy, Sai Sathish

    2014-12-01

    A facile surfactant free laser ablation mediated synthesis (LAMS) of gold-graphene composite is reported here. The material was characterized using transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, powdered X-ray diffraction, Raman spectroscopy, Zeta potential measurements and UV-Visible spectroscopic techniques. The as-synthesized gold-graphene composite was effectively utilized as catalyst for decolorization of 4 important textile and laser dyes. The integration of gold nanoparticles (AuNPs) with high surface area graphene has enhanced the catalytic activity of AuNPs. This enhanced activity is attributed to the synergistic interplay of pristine gold's electronic relay and π-π stacking of graphene with the dyes. This is evident when the Rhodamine B (RB) reduction rate of the composite is nearly twice faster than that of commercial citrate capped AuNPs of similar size. In case of Methylene blue (MB) the rate of reduction is 17,000 times faster than uncatalyzed reaction. This synthetic method opens door to laser ablation based fabrication of metal catalysts on graphene for improved performance without the aid of linkers and surfactants.

  17. Theoretical Models for the Quantification of Lung Injury Using Ventilation and Perfusion Distributions

    Directory of Open Access Journals (Sweden)

    B. S. Brook

    2009-01-01

    Full Text Available This paper describes two approaches to modelling lung disease: one based on a multi-compartment statistical model with a log normal distribution of ventilation perfusion ratio (V˙/Q˙ values; and the other on a bifurcating tree which emulates the anatomical structure of the lung. In the statistical model, the distribution becomes bimodal, when the V˙/Q˙ values of a randomly selected number of compartments are reduced by 85% to simulate lung disease. For the bifurcating tree model a difference in flow to the left and right branches coupled with a small random variation in flow ratio between generations results in a log normal distribution of flows in the terminal branches. Restricting flow through branches within the tree to simulate lung disease transforms this log normal distribution to a bi-modal one. These results are compatible with those obtained from experiments using the multiple inert gas elimination technique, where log normal distributions of V˙/Q˙ ratio become bimodal in the presence of lung disease.

  18. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

    Science.gov (United States)

    Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

    2017-01-01

    Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

  19. Characterization of free breathing patterns with 5D lung motion model

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Tianyu; Lu Wei; Yang Deshan; Mutic, Sasa; Noel, Camille E.; Parikh, Parag J.; Bradley, Jeffrey D.; Low, Daniel A. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri 63110 (United States)

    2009-11-15

    Purpose: To determine the quiet respiration breathing motion model parameters for lung cancer and nonlung cancer patients. Methods: 49 free breathing patient 4DCT image datasets (25 scans, cine mode) were collected with simultaneous quantitative spirometry. A cross-correlation registration technique was employed to track the lung tissue motion between scans. The registration results were applied to a lung motion model: X-vector=X-vector{sub 0}+{alpha}-vector{beta}-vector f, where X-vector is the position of a piece of tissue located at reference position X-vector{sub 0} during a reference breathing phase (zero tidal volume v, zero airflow f). {alpha}-vector is a parameter that characterizes the motion due to air filling (motion as a function of tidal volume v) and {beta}-vector is the parameter that accounts for the motion due to the imbalance of dynamical stress distributions during inspiration and exhalation that causes lung motion hysteresis (motion as a function of airflow f). The parameters {alpha}-vector and {beta}-vector together provide a quantitative characterization of breathing motion that inherently includes the complex hysteresis interplay. The {alpha}-vector and {beta}-vector distributions were examined for each patient to determine overall general patterns and interpatient pattern variations. Results: For 44 patients, the greatest values of |{alpha}-vector| were observed in the inferior and posterior lungs. For the rest of the patients, |{alpha}-vector| reached its maximum in the anterior lung in three patients and the lateral lung in two patients. The hysteresis motion {beta}-vector had greater variability, but for the majority of patients, |{beta}-vector| was largest in the lateral lungs. Conclusions: This is the first report of the three-dimensional breathing motion model parameters for a large cohort of patients. The model has the potential for noninvasively predicting lung motion. The majority of patients exhibited similar |{alpha}-vector| maps

  20. The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model

    Directory of Open Access Journals (Sweden)

    Pirofski Liise-Anne

    2007-01-01

    Full Text Available Abstract Background Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY have been implicated in the pathogenesis of pneumococcal pneumonia. Methods To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice. Results In bronchoalveolar lavages (BAL, total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues. Conclusion The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.

  1. Phosphine oxide surfactants revisited.

    Science.gov (United States)

    Stubenrauch, Cosima; Preisig, Natalie; Laughlin, Robert G

    2016-04-01

    This review summarizes everything we currently know about the nonionic surfactants alkyl dimethyl (C(n)DMPO) and alkyl diethyl (C(n)DEPO) phosphine oxide (PO surfactants). The review starts with the synthesis and the general properties (Section 2) of these compounds and continues with their interfacial properties (Section 3) such as surface tension, surface rheology, interfacial tension and adsorption at solid surfaces. We discuss studies on thin liquid films and foams stabilized by PO surfactants (Section 4) as well as studies on their self-assembly into lyotropic liquid crystals and microemulsions, respectively (Section 5). We aim at encouraging colleagues from both academia and industry to take on board PO surfactants whenever possible and feasible because of their broad variety of excellent properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

    Science.gov (United States)

    Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

    2017-08-01

    The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P intelligent diagnosis tool for lung cancer.

  3. The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury.

    Science.gov (United States)

    Zhou, Yan; Zhou, Xinqiao; Zhou, Wenjuan; Pang, Qingfeng; Wang, Zhiping

    2018-01-01

    To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (Pex vivo lungs.

  4. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    International Nuclear Information System (INIS)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

    2010-01-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  5. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  6. Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome.

    Science.gov (United States)

    Salvesen, Bodil; Curstedt, Tore; Mollnes, Tom Eirik; Saugstad, Ola Didrik

    2014-01-01

    Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome. © 2013 S. Karger AG, Basel.

  7. Metabolism of exogenously administered natural surfactant in the newborn lamb

    Energy Technology Data Exchange (ETDEWEB)

    Glatz, T.; Ikegami, M.; Jobe, A.

    1982-09-01

    (/sup 3/H)-Palmitate labeled natural lamb surfactant and free (/sup 14/C)-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to 96 h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent t 1/2 of phosphatidylcholine in the whole lung of 6.0 days. This half-life can be interpreted only as a rough estimate. Appearance of considerable (/sup 3/H) labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered (/sup 14/C)-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered (3H) and (14C) were found in pulmonary alveolar macrophages.

  8. Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis

    NARCIS (Netherlands)

    Noah, TL; Murphy, PC; Alink, JJ; Leigh, MW; Hull, WM; Stahlman, MT; Whitsett, JA

    2003-01-01

    The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway

  9. The late administration of surfactant | Ballot | South African Medical ...

    African Journals Online (AJOL)

    Current recommendations for surfactant replacement therapy (SRT) in the treatment of hyaline membrane disease (HMD) are to administer the drug as soon as possible after starting ventilation in order to prevent ventilator lung damage. We present a review of 18 infants (gestational age 32,4 ± 1,9 weeks and birth weight 1 ...

  10. NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction

    International Nuclear Information System (INIS)

    Wennberg, Berit M.; Baumann, Pia; Gagliardi, Giovanna

    2011-01-01

    Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/β = 3 Gy was used and the USC parameters used were: α/β = 3 Gy, D 0 = 1.0 Gy, n = 10, α 0.206 Gy-1 and d T = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether 'high doses to small volumes' or 'low doses to large volumes' are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D 50 = 20 Gy n = 0.93 with LQ correction and n 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling

  11. Real-time computed tomography fluoroscopy-guided solitary lung tumor model in a rabbit.

    Science.gov (United States)

    Choi, Byeong Hyeon; Young, Hwan Seok; Quan, Yu Hua; Rho, Ji Yun; Eo, Jae Seon; Han, Kook Nam; Choi, Young Ho; Kim, Hyun Koo

    2017-01-01

    Preclinical studies of lung cancer require suitable large-animal models to allow evaluation and development of surgical and interventional techniques. We assessed the feasibility and safety of a novel rabbit lung cancer model of solitary tumors, in which real-time computed tomography fluoroscopy is used to guide inoculation of VX2 carcinoma single-cell suspensions. Thirty-eight rabbits were divided into four groups according to the volume of the VX2 tissue or cell suspension, the volume of lipiodol, the volume of Matrigel, and the injection needle size. The mixtures were percutaneously injected into rabbit lungs under real-time computed tomography fluoroscopy guidance. Two weeks later, VX2 lung carcinomas were confirmed via positron emission tomography/computed tomography, necropsy, and histology. Real-time computed tomography fluoroscopy allowed the precise inoculation of the tumor cell suspensions containing lipiodol, while the use of Matrigel and a small needle prevented leakage of the suspensions into the lung parenchyma. Solitary lung tumors were successfully established in rabbits (n = 22) inoculated with single-cell suspensions (150 μL), lipiodol (150 μL), and Matrigel (150 μL) using a 26-gauge needle. This combination was determined to be optimal. Pneumothorax was observed in only two of the 38 rabbits (5.3%), both of which survived to the end of the study without any intervention. Real-time computed tomography fluoroscopy-guided inoculation of VX2 single-cell suspensions with lipiodol and Matrigel using a small needle is an easy and safe method to establish solitary lung tumors in rabbits.

  12. Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

    2013-07-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

  13. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    Science.gov (United States)

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

  14. EFFECTS OF CONSTRICTION IN A MECHANICAL MODEL OF LUNG PARENCHYMA

    Directory of Open Access Journals (Sweden)

    Clara Ionescu

    2011-02-01

    Full Text Available The demands on materials’ properties, for medical purposes, largely depend on the site of application and the function it has to restore. Ideally a replacement material should mimic the living tissue from a mechanical, chemical, biological, and functional point of view. The estimation of the mechanical characteristics of blood vessel walls, the values of modulus of elasticity and the coefficient of transversal strain serve to determine some aspects of reconstruction of blood vessels. The tissue growth, the blood clotting and the affecting blood elements are influenced by surface energy. In this study, we address the possibility to investigate the mechanical properties of the airways in a simulation study of the human lungs.

  15. Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs influences their oxidative and pro-inflammatory potential in vitro

    Directory of Open Access Journals (Sweden)

    Gasser Michael

    2012-05-01

    Full Text Available Abstract Background Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs. Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i human monocyte derived macrophages (MDM monocultures, and (ii a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH2 and carboxyl (−COOH surface modifications. Results Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α. In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8 was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. Conclusions The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary

  16. Equation Discovery for Model Identification in Respiratory Mechanics of the Mechanically Ventilated Human Lung

    Science.gov (United States)

    Ganzert, Steven; Guttmann, Josef; Steinmann, Daniel; Kramer, Stefan

    Lung protective ventilation strategies reduce the risk of ventilator associated lung injury. To develop such strategies, knowledge about mechanical properties of the mechanically ventilated human lung is essential. This study was designed to develop an equation discovery system to identify mathematical models of the respiratory system in time-series data obtained from mechanically ventilated patients. Two techniques were combined: (i) the usage of declarative bias to reduce search space complexity and inherently providing the processing of background knowledge. (ii) A newly developed heuristic for traversing the hypothesis space with a greedy, randomized strategy analogical to the GSAT algorithm. In 96.8% of all runs the applied equation discovery system was capable to detect the well-established equation of motion model of the respiratory system in the provided data. We see the potential of this semi-automatic approach to detect more complex mathematical descriptions of the respiratory system from respiratory data.

  17. Explanatory models of black lung: understanding the health-related behavior of Appalachian coal miners.

    Science.gov (United States)

    Friedl, J

    1982-03-01

    Many retired coal miners who are eligible for care in a black lung treatment center at little or no cost to themselves do not enter into available programs or discontinue soon after beginning therapy. Reasons for this behavior are related to the prevalent beliefs among Appalachians concerning the course of black lung and the appropriate treatment for it. The miners' health beliefs are clearly at odds with those of the health care providers who work in the centers. Using the concept of explanatory model, popular and professional health cultures are analyzed, focusing on course of disease, sick role, appropriate treatment, and expected outcome. Differences in explanatory models are discussed with regard to implications for the organization and delivery of care to retired coal miners with black lung.

  18. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    International Nuclear Information System (INIS)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

    2014-01-01

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

  19. The role of neutrophil myeloperoxidase in models of lung tumor development.

    Science.gov (United States)

    Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  20. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  1. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Directory of Open Access Journals (Sweden)

    Amy L. Rymaszewski

    2014-05-01

    Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  2. Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming.

    Science.gov (United States)

    Mahapatra, Subhashree; Albrecht, Melanie; Baru, Abdul M; Sparwasser, Tim; Herrick, Christina; Dittrich, Anna M

    2015-10-01

    We have previously shown that T helper type 2 (Th2)-polarized airway inflammation can facilitate priming to new antigens in the lungs, which we called "collateral priming". To investigate whether allergic skin inflammation can also facilitate priming toward new antigens, we developed an allergic skin inflammation model based on an allergic lung inflammation model. Mice were sensitized intraperitoneally toward the primary antigen, ovalbumin. Challenge was subsequently performed intranasally or epicutaneously with ovalbumin and a secondary antigen, keyhole limpet hemocyanin (KLH). Re-challenge consisted of local application of either antigen alone. Analysis of KLH-specific antibody responses, KLH-specific cytokines, and local inflammation demonstrated tolerance induction toward the secondary antigen in the skin, whereas in the lung priming had occurred. Flow-cytometric analysis revealed increased numbers of regulatory T cells (Tregs), increased cytotoxic T lymphocyte antigen-4 (CTLA-4) expression, and an enhanced suppressive capacity of Tregs from skin-draining lymph nodes when compared with Tregs from the lung-draining lymph nodes. Furthermore, depletion of Tregs resulted in restoration of collateral priming in the skin. These results demonstrate crucial local differences between the Treg function in the skin and lung to repetitive antigen exposure, which can decisively influence the immune response toward new antigens.

  3. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Claude Jourdan Le Saux

    Full Text Available The emergence of diseases associated with telomere dysfunction, including AIDS, aplastic anemia and pulmonary fibrosis, has bolstered interest in telomerase activators. We report identification of a new small molecule activator, GRN510, with activity ex vivo and in vivo. Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice. Treatment with GRN510 at 10 mg/kg/day activated telomerase 2-4 fold both in hematopoietic progenitors ex vivo and in bone marrow and lung tissue in vivo, respectively. Telomerase activation was countered by co-treatment with Imetelstat (GRN163L, a potent telomerase inhibitor. In this model of bleomycin-induced fibrosis, treatment with GRN510 suppressed the development of fibrosis and accumulation of senescent cells in the lung via a mechanism dependent upon telomerase activation. Treatment of small airway epithelial cells (SAEC or lung fibroblasts ex vivo with GRN510 revealed telomerase activating and replicative lifespan promoting effects only in the SAEC, suggesting that the mechanism accounting for the protective effects of GRN510 against induced lung fibrosis involves specific types of lung cells. Together, these results support the use of small molecule activators of telomerase in therapies to treat idiopathic pulmonary fibrosis.

  4. Analysis of the lung cancer mortality in Mayak worker cohort with a model of carcinogenesis

    International Nuclear Information System (INIS)

    Jacob, V.; Jacob, P.; Kusnetzova, I.

    2004-01-01

    Lung cancer mortality in the Mayak worker cohort is analysed with the two stage clonal expansion (TSCE) model of carcinogenesis. Mayak production association includes a nuclear reactor, radiochemical plant and plutonium production plant. Reactor workers were exposed to external g-ray and neutron exposures, and workers in the radiochemical and plutonium facilities additionally to internal exposures due to plutonium inhalant ion. the cohort used in this study involves male nuclear workers for whom plutonium measurements and smoking information (smoker/non-smoker) exists and with health follow-up to the end of 1999. A Subcohort with 5421 workers and 274 lung cancer deaths is analysed. Within the TSCE model, an action of radiation was assumed both in initiation and promotion. specific emphasis was given to the distinction of the effects of external and internal exposures. The baseline lung cancer mortality rate was derived from the cohort itself. Using the smoking information significantly increased the quality of the fit. Analysis showed no effect of radiation on transformation. Two models are found to five equally good fit of the data. Both models have a linear dose dependence in TSCE-model parameters for external and internal radiation. Both models have linear dependence either initiation or promotion on birth year effect. It is found that most of the lung cancer cases are due to plutonium inhalation. The estimated excess relative risk per unit dose due to the plutonium a particles is 0.13/Sv, in both models. For the g-ray component, the present analysis gives an excess relative risk for lung cancer mortality of 0.02/Sv, in both models. Resulting risk for plutonium exposures is compatible with the radiation weighting factor 20. In general no strong dose or dose-rate effects were observed within the cohort. (Author)

  5. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  6. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat......To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...

  7. Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent.

    Science.gov (United States)

    Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar; Green, Francis; Ling, Chang-Chun; Veldhuizen, Ruud; Ghandorah, Salim; Amrein, Matthias

    2018-04-01

    Pulmonary surfactant forms a cohesive film at the alveolar air-lung interface, lowering surface tension, and thus reducing the work of breathing and preventing atelectasis. Surfactant function becomes impaired during inflammation due to degradation of the surfactant lipids and proteins by free radicals. In this study, we examine the role of reactive nitrogen (RNS) and oxygen (ROS) species on surfactant function with and without physiological cholesterol levels (5-10%). Surface activity was assessed in vitro in a captive bubble surfactometer (CBS). Surfactant chemistry, monolayer fluidity and thermodynamic behavior were also recorded before and after oxidation. We report that physiologic amounts of cholesterol combined with oxidation results in severe impairment of surfactant function. We also show that surfactant polyunsaturated phospholipids are the most susceptible to oxidative alteration. Membrane thermodynamic experiments showed significant surfactant film stiffening after free radical exposure in the presence of cholesterol. These results point to a previously unappreciated role for cholesterol in amplifying defects in surface activity caused by oxidation of pulmonary surfactant, a finding that may have implications for treating several lung diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease

    Science.gov (United States)

    Jobe, Alan H.

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD. PMID:26301222

  9. In silico modelling and validation of differential expressed proteins in lung cancer

    Directory of Open Access Journals (Sweden)

    Bhagavathi S

    2012-05-01

    Full Text Available Objective: The present study aims predict the three dimensional structure of three major proteins responsible for causing Lung cancer. Methods: These are the differentially expressed proteins in lung cancer dataset. Initially, the structural template for these proteins is identified from structural database using homology search and perform homology modelling approach to predict its native 3D structure. Three-dimensional model obtained was validated using Ramachandran plot analysis to find the reliability of the model. Results: Four proteins were differentially expressed and were significant proteins in causing lung cancer. Among the four proteins, Matrixmetallo proteinase (P39900 had a known 3D structure and hence was not considered for modelling. The remaining proteins Polo like kinase I Q58A51, Trophinin B1AKF1, Thrombomodulin P07204 were modelled and validated. Conclusions: The three dimensional structure of proteins provides insights about the functional aspect and regulatory aspect of the protein. Thus, this study will be a breakthrough for further lung cancer related studies.

  10. Development of a dynamic model for the lung lobes and airway tree in the NCAT phantom

    Science.gov (United States)

    Garrity, J. M.; Segars, W. P.; Knisley, S. B.; Tsui, B. M. W.

    2003-06-01

    The four-dimensional (4-D) NCAT phantom was developed to realistically model human anatomy based on the visible human data and cardiac and respiratory motions based on 4-D tagged magnetic resonance imaging and respiratory-gated CT data from normal human subjects. Currently, the 4-D NCAT phantom does not include the airway tree or its motion within the lungs. Also, each lung is defined with a single surface; the individual lobes are not distinguished. The authors further the development of the phantom by creating dynamic models for the individual lung lobes and for the airway tree in each lobe. NURBS surfaces for the lobes and an initial airway tree model (/spl sim/ 4 generations) were created through manual segmentation of the visible human data. A mathematical algorithm with physiological constraints was used to extend the original airway model to fill each lobe. For each parent airway branch inside a lobe, the algorithm extends the airway tree by creating two daughter branches modeled with cylindrical tubes. Parameters for the cylindrical tubes such as diameter, length, and angle are constrained based on flow parameters and available lung space.

  11. Modeling the effects of surfactant, hardness, and natural organic matter on deposition and mobility of silver nanoparticles in saturated porous media.

    Science.gov (United States)

    Park, Chang Min; Heo, Jiyong; Her, Namguk; Chu, Kyoung Hoon; Jang, Min; Yoon, Yeomin

    2016-10-15

    This study aims to provide insights into the mechanisms governing the deposition and retention of silver nanoparticles (AgNPs) in saturated porous media. Column experiments were conducted with quartz sand under saturated conditions to investigate the deposition kinetics of AgNPs, their mobility at different groundwater hardnesses (10-400 mg/L as CaCO3), and humic acid (HA, 0-50 mg/L as dissolved organic carbon [DOC]). An anionic surfactant, sodium dodecyl sulfate (SDS), was used as a dispersing agent to prepare a SDS-AgNPs suspension. The deposition kinetics of AgNPs were highly sensitive to the surfactant concentration, ionic strength, and cation type in solution. The breakthrough curves (BTCs) of SDS-AgNPs suggested that the transport and retention were influenced by groundwater hardness and HA. At low water hardness and high HA, high mobility of SDS-AgNPs was observed in saturated conditions. However, the retention of SDS-AgNPs increased substantially in very hard water with a low concentration of HA, because of a decreased primary energy barrier and the straining effect during the course of transport experiments. A modified clean-bed filtration theory and a two-site kinetic attachment model showed good fits with the BTCs of SDS-AgNPs. The fitted model parameters (katt and kstr) could be used successfully to describe that the retention behaviors were dominated by electrostatic and electrosteric repulsion, based on extended Derjaguin-Landau-Vaerwey-Overbeek calculations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Comparison of actual tidal volume in neonatal lung model volume control ventilation using three ventilators.

    Science.gov (United States)

    Toyama, H; Endo, Y; Ejima, Y; Matsubara, M; Kurosawa, S

    2011-07-01

    In neonates, small changes in tidal volumes (V(T)) may lead to complications. Previous studies have shown a significant difference between ventilator-measured tidal volume and tidal volume delivered (actual V(T)). We evaluated the accuracy of three different ventilators to deliver small V(T) during volume-controlled ventilation. We tested Servo 300, 840 ventilator and Evita 4 Neoflow ventilators with lung models simulating normal and injured neonatal lung compliance models. Gas volume delivered from the ventilator into the test circuit (V(TV)) and actual V(T) to the test lung were measured using Ventrak respiration monitors at set V(T) (30 ml). The gas volume increase of the breathing circuit was then calculated. Tidal volumes of the SV300 and PB840 in both lung models were similar to the set V(T) and the actual tidal volumes in the injured model (20.7 ml and 19.8 ml, respectively) were significantly less than that in the normal model (27.4 ml and 23.4 ml). PB840 with circuit compliance compensation could not improve the actual V(T). V(TV) of the EV4N in the normal and the injured models (37.8 ml and 46.6 ml) were markedly increased compared with set V(T), and actual V(T) were similar to set V(T) in the normal and injured model (30.2 ml and 31.9 ml, respectively). EV4N measuring V(T) close to the lung could match actual V(T) to almost the same value as the set V(T) however the gas volume of the breathing circuit was increased. If an accurate value for the patient's actual V(T) is needed, this V(T) must be measured by a sensor located between the Y-piece and the tracheal tube.

  13. Comparative In Vivo Efficacies of Tedizolid in Neutropenic versus Immunocompetent Murine Streptococcus pneumoniae Lung Infection Models.

    Science.gov (United States)

    Abdelraouf, Kamilia; Nicolau, David P

    2017-01-01

    Given that tedizolid exhibits substantial lung penetration, we hypothesize that it could achieve good efficacy against Streptococcus pneumoniae lung infections. We evaluated the pharmacodynamics of tedizolid for treatment of S. pneumoniae lung infections and compared the efficacies of tedizolid human-simulated epithelial lining fluid (ELF) exposures in immunocompetent and neutropenic murine lung infection models. ICR mice were rendered neutropenic via intraperitoneal cyclophosphamide injections and then inoculated intranasally with S. pneumoniae suspensions. Immunocompetent CBA/J mice were inoculated similarly. Single daily tedizolid doses were administered 4 h postinoculation (termed 0 h). Changes in log 10 CFU at 24 h compared with 0-h controls were estimated. Ratios of area under the free-drug concentration-time curve to MIC (fAUC 0-24 /MIC) required to achieve various efficacy endpoints against each isolate were estimated using the Hill equation. Tedizolid doses in neutropenic and immunocompetent mice that mimic the human-simulated ELF exposure were examined. Stasis, 1-log reduction, and 2-log reduction were achieved at fAUC 0-24 /MIC of 8.96, 24.62, and 48.34, respectively, in immunocompetent mice and 19.21, 48.29, and 103.95, respectively, in neutropenic mice. Tedizolid at 40 mg/kg of body weight/day and 55 mg/kg/day in immunocompetent and neutropenic mice, respectively, resulted in ELF AUC 0-24 comparable to that achieved in humans following a 200-mg once-daily clinical dose. These human-simulated ELF exposures were adequate to attain >2-log reduction in bacterial burden at 24 h in 3 out of 4 isolates in both models and 1.58- and 0.74-log reductions with the fourth isolate in immunocompetent and neutropenic mice, respectively. Tedizolid showed potent in vivo efficacy against S. pneumoniae in both immunocompetent and neutropenic lung infection models, which support its consideration for S. pneumoniae lung infections. Copyright © 2016 American Society for

  14. Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

    Science.gov (United States)

    Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

    2009-04-01

    Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

  15. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

    NARCIS (Netherlands)

    K. ten Haaf (Kevin); J. Jeon (Jihyoun); M.C. Tammemagi (Martin); S.S. Han (Summer); C.Y. Kong (Chung Yin); S.K. Plevritis (Sylvia); E. Feuer (Eric); H.J. de Koning (Harry); E.W. Steyerberg (Ewout W.); R. Meza (Rafael)

    2017-01-01

    textabstractBackground: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most

  16. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis

    DEFF Research Database (Denmark)

    Moser, Claus; van Gennip, Maria; Bjarnsholt, Thomas

    2009-01-01

    Moser C, van Gennip M, Bjarnsholt T, Jensen PO, Lee B, Hougen HP, Calum H, Ciofu O, Givskov M, Molin S, Hoiby N. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 2009; 117: 95-107. The dominant cause of premature...... death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes...... and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production...

  17. Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids

    Science.gov (United States)

    Grier, Bonnie L.; Waite, B. Moseley; Veldhuizen, Ruud A.; Possmayer, Fred; Yao, Li-Juan; Seeds, Michael C.

    2012-01-01

    Hydrolysis of surfactant phospholipids (PL) by secretory phospholipases A2 (sPLA2) contributes to surfactant damage in inflammatory airway diseases such as acute lung injury/acute respiratory distress syndrome. We and others have reported that each sPLA2 exhibits specificity in hydrolyzing different PLs in pulmonary surfactant and that the presence of hydrophilic surfactant protein A (SP-A) alters sPLA2-mediated hydrolysis. This report tests the hypothesis that hydrophobic SP-B also inhibits sPLA2-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): 1) washed ovine surfactant (OS) (pre- and postorganic extraction) compared with Survanta (protein poor), 2) Survanta supplemented with purified bovine SP-B (1–5%, wt/wt), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA2 (PLA2G1A) was significantly lower in the extracted OS, which contains SP-B, compared with Survanta (P = 0.005), which is SP-B poor. Hydrolysis of PG and PC in nonextracted OS, which contains all SPs, was lower than both Survanta and extracted OS. When Survanta was supplemented with 1% SP-B, PG and PC hydrolysis by PLA2G1B was significantly lower (P hydrolysis by both PLA2G1B and Group IIA sPLA2 (PLA2G2A). In films, PLA2G1B hydrolyzed surfactant PL monolayers at surface pressures ≤30 mN/m (P hydrolysis can occur. These results suggest the hydrophobic SP, SP-B, protects alveolar surfactant PL from hydrolysis mediated by multiple sPLA2 in both vesicles (alveolar subphase) and monomolecular films (air-liquid interface). PMID:22037357

  18. New mechanisms for phase separation in polymer-surfactant mixtures

    NARCIS (Netherlands)

    Currie, E.P.K.; Cohen Stuart, M.A.; Borisov, O.V.

    2000-01-01

    The cooperative association of ionic surfactants with polymer chains leads to quite novel features in the phase behaviour of polymer solutions. Using an analytic mean-field model, we analyze phase equilibria in solutions of neutral polymers mixed with ionic surfactants. We predict the possibilities

  19. Removal of cationic surfactant (CTAB from aqueous solution on to activated carbon obtained from corncob.

    Directory of Open Access Journals (Sweden)

    S. M. Yakout

    2009-05-01

    Full Text Available Direct and indirect releases of large quantities of surfactants to the environment may result in serious health and environmental problems. Therefore, surfactants should be removed from water before water is released to the environment or delivered for public use. Using powdered activated carbon (PAC as adsorbent may be an effective technique to remove surfactants. In this study, the removal of surfactants by PAC was investigated and the influencesof the operating parameters on the effectiveness on adsorption rate were studied. Cationic surfactant, Cetyl trimethyl ammonium bromide (CTAB was selected for the experiments. A series of batch experiments were performed to determine the sorption isotherms of surfactants to PAC. The results showed that carbon structure affect mainly on the surfactant adsorption. Surfactant equilibrium data fitted very well to the binary langmuir model. The pseudo first-,second- order and intraparticle diffusion kinetic models were applied. Both, the external mass transfer and intraparticle diffusion mechanisms involve in CTAB sorption.

  20. Stereological and biophysical characteristics of the ovine surfactant system and its changes caused by ovine pulmonary adenocarcinoma.

    Science.gov (United States)

    Jörger, Ariane; Acevedo, Christa; Busley, Diana; Ganter, Martin; Schmiedl, Andreas; Humann-Ziehank, Esther

    2017-10-01

    Surfactant covers the inner surface of lung alveoli and lowers the surface tension to prevent alveoli from collapsing. A lack of surfactant or its dysfunction causes dyspnea. The Jaagsiekte Sheep Retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA), whose typical clinical appearance is fluid running from nostrils. This fluid might contain surfactant as alveolar type II pneumocytes (AEII) are target cells for JSRV. Therefore, the progressive dyspnea during OPA might be caused partially by surfactant alterations. Bronchoalveolar and intracellular surfactant as well as the biophysical function of surfactant were analyzed in OPA sheep and controls. Transmission electron microscopy and stereological methods were used to characterize ultrastructure and distribution of surfactant subtypes in AEII and bronchoalveolar lavage fluid (BALF). Pulsating Bubble Surfactometry enabled studying the surface activity of the surfactant, while lung volumes were detected by computed tomography. The methods used are suitable to determine intraalveolar and intracellular surfactant subtypes in OPA sheep and controls. OPA sheep showed more lamellar body-like forms, multivesicular vesicles and tubular myelin in BALF compared to controls. These higher amounts of active surfactant subtypes might be a consequence of a higher surfactant production and release. Surfactant subtypes in AEII of OPA sheep showed smaller and more immature lamellar bodies compared to controls. The surfactant surface activity of OPA sheep does not show obvious defects. In conclusion, the general quality of surfactant in OPA appears to be equivalent to surfactant produced in controls, however, dyspnea of OPA might be triggered by quantity of fluid production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Comparison of two lung clearance models based on the dissolution rates of oxidized depleted uranium

    International Nuclear Information System (INIS)

    Crist, K.C.

    1984-10-01

    An in-vitro dissolution study was conducted on two respirable oxidized depleted uranium samples. The dissolution rates generated from this study were then utilized in the International Commission on Radiological Protection Task Group lung clearance model and a lung clearance model proposed by Cuddihy. Predictions from both models based on the dissolution rates of the amount of oxidized depleted uranium that would be cleared to blood from the pulmonary region following an inhalation exposure were compared. It was found that the predictions made by both models differed considerably. The difference between the predictions was attributed to the differences in the way each model perceives the clearance from the pulmonary region. 33 references, 11 figures, 9 tables

  2. Comparison of two lung clearance models based on the dissolution rates of oxidized depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Crist, K.C.

    1984-10-01

    An in-vitro dissolution study was conducted on two respirable oxidized depleted uranium samples. The dissolution rates generated from this study were then utilized in the International Commission on Radiological Protection Task Group lung clearance model and a lung clearance model proposed by Cuddihy. Predictions from both models based on the dissolution rates of the amount of oxidized depleted uranium that would be cleared to blood from the pulmonary region following an inhalation exposure were compared. It was found that the predictions made by both models differed considerably. The difference between the predictions was attributed to the differences in the way each model perceives the clearance from the pulmonary region. 33 references, 11 figures, 9 tables.

  3. Modelling lung cancer due to radon and smoking in WISMUT miners: Preliminary results

    International Nuclear Information System (INIS)

    Bijwaard, H.; Dekkers, F.; Van Dillen, T.

    2011-01-01

    A mechanistic two-stage carcinogenesis model has been applied to model lung-cancer mortality in the largest uranium-miner cohort available. Models with and without smoking action both fit the data well. As smoking information is largely missing from the cohort data, a method has been devised to project this information from a case-control study onto the cohort. Model calculations using 256 projections show that the method works well. Preliminary results show that if an explicit smoking action is absent in the model, this is compensated by the values of the baseline parameters. This indicates that in earlier studies performed without smoking information, the results obtained for the radiation parameters are still valid. More importantly, the inclusion of smoking-related parameters shows that these mainly influence the later stages of lung-cancer development. (authors)

  4. Simulation of parametric model towards the fixed covariate of right censored lung cancer data

    Science.gov (United States)

    Afiqah Muhamad Jamil, Siti; Asrul Affendi Abdullah, M.; Kek, Sie Long; Ridwan Olaniran, Oyebayo; Enera Amran, Syahila

    2017-09-01

    In this study, simulation procedure was applied to measure the fixed covariate of right censored data by using parametric survival model. The scale and shape parameter were modified to differentiate the analysis of parametric regression survival model. Statistically, the biases, mean biases and the coverage probability were used in this analysis. Consequently, different sample sizes were employed to distinguish the impact of parametric regression model towards right censored data with 50, 100, 150 and 200 number of sample. R-statistical software was utilised to develop the coding simulation with right censored data. Besides, the final model of right censored simulation was compared with the right censored lung cancer data in Malaysia. It was found that different values of shape and scale parameter with different sample size, help to improve the simulation strategy for right censored data and Weibull regression survival model is suitable fit towards the simulation of survival of lung cancer patients data in Malaysia.

  5. Phase transitions in surfactant monolayers

    International Nuclear Information System (INIS)

    Casson, B.D.

    1998-01-01

    Two-dimensional phase transitions have been studied in surfactant monolayers at the air/water interface by sum-frequency spectroscopy and ellipsometry. In equilibrium monolayers of medium-chain alcohols C n H 2n+1 OH (n = 9-14) a transition from a two-dimensional crystalline phase to a liquid was observed at temperatures above the bulk melting point. The small population of gauche defects in the solid phase increased only slightly at the phase transition. A model of the hydrocarbon chains as freely rotating rigid rods allowed the area per molecule and chain tilt in the liquid phase to be determined. The area per molecule, chain tilt and density of the liquid phase all increased with increasing chain length, but for each chain length the density was higher than in a bulk liquid hydrocarbon. In a monolayer of decanol adsorbed at the air/water interface a transition from a two-dimensional liquid to a gas was observed. A clear discontinuity in the coefficient of ellipticity as a function of temperature showed that the transition is first-order. This result suggests that liquid-gas phase transitions in surfactant monolayers may be more widespread than once thought. A solid-liquid phase transition has also been studied in mixed monolayers of dodecanol with an anionic surfactant (sodium dodecyl sulphate) and with a homologous series of cationic surfactants (alkyltrimethylammonium bromides: C n TABs, n = 12, 14, 16). The composition and structure of the mixed monolayers was studied above and below the phase transition. At low temperatures the mixed monolayers were as densely packed as a monolayer of pure dodecanol in its solid phase. At a fixed temperature the monolayers under-went a first-order phase transition to form a phase that was less dense and more conformationally disordered. The proportion of ionic surfactant in the mixed monolayer was greatest in the high temperature phase. As the chain length of the C n TAB increased the number of conformational defects

  6. Calibration of lung counter using a CT model of Torso phantom and Monte Carlo method

    International Nuclear Information System (INIS)

    Zhang Binquan; Ma Jizeng; Yang Duanjie; Liu Liye; Cheng Jianping

    2006-01-01

    Tomography image of a Torso phantom was obtained from CT-Scan. The Torso phantom represents the trunk of an adult man that is 170 cm high and weight of 65 kg. After these images were segmented, cropped, and resized, a 3-dimension voxel phantom was created. The voxel phantom includes more than 2 million voxels, which size was 2.73 mm x 2.73 mm x 3 mm. This model could be used for the calibration of lung counter with Monte Carlo method. On the assumption that radioactive material was homogeneously distributed throughout the lung, counting efficiencies of a HPGe detector in different positions were calculated as Adipose Mass fraction (AMF) was different in the soft tissue in chest. The results showed that counting efficiencies of the lung counter changed up to 67% for 17.5 keV γ ray and 20% for 25 keV γ ray when AMF changed from 0 to 40%. (authors)

  7. Role of Lung-marginated Monocytes in an In Vivo Mouse Model of Ventilator-induced Lung Injury

    NARCIS (Netherlands)

    Wilson, M.; O'Dea, K.P.; Zhang, D.; Shearman, A.D.; Rooijen, van N.; Takata, M.

    2009-01-01

    Rationale: Recruited leukocytes play an important role in ventilator-induced lung injury, although studies have focused predominantly on neutrophils. Inflammatory subset Gr-1(high) monocytes are recruited to sites of inflammation and have been implicated in acute lung injury induced by systemic

  8. Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

    Directory of Open Access Journals (Sweden)

    Yongchun ZHOU

    2012-08-01

    Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

  9. Target dose conversion modeling from pencil beam (PB) to Monte Carlo (MC) for lung SBRT

    International Nuclear Information System (INIS)

    Zheng, Dandan; Zhu, Xiaofeng; Zhang, Qinghui; Liang, Xiaoying; Zhen, Weining; Lin, Chi; Verma, Vivek; Wang, Shuo; Wahl, Andrew; Lei, Yu; Zhou, Sumin; Zhang, Chi

    2016-01-01

    A challenge preventing routine clinical implementation of Monte Carlo (MC)-based lung SBRT is the difficulty of reinterpreting historical outcome data calculated with inaccurate dose algorithms, because the target dose was found to decrease to varying degrees when recalculated with MC. The large variability was previously found to be affected by factors such as tumour size, location, and lung density, usually through sub-group comparisons. We hereby conducted a pilot study to systematically and quantitatively analyze these patient factors and explore accurate target dose conversion models, so that large-scale historical outcome data can be correlated with more accurate MC dose without recalculation. Twenty-one patients that underwent SBRT for early-stage lung cancer were replanned with 6MV 360° dynamic conformal arcs using pencil-beam (PB) and recalculated with MC. The percent D95 difference (PB-MC) was calculated for the PTV and GTV. Using single linear regression, this difference was correlated with the following quantitative patient indices: maximum tumour diameter (MaxD); PTV and GTV volumes; minimum distance from tumour to soft tissue (dmin); and mean density and standard deviation of the PTV, GTV, PTV margin, lung, and 2 mm, 15 mm, 50 mm shells outside the PTV. Multiple linear regression and artificial neural network (ANN) were employed to model multiple factors and improve dose conversion accuracy. Single linear regression with PTV D95 deficiency identified the strongest correlation on mean-density (location) indices, weaker on lung density, and the weakest on size indices, with the following R 2 values in decreasing orders: shell2mm (0.71), PTV (0.68), PTV margin (0.65), shell15mm (0.62), shell50mm (0.49), lung (0.40), dmin (0.22), GTV (0.19), MaxD (0.17), PTV volume (0.15), and GTV volume (0.08). A multiple linear regression model yielded the significance factor of 3.0E-7 using two independent features: mean density of shell2mm (P = 1.6E-7) and PTV volume

  10. LUNG AND LIVER CHANGES DUE TO THE INDUCTION OF CIRRHOSIS IN TWO EXPERIMENTAL MODELS

    Directory of Open Access Journals (Sweden)

    Renata Salatti FERRARI

    2013-09-01

    Full Text Available Context To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl4 and bile duct ligation (BDL. Methods Twenty-four male Wistar rats were divided into a control group (CO and an experimental group (EX. We evaluated the liver transaminases (AST, ALT, AP, arterial blood gases (PaO2, PCO2 and SpO2 and lipid peroxidation by TBARS (substances that react to thiobarbituric acid and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD and histology of lung tissue and liver. Results There were significant differences in AST, ALT, ALP and PaO2 between CO group and EX group (P<0.05. The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05, respectively. In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Conclusion Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange.

  11. Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

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    Pullamsetti Soni S

    2008-12-01

    Full Text Available Abstract Background New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole. Methods Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole. Results Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight. At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension. Conclusion Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.

  12. Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer

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    Du, Shisuo; Lockamy, Virginia [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Zhou, Lin [Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China); Xue, Christine; LeBlanc, Justin [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Glenn, Shonna [Xstrahl, Inc, Suwanee, Georgia (United States); Shukla, Gaurav; Yu, Yan; Dicker, Adam P.; Leeper, Dennis B. [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Lu, You [Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China); Lu, Bo, E-mail: bo.lu@jefferson.edu [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2016-11-01

    Purpose: To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. Methods and Materials: A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. Results: The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. Conclusions: It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics.

  13. Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental

    DEFF Research Database (Denmark)

    Taeusch, H William; de la Serna, Jorge Bernardino; Perez-Gil, Jesus

    2005-01-01

    The rate of change of surface pressure, pi, in a Langmuir trough following the deposition of surfactant suspensions on subphases containing serum, with or without polymers, is used to model a likely cause of surfactant inactivation in vivo: inhibition of surfactant adsorption due to competitive a...

  14. Surfactant therapy for maternal blood aspiration: an unusual cause of neonatal respiratory distress syndrome.

    Science.gov (United States)

    Celik, Istemi Han; Demirel, Gamze; Canpolat, Fuat Emre; Erdeve, Omer; Dilmen, Ugur

    2012-10-01

    Surfactant replacement therapy is the main treatment of neonatal respiratory distress syndrome. However, surfactant therapy has been shown to be effective in the treatment of other diseases causing neonatal respiratory diseases such as pulmonary hemorrhage, meconium aspiration syndrome, pneumonia/sepsis, pulmonary edema or acute lung injury resulting a secondary surfactant deficiency (SSD). Rarely, as like as in the present patient, exogenous blood aspiration such as breast milk or formula aspiration may lead to SSD. Blood in alveolus leads to a significant biochemical and functional disturbance of the surfactant system and inhibits surfactant production. Here, the authors report a preterm infant of 33 wk gestational age with secondary surfactant deficiency due to maternal blood aspiration because of abruptio placentae. She was received two courses of beractant, a natural bovine surfactant, therapy in 24 h. She was extubated on second day and did not require oxygen on 4(th) day. To the authors' knowledge, this is the first reported case of SSD due to maternal blood aspiration treated with surfactant. In conditions such as abruptio placentae, infant should be protected from blood aspiration and if respiratory distress occurs, surfactant inhibition and need for surfactant administration should be considered.

  15. Meconium Impairs Pulmonary Surfactant by a Combined Action of Cholesterol and Bile Acids

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Echaide, Mercedes; Cruz, Antonio; Taeusch, H. William; Perez-Gil, Jesus

    2011-01-01

    Mechanisms for meconium-induced inactivation of pulmonary surfactant as part of the meconium aspiration syndrome in newborn infants, to our knowledge, are not clearly understood. Here we have studied the biophysical mechanisms of how meconium affects surface activity of pulmonary surfactant and whether the membrane-perturbing effects of meconium can be mimicked by exposure of surfactant to a mixture of bile acids and cholesterol. Surface activity of pulmonary surfactant complexes purified from animal lungs was analyzed in the absence and in the presence of meconium in standard surface balances and in a captive bubble surfactometer. We have also evaluated accumulation of surfactant at the air-liquid interface by what we believe to be a novel microtiter plate fluorescent assay, and the effect of meconium components on surfactant membrane fluidity using Laurdan fluorescence thermotropic profiles and differential scanning calorimetry thermograms. Rapid interfacial adsorption, low surface tension upon film compression, efficient film replenishment upon expansion, and thermotropic properties of surfactant complexes are all adversely affected by meconium, and, in a similar manner, they are affected by cholesterol/taurocholate mixtures but not by taurocholate alone. We conclude that inhibition of surfactant by meconium can be mimicked by a bile salt-promoted incorporation of excess cholesterol into surfactant complexes. These results highlight the potential pathogenic role of cholesterol-mobilizing agents as a crucial factor resulting in cholesterol induced alterations of structure and dynamics of surfactant membranes and films. PMID:21281579

  16. A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

    2015-10-05

    Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

  17. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

    Full Text Available Abstract Background Proline-rich tyrosine kinase 2 (Pyk2 is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1 myeloperoxidase content in lung tissues, 2 vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3 the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and

  18. [Economic impact of lung cancer screening in France: A modeling study].

    Science.gov (United States)

    Gendarme, S; Perrot, É; Reskot, F; Bhoowabul, V; Fourre, G; Souquet, P-J; Milleron, B; Couraud, S

    2017-09-01

    The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported. This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%. According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs. Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Estimating the contribution of surfactant replacement therapy to the alveolar pool: an in vivo study based on 13 C natural abundance in rabbits.

    Science.gov (United States)

    Giambelluca, Sonia; Ricci, Francesca; Simonato, Manuela; Correani, Alessio; Casiraghi, Costanza; Storti, Matteo; Cogo, Paola; Salomone, Fabrizio; Carnielli, Virgilio Paolo

    2018-04-06

    Variation of the isotopic abundance of selected nutrients and molecules have been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of 13 C/ 12 C ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The 13 C content of DSPC-PA was measured by Isotope Ratio Mass Spectrometry. The mean DSPC-PA 13 C/ 12 C ratio of the 7 lots of poractant alfa was -18.8 ‰ with a SD of 0.1 ‰ [Range: -18.9 ‰; -18.6 ‰]. The mean 13 C/ 12 C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8±1.2 ‰ [Range: -31.7 ‰; -25.7 ‰]. The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits and it ranged from 83.9 to 89.6 %. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13 C and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants. This article is protected by copyright. All rights reserved.

  20. Predictive accuracy of the PanCan lung cancer risk prediction model - external validation based on CT from the Danish Lung Cancer Screening Trial

    International Nuclear Information System (INIS)

    Winkler Wille, Mathilde M.; Dirksen, Asger; Riel, Sarah J. van; Jacobs, Colin; Scholten, Ernst T.; Ginneken, Bram van; Saghir, Zaigham; Pedersen, Jesper Holst; Hohwue Thomsen, Laura; Skovgaard, Lene T.

    2015-01-01

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. (orig.)

  1. Predictive accuracy of the PanCan lung cancer risk prediction model - external validation based on CT from the Danish Lung Cancer Screening Trial

    Energy Technology Data Exchange (ETDEWEB)

    Winkler Wille, Mathilde M.; Dirksen, Asger [Gentofte Hospital, Department of Respiratory Medicine, Hellerup (Denmark); Riel, Sarah J. van; Jacobs, Colin; Scholten, Ernst T.; Ginneken, Bram van [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Saghir, Zaigham [Herlev Hospital, Department of Respiratory Medicine, Herlev (Denmark); Pedersen, Jesper Holst [Copenhagen University Hospital, Department of Thoracic Surgery, Rigshospitalet, Koebenhavn Oe (Denmark); Hohwue Thomsen, Laura [Hvidovre Hospital, Department of Respiratory Medicine, Hvidovre (Denmark); Skovgaard, Lene T. [University of Copenhagen, Department of Biostatistics, Koebenhavn Oe (Denmark)

    2015-10-15

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. (orig.)

  2. High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Somin Lee

    Full Text Available Inorganic phosphate (Pi is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD in a mouse model of adenocarcinoma. K-rasLA1 mice were fed a normal diet (0.3% Pi or an HPD (1% Pi for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis, changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention.

  3. Automatic Lung Tumor Segmentation on PET/CT Images Using Fuzzy Markov Random Field Model

    Directory of Open Access Journals (Sweden)

    Yu Guo

    2014-01-01

    Full Text Available The combination of positron emission tomography (PET and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice’s similarity coefficient (DSC was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.

  4. Modeling intention to participate in face-to-face and online lung cancer support groups.

    Science.gov (United States)

    Xu, Yangmu; Testerman, Laura S; Owen, Jason E; Bantum, Erin O; Thornton, Andrea A; Stanton, Annette L

    2014-05-01

    Lung cancer patients and survivors are significantly less likely to use support groups than those with other cancers. In this study, we evaluated the utility and specificity of the Behavioral Model for Vulnerable Populations for modeling intention to participate in face-to-face (F2F) and online lung cancer support groups. Adults diagnosed with lung cancer (n = 230) completed measures assessing predisposing, enabling, and need factors associated with intention to use support services. Intention to join a F2F support group (found among 36.4% of survivors) was associated with positive attitude about F2F support groups, fewer perceived time constraints, less travel time from the clinic, and not having enough social support. Intention to join an online support group (34% of survivors) was associated with having more positive attitudes about online support, greater use of avoidance coping strategies, more comfort using computers, and fewer perceived time constraints. Demographics, medical history, health status, and psychological status were not associated with intention to join either type of group. Reducing barriers to participation and addressing attitudes about support services may be the most effective ways to increase utilization of lung cancer support services. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

    Science.gov (United States)

    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Surfactant therapy for acute respiratory distress in infants

    Directory of Open Access Journals (Sweden)

    Corrado Moretti

    2014-06-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains the primary indication for admission to paediatric intensive care units and accounts for significant mortality, morbidity and resource utilization. Respiratory infections, in particular pneumonia and severe bronchiolitis, are the most common causes of respiratory failure requiring mechanical ventilation in infants and children. This paper reviews the pathophysiology of ARDS and the management of paediatric patients with acute lung injury. Data indicate that adoption of a lung protective ventilation with low tidal volumes and of an open-lung ventilation strategy, characterized by sufficient positive end-expiratory pressure (PEEP to avoid atelectasis, provides the greatest likelihood of survival and minimizes lung injury. The relative benefits of strategies such as high frequency oscillatory ventilation (HFOV, inhaled nitric oxide (iNO, recruiting manoeuvres and prone position are also considered. Moreover this article examines exogenous lung surfactant replacement therapy and its efficacy in the treatment of paediatric ARDS. In infants and children with acute lung injury the endogenous surfactant system is not only deficient, as observed in preterm infants, but altered via a variety of other mechanisms like inhibition and dysfunction. All factors contribute to the altered physiology seen in ARDS. The role of exogenous surfactant in lung injury beyond the neonatal period is therefore more complex and its limited efficacy may be related to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution or, simply, an inability of the drug to counteract the underlying pathophysiology of ARDS. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS, however some studies have shown that this therapy can improve oxygenation and decrease mortality in some specific

  7. The interrelationship of recruitment maneuver at birth, antenatal steroids, and exogenous surfactant on compliance and oxygenation in preterm lambs.

    Science.gov (United States)

    Tingay, David G; Rajapaksa, Anushi; McCall, Karen; Zonneveld, Cornelis E E; Black, Don; Perkins, Elizabeth; Sourial, Magdy; Lavizzari, Anna; Davis, Peter G

    2016-06-01

    To describe the interrelationship between antenatal steroids, exogenous surfactant, and two approaches to lung recruitment at birth on oxygenation and respiratory system compliance (Cdyn) in preterm lambs. Lambs (n = 63; gestational age 127 ± 1 d) received either surfactant at 10-min life (Surfactant), antenatal corticosteroids (Steroid), or neither (Control). Within each epoch lambs were randomly assigned to a 30-s 40 cmH2O sustained inflation (SI) or an initial stepwise positive end-expiratory pressure (PEEP) open lung ventilation (OLV) maneuver at birth. All lambs then received the same management for 60-min with alveolar-arterial oxygen difference (AaDO2) and Cdyn measured at regular time points. Overall, the OLV strategy improved Cdyn and AaDO2 (all epochs except Surfactant) compared to SI (all P < 0.05; two-way ANOVA). Irrespective of strategy, Cdyn was better in the Steroid group in the first 10 min (all P < 0.05). Thereafter, Cdyn was similar to Steroid epoch in the OLV + Surfactant, but not SI + Surfactant group. OLV influenced the effect of steroid and surfactant (P = 0.005) on AaDO2 more than SI (P = 0.235). The antenatal state of the lung influences the type and impact of a recruitment maneuver at birth. The effectiveness of surfactant maybe enhanced using PEEP-based time-dependent recruitment strategies rather than approaches solely aimed at initial lung liquid clearance.

  8. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    Energy Technology Data Exchange (ETDEWEB)

    Diamant, A; Ybarra, N; Seuntjens, J [McGill University, Montreal, Quebec (Canada); El Naqa, I [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  9. Volume Oscillations Delivered to a Lung Model Using 4 Different Bubble CPAP Systems.

    Science.gov (United States)

    Poli, Jonathan A; Richardson, C Peter; DiBlasi, Robert M

    2015-03-01

    High-frequency pressure oscillations created by gas bubbling through an underwater seal during bubble CPAP may enhance ventilation and aid in lung recruitment in premature infants. We hypothesized that there are no differences in the magnitude of oscillations in lung volume (ΔV) in a preterm neonatal lung model when different bubble CPAP systems are used. An anatomically realistic replica of an infant nasal airway model was attached to a Silastic test lung sealed within a calibrated plethysmograph. Nasal prongs were affixed to the simulated neonate and supported using bubble CPAP systems set at 6 cm H2O. ΔV was calculated using pressure measurements obtained from the plethysmograph. The Fisher & Paykel Healthcare bubble CPAP system provided greater ΔV than any of the other devices at all of the respective bias flows (P CPAP systems. The magnitude of ΔV increased at bias flows of > 4 L/min in the Fisher & Paykel Healthcare, Airways Development, and homemade systems, but appeared to decrease as bias flow increased with the Babi.Plus system. The major finding of this study is that bubble CPAP can provide measureable ventilation effects in an infant lung model. We speculate that the differences noted in ΔV between the different devices are a combination of the circuit/nasal prong configuration, bubbler configuration, and frequency of oscillations. Additional testing is needed in spontaneously breathing infants to determine whether a physiologic benefit exists when using the different bubble CPAP systems. Copyright © 2015 by Daedalus Enterprises.

  10. A Validated Clinical Risk Prediction Model for Lung Cancer in Smokers of All Ages and Exposure Types

    DEFF Research Database (Denmark)

    Markaki, Maria; Tsamardinos, Ioannis; Langhammer, Arnulf

    2018-01-01

    Lung cancer causes >1·6 million deaths annually, with early diagnosis being paramount to effective treatment. Here we present a validated risk assessment model for lung cancer screening. The prospective HUNT2 population study in Norway examined 65,237 people aged >20years in 1995-97. After a median...

  11. Single breath study for lung scan with krypton-81m: proposition of a mathematical model

    International Nuclear Information System (INIS)

    Pommet, R.; Mathieu, E.

    1981-01-01

    A single breath study with sup(81m)Kr was proceeded in patients, and we studied a theorical model. Based on experimental datas, the model was extrapolated by simple compartimental hypothesis, permitting a study per area of the instant alveolar lung flow by a deconvolution operation. An other approach to present the local ventilation is proposed too. Based on the average flow of ventilation index, calculation is obtained easier than by deconvolution method, and this method fully agree with the proposed model. This index allows the realisation of functionnal views of the local ventilation flow, made possible by the use of a computer for the study of each elementary area of the lung and the realisation of the activity curve recorded during the sup(81m)Kr first breath [fr

  12. Mice and rabbit models for oral and percutaneous absorption and disposition of amphoteric surfactant C31G.

    Science.gov (United States)

    Michaels, E B; Hahn, E C; Kenyon, A J

    1983-10-01

    A topical antimicrobial agent (C31G), composed of amphoteric surfactants (alkyl betaines and alkyl amine oxides), had a significant (P less than 0.001) and concentration dependent rate of percutaneous absorption in mice and rabbits. Percutaneous absorption studies (3 concentrations for 3 exposure periods) in mice indicated that dermal interaction resulted in nonlinear changes for rate of penetration and transport as a function of exposure and concentration. Kinetic studies of absorption and disposition after oral dosing in mice with [3H]C31G were used to determine the body burden (0.21 g/kg of body weight) at a no effect level. Dermal penetration (P) and transport (T) resulting from percutaneous exposure at variations of time and dosage concentrations were shown to fit the equation T = a + k ln t. The regression coefficient k represents the characteristic change of T with exposure time (t). For low concentrations k equaled 1.89 and at the high concentration k equaled 2.68. This increase of T indicated the interaction of the agent with the dermal barrier at high concentrations. Dermal transport in the rabbit was less than one-fourth of that in the mouse. Excretion of C31G after oral or dermal dosing was predominantly renal at higher dosage levels, whereas fecal excretion dominated at the lowest dosage levels. The half-life of [3H]C31G in the mouse was 68 hours and 86 hours in the rabbit. Data and statistical methods allowed prediction of the effects of daily exposures

  13. Effect of position, nitric oxide, and almitrine on lung perfusion in a porcine model of acute lung injury.

    Science.gov (United States)

    Richard, J C; Janier, M; Lavenne, F; Berthier, V; Lebars, D; Annat, G; Decailliot, F; Guerin, C

    2002-12-01

    In a porcine model of oleic acid-induced lung injury, the effects of inhaled nitric oxide (iNO) and intravenous almitrine bismesylate (ivALM), which enhances the hypoxic pulmonary vasoconstriction on the distribution of regional pulmonary blood flow (PBF), were assessed. After injection of 0.12 ml/kg oleic acid, 20 anesthetized and mechanically ventilated piglets [weight of 25 +/- 2.6 (SD) kg] were randomly divided into four groups: supine position, prone position, and 10 ppm iNO for 40 min followed by 4 microg x kg(-1) x min(-1) ivALM for 40 min in supine position and in prone position. PBF was measured with positron emission tomography and H(2)15O. The redistribution of PBF was studied on a pixel-by-pixel basis. Positron emission tomography scans were performed before and then 120, 160, and 200 min after injury. With prone position alone, although PBF remained prevalent in the dorsal regions it was significantly redistributed toward the ventral regions (P < 0.001). A ventral redistribution of PBF was also obtained with iNO regardless of the position (P = 0.043). Adjunction of ivALM had no further effect on PBF redistribution. PP and iNO have an additive effect on ventral redistribution of PBF.

  14. Cholesterol rules: direct observation of the coexistence of two fluid phases in native pulmonary surfactant membranes at physiological temperatures

    DEFF Research Database (Denmark)

    Bernardino de la Serna, Jorge; Perez-Gil, Jesus; Simonsen, Adam C

    2004-01-01

    Pulmonary surfactant, the lipid-protein material that stabilizes the respiratory surface of the lungs, contains approximately equimolar amounts of saturated and unsaturated phospholipid species and significant proportions of cholesterol. Such lipid composition suggests that the membranes taking p...

  15. A Minimal Path Searching Approach for Active Shape Model (ASM)-based Segmentation of the Lung.

    Science.gov (United States)

    Guo, Shengwen; Fei, Baowei

    2009-03-27

    We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 ± 0.33 pixels, while the error is 1.99 ± 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs.

  16. Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Johnatas Dutra Silva

    2016-02-01

    Full Text Available Background/Aims: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS, but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. Methods: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL. After surgery (6 hours, CTRL and ARDS animals were assigned to receive: (1 sterile saline solution; (2 LASSBio596; (3 exogenous surfactant or (4 LASSBio596 plus exogenous surfactant (n = 22/group. Results: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. Conclusion: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

  17. Role of TNFR1 in lung injury and altered lung function induced by the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    International Nuclear Information System (INIS)

    Sunil, Vasanthi R.; Patel-Vayas, Kinal; Shen, Jianliang; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-01-01

    Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were sacrificed 3, 7 or 14 days later and bronchoalveolar lavage (BAL) fluid and lung tissue collected. Treatment of mice with CEES resulted in an increase in BAL protein, an indication of alveolar epithelial damage, within 3 days. Expression of Ym1, an oxidative stress marker also increased in the lung, along with inducible nitric oxide synthase, and at 14 days, cyclooxygenase-2 and monocyte chemotactic protein-1, inflammatory proteins implicated in tissue injury. These responses were attenuated in mice lacking the p55 receptor for TNFα (TNFR1-/-), demonstrating that signaling via TNFR1 is key to CEES-induced injury, oxidative stress, and inflammation. CEES-induced upregulation of CuZn-superoxide dismutase (SOD) and MnSOD was delayed or absent in TNFR1-/- mice, relative to WT mice, suggesting that TNFα mediates early antioxidant responses to lung toxicants. Treatment of WT mice with CEES also resulted in functional alterations in the lung including decreases in compliance and increases in elastance. Additionally, methacholine-induced alterations in total lung resistance and central airway resistance were dampened by CEES. Loss of TNFR1 resulted in blunted functional responses to CEES. These effects were most notable in the airways. These data suggest that targeting TNFα signaling may be useful in mitigating lung injury, inflammation and functional alterations induced by vesicants.

  18. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer.

    Science.gov (United States)

    López-Rodríguez, Elena; Ospina, Olga Lucía; Echaide, Mercedes; Taeusch, H William; Pérez-Gil, Jesús

    2012-10-03

    Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant's interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats

    International Nuclear Information System (INIS)

    Trivillin, V.A.; Garabalino, M.A.; Colombo, L.L.

    2013-01-01

    Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats Introduction: Boron Neutron Capture Therapy (BNCT) is based on selective tumor uptake of boron compounds, followed by neutron irradiation. BNCT was proposed for the treatment of unresectable, diffuse lung metastases. The aim of the present study was to perform BNCT studies in an experimental model of lung metastases. Materials and Methods: 3 x 106/0.5 ml colon carcinoma cells (DHD/K12/TRb) were injected iv in syngeneic BDIX rats. Three weeks post-inoculation, rats with diffuse lung metastases were used for in vivo BNCT studies in the RA-3 Nuclear Reactor. Based on previous biodistribution studies and computational dosimetry with Monte Carlo simulation, 2 doses were prescribed, i.e. 4 Gy and 8 Gy minimum absorbed dose to tumor. The animals were assigned to 5 experimental groups (n= 4 to 8) at each dose level: T0 (euthanized pre-treatment), BPA-BNCT, Comb-BNCT (BPA+GB-10), Beam only (background dose) and Sham (same manipulation, no treatment). Boron concentration was measured in a blood sample taken pre-irradiation to verify that the value was in the range established in previous biodistribution studies. The animals were followed clinically for 2 weeks after neutron irradiation and then euthanized to assess the response of tumor and normal lung, macroscopically and histologically. To date we have evaluated the end-point weight of lung (normal lung + metastases) and % lung weight/body weight as an indicator of tumor growth. Results: The statistical analysis (ANOVA) of % lung weight/body weight showed statistically significant differences (p<0.05) between groups T0 (0.79 ± 0.38) and Sham (1.87 ± 0.91). No statistically significant differences were observed between the Beam only groups (at both dose levels) and Sham. Similar and statistically significant tumor control was induced in the groups BPA-BNCT Low dose (LD) (0.56 ± 0.11), BPA-BNCT High dose (HD) (0.80 ± 0.16), Comb

  20. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System Phase I: Hypo-Elastic Model for CFD Implementation

    Energy Technology Data Exchange (ETDEWEB)

    Freed, Alan D.; Einstein, Daniel R.

    2011-04-14

    An isotropic constitutive model for the parenchyma of lung has been derived from the theory of hypo-elasticity. The intent is to use it to represent the mechanical response of this soft tissue in sophisticated, computational, fluid-dynamic models of the lung. This demands that the continuum model be accurate, yet simple and effcient. An objective algorithm for its numeric integration is provided. The response of the model is determined for several boundary-value problems whose experiments are used for material characterization. The effective elastic, bulk, and shear moduli, and Poisson’s ratio, as tangent functions, are also derived. The model is characterized against published experimental data for lung. A bridge between this continuum model and a dodecahedral model of alveolar geometry is investigated, with preliminary findings being reported.

  1. Micellar solubilization of poorly water-soluble drugs: effect of surfactant and solubilizate molecular structure.

    Science.gov (United States)

    Vinarov, Zahari; Katev, V; Radeva, D; Tcholakova, S; Denkov, N D

    2018-04-01

    This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions. (1) Rationale for surfactant selection is provided; (2) the large data set can be used for validation of the drug solubility parameters used in oral absorption models. Equilibrium solubility of two hydrophobic drugs and one model hydrophobic steroid in micellar solutions of 19 surfactants was measured by HPLC. The drug solubilization locus in the micelles was assessed by UV spectrometry. Danazol is solubilized much more efficiently than fenofibrate by ionic surfactants due to ion-dipole interactions between the charged surfactant head groups and the polar steroid backbone. Drug solubilization increases linearly with the increase of hydrophobic chain length for all studied surfactant types. Addition of 1-3 ethylene oxide (EO) units in the head group of dodecyl sulfate surfactants reduces significantly the solubilization of both studied drugs and decreases linearly the solubilization locus polarity of fenofibrate. The locus of fenofibrate solubilization is in the hydrophobic core of nonionic surfactant micelles and in the palisade layer of ionic surfactant micelles. Highest drug solubility can be obtained by using surfactants molecules with long chain length coupled with hydrophilic head group that provides additional drug-surfactant interactions (i.e. ion-dipole) in the micelles.

  2. Towards lung EIT image segmentation: automatic classification of lung tissue state from analysis of EIT monitored recruitment manoeuvres

    International Nuclear Information System (INIS)

    Grychtol, Bartłomiej; Wolf, Gerhard K; Arnold, John H; Adler, Andy

    2010-01-01

    There is emerging evidence that the ventilation strategy used in acute lung injury (ALI) makes a significant difference in outcome and that an inappropriate ventilation strategy may produce ventilator-associated lung injury. Most harmful during mechanical ventilation are lung overdistension and lung collapse or atelectasis. Electrical impedance tomography (EIT) as a non-invasive imaging technology may be helpful to identify lung areas at risk. Currently, no automated method is routinely available to identify lung areas that are overdistended, collapsed or ventilated appropriately. We propose a fuzzy logic-based algorithm to analyse EIT images obtained during stepwise changes of mean airway pressures during mechanical ventilation. The algorithm is tested on data from two published studies of stepwise inflation–deflation manoeuvres in an animal model of ALI using conventional and high-frequency oscillatory ventilation. The timing of lung opening and collapsing on segmented images obtained using the algorithm during an inflation–deflation manoeuvre is in agreement with well-known effects of surfactant administration and changes in shunt fraction. While the performance of the algorithm has not been verified against a gold standard, we feel that it presents an important first step in tackling this challenging and important problem

  3. RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Vera L. Oliveira-Freitas

    2015-01-01

    Full Text Available RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR, RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P<0.001. The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P=0.005. Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P<0.013. No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P=0.159 and TNF-α (P=0.260, as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.

  4. Creation of a uniform pleural defect model for the study of lung sealants.

    Science.gov (United States)

    Araki, Masato; Tao, Hiroyuki; Sato, Toshihiko; Nakajima, Naoki; Sugai, Hajime; Hyon, Suong-Hyu; Nagayasu, Takeshi; Nakamura, Tatsuo

    2007-07-01

    Animal models are indispensable for the development of new therapeutic methods for the closure of alveolar air leakage. However, it is difficult to create a uniform pleural defect model. The purpose of this study was to establish an appropriate animal model for assessing the efficacy and histotoxicity of synthetic sealants for lung surgery. Nine beagle dogs were used to evaluate the pleural defect model in comparison with conventional resection procedures. A donut-shaped silicon ring with an inner diameter of 15 mm was placed on the pleura, and 0.1 mL of cyanoacrylate was dropped into the ring. A pleural defect was created by sliding a microtome blade just beneath the polymerized cyanoacrylate. Hemostasis was performed by pressure with a sponge. Morphologically, round areas of the pleura were uniformly resected with our procedure. The resected tissue consisted of pleura and thin underlying lung parenchyma. Among the results from 3 surgeons, there were no significant differences in the mean time required for hemostasis (P = .69), the mean thickness of the resected tissue (P = .13), and the mean amount of air leakage from the resected area (P = .19). No penetration of cyanoacrylate into the lung parenchyma was evidenced by immunofluorescence microscopy. Histologically, when the pleura was resected without using cyanoacrylate, a thick fibrocellular layer extended to the lung parenchyma. Furthermore, severe fibrosis was observed when electrocautery was used for hemostasis. However, when the pleura was resected using cyanoacrylate, the normal alveolar structure was preserved. Our uniform pleural defect model using cyanoacrylate may be feasible for the evaluation of synthetic sealants for alveolar air leakage.

  5. Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

    Science.gov (United States)

    Wu, Yu-Chung; Wei, Nien-Chih; Hung, Jung-Jyh; Yeh, Yi-Chen; Su, Li-Jen; Hsu, Wen-Hu; Chou, Teh-Ying

    2017-10-03

    Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I-IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB ( p model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

  6. Dynamic Characteristics of Mechanical Ventilation System of Double Lungs with Bi-Level Positive Airway Pressure Model

    Directory of Open Access Journals (Sweden)

    Dongkai Shen

    2016-01-01

    Full Text Available In recent studies on the dynamic characteristics of ventilation system, it was considered that human had only one lung, and the coupling effect of double lungs on the air flow can not be illustrated, which has been in regard to be vital to life support of patients. In this article, to illustrate coupling effect of double lungs on flow dynamics of mechanical ventilation system, a mathematical model of a mechanical ventilation system, which consists of double lungs and a bi-level positive airway pressure (BIPAP controlled ventilator, was proposed. To verify the mathematical model, a prototype of BIPAP system with a double-lung simulators and a BIPAP ventilator was set up for experimental study. Lastly, the study on the influences of key parameters of BIPAP system on dynamic characteristics was carried out. The study can be referred to in the development of research on BIPAP ventilation treatment and real respiratory diagnostics.

  7. Surfactants, interfaces and pores : a theoretical study

    NARCIS (Netherlands)

    Huinink, H.

    1998-01-01

    The aim of this study was to investigate the behavior of surfactants in porous media by theoretical means. The influence of curvature of a surface on the adsorption has been studied with a mean field lattice (MFL) model, as developed by Scheutjens and Fleer. An analytical theory has been

  8. Are lung-protective ventilation strategies worth the effort?

    African Journals Online (AJOL)

    Patients are at risk of acquiring several types of lung injury in the perioperative period. ... of patients in the perioperative period, from patients with healthy lungs and patients with at-risk lungs through to patients with established ALI. ..... surfactant, prone positioning, inhaled nitric oxide and anti- inflammatories, have not ...

  9. Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants

    NARCIS (Netherlands)

    Miedema, Martijn; de Jongh, Frans H.; Frerichs, Inez; van Veenendaal, Mariëtte B.; van Kaam, Anton H.

    2012-01-01

    To assess the regional respiratory time constants of lung volume changes during stepwise lung recruitment before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. A stepwise oxygenation-guided recruitment procedure was performed before and after surfactant

  10. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia

    Directory of Open Access Journals (Sweden)

    K Rennis Davis

    2015-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia.

  11. Characterization of lung stem cell niches in a mouse model of bleomycin-induced fibrosis

    Science.gov (United States)

    2012-01-01

    Introduction In lung fibrosis, alveolar epithelium degenerates progressively. The goal of regenerative medicine is to aid repair and regeneration of the lost tissues in parenchyma and airways for which mobilization of tissue-resident endogenous or bone marrow-derived exogenous stem cells niches is a critical step. We used a lung injury model in mice to identify and characterize functional lung stem cells to clarify how stem cell niches counteract this degenerative process. Methods Short term assay (STA) - Bleomycin-induced lung inflammation and fibrosis were assessed in a model of idiopathic pulmonary fibrosis in wild-type (WT), gp91phox-/- (NOX-/-), and gp91phoxMMP-12 double knockout (DKO) mice on C57Bl/6 background and Hoechst 33322 dye effluxing side population (SP) cells characterized. Long term assay (LTA) - In a bleomycin induced lung fibrosis model in C57Bl6 mice, the number of mature cells were quantified over 7, 14, and 21 days in bone marrow (BM), peripheral blood (PB), lung parenchyma (LP) and brochoalveolar lavage (BAL) fluid by FACS. BrdU pulse chase experiment (10 weeks) was used to identify label retaining cells (LRC). BrdU+ and BrdU- cells were characterized by hematopoietic (CD45+), pluripotency (TTF1+, Oct3/4+, SSEA-3+, SSEA-4+, Sca1+, Lin-, CD34+, CD31+), and lung lineage-specific (SPC+, AQP-5+, CC-10+) markers. Clonogenic potential of LRCs were measured by CFU-c assays. Results STA- In lung, cellularity increased by 5-fold in WT and 6-fold in NOX-/- by d7. Lung epithelial markers were very low in expression in all SP flow sorted from lung of all three genotypes cultured ex vivo. (p bleomycin, the SP in NOX-/- lung increased by 3.6-fold over WT where it increased by 20-fold over controls. Type I and II alveolar epithelial cells progressively diminished in all three genotypes by d21 post-bleomycin. D7 post-bleomycin, CD45+ cells in BALf in NOX-/- was 1.7-fold > WT, 57% of which were Mf that decreased by 67% in WT and 83% in NOX-/- by d21.LTA

  12. A comparison of excretion and retention between the current ICRP lung model and a proposed new model

    International Nuclear Information System (INIS)

    Johnson, J.R.; Milencoff, S.

    1989-01-01

    The current International Commission on Radiation Protection (ICRP) lung model was developed from information available in the early 1960s. Since that time considerable new information on lung morphology, deposition, and retention has become available and, where appropriate, has been incorporated into a new model being discussed by a Task Group of the ICRP. This new model is conceptually much simpler in that it contains only three compartments, as opposed to 11 in the current model. The intent of this simpler model is to make it easier to model experimental retention and excretion data, either from in vitro studies, animal or human experiments, or human experience. However, this conceptually simpler model is somewhat more difficult to use than the current model as the new model parameters vary with time after exposure. That is, parameters are time-varying functions rather than constants, as they are in the current model, and retention is not given by the familiar Bateman equations. Default time-varying parameters for the new model have been developed that give results comparable to the current model for Classes D, W, and Y compounds. In addition, parameters have been developed for U ore dust, based on in vitro and in vivo studies, and for UO2 from human experience in U fuel fabrication facilities. The development of these parameters will be described, and the results with the new model compared with those obtained with the current model

  13. CANADIAN POPULATION RISK OF RADON INDUCED LUNG CANCER-VARIATION RANGE ASSESSMENT BASED ON VARIOUS RADON RISK MODELS.

    Science.gov (United States)

    Chen, Jing

    2017-11-01

    To address public concerns regarding radon risk and variations in risk estimates based on various risk models available in the literature, lifetime lung cancer risks were calculated with five well-known risk models using more recent Canadian vital statistics (5-year averages from 2008 to 2012). Variations in population risk estimation among various models were assessed. The results showed that the Canadian population risk of radon induced lung cancer can vary from 5.0 to 17% for men and 5.1 to 18% for women based on different radon risk models. Averaged over the estimates from various risk models with better radon dosimetry, 13% of lung cancer deaths among Canadian males and 14% of lung cancer deaths among Canadian females were attributable to long-term indoor radon exposure. © Crown copyright 2017.

  14. Computer simulation-molecular-thermodynamic framework to predict the micellization behavior of mixtures of surfactants: application to binary surfactant mixtures.

    Science.gov (United States)

    Iyer, Jaisree; Mendenhall, Jonathan D; Blankschtein, Daniel

    2013-05-30

    We present a computer simulation-molecular-thermodynamic (CSMT) framework to model the micellization behavior of mixtures of surfactants in which hydration information from all-atomistic simulations of surfactant mixed micelles and monomers in aqueous solution is incorporated into a well-established molecular-thermodynamic framework for mixed surfactant micellization. In addition, we address the challenges associated with the practical implementation of the CSMT framework by formulating a simpler mixture CSMT model based on a composition-weighted average approach involving single-component micelle simulations of the mixture constituents. We show that the simpler mixture CSMT model works well for all of the binary surfactant mixtures considered, except for those containing alkyl ethoxylate surfactants, and rationalize this finding molecularly. The mixture CSMT model is then utilized to predict mixture CMCs, and we find that the predicted CMCs compare very well with the experimental CMCs for various binary mixtures of linear surfactants. This paper lays the foundation for the mixture CSMT framework, which can be used to predict the micellization properties of mixtures of surfactants that possess a complex chemical architecture, and are therefore not amenable to traditional molecular-thermodynamic modeling.

  15. Surfactant protein-D and pulmonary host defense

    Directory of Open Access Journals (Sweden)

    Crouch Erika C

    2000-08-01

    Full Text Available Abstract Surfactant protein-D (SP-D participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin, binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases.

  16. Two alternative models concerning the perialveolar microcirculation in mammalian lungs

    Directory of Open Access Journals (Sweden)

    BRUNO GÜNTHER

    2005-01-01

    Full Text Available Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

  17. Progress in lung modelling by the ICRP Task Group

    International Nuclear Information System (INIS)

    James, A.C.; Birchall, A.

    1989-01-01

    The Task Group has reviewed the data on: (a) morphology and physiology of the human respiratory tract; (b) inspirability of aerosols and their deposition in anatomical regions as functions of respiratory parameters; (c) clearance of particles within and from the respiratory tract; (d) absorption of different materials into the blood in humans and in animals. The Task Group proposes a new model which predicts the deposition, retention and systemic uptake of materials, enabling doses absorbed by different respiratory tissues and other body organs to be evaluated. In the proposed model, clearance is described in terms of competition between the processes moving particles to the oropharynx or to lymph nodes and that of absorption into the blood. From studies with human subjects, characteristic rates and pathways are defined to represent mechanical clearance of particles from each region, which do not depend on the material. Conversely, the absorption rate is determined solely by the material: it is assumed to be the same in all parts of the respiratory tract and in other animal species. For several of the radiologically important forms of actinides, absorption rates can be derived from animal experiments, or, in some cases, directly from human data. Otherwise, default values are used, based on the current D, W and Y classification system. (author)

  18. Coacervation with surfactants: From single-chain surfactants to gemini surfactants.

    Science.gov (United States)

    Zhao, Weiwei; Wang, Yilin

    2017-01-01

    Coacervation is a spontaneous process during which a colloidal dispersion separates into two immiscible liquid phases: a colloid-rich liquid phase in equilibrium with a diluted phase. Coacervation is usually divided into simple coacervation and complex coacervation according to the number of components. Surfactant-based coacervation normally contains traditional single-chain surfactants. With the development of surfactants, gemini surfactants with two amphiphilic moieties have been applied to form coacervation. This review summarizes the development of simple coacervation and complex coacervation in the systems of single-chain surfactants and gemini surfactants. Simple coacervation in surfactant solutions with additives or at elevated temperature and complex coacervation in surfactant/polymer mixtures by changing charge densities, molecular weight, ionic strength, pH, or temperature are reviewed. The comparison between gemini surfactants and corresponding monomeric single-chain surfactants reveals that the unique structures of gemini surfactants endow them with higher propensity to generate coacervation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Enhanced cough reflex in a model of bleomycin-induced lung fibrosis in guinea pigs.

    Science.gov (United States)

    Fernández-Blanco, Joan Antoni; Aguilera, Mònica; Domènech, Anna; Tarrasón, Gema; Prats, Neus; Miralpeix, Montse; De Alba, Jorge

    2015-12-01

    Fibrotic lung diseases, such as idiopathic pulmonary fibrosis, are associated with spontaneous dry cough and hypersensitivity to tussive agents. Understanding the pathophysiology driving enhanced cough may help us to define better therapies for patients. We hypothesized that lung fibrosis induced by intratracheal bleomycin would exacerbate the cough reflex induced by tussive agents in guinea pigs. Disease progression in the lungs was characterized at days 1, 7, 14, 21 and 28 after bleomycin administration. Inflammatory and fibrotic markers, as well as neurotrophin levels, were assessed in bronchoalveolar lavage fluid and/or lung tissue. Cough sensitivity to citric acid, capsaicin and allylisothiocyanate was evaluated in conscious animals at days 14 and 21 after bleomycin administration. Pulmonary lesions evolved from an early inflammatory phase (from day 1 to day 7) to a fibrotic stage (between days 14 and 28). Fibrosis was related to increased levels of matrix metalloproteinase-2 in bronchoalveolar lavage fluid (day 21: saline, 0.26 ng/ml; bleomycin, 0.49 ng/ml). At day 14, we also observed increased cough reflexes to citric acid (163%), capsaicin (125%) and allylisothiocyanate (178%). Cough exacerbation persisted, but at a lower extent, by day 21 for capsaicin (100%) and allylisothiocyanate (54%). Moreover, bronchoalveolar lavage fluid concentrations of brain-derived neurotrophic factor, suggested to induce nerve remodelling in chronic cough, were also enhanced (day 1: saline, 14.21 pg/ml; bleomycin, 30.09 pg/ml). In summary, our model of bleomycin-induced cough exacerbation may be a valuable tool to investigate cough hypersensitivity and develop antitussive therapies for fibrotic lung diseases. © 2015 Authors; published by Portland Press Limited.

  20. Modeling Lung Carcinogenesis in Radon-Exposed Miner Cohorts: Accounting for Missing Information on Smoking.

    Science.gov (United States)

    van Dillen, Teun; Dekkers, Fieke; Bijwaard, Harmen; Brüske, Irene; Wichmann, H-Erich; Kreuzer, Michaela; Grosche, Bernd

    2016-05-01

    Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a case-control study onto an entire cohort by means of a Monte Carlo resampling technique. As a proof of principle, this method is tested on a subcohort of 35,084 former uranium miners employed at the WISMUT company (Germany), with 461 lung cancer deaths in the follow-up period 1955-1998. After applying the proposed imputation technique, a biologically-based carcinogenesis model is employed to analyze the cohort's lung cancer mortality data. A sensitivity analysis based on a set of 200 independent projections with subsequent model analyses yields narrow distributions of the free model parameters, indicating that parameter values are relatively stable and independent of individual projections. This technique thus offers a possibility to account for unknown smoking habits, enabling us to unravel risks related to radon, to smoking, and to the combination of both. © 2015 Society for Risk Analysis.

  1. Pulmonary surfactant disaturated-phosphatidylcholine (DSPC) turnover and pool size in newborn infants with congenital diaphragmatic hernia (CDH).

    Science.gov (United States)

    Cogo, Paola E; Zimmermann, Luc J I; Meneghini, Luisa; Mainini, Nicoletta; Bordignon, Linda; Suma, Vincenzo; Buffo, Marika; Carnielli, Virgilio P

    2003-11-01

    In animal CDH models, surfactant deficiency contributes to the pathophysiology of the condition but information on human disease is very limited. The aim of our study was to investigate surfactant kinetics in CDH newborns. We studied surfactant disaturated-phosphatidylcholine (DSPC) half-life, turnover and apparent pool size by stable isotope methodology in CDH newborns with no ExtraCorporeal Membrane Oxygenation (ECMO) support (n = 13, birth weight (BW) 3.2 +/- 2.2 kg, gestational age (GA) 39 +/- 0.4 wks, postnatal age 43 +/- 11 h) and in 8 term infants with no lung disease (CONTROLS, BW 2.7 +/- 0 kg, GA 38 +/- 0.8 wks, postnatal age 96 +/- 26 h). We administered a trace dose of 13C-palmitic acid dipalmitoyl-phosphatidylcholine (DPPC) through the endotracheal (ET) tube and we measured DSPC kinetics by gas chromatography-mass spectrometry from DSPC13C-enrichment decay curves obtained from sequential tracheal aspirates. DSPC amount from tracheal aspirates (TA-DSPC) was measured by gas chromatography. In CDH infants DSPC half-life was shorter (24 +/- 4 and 53 +/- 11 h, p = 0.01), turnover faster (0.6 +/- 0.1 and 1.5 +/- 0.3 d-1 p = 0.01), apparent pool size smaller (34 +/- 6 and 57 +/- 7 mg/kg body weight, p = 0.02) and tracheal aspirates DSPC amount lower (2.4 +/- 0.4 and 4.6 +/- 0.5 mg/mL Epithelial Lining Fluid (ELF), p = 0.007) than in CONTROLS. In conclusion surfactant kinetics is grossly abnormal in mechanically ventilated CDH. Whether alterations of DSPC kinetics in CDH infants are caused by a primary surfactant deficiency or are secondary to oxygen therapy and ventilator support has still to be determined.

  2. Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model.

    Science.gov (United States)

    Little, M P

    2002-03-01

    To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk. Fitting two sorts of time- and age-adjusted relative risk models to a case-control dataset nested within the Colorado Plateau uranium miner cohort and to the Japanese atomic (A)-bomb survivor mortality data. If all A-bomb survivors are compared with the Colorado data, there are statistically significant (two-sided p model with exponential adjustments for the effects of radiation for time since exposure and age at exposure, and 1.9 x 10(-2) Sv WLM(-1) (95% CI 6.2 x 10(-3), 1.6 x 10(-1)) using a model with adjustments for the effects of radiation proportional to powers of time since exposure and attained age. Estimates of the risk conversion factor calculated using variant assumptions as to the definition of lung cancer in the Colorado data, or by excluding miners for whom exposure estimates may be less reliable, are very similar. The absence of information on cigarette smoking in the Japanese A-bomb survivors, and the possibility that this may confound the time trends in radiation-induced lung cancer risk in that cohort, imply that these findings should be interpreted with caution. There are no statistically significant differences between the male A-bomb survivors data and the Colorado miner data in the pattern of variation of relative risk with time after exposure and age at exposure. The risk conversion factor is very close to the value suggested by the latest ICRP lung model, albeit with substantial uncertainties.

  3. Simulation model of lung cancer incidence related to smoking and radon daughter exposure

    International Nuclear Information System (INIS)

    Stolowijk, J.A.J.

    1990-01-01

    A mathematical model of lung cancer and radon daughter exposure is presented. It is aimed to provide a quantitative estimate in the form of dose-effect relationship. The nature of the cigarette smoking and radon exposure interaction it is shown to be a multiplicative or sub-multiplicative function rather than a simpler model in which the effect of the two exposures would be summed. The model was written in the SAS programming language. An annotated listing of the program is given. 4 refs

  4. Computational modeling of a forward lunge: towards a better understanding of the function of the cruciate ligaments

    Science.gov (United States)

    Alkjær, Tine; Wieland, Maja R; Andersen, Michael S; Simonsen, Erik B; Rasmussen, John

    2012-01-01

    This study investigated the function of the cruciate ligaments during a forward lunge movement. The mechanical roles of the anterior and posterior cruciate ligament (ACL, PCL) during sagittal plane movements, such as forward lunging, are unclear. A forward lunge movement contains a knee joint flexion and extension that is controlled by the quadriceps muscle. The contraction of the quadriceps can cause anterior tibial translation, which may strain the ACL at knee joint positions close to full extension. However, recent findings suggest that it is the PCL rather than the ACL which is strained during forward lunging. Thus, the purpose of the present study was to establish a musculoskeletal model of the forward lunge to computationally investigate the complete mechanical force equilibrium of the tibia during the movement to examine the loading pattern of the cruciate ligaments. A healthy female was selected from a group of healthy subjects who all performed a forward lunge on a force platform, targeting a knee flexion angle of 90°. Skin-markers were placed on anatomical landmarks on the subject and the movement was recorded by five video cameras. The three-dimensional kinematic data describing the forward lunge movement were extracted and used to develop a biomechanical model of the lunge movement. The model comprised two legs including femur, crus, rigid foot segments and the pelvis. Each leg had 35 independent muscle units, which were recruited according to a minimum fatigue criterion. This approach allowed a full understanding of the mechanical equilibrium of the knee joint, which revealed that the PCL had an important stabilizing role in the forward lunge movement. In contrast, the ACL did not have any significant mechanical function during the lunge movement. Furthermore, the results showed that m. gluteus maximus may play a role as a knee stabilizer in addition to the hamstring muscles. PMID:23057673

  5. Animal derived surfactant extract versus protein free synthetic surfactant for the prevention and treatment of respiratory distress syndrome.

    Science.gov (United States)

    Ardell, Stephanie; Pfister, Robert H; Soll, Roger

    2015-08-24

    A wide variety of surfactant preparations have been developed and tested including synthetic surfactants and surfactants derived from animal sources. Although clinical trials have demonstrated that both synthetic surfactant and animal derived surfactant preparations are effective, comparison in animal models has suggested that there may be greater efficacy of animal derived surfactant products, perhaps due to the protein content of animal derived surfactant. To compare the effect of animal derived surfactant to protein free synthetic surfactant preparations in preterm infants at risk for or having respiratory distress syndrome (RDS). Searches were updated of the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014), PubMed, CINAHL and EMBASE (1975 through November 2014). All languages were included. Randomized controlled trials comparing administration of protein free synthetic surfactants to administration of animal derived surfactant extracts in preterm infants at risk for or having respiratory distress syndrome were considered for this review. Data collection and analysis were conducted according to the standards of the Cochrane Neonatal Review Group. Fifteen trials met the inclusion criteria. The meta-analysis showed that the use of animal derived surfactant rather than protein free synthetic surfactant resulted in a significant reduction in the risk of pneumothorax [typical relative risk (RR) 0.65, 95% CI 0.55 to 0.77; typical risk difference (RD) -0.04, 95% CI -0.06 to -0.02; number needed to treat to benefit (NNTB) 25; 11 studies, 5356 infants] and a marginal reduction in the risk of mortality (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD -0.02, 95% CI -0.04 to -0.00; NNTB 50; 13 studies, 5413 infants).Animal derived surfactant was associated with an increase in the risk of necrotizing enterocolitis [typical RR 1.38, 95% CI 1.08 to 1.76; typical RD 0.02, 95% CI 0.01 to 0.04; number needed to treat to harm (NNTH) 50; 8

  6. Studies in a Rat Lung Tumor Model: Cellular Biochemistry and Cytogenetics

    Science.gov (United States)

    1983-08-01

    returned to control levels at times when lung enzymes were still well above controls. This result suggests that xenobiotics reaching the lung via the...such effect, either in the lung or liver. This lung-specific enzyme induction by 2-NN is unusual, since most xenobiotics induce activity primarily in the...3 H-BaP by Lung and Liver Microsomes from MCA-- meated Rats After a single Intratracheal inoculation with 1.0 mg MCA the enzyme activity in lung

  7. Central focused convolutional neural networks: Developing a data-driven model for lung nodule segmentation.

    Science.gov (United States)

    Wang, Shuo; Zhou, Mu; Liu, Zaiyi; Liu, Zhenyu; Gu, Dongsheng; Zang, Yali; Dong, Di; Gevaert, Olivier; Tian, Jie

    2017-08-01

    Accurate lung nodule segmentation from computed tomography (CT) images is of great importance for image-driven lung cancer analysis. However, the heterogeneity of lung nodules and the presence of similar visual characteristics between nodules and their surroundings make it difficult for robust nodule segmentation. In this study, we propose a data-driven model, termed the Central Focused Convolutional Neural Networks (CF-CNN), to segment lung nodules from heterogeneous CT images. Our approach combines two key insights: 1) the proposed model captures a diverse set of nodule-sensitive features from both 3-D and 2-D CT images simultaneously; 2) when classifying an image voxel, the effects of its neighbor voxels can vary according to their spatial locations. We describe this phenomenon by proposing a novel central pooling layer retaining much information on voxel patch center, followed by a multi-scale patch learning strategy. Moreover, we design a weighted sampling to facilitate the model training, where training samples are selected according to their degree of segmentation difficulty. The proposed method has been extensively evaluated on the public LIDC dataset including 893 nodules and an independent dataset with 74 nodules from Guangdong General Hospital (GDGH). We showed that CF-CNN achieved superior segmentation performance with average dice scores of 82.15% and 80.02% for the two datasets respectively. Moreover, we compared our results with the inter-radiologists consistency on LIDC dataset, showing a difference in average dice score of only 1.98%. Copyright © 2017. Published by Elsevier B.V.

  8. The Emulsified PFC Oxycyte®Improved Oxygen Content and Lung Injury Score in a Swine Model of Oleic Acid Lung Injury (OALI).

    Science.gov (United States)

    Haque, Ashraful; Scultetus, Anke H; Arnaud, Francoise; Dickson, Leonora J; Chun, Steve; McNamee, George; Auker, Charles R; McCarron, Richard M; Mahon, Richard T

    2016-12-01

    Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte ® would improve tissue oxygenation and thereby mitigate the effects of acute lung injury. Intravenous oleic acid (OA) was used to induce lung injury in anesthetized and instrumented Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received Oxycyte ® (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC pre-OA received Oxycyte ® 45 min before OALI; and (3) Controls which received equivalent dose of normal saline. Animals were observed for 3 h after OALI began, and then euthanized. The median survival times for PFC post-OA, PFC pre-OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean arterial pressure and mean pulmonary arterial pressure were both higher in the PFC post-OA (p lung injury indicated that edema and congestion was significantly less severe in the PFC post-OA compared to control (p = 0.001). The intravenous PFC Oxycyte ® improves blood oxygen content and lung histology when used as a treatment after OALI, while Oxycyte ® used prior to OALI was associated with increased mortality. Further exploration in other injury models is indicated.

  9. A relative permeability model to derive fractional-flow functions of water-alternating-gas and surfactant-alternating-gas foam core-floods

    International Nuclear Information System (INIS)

    Al-Mossawy, Mohammed Idrees; Demiral, Birol; Raja, D M Anwar

    2013-01-01

    Foam is used in enhanced oil recovery to improve the sweep efficiency by controlling the gas mobility. The surfactant-alternating-gas (SAG) foam process is used as an alternative to the water-alternating-gas (WAG) injection. In the WAG technique, the high mobility and the low density of the gas lead the gas to flow in channels through the high permeability zones of the reservoir and to rise to the top of the reservoir by gravity segregation. As a result, the sweep efficiency decreases and there will be more residual oil in the reservoir. The foam can trap the gas in liquid films and reduces the gas mobility. The fractional-flow method describes the physics of immiscible displacements in porous media. Finding the water fractional flow theoretically or experimentally as a function of the water saturation represents the heart of this method. The relative permeability function is the conventional way to derive the fractional-flow function. This study presents an improved relative permeability model to derive the fractional-flow functions for WAG and SAG foam core-floods. The SAG flow regimes are characterized into weak foam, strong foam without a shock front and strong foam with a shock front. (paper)

  10. A relative permeability model to derive fractional-flow functions of water-alternating-gas and surfactant-alternating-gas foam core-floods

    Science.gov (United States)

    Idrees Al-Mossawy, Mohammed; Demiral, Birol; Raja, D. M. Anwar

    2013-04-01

    Foam is used in enhanced oil recovery to improve the sweep efficiency by controlling the gas mobility. The surfactant-alternating-gas (SAG) foam process is used as an alternative to the water-alternating-gas (WAG) injection. In the WAG technique, the high mobility and the low density of the gas lead the gas to flow in channels through the high permeability zones of the reservoir and to rise to the top of the reservoir by gravity segregation. As a result, the sweep efficiency decreases and there will be more residual oil in the reservoir. The foam can trap the gas in liquid films and reduces the gas mobility. The fractional-flow method describes the physics of immiscible displacements in porous media. Finding the water fractional flow theoretically or experimentally as a function of the water saturation represents the heart of this method. The relative permeability function is the conventional way to derive the fractional-flow function. This study presents an improved relative permeability model to derive the fractional-flow functions for WAG and SAG foam core-floods. The SAG flow regimes are characterized into weak foam, strong foam without a shock front and strong foam with a shock front.

  11. Mortality Risk Prediction in Scleroderma-Related Interstitial Lung Disease: The SADL Model.

    Science.gov (United States)

    Morisset, Julie; Vittinghoff, Eric; Elicker, Brett M; Hu, Xiaowen; Le, Stephanie; Ryu, Jay H; Jones, Kirk D; Haemel, Anna; Golden, Jeffrey A; Boin, Francesco; Ley, Brett; Wolters, Paul J; King, Talmadge E; Collard, Harold R; Lee, Joyce S

    2017-11-01

    Interstitial lung disease (ILD) is an important cause of morbidity and mortality in patients with scleroderma (Scl). Risk prediction and prognostication in patients with Scl-ILD are challenging because of heterogeneity in the disease course. We aimed to develop a clinical mortality risk prediction model for Scl-ILD. Patients with Scl-ILD were identified from two ongoing longitudinal cohorts: 135 patients at the University of California, San Francisco (derivation cohort) and 90 patients at the Mayo Clinic (validation cohort). Using these two separate cohorts, a mortality risk prediction model was developed and validated by testing every potential candidate Cox model, each including three or four variables of a possible 19 clinical predictors, for time to death. Model discrimination was assessed using the C-index. Three variables were included in the final risk prediction model (SADL): ever smoking history, age, and diffusing capacity of the lung for carbon monoxide (% predicted). This continuous model had similar performance in the derivation (C-index, 0.88) and validation (C-index, 0.84) cohorts. We created a point scoring system using the combined cohort (C-index, 0.82) and used it to identify a classification with low, moderate, and high mortality risk at 3 years. The SADL model uses simple, readily accessible clinical variables to predict all-cause mortality in Scl-ILD. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. Off-the-job training for VATS employing anatomically correct lung models.

    Science.gov (United States)

    Obuchi, Toshiro; Imakiire, Takayuki; Miyahara, Sou; Nakashima, Hiroyasu; Hamanaka, Wakako; Yanagisawa, Jun; Hamatake, Daisuke; Shiraishi, Takeshi; Moriyama, Shigeharu; Iwasaki, Akinori

    2012-02-01

    We evaluated our simulated major lung resection employing anatomically correct lung models as "off-the-job training" for video-assisted thoracic surgery trainees. A total of 76 surgeons voluntarily participated in our study. They performed video-assisted thoracic surgical lobectomy employing anatomically correct lung models, which are made of sponges so that vessels and bronchi can be cut using usual surgical techniques with typical forceps. After the simulation surgery, participants answered questionnaires on a visual analogue scale, in terms of their level of interest and the reality of our training method as off-the-job training for trainees. We considered that the closer a score was to 10, the more useful our method would be for training new surgeons. Regarding the appeal or level of interest in this simulation surgery, the mean score was 8.3 of 10, and regarding reality, it was 7.0. The participants could feel some of the real sensations of the surgery and seemed to be satisfied to perform the simulation lobectomy. Our training method is considered to be suitable as an appropriate type of surgical off-the-job training.

  13. Novel electrospun gelatin/oxycellulose nanofibers as a suitable platform for lung disease modeling.

    Science.gov (United States)

    Švachová, Veronika; Vojtová, Lucy; Pavliňák, David; Vojtek, Libor; Sedláková, Veronika; Hyršl, Pavel; Alberti, Milan; Jaroš, Josef; Hampl, Aleš; Jančář, Josef

    2016-10-01

    Novel hydrolytically stable gelatin nanofibers modified with sodium or calcium salt of oxycellulose were prepared by electrospinning method. The unique inhibitory effect of these nanofibers against Escherichia coli bacteria was examined by luminometric method. Biocompatibility of these gelatin/oxycellulose nanofibers with eukaryotic cells was tested using human lung adenocarcinoma cell line NCI-H441. Cells firmly adhered to nanofiber surface, as determined by scanning electron microscopy, and no signs of cell dying were detected by fluorescent live/dead assay. We propose that the newly developed gelatin/oxycellulose nanofibers could be used as promising scaffold for lung disease modeling and anti-cancer drug testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. An experimental randomized study of six different ventilatory modes in a piglet model with normal lungs

    DEFF Research Database (Denmark)

    Nielsen, J B; Sjöstrand, U H; Henneberg, S W

    1991-01-01

    A randomized study of 6 ventilatory modes was made in 7 piglets with normal lungs. Using a Servo HFV 970 (prototype system) and a Servo ventilator 900 C the ventilatory modes examined were as follows: SV-20V, i.e. volume-controlled intermittent positive-pressure ventilation (IPPV); SV-20VIosc, i...... ventilatory modes. Also the mean airway pressures were lower with the HFV modes 8-9 cm H2O compared to 11-14 cm H2O for the other modes. The gas distribution was evaluated by N2 wash-out and a modified lung clearance index. All modes showed N2 wash-out according to a two-compartment model. The SV-20P mode had...

  15. Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model.

    Directory of Open Access Journals (Sweden)

    Jiwang Chen

    Full Text Available Linezolid (LZD is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.

  16. Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

    Directory of Open Access Journals (Sweden)

    Anastasia Velalopoulou

    2017-11-01

    Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor w