WorldWideScience

Sample records for human pulmonary deposition

  1. Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Smaldone, G.C.; Fuhrer, J.; Steigbigel, R.T.; McPeck, M. (State Univ. of New York, Stony Brook (USA))

    1991-04-01

    Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan. Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout.

  2. Pulmonary deposition of a nebulised aerosol during mechanical ventilation.

    Science.gov (United States)

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

    1993-01-01

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

  3. [Human pulmonary trichomonoses].

    Science.gov (United States)

    Duboucher, Christophe; Caby, Stéphanie; Chabé, Magali; Gantois, Nausicaa; Delgado-Viscogliosi, Pilar; Pierce, Raymond; Capron, Monique; Dei-Cas, Eduardo; Viscogliosi, Eric

    2007-05-01

    Colonization of human lungs by various Trichomonas species is a frequent occurrence, but is unknown to most physicians. At this site of infection, the parasite develops into an amoeboid form that renders it unrecognizable. For this reason it has been overlooked until recently. Morphological identification is not feasible under these conditions and molecular tools provide the only means of identification. The species involved are not restricted to Trichomonas tenax, a saprophyte of the mouth that is usually cited in the rare cases of pleuropulmonary trichomoniasis reported in the literature. The recent discovery of species previously unknown in humans raises further questions, including the zoonotic potential of these microorganisms and the existence of species of animal origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar lumen, rather than immunodepression, seems to be the factor that promotes proliferation of this parasite. The diagnosis of trichomoniasis and its treatment by specific drugs will make it possible to evaluate the pathogenicity of these parasites.

  4. Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.

    Science.gov (United States)

    Thomas, S H; O'Doherty, M J; Graham, A; Page, C J; Blower, P; Geddes, D M; Nunan, T O

    1991-01-01

    BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials. Images PMID:1750018

  5. Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill.

    Science.gov (United States)

    O'Doherty, M; Thomas, S; Page, C; Bradbeer, C; Nunan, T; Bateman, N

    1990-01-01

    An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22

  6. Pulmonary oedema following exercise in humans.

    Science.gov (United States)

    Hodges, Alastair N H; Mayo, John R; McKenzie, Donald C

    2006-01-01

    Pulmonary physiologists have documented many transient changes in the lung and the respiratory system during and following exercise, including the incomplete oxygen saturation of arterial blood in some subjects, possibly due to transient pulmonary oedema. The large increase in pulmonary arterial pressure during exercise, leading to either increased pulmonary capillary leakage and/or pulmonary capillary stress failure, is likely to be responsible for any increase in extravascular lung water during exercise. The purpose of this article is to summarise the studies to date that have specifically examined lung water following exercise. A limited number of studies have been completed with the specific purpose of identifying pulmonary oedema following exercise or a similar intervention. Of these, approximately 50% have observed a positive change and the remaining have provided results that are either inconclusive or show no change in extravascular lung water. While it is difficult to draw a firm conclusion from these studies, we believe that pulmonary oedema does occur in some humans following exercise. As such, this is a phenomenon of significance to pulmonary and exercise physiologists. This possibility warrants further study in the area with more precise measurement tools than has previously been undertaken.

  7. Granulomatous disease associated with pulmonary deposition of titanium.

    Science.gov (United States)

    Redline, S; Barna, B P; Tomashefski, J F; Abraham, J L

    1986-10-01

    A patient presented with granulomatous lung disease associated with the pulmonary deposition of various metallic particles. To evaluate the relation between the metallic dust and the granulomatous process, lymphocyte transformation tests to aluminium sulphate, titanium chloride, beryllium sulphate, and nickel sulphate were performed. A lymphocyte proliferative response to titanium chloride was observed on two separate occasions; no responses to the other metals were shown. These results are consistent with hypersensitivity to titanium, and suggest, in this individual, a possible aetiological role between the inhalation of titanium and a granulomatous disease process.

  8. Pulmonary deposition of aerosolised pentamidine using a new nebuliser: efficiency measurements in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, P.P. (Servizio di Fisica Sanitaria, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Versari, A. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Gafa, S.I. (Div. di Malattie Infettive, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Becquemin, M.H. (Service Central d' Explorations Functionnelles Respiratoires, Groupe Hospitalier Pitie-Salpetriere, Paris (France)); Barchi, E. (Div. di Malattie Infettive, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Serafini, D. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Roy, M. (Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France)); Salvo, D. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Bouchikhi, A. (Service Central d' Explorations Functionnelles Respiratoires, Groupe Hospitalier Pitie-Salpetriere, Paris (France))

    1994-05-01

    We studied the performance of a new nebuliser (Pentasave) by comparison both in vitro and in vivo with a standard nebuliser (Respirgard II). In vitro, deposition of pentamidine labelled with technetium-99m human serum albumin was measured indirectly by capturing inhaled particles on an absolute filter and measuring radioactivity with a gamma camera. The nebulisers were initially assessed with a pentamidine dose of 100 mg in 5 ml al 44 psi and an air flow of 10 l/min for Respirgard II and 16 l/min for Pentasave. Nebuliser output, expressed as the percentage of the initial nebuliser radioactivity captured by the inhalation filter, was 15%[+-]2% (mean[+-]SD) for Respirgard II, and significantly increased to 23%[+-]3% for an initial version and to 33%[+-]2% for the final version of Pentasave. Measurements with a gamma camera in a group of ten patients with human immuno-deficiency virus infection were made in vivo. The results revealed that pulmonary drug distributions are good using both Respirgard II and Pentasave. We measured pulmonary pentamidine deposition of 20.22[+-]4.31 mg using Respirgard II (with 300 mg in 5 ml) and of 16.00[+-]7.18 mg using Pentasave (with 150 mg in 6 ml). These findings show that the therepeutic dose of pentamidine (9 mg) was widely exceeded with both nebulisers. (orig./MG)

  9. Adiaspiromicose pulmonar humana Human pulmonary adiaspiromycosis

    Directory of Open Access Journals (Sweden)

    Lina Gomes dos Santos

    2009-08-01

    Full Text Available A adiaspiromicose é uma doença fúngica sistêmica que acomete usualmente roedores e raramente atinge o homem. É causada pelo fungo Emmonsia crescens e ocorre após a inalação da forma contagiante (conídios. Embora estas formas não se multipliquem nem se disseminem no organismo humano, induzem uma reação inflamatória crônica granulomatosa de padrão miliar que pode levar a falência respiratória e morte. Apresentamos aqui um caso de adiaspiromicose pulmonar humana em paciente imunocompetente que exibia infiltrado intersticial pulmonar difuso ao exame de imagem e fora diagnosticado mediante biópsia pulmonar.Adiaspiromycosis is a systemic fungal disease that usually affects rodents and rarely infects humans. It is caused by the fungus Emmonsia crescens and occurs after inhalation of its contagious form (conidia. Although these forms neither multiply nor spread in the human body, they cause a chronic granulomatous inflammatory reaction of miliary pattern, which may lead to respiratory failure and death. In this study we present a case of human pulmonary adiaspiromycosis in an immunocompetent patient that showed a diffuse pulmonary interstitial infiltrate diagnosed by pulmonary biopsy.

  10. Acute pulmonary vasodilatory properties of amlodipine in humans with pulmonary hypertension.

    OpenAIRE

    Woodmansey, P. A.; O'Toole, L.; Channer, K S; Morice, A H

    1996-01-01

    OBJECTIVE: Calcium antagonists are the only oral vasodilators shown to influence mortality in primary pulmonary hypertension, but the high doses required are often poorly tolerated. Amlodipine is a novel, relatively well tolerated, calcium antagonist. It has not been previously tested in humans with pulmonary hypertension. DESIGN: Calcium antagonists are claimed to be of benefit in the 20-30% of patients who respond--that is, whose mean pulmonary artery pressure and pulmonary vascular resista...

  11. Human respiratory deposition of particles during oronasal breathing

    Science.gov (United States)

    Swift, David L.; Proctor, Donald F.

    Deposition of particles in the tracheobronchial and pulmonary airways is computed as a function of particle size, correcting for deposition in the parallel nasal and oral airways with oronasal breathing. Thoracic deposition is lower at all sizes for oronasal breathing than for mouth breathing via tube, and is negligible for aerodynamic equivalent diameters of 10 μm or larger.

  12. An Emerging Pulmonary Haemorrhagic Syndrome in Dogs: Similar to the Human Leptospiral Pulmonary Haemorrhagic Syndrome?

    Directory of Open Access Journals (Sweden)

    R. Klopfleisch

    2010-01-01

    Full Text Available Severe pulmonary haemorrhage is a rare necropsy finding in dogs but the leptospiral pulmonary haemorrhagic syndrome (LPHS is a well recognized disease in humans. Here we report a pulmonary haemorrhagic syndrome in dogs that closely resembles the human disease. All 15 dogs had massive, pulmonary haemorrhage affecting all lung lobes while haemorrhage in other organs was minimal. Histologically, pulmonary lesions were characterized by acute, alveolar haemorrhage without identifiable vascular lesions. Seven dogs had mild alveolar wall necrosis with hyaline membranes and minimal intraalveolar fibrin. In addition, eight dogs had acute renal tubular necrosis. Six dogs had a clinical diagnosis of leptospirosis based on renal and hepatic failure, positive microscopic agglutination test (MAT and/or positive blood/urine Leptospira-specific PCR. Leptospira could not be cultured post mortem from the lungs or kidneys. However, Leptospira-specific PCR was positive in lung, liver or kidneys of three dogs. In summary, a novel pulmonary haemorrhagic syndrome was identified in dogs but the mechanism of the massive pulmonary erythrocyte extravasation remains elusive. The lack of a consistent post mortem identification of Leptospira spp. in dogs with pulmonary haemorrhage raise questions as to whether additional factors besides Leptospira may cause this as yet unrecognized entity in dogs.

  13. Regional aerosol deposition in human upper airways

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1991-11-01

    During the current report experimental studies of upper respiratory deposition of radon progeny aerosols and stimulant aerosols were carried out in replicate casts of nasal and oral passages of adults and children. Additionally, preliminary studies of nasal passage deposition of unattached Po{sup 218} particles was carried out in four human subjects. Data on nasal inspiratory deposition in replicate models of adults and infants from three collaborating laboratories were compared and a best-fit curve of deposition efficiency for both attached and unattached particles was obtained, showing excellent inter-laboratory agreement. This curve demonstrates that nasal inspiratory deposition of radon progeny is weakly dependent upon flow rate over physiologically realistic ranges of flow, does not show a significant age effect, and is relatively independent of nasal passage dimensions for a given age range. Improved replicate models of the human adult oral passage extending to the mid-trachea were constructed for medium and higher flow mouth breathing states; these models were used to assess the deposition of unattached Po{sup 218} particles during oronasal breathing in the oral passage and demonstrated lower deposition efficiency than the nasal passage. Measurements of both Po{sup 218} particle and attached fraction particle size deposition were performed in replicate nasal passage of a four week old infant. 5 refs., 1 fig.

  14. Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis.

    Science.gov (United States)

    Kaplan, Batia; Martin, Brian M; Boykov, Olga; Gal, Rivka; Pras, Mordechai; Shechtman, Itzhak; Saute, Milton; Kramer, Mordechai R

    2005-10-01

    Localized pulmonary amyloidosis is a rare condition whose pathogenesis is insufficiently understood. In the present study, we report a case of localized pulmonary amyloidosis associated with lung-restricted lymphoplasmacytoid lymphoma, monoclonal for immunoglobulin (Ig) G lambda (lambda). Biochemical microtechniques have been applied for extraction, purification, and characterization of amyloid proteins. Surprisingly, chemical analysis of these proteins revealed a not-previously-described case of combined deposits containing Ig fragments of gamma heavy chain (variable domain) and lambda light chain (constant domain). In view of the absence of circulating monoclonal Ig, this case supports the hypothesis that localized amyloid is formed by local plasmacytoid cells.

  15. [Pulmonary complications in children with human immunodeficiency virus infection].

    Science.gov (United States)

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  16. Deposition of contaminant aerosol on human skin

    DEFF Research Database (Denmark)

    Andersson, Kasper Grann; Roed, Jørn; Byrne, M.A.

    2006-01-01

    Over recent years, it has been established that deposition of various types of pollutant aerosols (e.g., radioactive) on human skin can have serious deleterious effects on health. However. only few investigations in the past have been devoted to measurement of deposition velocities on skin...... of particles of the potentially problematic sizes. An experimental programme has shown the deposition velocities on skin of particles in the ca. 0.5-5 mu m AMAD range to be high and generally associated with great variations. A series of investigations have been made to identify some of the factors that lead...... to this variation. Part of the variation was found to be caused by differences between individuals, whereas another part was found to be related to environmental factors, The identification of major influences on skin contaminant deposition is important in estimating health effects as well as in identifying means...

  17. Influence of breathing pattern on pulmonary aerosol deposition in patients with cystic fibrosis (CF): A pharmacokinetic approach

    NARCIS (Netherlands)

    Van Velzen, A.J.; Uges, J.W.F.; Le Brun, P.P.H.; Shahbabai, P.; Touw, D.J.; Heijerman, H.G.M.

    2014-01-01

    The therapeutic effect of inhaled antibiotics on lung infection in CF patients is dependent on the aerosol deposition achieved in the lungs. Objectives: To evaluate the influence of two breathing patterns on pulmonary aerosol deposition using pharmacokinetic parameters as surrogate for deposition. M

  18. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi...

  19. Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness.

    Science.gov (United States)

    Mehlotra, R K; Hall, L R; Higgins, A W; Dreshaj, I A; Haxhiu, M A; Kazura, J W; Pearlman, E

    1998-10-01

    Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology.

  20. Legionella pneumophila induces human beta Defensin-3 in pulmonary cells

    Directory of Open Access Journals (Sweden)

    Hippenstiel Stefan

    2010-07-01

    Full Text Available Abstract Background Legionella pneumophila is an important causative agent of severe pneumonia in humans. Human alveolar epithelium and macrophages are effective barriers for inhaled microorganisms and actively participate in the initiation of innate host defense. The beta defensin-3 (hBD-3, an antimicrobial peptide is an important component of the innate immune response of the human lung. Therefore we hypothesize that hBD-3 might be important for immune defense towards L. pneumophila. Methods We investigated the effects of L. pneumophila and different TLR agonists on pulmonary cells in regard to hBD-3 expression by ELISA. Furthermore, siRNA-mediated inhibition of TLRs as well as chemical inhibition of potential downstream signaling molecules was used for functional analysis. Results L. pneumophila induced release of hBD-3 in pulmonary epithelium and alveolar macrophages. A similar response was observed when epithelial cells were treated with different TLR agonists. Inhibition of TLR2, TLR5, and TLR9 expression led to a decreased hBD-3 expression. Furthermore expression of hBD-3 was mediated through a JNK dependent activation of AP-1 (c-Jun but appeared to be independent of NF-κB. Additionally, we demonstrate that hBD-3 elicited a strong antimicrobial effect on L. pneumophila replication. Conclusions Taken together, human pulmonary cells produce hBD-3 upon L. pneumophila infection via a TLR-JNK-AP-1-dependent pathway which may contribute to an efficient innate immune defense.

  1. Pulmonary capillary recruitment in response to hypoxia in healthy humans: a possible role for hypoxic pulmonary venoconstriction?

    DEFF Research Database (Denmark)

    Taylor, Bryan J; Kjaergaard, Jesper; Snyder, Eric M;

    2011-01-01

    capillary blood volume (Vc) were measured before and after saline infusion and hypoxic-exposure by a rebreathing method. Pulmonary artery systolic pressure (sPpa) and left ventricular (LV) diastolic function were assessed before and after hypoxic-exposure via echocardiography. Saline infusion increased Q......Ppa and LV diastolic function. In conclusion, hypoxia-induced pulmonary capillary recruitment in humans is only partly accounted for by changes in Q, sPpa and LV diastolic function. We speculate that hypoxic pulmonary venoconstriction may play a role in such recruitment.......We examined mechanisms by which hypoxia may elicit pulmonary capillary recruitment in humans. On separate occasions, twenty-five healthy adults underwent exposure to intravenous saline infusion (30 ml/kg ∼ 15 min) or 17-h normobaric hypoxia ( [FIO2 = 12.5%). Cardiac output (Q) and pulmonary...

  2. Aerosol deposition in the human respiratory system. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C.P.

    1988-01-01

    Attempts were made to develop mathematical models for the deposition of aerosols in the human respiratory system. Expressions were obtained for the mean deposition efficiency for nasal inspiration, nasal expiration, and mouth inspiration. A determination was made of statistical properties associated with each deposition efficiency due to intersubject and intrasubject variabilities. Expressions were then derived for head deposition with combined nose and mouth breathing. In the lung, deposition is a result primarily of impaction, sedimentation, and diffusion. While there was no adequate model for impaction, several deposition formulae for sedimentation were derived as well as ones for diffusion. Studies were also made of the particle charge effect, as the electrostatic image force on a particle contributes to its deposition. There is, however, a threshold charge per particle below which the particle charge has no effect on deposition. Deposition data on ultrafine particles is scarce due to the difficulties in conducting proper experiments.

  3. Iron deposition and increased alveolar septal capillary density in nonfibrotic lung tissue are associated with pulmonary hypertension in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Bartholmai Brian J

    2010-04-01

    Full Text Available Abstract Background Early diagnosis of pulmonary hypertension (PH in idiopathic pulmonary fibrosis (IPF has potential prognostic and therapeutic implications but can be difficult due to the lack of specific clinical manifestations or accurate non-invasive tests. Histopathologic parameters correlating with PH in IPF are also not known. Remodeling of postcapillary pulmonary vessels has been reported in the nonfibrotic areas of explanted lungs from IPF patients. We hypothesized that iron deposition and increased alveolar capillaries, the findings often seen in postcapillary PH, might predict the presence of clinical PH, independent of the severity of fibrosis or ventilatory dysfunction in IPF patients. To test this hypothesis, we examined the association between these histologic parameters and the degree of PH, with consideration of the severity of disease in IPF. Methods Iron deposition and alveolar septal capillary density (ASCD were evaluated on histologic sections with hematoxylin-eosin, iron, elastin and CD34 stainings. Percentage of predicted forced vital capacity (FVC% was used for grading pulmonary function status. Fibrosis score assessed on high resolution computed tomography (HRCT was used for evaluating overall degree of fibrosis in whole lungs. Right ventricular systolic pressure (RVSP by transthoracic echocardiography was used for the estimation of PH. Univariate and multivariate regression analyses were performed. Results A cohort of 154 patients was studied who had the clinicopathological diagnosis of IPF with surgical lung biopsies or explants during the period of 1997 to 2006 at Mayo Clinic Rochester. In univariate analysis, RVSP in our IPF cases was associated with both iron deposition and ASCD (p Conclusions Iron deposition and ASCD in non fibrotic lung tissue showed an association with RVSP, suggesting that these features are possible morphologic predictors of PH in IPF.

  4. Numerical Simulation of Particle Deposition in the Human Lungs

    OpenAIRE

    Gengenbach, Thomas

    2012-01-01

    We model, simulate and calculate breathing and particle depositions in the human lungs. We review the theory and discretization of fluid mechanics, the anatomy, physiology and measuring methods of lungs. A new model is introduced and investigated with a sensitivity analysis using the singular value decomposition. Particle depositions are simulated in patient-specific and schematized human lungs and compared to the particle deposition in a multiplicative model of subsequent bifurcations.

  5. Characterization of optimal resting tension in human pulmonary arteries

    Science.gov (United States)

    Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud

    2016-01-01

    AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938

  6. Aerosol deposition in the human lung in reduced gravity.

    Science.gov (United States)

    Darquenne, Chantal

    2014-06-01

    The deposition of aerosol in the human lung occurs mainly through a combination of inertial impaction, gravitational sedimentation, and diffusion. For 0.5- to 5-μm-diameter particles and resting breathing conditions, the primary mechanism of deposition in the intrathoracic airways is sedimentation, and therefore the fate of these particles is markedly affected by gravity. Studies of aerosol deposition in altered gravity have mostly been performed in humans during parabolic flights in both microgravity (μG) and hypergravity (~1.6G), where both total deposition during continuous aerosol mouth breathing and regional deposition using aerosol bolus inhalations were performed with 0.5- to 3-μm particles. Although total deposition increased with increasing gravity level, only peripheral deposition as measured by aerosol bolus inhalations was strongly dependent on gravity, with central deposition (lung depthlung was assessed using planar gamma scintigraphy. The absence of gravity caused a smaller portion of 5-μm particles to deposit in the lung periphery than in the central region, where deposition occurred mainly in the airways. Indeed, 5-μm-diameter particles deposit either by inertial impaction, a mechanism most efficient in the large and medium-sized airways, or by gravitational sedimentation, which is most efficient in the distal lung. On the contrary, for fine particles (~1 μm), both aerosol bolus inhalations and studies in small animals suggest that particles deposit more peripherally in μG than in 1G, beyond the reach of the mucociliary clearance system.

  7. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    Science.gov (United States)

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  8. Human Multidrug Resistance 1 gene polymorphisms and Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Martinelli, Marcella; Scapoli, Luca; Pacilli, Angela Maria Grazia; Carbonara, Paolo; Girardi, Ambra; Mattei, Gabriella; Rodia, Maria Teresa; Solmi, Rossella

    2015-01-01

    Background: For the first time we tested an association between the human multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in which they modify the drug susceptibility and pharmacokinetics. Materials and Methods: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control subjects with Italian origins. Results: No evidence of association was detected. Conclusion: There are 50 known MDR1 SNPs, and their role is explored in terms of the effectiveness of drug therapy. We consider our small-scale preliminary study as a starting point for further research. PMID:25767528

  9. In vivo-in vitro correlations: predicting pulmonary drug deposition from pharmaceutical aerosols.

    Science.gov (United States)

    Byron, Peter R; Hindle, Michael; Lange, Carlos F; Longest, P Worth; McRobbie, Donald; Oldham, Michael J; Olsson, Bo; Thiel, Charles G; Wachtel, Herbert; Finlay, Warren H

    2010-12-01

    In order to answer the question "what research remains to be done?" we review the current state of the art in pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled pharmaceutical aerosol deposition is possible.

  10. Pulmonary deposition modeling with airborne fiber exposure data: a study of workers manufacturing refractory ceramic fibers.

    Science.gov (United States)

    Lentz, Thomas J; Rice, Carol H; Succop, Paul A; Lockey, James E; Dement, John M; LeMasters, Grace K

    2003-04-01

    Increasing production of refractory ceramic fiber (RCF), a synthetic vitreous material with industrial applications (e.g., kiln insulation), has created interest in potential respiratory effects of exposure to airborne fibers during manufacturing. An ongoing study of RCF manufacturing workers in the United States has indicated an association between cumulative fiber exposure and pleural plaques. Fiber sizing data, obtained from electron microscopy analyses of 118 air samples collected in three independent studies over a 20-year period (1976-1995), were used with a computer deposition model to estimate pulmonary dose of fibers of specified dimensions for 652 former and current RCF production workers. Separate dose correction factors reflecting differences in fiber dimensions in six uniform job title groups were used with data on airborne fiber concentration and employment duration to calculate cumulative dose estimates for each worker. From review of the literature, critical dimensions (diameter <0.4 microm, length <10 microm) were defined for fibers that may translocate to the parietal pleura. Each of three continuous exposure/dose metrics analyzed in separate logistic regression models was significantly related to plaques, even after adjusting for possible past asbestos exposure: cumulative fiber exposure, chi(2) = 15.2 (p < 0.01); cumulative pulmonary dose (all fibers), chi(2) = 14.6 (p < 0.01); cumulative pulmonary dose (critical dimension fibers), chi(2) = 12.4 (p < 0.01). Odds ratios (ORs) were calculated for levels of each metric. Increasing ORs were statistically significant for the two highest dose levels of critical dimension fibers (level three, OR = 11, 95%CI = [1.4, 98]; level four, OR = 25, 95%CI = [3.2, 190]). Similar associations existed for all metrics after adjustment for possible asbestos exposure. It was concluded that development of pleural plaques follows exposure- and dose-response patterns, and that airborne fibers in RCF manufacturing

  11. Pulmonary deposition of urban atmospheric aerosol. Assessments of the mass, number and surface of the deposited particles; Deposizione polmonare dell'aerosol atmosferico urbano in termini di massa, numero e superficie delle particelle

    Energy Technology Data Exchange (ETDEWEB)

    Luciani, A.; Berico, M.; Castellani, C.M. [ENEA, Centro Ricerche Ezio Clementel, Bologna (Italy). Dipt. Ambiente

    1998-07-01

    Pulmonary deposition of urban atmospheric aerosol has been calculated by means of the data derived from March 1995 measurement campaign of urban aerosol. The human respiratory tract model of the International Commission on Radiological Protection (n. 66) developed for radiation protection purposes has been used. The number and surface of the deposited particles, as well as the mass, have been also evaluated. [Italian] I dati relativi alla campagna di misure effettuata nel marzo 1995 sono stati rielaborati al fine di valutare la deposizione polmonare dell'aerosol atmosferico in area urbana. Le valutazioni di deposizione nel tratto respiratorio umano sono state condotte mediante l'utilizzo del modello del tratto respiratorio umano presentato per fini radioprotezionistici dalla International Commission on Radiological Protection (n. 66). Sono state effettuate valutazioni di deposizione in massa e in termini di numero e superficie delle particelle.

  12. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  13. Deposition of insoluble elastin by pulmonary fibroblasts from patients with COPD is increased by treatment with versican siRNA

    Directory of Open Access Journals (Sweden)

    Wu L

    2017-01-01

    Full Text Available Lian Wu,1,2 Jing Zhang,3 Jie Ming Qu,4 Chun-xue Bai,3 Mervyn J Merrilees5 1Department of Community and Health Services, Unitec, 2Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand; 3Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 4Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand Abstract: A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (P<0.01 and significantly increased deposition of insoluble elastin in the COPD cell cultures (P<0.05. The treatment, however, did not significantly affect production of soluble elastin (tropoelastin in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung. Keywords: pulmonary fibroblasts, COPD, elastin, versican

  14. Respiratory tract deposition of polydisperse aerosols in humans.

    Science.gov (United States)

    Diu, C K; Yu, C P

    1983-01-01

    Total and regional deposition of polydisperse aerosols in the human respiratory tract are studied theoretically. The size distribution of the aerosol is assumed to be lognormal. For a given mass median particle diameter, mass deposition fraction is found to vary with the geometric standard deviation of the aerosol. The departure of the deposition pattern in various regions of the respiratory system from that of a monodisperse aerosol is interpreted in terms of the average mobility effect and deposition limitation effect of the polydisperse aerosol together with the sequential filtering effect of the respiratory tract.

  15. Histamine releases PGI2 from human pulmonary artery.

    Science.gov (United States)

    Schellenberg, R R; Duff, M J; Foster, A; Paddon, H B

    1986-08-01

    Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hydroxytryptamine, leukotriene D4, and KCl. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissue with 1 microM indomethacin. Measurement of the PGI2 degradation product 6-keto-PGF1 alpha in supernatants from histamine-challenged tissues confirmed the synthesis of PGI2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF1 alpha. The histamine H1 antagonist diphenydramine inhibited both the contractile and relaxant responses to histamine whereas the H2 antagonist cimetidine affected neither component. The released PGI2 significantly altered the dose-response curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI2 formation from pulmonary arterial endothelium via an H1 receptor.

  16. Regional aerosol deposition in human upper airways. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1997-11-01

    During the award period, a number of studies have been carried out related to the overall objective of the project which is to elucidate important factors which influence the upper airway deposition and dose of particles in the size range 0.5 nm - 10 {mu}m, such as particle size, breathing conditions, age, airway geometry, and mode of breathing. These studies are listed below. (1) A high voltage electrospray system was constructed to generate polydispersed 1-10 {mu}m diameter di-ethylhexyl sebacate aerosol for particle deposition studies in nasal casts and in human subjects. (2) The effect of nostril dimensions, nasal passage geometry, and nasal resistance on particle deposition efficiency in forty healthy, nonsmoking adults at a constant flowrate were studied. (3) The effect of nostril dimensions, nasal passage dimensions and nasal resistance on the percentage of particle deposition in the anterior 3 cm of the nasal passage of spontaneously breathing humans were studied. (4) The region of deposition of monodispersed aerosols were studied using replicate casts. (5) Ultrafine aerosol deposition using simulated breath holding path and natural path was compared. (6) An experimental technique was proposed and tested to measure the oral deposition of inhaled ultrafine particles. (7) We have calculated the total deposition fraction of ultrafine aerosols from 5 to 200 n in the extrathoracic airways and in the lung. (8) The deposition fraction of radon progeny in the head airways was studied using several head airway models.

  17. Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation.

    Science.gov (United States)

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

    1995-01-01

    BACKGROUND--Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition of a spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo. METHODS--Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labelled human serum albumin (99mTc-HSA (50 micrograms); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple T-piece or a 600 ml spacer. RESULTS--The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2.2 (0.7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18.2 min v 18.3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46.2% v 47.1% respectively). CONCLUSIONS--The combination of a spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation. Images PMID:7886649

  18. Pulmonary vein and atrial wall pathology in human total anomalous pulmonary venous connection

    NARCIS (Netherlands)

    Douglas, Yvonne L.; Jongbloed, Monique R. M.; den Hartog, Wietske C. E.; Bartelings, Margot M.; Bogers, Ad J. J. C.; Ebels, Tjark; DeRuiter, Marco C.; Gittenberger-de Groot, Adriana C.

    2009-01-01

    Background: Normally, the inside of the left atrial (LA) body and pulmonary veins (PVs) is lined by vessel wall tissue covered by myocardium. In total anomalous pulmonary venous connection (TAPVC), no connection of the PVs with the LA body exists. These veins have an increased incidence of PV

  19. Applying cybernetic technology to diagnose human pulmonary sounds.

    Science.gov (United States)

    Chen, Mei-Yung; Chou, Cheng-Han

    2014-06-01

    Chest auscultation is a crucial and efficient method for diagnosing lung disease; however, it is a subjective process that relies on physician experience and the ability to differentiate between various sound patterns. Because the physiological signals composed of heart sounds and pulmonary sounds (PSs) are greater than 120 Hz and the human ear is not sensitive to low frequencies, successfully making diagnostic classifications is difficult. To solve this problem, we constructed various PS recognition systems for classifying six PS classes: vesicular breath sounds, bronchial breath sounds, tracheal breath sounds, crackles, wheezes, and stridor sounds. First, we used a piezoelectric microphone and data acquisition card to acquire PS signals and perform signal preprocessing. A wavelet transform was used for feature extraction, and the PS signals were decomposed into frequency subbands. Using a statistical method, we extracted 17 features that were used as the input vectors of a neural network. We proposed a 2-stage classifier combined with a back-propagation (BP) neural network and learning vector quantization (LVQ) neural network, which improves classification accuracy by using a haploid neural network. The receiver operating characteristic (ROC) curve verifies the high performance level of the neural network. To expand traditional auscultation methods, we constructed various PS diagnostic systems that can correctly classify the six common PSs. The proposed device overcomes the lack of human sensitivity to low-frequency sounds and various PS waves, characteristic values, and a spectral analysis charts are provided to elucidate the design of the human-machine interface.

  20. Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.

    Science.gov (United States)

    Talbot, Nick P; Croft, Quentin P; Curtis, M Kate; Turner, Brandon E; Dorrington, Keith L; Robbins, Peter A; Smith, Thomas G

    2014-12-01

    Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.

  1. Deposition of graphene nanomaterial aerosols in human upper airways.

    Science.gov (United States)

    Su, Wei-Chung; Ku, Bon Ki; Kulkarni, Pramod; Cheng, Yung Sung

    2016-01-01

    Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

  2. Copper dependence of angioproliferation in pulmonary arterial hypertension in rats and humans.

    Science.gov (United States)

    Bogaard, Harm J; Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C; Humbert, Marc; Vonk Noordegraaf, Anton; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F

    2012-05-01

    Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation-induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension.

  3. Metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages

    DEFF Research Database (Denmark)

    1978-01-01

    The metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchial epithelium and pulmonary alveolar macrophages was studied. Explants of bronchus were prepared and pulmonary alveolar macrophages were isolated from peripheral lung by trypsinization and by differential adhesion to plastic tissue...

  4. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  5. Deposition of insoluble elastin by pulmonary fibroblasts from patients with COPD is increased by treatment with versican siRNA

    Science.gov (United States)

    Wu, Lian; Zhang, Jing; Qu, Jie Ming; Bai, Chun-xue; Merrilees, Mervyn J

    2017-01-01

    A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (P<0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures (P<0.05). The treatment, however, did not significantly affect production of soluble elastin (tropoelastin) in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung. PMID:28138236

  6. Doppler ultrasonography of the human fetal pulmonary circulation

    NARCIS (Netherlands)

    J.A.M. Laudij (Jacqueline)

    2000-01-01

    textabstractPulmonary hypoplasia is a condition characterized by a decrease in the number of lung cells, airways and alveoli with a resulting decrease in organ size and weight. The reported incidence of pulmonary hypoplasia in the general population is about 1 per 1000 live births and it is one of t

  7. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

    Energy Technology Data Exchange (ETDEWEB)

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  8. Atmospheric iron deposition: global distribution, variability, and human perturbations.

    Science.gov (United States)

    Mahowald, Natalie M; Engelstaedter, Sebastian; Luo, Chao; Sealy, Andrea; Artaxo, Paulo; Benitez-Nelson, Claudia; Bonnet, Sophie; Chen, Ying; Chuang, Patrick Y; Cohen, David D; Dulac, Francois; Herut, Barak; Johansen, Anne M; Kubilay, Nilgun; Losno, Remi; Maenhaut, Willy; Paytan, Adina; Prospero, Joseph M; Shank, Lindsey M; Siefert, Ronald L

    2009-01-01

    Atmospheric inputs of iron to the open ocean are hypothesized to modulate ocean biogeochemistry. This review presents an integration of available observations of atmospheric iron and iron deposition, and also covers bioavailable iron distributions. Methods for estimating temporal variability in ocean deposition over the recent past are reviewed. Desert dust iron is estimated to represent 95% of the global atmospheric iron cycle, and combustion sources of iron are responsible for the remaining 5%. Humans may be significantly perturbing desert dust (up to 50%). The sources of bioavailable iron are less well understood than those of iron, partly because we do not know what speciation of the iron is bioavailable. Bioavailable iron can derive from atmospheric processing of relatively insoluble desert dust iron or from direct emissions of soluble iron from combustion sources. These results imply that humans could be substantially impacting iron and bioavailable iron deposition to ocean regions, but there are large uncertainties in our understanding.

  9. Regional deposition of radon decay products in human airways

    Energy Technology Data Exchange (ETDEWEB)

    Falk, R.; Moere, H.; Nyblom, L.; Oestergren, I. (Swedish Radiation Protection Inst., Stockholm (Sweden))

    1992-01-01

    Experimental studies of the uptake and deposition pattern in the human airways of inhaled radon decay products have been carried out using two different techniques. The deposition in the nasal, bronchial and lung regions was assessed by external gamma measurements on the subject. The exposure of the subject was performed in a 'walk-in' radon chamber with controlled conditions. Results from exposure with high and low aerosol concentrations show that no rapid clearance occurred for the deposited decay products. About 20% of the attached inhaled decay products are retained and deposited in the lungs when mouth breathing during resting conditions, while nasal breathing gave about 26% retention, of which 5% was deposited in the nasal region and about 21% in the lungs. Exposure at low aerosol concentration with unattached fraction of about 80% shows a total retention of about 90% indicating a 100% retention of the unattached fraction. Only about 20% of the unattached fraction is found to penetrate the nasal cavity and it seems to be deposited in the bronchial region. (author).

  10. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    DEFF Research Database (Denmark)

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

    2010-01-01

    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo......BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response...... 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2...

  11. Lipopolysaccharide and Interleukin 1 Augment the Effects of Hypoxia and Inflammation in Human Pulmonary Arterial Tissue

    Science.gov (United States)

    Ziesche, Rolf; Petkov, Venzeslav; Williams, John; Zakeri, Schaker M.; Mosgoller, Wilhelm; Knofler, Martin; Block, Lutz H.

    1996-10-01

    The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor α on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1β , or tumor necrosis factor α augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.

  12. Regional pulmonary perfusion following human heart-lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. (Royal Victoria Hospital, Montreal, Quebec (Canada))

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  13. Influence of Cold Exposure on Ventilation, Respiratory Heat Loss, and Pulmonary Deposition/Clearance

    Science.gov (United States)

    1990-06-25

    13 Particle Deposition in the Lung. .......... 15 Particle Clearance from the Airways . ........ 17 REFERENCES.........................21 III... airways and lung. Should hypoventilation result in increased deposition or decreased clearance , it could not be considered advantageous in this regard, but...cold and cold-induced hypoventilation upon the clearance rate of particles from the upper airways is addressed in Chapter V. Nasal clearance rate was

  14. Transport and deposition of cohesive pharmaceutical powders in human airway

    Science.gov (United States)

    Wang, Yuan; Chu, Kaiwei; Yu, Aibing

    2017-06-01

    Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD) and discrete element method (DEM). The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

  15. Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature

    Directory of Open Access Journals (Sweden)

    Gehr Peter

    2007-08-01

    Full Text Available Abstract Background Translocation of nanoparticles (NP from the pulmonary airways into other pulmonary compartments or the systemic circulation is controversially discussed in the literature. In a previous study it was shown that titanium dioxide (TiO2 NP were "distributed in four lung compartments (air-filled spaces, epithelium/endothelium, connective tissue, capillary lumen in correlation with compartment size". It was concluded that particles can move freely between these tissue compartments. To analyze whether the distribution of TiO2 NP in the lungs is really random or shows a preferential targeting we applied a newly developed method for comparing NP distributions. Methods Rat lungs exposed to an aerosol containing TiO2 NP were prepared for light and electron microscopy at 1 h and at 24 h after exposure. Numbers of TiO2 NP associated with each compartment were counted using energy filtering transmission electron microscopy. Compartment size was estimated by unbiased stereology from systematically sampled light micrographs. Numbers of particles were related to compartment size using a relative deposition index and chi-squared analysis. Results Nanoparticle distribution within the four compartments was not random at 1 h or at 24 h after exposure. At 1 h the connective tissue was the preferential target of the particles. At 24 h the NP were preferentially located in the capillary lumen. Conclusion We conclude that TiO2 NP do not move freely between pulmonary tissue compartments, although they can pass from one compartment to another with relative ease. The residence time of NP in each tissue compartment of the respiratory system depends on the compartment and the time after exposure. It is suggested that a small fraction of TiO2 NP are rapidly transported from the airway lumen to the connective tissue and subsequently released into the systemic circulation.

  16. Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin Induced Pulmonary Fibrosis: Comparison with Pirfenidone

    Science.gov (United States)

    Reddy, Manoj; Fonseca, Lyle; Gowda, Shashank; Chougule, Basavraj; Hari, Aarya; Totey, Satish

    2016-01-01

    Background and Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model. Methods Human AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward. AD-MSCs were labelled with PKH-67 before administration to detect engraftment. Disease severity and improvement was assessed and compared between sham control and vehicle control groups using Kaplan-Meier survival analysis, biochemical and molecular analysis, histopathology and high resolution computed tomography (HRCT) parameters at the end of study. Results Results demonstrated that AD-MSCs significantly increase survivability; reduce organ weight and collagen deposition better than pirfenidone group. Histological analyses and HRCT of the lung revealed that AD-MSCs afforded protection against bleomycin induced fibrosis and protect architecture of the lung. Gene expression analysis revealed that AD-MSCs potently suppressed pro-fibrotic genes induced by bleomycin. More importantly, AD-MSCs were found to inhibit pro-inflammatory related transcripts. Conclusions Our results provided direct evidence that AD-MSC-mediated immunomodulation and anti-fibrotic effect in the lungs resulted in marked protection in pulmonary fibrosis, but at an early stage of disease. PMID:27871152

  17. Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Butrous Ghazwan S

    2011-10-01

    Full Text Available Abstract Background Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. Methods Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin, lipophobic (pravastatin and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. Results Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550 was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. Conclusions Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.

  18. Cigarette smoke toxins deposited on surfaces: implications for human health.

    Directory of Open Access Journals (Sweden)

    Manuela Martins-Green

    Full Text Available Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered - Thirdhand smoke (THS - the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker similar to those found in children exposed to SHS (and consequently to THS. In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.

  19. Increased deposition of chondroitin/dermatan sulfate glycosaminoglycan and upregulation of β1,3-glucuronosyltransferase I in pulmonary fibrosis.

    Science.gov (United States)

    Venkatesan, Narayanan; Ouzzine, Mohamed; Kolb, Martin; Netter, Patrick; Ludwig, Mara S

    2011-02-01

    Pulmonary fibrosis (PF) is characterized by increased deposition of proteoglycans (PGs), in particular core proteins. Glycosaminoglycans (GAGs) are key players in tissue repair and fibrosis, and we investigated whether PF is associated with changes in the expression and structure of GAGs as well as in the expression of β1,3-glucuronosyltransferase I (GlcAT-I), a rate-limiting enzyme in GAG synthesis. Lung biopsies from idiopathic pulmonary fibrosis (IPF) patients and lung tissue from a rat model of bleomycin (BLM)-induced PF were immunostained for chondroitin sulfated-GAGs and GlcAT-I expression. Alterations in disaccharide composition and sulfation of chondroitin/dermatan sulfate (CS/DS) were evaluated by fluorophore-assisted carbohydrate electrophoresis (FACE) in BLM rats. Lung fibroblasts isolated from control (saline-instilled) or BLM rat lungs were assessed for GAG structure and GlcAT-I expression. Disaccharide analysis showed that 4- and 6-sulfated disaccharides were increased in the lungs and lung fibroblasts obtained from fibrotic rats compared with controls. Fibrotic lung fibroblasts and transforming growth factor-β(1) (TGF-β(1))-treated normal lung fibroblasts expressed increased amounts of hyaluronan and 4- and 6-sulfated chondroitin, and neutralizing anti-TGF-β(1) antibody diminished the same. TGF-β(1) upregulated GlcAT-I and versican expression in lung fibroblasts, and signaling through TGF-β type I receptor/p38 MAPK was required for TGF-β(1)-mediated GlcAT-I and CS-GAG expression in fibroblasts. Our data show for the first time increased expression of CS-GAGs and GlcAT-I in IPF, fibrotic rat lungs, and fibrotic lung fibroblasts. These data suggest that alterations of sulfation isomers of CS/DS and upregulation of GlcAT-I contribute to the pathological PG-GAG accumulation in PF.

  20. Lecithin/TPGS-based spray-dried self-microemulsifying drug delivery systems: In vitro pulmonary deposition and cytotoxicity.

    Science.gov (United States)

    Ishak, Rania A H; Osman, Rihab

    2015-05-15

    The aim of the present work was to develop a new solid self-microemulsifying drug delivery system (SMEDDS) for the pulmonary delivery of the poorly water-soluble anti-cancer drug atorvastatin (AVT). Microemulsion (ME) was first developed using isopropyl myristate (IPM), a combination of 2 biocompatible surfactants: lecithin/d-α-tocopheryl polyethylene glycol succinate (TPGS) and ethanol as co-surfactant. Two types of lecithin with different phosphatidylcholine (PC) contents were compared. Phase diagram, physico-chemical characterization and stability studies were used to investigate ME region. Solid SMEDDS were then prepared by spray-drying the selected ME using a combination of carriers composed of sugars, leucine as dispersibility enhancer with or without polyethylene glycol (PEG) 6000. Yield, flow properties, particle size and in vitro pulmonary deposition were used to characterize the spray-dried powders. Reconstituted MEs were characterized in terms of morphology, particle size and size distribution. In vitro cytotoxicity study was undertaken on lung cancer cell line for the selected MEs and SD-SMEDDS formulae. Results showed that the most satisfactory MEs properties were obtained with 1:3 lecithin/TPGS, 1:1 lecithin/oil and 1:1 surfactant/co-surfactant ratios. A larger ME area was obtained with lecithin containing 100% PC compared to the less expensive lecithin containing 20% PC. By manipulating spray drying parameters, carrier composition and ratio of ME lipids to carrier, microparticles with more than 70% of respirable fraction could be prepared. The ME was efficiently recovered in simulated lung fluid even after removal of alcohol. The concurrent delivery of AVT with TPGS in solid SMEDDS greatly enhanced the cytotoxic activity on lung cancer cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Adult human case of toxocariasis with pulmonary migratory infiltrate and eosinophilia

    Directory of Open Access Journals (Sweden)

    Považan Đorđe

    2011-01-01

    Full Text Available Introduction. Toxocariasis is a zoonosis which is in Serbia characterized with a very high infection rate of dogs and excessive contamination of the soil with the eggs of Toxocara canis, the agent of the disease. Toxocara-induced infections have in recent years been established in a few hundreds of children, but toxocariasis has rather rarely been diagnosed in adults. Case report. We reported toxocariasis (visceral larva migrans in an adult, manifested by migratory pulmonary infiltrates and positive serological test finding to Toxocara. Conclusion. Human toxocariasis is a rare disease in adults, therefore it should be considered in adult patients presented with eosinophilia and migratory pulmonary infiltrates.

  2. Atmospheric aerosol in an urban area: Comparison of measurement instruments and methodologies and pulmonary deposition assessment; Aerosol atmosferico in area urbanae di misura e valutazione di deposizione polmonare

    Energy Technology Data Exchange (ETDEWEB)

    Berico, M.; Luciani, A.; Formignani, M. [ENEA, Centro Ricerche Bologna (Italy). Dip. Ambiente

    1996-07-01

    In March 1995 a measurement campaign of atmospheric aerosol in the Bologna urban area (Italy) was carried out. A transportable laboratory, set up by ENEA (Italian national Agency for New Technologies, Energy and the Environment) Environmental Department (Bologna), was utilized with instruments for measurement of atmospheric aerosol and meteorological parameters. The aim of this campaign was of dual purpose: to characterize aerosol in urban area and to compare different instruments and methodologies of measurements. Mass concentrations measurements, evaluated on a 23-hour period with total filter, PM10 dichotomous sampler and low pressure impactor (LPI Berner), have provided information respectively about total suspended particles, respirable fraction and granulometric parameters of aerosol. Eight meteorologic parameters, number concentration of submicromic fraction of aerosol and mass concentration of micromic fraction have been continually measured. Then, in a daytime period, several number granulometries of atmospheric aerosol have also been estimated by means of diffusion battery system. Results related to different measurement methodologies and granulometric characteristics of aerosol are presented here. Pulmonary deposition of atmospheric aerosol is finally calculated, using granulometries provided by LPI Brener and ICRP 66 human respiratory tract model.

  3. Deposition of combustion aerosols in the human respiratory tract: comparison of theoretical predictions with experimental data considering nonspherical shape.

    Science.gov (United States)

    Hofmann, W; Morawska, L; Winkler-Heil, R; Moustafa, M

    2009-12-01

    Total deposition of petrol and diesel combustion aerosols and environmental tobacco smoke (ETS) particles in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific pulmonary function parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol smoke, 24.0% for diesel smoke, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol smoke, 29.6% for diesel smoke, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the nonspherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel combustion particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.

  4. Humane metapneumovirus (HMPV) associated pulmonary infections in immunocompromised adults—Initial CT findings, disease course and comparison to respiratory-syncytial-virus (RSV) induced pulmonary infections

    Energy Technology Data Exchange (ETDEWEB)

    Syha, R., E-mail: roland.syha@med.uni-tuebingen.de [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany); Beck, R. [Institute of Medical Virology, Eberhard-Karls-University, Elfriede-Authorn-Str. 6, 72076 Tübingen (Germany); Hetzel, J. [Department of Medical Oncology and Hematology, Eberhard-Karls-University, Otfried-Müller-Str. 10, 72070 Tübingen (Germany); Ketelsen, D.; Grosse, U.; Springer, F.; Horger, M. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany)

    2012-12-15

    Aim: To describe computed tomography (CT)-imaging findings in human metapneumovirus (HMPV)-related pulmonary infection as well as their temporal course and to analyze resemblances/differences to pulmonary infection induced by the closely related respiratory-syncytial-virus (RSV) in immunocompromised patients. Materials and methods: Chest-CT-scans of 10 HMPV PCR-positive patients experiencing pulmonary symptoms were evaluated retrospectively with respect to imaging findings and their distribution and results were then compared with data acquired in 13 patients with RSV pulmonary infection. Subsequently, we analyzed the course of chest-findings in HMPV patients. Results: In HMPV, 8/10 patients showed asymmetric pulmonary findings, whereas 13/13 patients with RSV-pneumonia presented more symmetrical bilateral pulmonary infiltrates. Image analysis yielded in HMPV patients following results: ground-glass-opacity (GGO) (n = 6), parenchymal airspace consolidations (n = 5), ill-defined nodular-like centrilobular opacities (n = 9), bronchial wall thickening (n = 8). In comparison, results in RSV patients were: GGO (n = 10), parenchymal airspace consolidations (n = 9), ill-defined nodular-like centrilobular opacities (n = 10), bronchial wall thickening (n = 4). In the course of the disease, signs of acute HMPV interstitial pneumonia regressed transforming temporarily in part into findings compatible with bronchitis/bronchiolitis. Conclusions: Early chest-CT findings in patients with HMPV-related pulmonary symptoms are compatible with asymmetric acute interstitial pneumonia accompanied by signs of bronchitis; the former transforming with time into bronchitis and bronchiolitis before they resolve. On the contrary, RSV-induced pulmonary infection exhibits mainly symmetric acute interstitial pneumonia.

  5. Interactions between heart rate variability and pulmonary gas exchange efficiency in humans.

    Science.gov (United States)

    Sin, Peter Y W; Webber, Matthew R; Galletly, Duncan C; Ainslie, Philip N; Brown, Stephen J; Willie, Chris K; Sasse, Alexander; Larsen, Peter D; Tzeng, Yu-Chieh

    2010-07-01

    The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed-rate cardiac pacemakers and 10 healthy control subjects, we recorded R-R intervals, respiratory flow, end-tidal gas tension and the ventilatory equivalents for carbon dioxide and oxygen during 'fast' (0.25 Hz) and 'slow' paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, end-tidal CO(2), and were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5-fold RSA amplitude increase in control subjects (39 +/- 21 versus 97 +/- 45 ms, P exchange efficiency during variable-frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.

  6. Monitoring the initial pulmonary absorption of two different beclomethasone dipropionate aerosols employing a human lung reperfusion model

    Directory of Open Access Journals (Sweden)

    Fritz Peter

    2005-02-01

    Full Text Available Abstract Background The pulmonary residence time of inhaled glucocorticoids as well as their rate and extend of absorption into systemic circulation are important facets of their efficacy-safety profile. We evaluated a novel approach to elucidate the pulmonary absorption of an inhaled glucocorticoid. Our objective was to monitor and compare the combined process of drug particle dissolution, pro-drug activation and time course of initial distribution from human lung tissue into plasma for two different glucocorticoid formulations. Methods We chose beclomethasone dipropionate (BDP delivered by two different commercially available HFA-propelled metered dose inhalers (Sanasthmax®/Becloforte™ and Ventolair®/Qvar™. Initially we developed a simple dialysis model to assess the transfer of BDP and its active metabolite from human lung homogenate into human plasma. In a novel experimental setting we then administered the aerosols into the bronchus of an extracorporally ventilated and reperfused human lung lobe and monitored the concentrations of BDP and its metabolites in the reperfusion fluid. Results Unexpectedly, we observed differences between the two aerosol formulations Sanasthmax®/Becloforte™ and Ventolair®/Qvar™ in both the dialysis as well as in the human reperfusion model. The HFA-BDP formulated as Ventolair®/Qvar™ displayed a more rapid release from lung tissue compared to Sanasthmax®/Becloforte™. We succeeded to explain and illustrate the observed differences between the two aerosols with their unique particle topology and divergent dissolution behaviour in human bronchial fluid. Conclusion We conclude that though the ultrafine particles of Ventolair®/Qvar™ are beneficial for high lung deposition, they also yield a less desired more rapid systemic drug delivery. While the differences between Sanasthmax®/Becloforte™ and Ventolair®/Qvar™ were obvious in both the dialysis and lung perfusion experiments, the latter

  7. Puerarin induces mitochondria-dependent apoptosis in hypoxic human pulmonary arterial smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Chan Chen

    Full Text Available BACKGROUND: Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (PAH is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs. Puerarin, an isoflavone purified from the Chinese medicinal herb kudzu, ameliorates chronic hypoxic PAH in animal models. Here we investigated the effects of puerarin on apoptosis of hypoxic human PASMCs (HPASMCs, and to determine the possible underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: HPASMCs were cultured for 24 h in normoxia or hypoxia (5% O₂ conditions with and without puerarin. Cell number and viability were determined with a hemacytometer or a cell counting kit. Apoptosis was detected with a TUNEL test, rhodamine-123 (R-123 fluorescence, a colorimetric assay, western blots, immunohistochemical staining and RT-PCR. Hypoxia inhibited mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after puerarin (50 µM or more intervention, cell growth was inhibited and apoptosis was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by reduced mitochondrial membrane potential, cytochrome c release from the mitochondria, caspase-9 activation, and Bcl-2 down-regulation with concurrent Bax up-regulation. CONCLUSIONS/SIGNIFICANCE: Puerarin promoted apoptosis in hypoxic HPASMCs by acting on the mitochondria-dependent pathway. These results suggest a new mechanism of puerarin relevant to the management of clinical hypoxic pulmonary hypertension.

  8. Puerarin Induces Mitochondria-Dependent Apoptosis in Hypoxic Human Pulmonary Arterial Smooth Muscle Cells

    Science.gov (United States)

    Chen, Chan; Chen, Chun; Wang, Zhiyi; Wang, Liangxing; Yang, Lehe; Ding, Minjiao; Ding, Cheng; Sun, Yu; Lin, Quan; Huang, Xiaoying; Du, Xiaohong; Zhao, Xiaowei; Wang, Chuangyi

    2012-01-01

    Background Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (PAH) is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Puerarin, an isoflavone purified from the Chinese medicinal herb kudzu, ameliorates chronic hypoxic PAH in animal models. Here we investigated the effects of puerarin on apoptosis of hypoxic human PASMCs (HPASMCs), and to determine the possible underlying mechanisms. Methodology/Principal Findings HPASMCs were cultured for 24 h in normoxia or hypoxia (5% O2) conditions with and without puerarin. Cell number and viability were determined with a hemacytometer or a cell counting kit. Apoptosis was detected with a TUNEL test, rhodamine-123 (R-123) fluorescence, a colorimetric assay, western blots, immunohistochemical staining and RT-PCR. Hypoxia inhibited mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after puerarin (50 µM or more) intervention, cell growth was inhibited and apoptosis was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by reduced mitochondrial membrane potential, cytochrome c release from the mitochondria, caspase-9 activation, and Bcl-2 down-regulation with concurrent Bax up-regulation. Conclusions/Significance Puerarin promoted apoptosis in hypoxic HPASMCs by acting on the mitochondria-dependent pathway. These results suggest a new mechanism of puerarin relevant to the management of clinical hypoxic pulmonary hypertension. PMID:22457823

  9. Doppler echo evaluation of pulmonary venous-left atrial pressure gradients: human and numerical model studies

    Science.gov (United States)

    Firstenberg, M. S.; Greenberg, N. L.; Smedira, N. G.; Prior, D. L.; Scalia, G. M.; Thomas, J. D.; Garcia, M. J.

    2000-01-01

    The simplified Bernoulli equation relates fluid convective energy derived from flow velocities to a pressure gradient and is commonly used in clinical echocardiography to determine pressure differences across stenotic orifices. Its application to pulmonary venous flow has not been described in humans. Twelve patients undergoing cardiac surgery had simultaneous high-fidelity pulmonary venous and left atrial pressure measurements and pulmonary venous pulsed Doppler echocardiography performed. Convective gradients for the systolic (S), diastolic (D), and atrial reversal (AR) phases of pulmonary venous flow were determined using the simplified Bernoulli equation and correlated with measured actual pressure differences. A linear relationship was observed between the convective (y) and actual (x) pressure differences for the S (y = 0.23x + 0.0074, r = 0.82) and D (y = 0.22x + 0.092, r = 0.81) waves, but not for the AR wave (y = 0. 030x + 0.13, r = 0.10). Numerical modeling resulted in similar slopes for the S (y = 0.200x - 0.127, r = 0.97), D (y = 0.247x - 0. 354, r = 0.99), and AR (y = 0.087x - 0.083, r = 0.96) waves. Consistent with numerical modeling, the convective term strongly correlates with but significantly underestimates actual gradient because of large inertial forces.

  10. Rodent models of pulmonary hypertension: harmonisation with the world health organisation's categorisation of human PH.

    Science.gov (United States)

    Ryan, J; Bloch, K; Archer, S L

    2011-08-01

    The WHO classification of pulmonary hypertension (PH) recognises five distinct groups, all sharing a mean, resting, pulmonary artery pressure (PAP) > 25 mmHg. The aetiology of PH varies by group (1-pulmonary vascular disease, 2-high left heart filling pressures, 3-hypoxia, 4-unresolved pulmonary embolism and 5-miscellaneous). Inclusion in a group reflects shared histological, haemodynamic and pathophysiological features and has therapeutic implications. Advantages of using rodent models to understand the pathophysiology of human PH and to test experimental therapies include the economy, safety and mechanistic certainty they provide. As rodent models are meant to reflect human PH, they should be categorised by a parallel PH classification and limitations in achieving this ideal recognised. Challenges with rodent models include: accurate phenotypic characterisation (haemodynamics, histology and imaging), species and strain variations in the natural history of PH, and poor fidelity to the relevant human PH group. Rat models of group 1 PH include: monocrotaline (± pneumonectomy), chronic hypoxia + SU-5416 (a VEGF receptor inhibitor) and the fawn-hooded rat (FHR). Mouse models of group 1 PH include: transgenic mice overexpressing the serotonin transporter or dominant-negative mutants of bone morphogenetic protein receptor-2. Group 1 PH is also created by infecting S100A4/Mts1 mice with γ-herpesvirus. The histological features of group 1 PH, but not PH itself, are induced by exposure to Schistosoma mansoni or Stachybotrys chartarum. Group 3 PH is modelled by exposure of rats or mice to chronic hypoxia. Rodent models of groups 2, 4 and 5 PH are needed. Comprehensive haemodynamic, histological and molecular phenotyping, coupled with categorisation into WHO PH groups, enhances the utility of rodent models.

  11. Decellularization of human and porcine lung tissues for pulmonary tissue engineering.

    Science.gov (United States)

    O'Neill, John D; Anfang, Rachel; Anandappa, Annabelle; Costa, Joseph; Javidfar, Jeffrey; Wobma, Holly M; Singh, Gopal; Freytes, Donald O; Bacchetta, Matthew D; Sonett, Joshua R; Vunjak-Novakovic, Gordana

    2013-09-01

    The only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide "ideal" biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies. Human and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days. Decellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM. Porcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Fused pulmonary lobes is a rat model of human Fraser syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kiyozumi, Daiji; Nakano, Itsuko [Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takahashi, Ken L.; Hojo, Hitoshi; Aoyama, Hiroaki [Toxicology Division, Institute of Environmental Toxicology, 4321 Uchimoriya, Joso, Ibaraki 303-0043 (Japan); Sekiguchi, Kiyotoshi, E-mail: sekiguch@protein.osaka-u.ac.jp [Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2011-07-29

    Highlights: {yields} Fused pulmonary lobes (fpl) mutant rats exhibit similar phenotypes to Fraser syndrome. {yields} The fpl gene harbors a nonsense mutation in Fraser syndrome-associated gene Frem2. {yields} Fpl mutant is defined as a first model of human Fraser syndrome in rats. -- Abstract: Fused pulmonary lobes (fpl) is a mutant gene that is inherited in an autosomal recessive manner and causes various developmental defects, including fusion of pulmonary lobes, and eyelid and digit anomalies in rats. Since these developmental defects closely resemble those observed in patients with Fraser syndrome, a recessive multiorgan disorder, and its model animals, we investigated whether the abnormal phenotypes observed in fpl/fpl mutant rats are attributable to a genetic disorder similar to Fraser syndrome. At the epidermal basement membrane in fpl/fpl mutant neonates, the expression of QBRICK, a basement membrane protein whose expression is attenuated in Fraser syndrome model mice, was greatly diminished compared with control littermates. Quantitative RT-PCR analyses of Fraser syndrome-related genes revealed that Frem2 transcripts were markedly diminished in QBRICK-negative embryos. Genomic DNA sequencing of the fpl/fpl mutant identified a nonsense mutation that introduced a stop codon at serine 2005 in Frem2. These findings indicate that the fpl mutant is a rat model of human Fraser syndrome.

  13. Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Afzal Saliha

    2006-01-01

    Full Text Available Abstract Background Pulmonary arterial hypertension is a proliferative vascular disease, characterized by aberrant regulation of smooth muscle cell proliferation and apoptosis in distal pulmonary arteries. Prostacyclin (PGI2 analogues have anti-proliferative effects on distal human pulmonary artery smooth muscle cells (PASMCs, which are dependent on intracellular cAMP stimulation. We therefore sought to investigate the involvement of the main cAMP-specific enzymes, phosphodiesterase type 4 (PDE4, responsible for cAMP hydrolysis. Methods Distal human PASMCs were derived from pulmonary arteries by explant culture (n = 14, passage 3–12. Responses to platelet-derived growth factor-BB (5–10 ng/ml, serum, PGI2 analogues (cicaprost, iloprost and PDE4 inhibitors (roflumilast, rolipram, cilomilast were determined by measuring cAMP phosphodiesterase activity, intracellular cAMP levels, DNA synthesis, apoptosis (as measured by DNA fragmentation and nuclear condensation and matrix metalloproteinase-2 and -9 (MMP-2, MMP-9 production. Results Expression of all four PDE4A-D genes was detected in PASMC isolates. PDE4 contributed to the main proportion (35.9 ± 2.3%, n = 5 of cAMP-specific hydrolytic activity demonstrated in PASMCs, compared to PDE3 (21.5 ± 2.5%, PDE2 (15.8 ± 3.4% or PDE1 activity (14.5 ± 4.2%. Intracellular cAMP levels were increased by PGI2 analogues and further elevated in cells co-treated with roflumilast, rolipram and cilomilast. DNA synthesis was attenuated by 1 μM roflumilast (49 ± 6% inhibition, rolipram (37 ± 6% and cilomilast (30 ± 4% and, in the presence of 5 nM cicaprost, these compounds exhibited EC50 values of 4.4 (2.6–6.1 nM (Mean and 95% confidence interval, 59 (36–83 nM and 97 (66–130 nM respectively. Roflumilast attenuated cell proliferation and gelatinase (MMP-2 and MMP-9 production and promoted the anti-proliferative effects of PGI2 analogues. The cAMP activators iloprost and forskolin also induced apoptosis

  14. Low level CO2 effects on pulmonary function in humans

    Science.gov (United States)

    Sexton, J.; Mueller, K.; Elliott, A.; Gerzer, D.; Strohl, K. P.; West, J. B. (Principal Investigator)

    1998-01-01

    The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

  15. Air Pollution by Hydrothermal Volcanism and Human Pulmonary Function

    Directory of Open Access Journals (Sweden)

    Diana Linhares

    2015-01-01

    Full Text Available The aim of this study was to assess whether chronic exposure to volcanogenic air pollution by hydrothermal soil diffuse degassing is associated with respiratory defects in humans. This study was carried in the archipelago of the Azores, an area with active volcanism located in the Atlantic Ocean where Eurasian, African, and American lithospheric plates meet. A cross-sectional study was performed on a study group of 146 individuals inhabiting an area where volcanic activity is marked by active fumarolic fields and soil degassing (hydrothermal area and a reference group of 359 individuals inhabiting an area without these secondary manifestations of volcanism (nonhydrothermal area. Odds ratio (OR and 95% confidence intervals (CIs were adjusted for age, gender, fatigue, asthma, and smoking. The OR for restrictive defects and for exacerbation of obstructive defects (COPD in the hydrothermal area was 4.4 (95% CI 1.78–10.69 and 3.2 (95% CI 1.82–5.58, respectively. Increased prevalence of restrictions and all COPD severity ranks (mild, moderate, and severe was observed in the population from the hydrothermal area. These findings may assist health officials in advising and keeping up with these populations to prevent and minimize the risk of respiratory diseases.

  16. Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

    Science.gov (United States)

    Newman, S; Malik, S; Hirst, R; Pitcairn, G; Heide, A; Pabst, J; Dinkelaker, A; Fleischer, W

    2002-12-01

    The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

  17. [The stimulation of human pulmonary artery endothelial cells by cigarette smoke extract contributed to cell senescence and induced human pulmonary artery smooth cell migration].

    Science.gov (United States)

    Cai, L; Zhu, P C; Wang, Y E; Gao, Y T; Ao, Q L

    2017-06-12

    Objective: To observe the senescent effect of human pulmonary arterial endothelial cells (HPAEC) stimulated by cigarette smoke extract (CSE) and the effect of secretion of senescent cells on human pulmonary arterial smooth muscles cell (HPASMC) proliferation and migration. Methods: HPAEC was treated with different concentrations of CSE in vitro and cell proliferation was determined by CCK8, senescence cells analyzed by detecting the β-gal activity, and the senescent proteins of cells measured by Western blot. The concentration of senescence-associated secretory phenotype (SASP) was detected by ELISA and the expression of MCP-1 and TGF-β1 was measured by Real-time PCR. The number of the proliferated cells was measured by Transwell assay and immunoflurescence. Results: The HPAEC was aging with the stimulation concentration of CSE increasing and the stimulation time prolonging (Pcells increased as the exposure time prolonged. Compared with the control group, cell viability of 48 h group(1.8±0.1) and 72 h group (1.8±0.1) decreased significantly. The flow cytometry showed a significant difference between the CSE group(14.1±1.2) and the control group(28.5±1.8) in S phase(Pcell cycle arrest. The SASP was increasing as the CSE-exposure prolonged. Compared with the control group(177±39), the 48 h group(460±43) and the 72 h group(609±64) showed a marked increase in MCP-1(Pcells could secrete SASP which induced HPASMC proliferation. After different times of conditioned medium stimulation, HPASMC proliferated especially at 72 h(P<0.05) . The immnoflorescence and Transwell assay confirmed this finding. Conclusion: CSE could induce senescence of HPAEC and SASP production which improved HPASMC proliferation and migration.

  18. Cell cycle regulation by glucosamine in human pulmonary epithelial cells.

    Science.gov (United States)

    Chuang, Kun-Han; Lu, Chih-Shen; Kou, Yu Ru; Wu, Yuh-Lin

    2013-04-01

    Airway epithelial cells play an important role against intruding pathogens. Glucosamine, a commonly used supplemental compound, has recently begun to be regarded as a potential anti-inflammatory molecule. This study aimed to uncover how glucosamine impacts on cellular proliferation in human alveolar epithelial cells (A549) and bronchial epithelial cells (HBECs). With trypan blue-exclusion assay, we observed that glucosamine (10, 20, 50 mM) caused a decrease in cell number at 24 and 48 h; with a flow cytometric analysis, we also noted an enhanced cell accumulation within the G(0)/G(1) phase at 24 h and induction of late apoptosis at 24 and 48 h by glucosamine (10, 20, 50 mM) in A549 cells and HBECs. Examination of phosphorylation in retinoblastoma (Rb) protein, we found an inhibitory effect by glucosamine at 20 and 50 mM. Glucosamine at 50 mM was demonstrated to elevate both the mRNA and protein expression of p53 and heme oxygenase-1 (HO-1), but also caused a reduction in p21 protein expression. In addition, glucosamine attenuated p21 protein stability via the proteasomal proteolytic pathway, as well as inducing p21 nuclear accumulation. Altogether, our results suggest that a high dose of glucosamine may inhibit cell proliferation through apoptosis and disturb cell cycle progression with a halt at G(0)/G(1) phase, and that this occurs, at least in part, by a reduction in Rb phosphorylation together with modulation of p21, p53 and HO-1 expression, and nuclear p21 accumulation.

  19. Dynamic Changes of Pulmonary Arterial Pressure and Ductus Arteriosus in Human Newborns From Birth to 72 Hours of Age

    OpenAIRE

    2016-01-01

    Abstract Normal pulmonary artery pressure and pulmonary hypertension assessment of newborns is rarely reported. The aim of the study is to explore dynamic changes of pulmonary arterial pressure and ductus arteriosus in human newborns from birth to 72 h of age with echocardiography. A total of 76 cases of normal newborns were prospectively detected by echocardiography after birth of 2 h, 6 h, 12 h, 24 h, 48 h, and 72 h, respectively. Ductus arteriosus diameter, blood shunt direction, blood flo...

  20. Reduced Gravity and Aerosol Deposition in the Human Lung

    Science.gov (United States)

    Darquenne, C.; Prisk, G. K.

    2017-06-01

    Studies during parabolic flights showed a significant effect of gravity on the amount and site of aerosol deposition in the lung, which may affect subsequent clearance and greatly increase the toxicological impact of inhaled lunar or martian dust.

  1. Atmospheric iron deposition: global distribution, variability, and human perturbations

    OpenAIRE

    N. Mahowald; S. Engelstaedter; Luo, C; Sealy, A.; Artaxo, P.; Benitez-Nelson, C.R.; Bonnet, S.; Chen, Y.; Chuang, P. Y.; Cohen, D.; Dulac, F.; B. Herut; Johansen, A.M.; N. Kubilay; Losno, R.

    2009-01-01

    Atmospheric inputs of iron to the open ocean are hypothesized to modulate ocean biogeochemistry. This review presents an integration of available observations of atmospheric iron and iron deposition, and also covers bioavailable iron distributions. Methods for estimating temporal variability in ocean deposition over the recent past are reviewed. Desert dust iron is estimated to represent 95% of the global atmospheric iron cycle, and combustion sources of iron are responsible for the remaining...

  2. Human C-C chemokine receptor 3 monoclonal antibody inhibits pulmonary inflammation in allergic mice

    Institute of Scientific and Technical Information of China (English)

    Kai WANG; Hua-hao SHEN; Wen LI; Hua-qiong HUANG

    2007-01-01

    Aim:To evaluate the effect of C-C chemokine receptor 3 (CCR3) blockade on pulmonary inflammation and mucus production in allergic mice. Methods:We used the synthetic peptide of the CCR3 NH2-terminal as the immunizing antigen and generated murine monoclonal antibody against the human CCR3. In addition,the generated antibody was administered to mice sensitized and challenged with ovalbumin. The inflammatory cells in bronchoalveolar lavage,cytokine levels,pulmonary histopathology,and mucus secretion were examined. Results:The Western blotting analysis indicated that the generated antibody bound to CCR3 specifically. The allergic mice treated with the antihuman CCR3 antibody exhibited a significant reduction of pulmonary inflammation accompanied with the alteration of cytokine. Conclusion:The antibody we generated was specific to CCR3. The inhibition of airway inflammation and mucus overproduction by the antibody suggested that the blockade of CCR3 is an appealing therapeutical target for asthma. The present research may provide an experimental basis for the further study of this agent.

  3. [Effects of airborne fine particulate matter on human respiratory symptoms and pulmonary function].

    Science.gov (United States)

    Gao, Zhi-Yi; Li, Peng-Kun; Zhao, Jin-Zhuo; Jiang, Rong-Fang; Yang, Bin-Jie; Zhang, Min-Hua; Song, Wei-Min

    2010-10-01

    to explore effects of airborne fine particulate matter exposure on human respiratory symptoms and pulmonary function. one hundred and seven field traffic policemen were recruited as airborne fine particulate matter high-exposure group and one hundred and one male residents as common exposure group. The individual sampler was used to measure fine particulate matter exposure levels of the two groups. To obtain personal information, especially respiratory symptoms such as cough, sputum, etc. a questionnaire survey was used. The pulmonary ventilation function was detected: forced expiratory vital capacity (FVC), the first 1 second forced expiratory volume (FEV1.0), FVC/FEV1.0% and peak flow values (PEF), and the difference of fine particulate matter exposure level and respiratory function of the two groups was compared. 24 h individual average fine particulate matter exposure concentration of traffic police and residents were respectively (115.4 ± 46.17) microg/m(3) and (74.94 ± 40.09) microg/m(3), the traffic police PM2.5 exposure levels were significantly higher than the residents. In the incidence of respiratory symptoms, compared with high-exposure group and common exposure group, coughing, expectoration, throat unwell, asthma, short of breath and nose discomfort, traffic police group was higher than residents group (P matter exposure, may impact respiratory health and impair pulmonary function.

  4. Pulmonary alveolar proteinosis in a cat

    NARCIS (Netherlands)

    Szatmári, Viktor; Teske, Erik; Nikkels, Peter G J; Griese, Matthias; de Jong, Pim A; Grinwis, Guy; Theegarten, Dirk; Veraa, Stefanie; van Steenbeek, Frank G; Drent, Marjolein; Bonella, Francesco

    2015-01-01

    BACKGROUND: Pulmonary alveolar proteinosis is an extremely rare lung disease in animals and humans. It is characterized by the deposition of a large amount of phospholipoproteinaceous material in the alveoli. There are several possible etiologies, both congenital and acquired. Alveolar macrophages

  5. Pulmonary alveolar proteinosis in a cat

    NARCIS (Netherlands)

    Szatmári, Viktor; Teske, Erik; Nikkels, Peter G J; Griese, Matthias; de Jong, Pim A; Grinwis, Guy; Theegarten, Dirk; Veraa, Stefanie; van Steenbeek, Frank G; Drent, Marjolein; Bonella, Francesco

    2015-01-01

    BACKGROUND: Pulmonary alveolar proteinosis is an extremely rare lung disease in animals and humans. It is characterized by the deposition of a large amount of phospholipoproteinaceous material in the alveoli. There are several possible etiologies, both congenital and acquired. Alveolar macrophages p

  6. Focal adhesion kinase antisense oligodeoxynucleotides inhibit human pulmonary artery smooth muscle cells proliferation and promote human pulmonary artery smooth muscle cells apoptosis

    Institute of Scientific and Technical Information of China (English)

    LIN Chun-long; ZHANG Zhen-xiang; XU Yong-jian; NI Wang; CHEN Shi-xin

    2005-01-01

    Background Pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in pulmonary vessel structural remodelling. At present, the mechanisms related to proliferation of PASMCs are not clear. Focal adhesion kinase (FAK) is a widely expressed nonreceptor protein tyrosine kinase. Recent research indicates that FAK is implicated in signalling pathways which regulate cytoskeletal organization, adhesion, migration, survival and proliferation of cells. Furthermore, there are no reports about the role of FAK in human pulmonary artery smooth muscle cells (HPASMCs). We investigated whether FAK takes part in the intracellular signalling pathway involved in HPASMCs proliferation and apoptosis, by using antisense oligodeoxynucleotides (ODNs) to selectively suppress the expression of FAK protein.Methods Cultured HPASMCs stimulated by fibronectin (40 μg/ml) were passively transfected with ODNs, sense FAK, mismatch sense and antisense-FAK respectively. Expression of FAK, Jun NH2-terminal kinase (JNK), cyclin-dependent kinase 2 (CDK 2) and caspase-3 proteins were detected by immunoprecipitation and Western blots. Cell cycle and cell apoptosis were analysed by flow cytometry. In addition, cytoplasmic FAK expression was detected by immunocytochemical staining.Results When compared with mismatch sense group, the protein expressions of FAK, JNK and CDK 2 in HPASMCs decreased in antisense-FAK ODNs group and increased in sense-FAK ODNs group significantly. Caspase-3 expression upregulated in HPASMCs when treated with antisense ODNs and downregulated when treated with sense ODNs. When compared with mismatch sense ODNs group, the proportion of cells at G1 phase decreased significantly in sense ODNs group, while the proportion of cells at S phase increased significantly. In contrast, compared with mismatch sense ODNs group, the proportion of cells at G1 phase was increased significantly in antisense-FAK ODNs group. The level of cell apoptosis in antisense-FAK group

  7. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    Directory of Open Access Journals (Sweden)

    Rafael Ramírez-Romero

    2012-01-01

    Full Text Available Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP and chronic obstructive pulmonary disease (COPD in human beings, calves are proposed as an alternative animal model.

  8. [Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

    Science.gov (United States)

    Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

    2014-12-01

    A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

  9. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    Science.gov (United States)

    Ramírez-Romero, Rafael; Nevárez-Garza, Alicia M.; Rodríguez-Tovar, Luis E.; Wong-González, Alfredo; Ledezma-Torres, Rogelio A.; Hernández-Vidal, Gustavo

    2012-01-01

    Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model. PMID:22629176

  10. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    Science.gov (United States)

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.

  11. Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract.

    Science.gov (United States)

    Nordlund, Markus; Belka, Miloslav; Kuczaj, Arkadiusz K; Lizal, Frantisek; Jedelsky, Jan; Elcner, Jakub; Jicha, Miroslav; Sauser, Youri; Le Bouhellec, Soazig; Cosandey, Stephane; Majeed, Shoaib; Vuillaume, Grégory; Peitsch, Manuel C; Hoeng, Julia

    2017-02-01

    Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 μm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 μm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways.

  12. Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

    Science.gov (United States)

    Simonet, W S; DeRose, M L; Bucay, N; Nguyen, H Q; Wert, S E; Zhou, L; Ulich, T R; Thomason, A; Danilenko, D M; Whitsett, J A

    1995-01-01

    Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5(E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development. Images Fig. 1 Fig. 2 Fig. 3 PMID:8618921

  13. Nebulization and selective deposition of LTD4 in human lungs

    DEFF Research Database (Denmark)

    Bisgaard, H; Poulsen, L; Søndergaard, I

    1987-01-01

    compared to challenges with a relatively central deposition pattern as ensured by inhalation directly from the nebulizer with brisk inhalation maneuvers. The diffuse deposition pattern caused minimal changes in FEV1 but pronounced effect in Vmax30. The effects of LTD4 and histamine on FEV1 and Vmax30.......4. Nebulization of tritiated LTD4 in this phosphate buffer did not cause any appreciable deterioration of the leukotriene, as demonstrated by an unchanged ratio between radioactivity and LTD4 concentration in the test solution before and after nebulization as well as in the condensed aerosol. The aerosol...... volunteers were challenged on separate days with 40 nmol LTD4 or 100 mumol histamine, and the changes in FEV1 and partial flow volume curves initiated at 50% of vital capacity (Vmax30) were measured. A relative diffuse deposition pattern was ensured by inhalation via a settling bag. These results were...

  14. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...... of KS. We hypothesized that these sequences are present in samples obtained by bronchoalveolar lavage (BAL) in patients with pulmonary KS. Utilizing a nested polymerase chain reaction (PCR), 7/12 BAL cell samples from HIV-infected patients with endobronchial KS were positive for HHV-8 DNA. In contrast......, only 2/39 samples from HIV-infected patients without evidence of KS were positive (p = 0.007). Detection of HHV-8 in BAL cells of patients with pulmonary KS was highly specific (95%), with a sensitivity of 58% and a positive predictive value of 78%. In conclusion, HHV-8 is associated with pulmonary KS...

  15. Numerical Simulation on Movement and Deposition of PM2. 5 in Pulmonary Acinus%PM2.5细颗粒物在肺腺泡区运动及沉积的数值模拟

    Institute of Scientific and Technical Information of China (English)

    张鸿雁; 李彦辉; 崔海航

    2015-01-01

    采用数值模拟方法研究了肺腺泡区气流和可吸入颗粒的运动沉积规律.区别于以往的单级固定壁研究方法,本文利用Weibel-A模型中的肺腺泡几何数据,建立了完整覆盖0~8级肺腺泡区的二维几何模型,并通过动边界方法引入节律收缩/扩张的呼吸动力学机制.随后针对正常成年人平静呼吸状态,研究了人体肺腺泡区的非定常流场特性.在此基础上,在拉格朗日框架下研究了可吸入颗粒物的运动,统计了颗粒物的沉积率并对主要沉积机理进行了分析.结果表明:布朗扩散是粒径较小颗粒(0.01μm≤dp≤0.50μm)传输和沉积的主导因素,而重力沉降是粒径较大颗粒(0.50μmdeposition of inhalational particles in human pulmonary acinus. Different from the research method of single generation with stationary wall, 2D model of the whole pulmonary acinus of 0—8 genera-tions was established based on Weibel-A model. The dynamic mechanism of rhythmic contraction/expan-sion through moving boundary method was applied to simulating unsteady airflow patterns in human pul-monary acinus under breathing scenarios of sedentary tidal volume breathing. Particles were traced in the Lagrangian frame, and the particle deposition rate and main deposition mechanisms of particle deposition were analyzed. Results show that while Brownian diffusion dominates the transport of small particles (0. 01μm≤dp≤0. 50μm), gravitational sedimentation dominates that of large particles(0. 5μmdeposition rate is closely related to particle density

  16. Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Catherine W M Ong

    2015-05-01

    Full Text Available Pulmonary cavities, the hallmark of tuberculosis (TB, are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8 secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.

  17. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

    Science.gov (United States)

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S D; Trajanoski, Zlatko; Speicher, Michael R; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W; Hoefler, Gerald

    2016-06-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

  18. Human pulmonary dirofilariasis coexisting with intercostal neurilemmoma: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Chia-Ying Li

    2013-10-01

    Full Text Available Human pulmonary dirofilariasis (HPD is a rare zoonotic infection caused by Dirofilaria immitis. Dogs are the definite hosts and humans are infected occasionally via a vector, generally a mosquito. Most thoracic neurilemmoma arise in the mediastinum and fewer tumors originate peripherally from the intercostal nerves. Most patients with HPD or thoracic neurilemmoma are asymptomatic and these diseases are often discovered incidentally. We present a 53-year-old female who was found to have a pulmonary nodule and a chest wall nodule during a routine health examination. She underwent a video-assisted thoracoscopic surgery (VATS with partial lung resection and local excision of the chest wall. The pathological examination revealed a coiled, degenerating Dirofilariasis immitis worm surrounded by granulomatous inflammation with caseous necrosis and a neurilemmoma composed of S-100 protein immunoreactive but smooth muscle actin negative spindle cells. Because these diseases are self-limiting and make further treatment unnecessary, video-assisted thoracoscopic surgery (VATS is considered preferable and less invasive for definitive diagnosis and management.

  19. Epoxy composite dusts with and without carbon nanotubes cause similar pulmonary responses, but differences in liver histology in mice following pulmonary deposition

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Mortensen, Alicja; Szarek, Jozef;

    2016-01-01

    . Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory......Background: The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison.Methods: Mice...... received a single intratracheal instillation of 18, 54 and 162 mu g of CNT or 54, 162 and 486 mu g of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore...

  20. Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge

    DEFF Research Database (Denmark)

    Koullapis, P. G.; Kassinos, S. C.; Bivolarova, Mariya Petrova

    2016-01-01

    Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work......, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200 kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects....... Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected...

  1. Predictive models for deposition of inhaled diesel exhaust particles in humans and laboratory species

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C.P.; Xu, G.B. (State Univ. of New York at Buffalo, Amherst (USA))

    1987-01-01

    Mathematical and computer models of the respiratory tracts of human beings and of laboratory animals (rats, hamsters, guinea pigs) were used to estimate the deposition patterns of inhaled diesel exhaust particles from automobile emissions. Our goal was to be able to predict the relation between exposure to diesel exhaust particles and the deposition of these particles in the lungs of humans of various ages. Diesel exhaust particles are aggregates with a mass median aerodynamic diameter of approximately 0.2 micron. Their actual size depends on the conditions under which they are generated. Using an appropriate particle model, we derived mathematical expressions that describe the effects of diffusion, sedimentation, impaction, and interception on the deposition of these particles. Because of their small size, we found that most diesel exhaust particles deposited through diffusion, and that the role of the other mechanisms was minor. Anatomical models of the human lung from birth to adulthood, as well as models of the lungs of laboratory species were formulated mathematically using available morphometric data. We used these lung models, together with the corresponding ventilation conditions of each species, to calculate deposition of diesel exhaust particles in the lungs. Under normal breathing conditions, we calculated that 7 to 13 percent (depending on particle size) of inhaled diesel exhaust particles deposit in the alveolar region of the adult human lung. Although the breathing mode (nose or mouth breathing) did not appear to affect alveolar deposition, increasing the minute ventilation increased alveolar deposition significantly. The calculated deposition patterns for diesel exhaust particles in younger humans (under age 25) were similar.

  2. Pulmonary diseases in patients infected with the human immunodeficiency virus in Zimbabwe, Central Africa.

    Science.gov (United States)

    McLeod, D T; Neill, P; Robertson, V J; Latif, A S; Emmanuel, J C; Els, J E; Gwanzura, L K; Trijssenaar, F E; Nziramasanga, P; Jongeling, G R

    1989-01-01

    During the 11 month period up to 30 September 1987, 37 patients (26 male, 11 female, mean age 27 years) with respiratory symptoms who were human immunodeficiency virus (HIV) positive, were studied prospectively on 40 occasions to determine the cause of any pulmonary complications. HIV was heterosexually transmitted. Predominant symptoms were cough (89%), fever (89%), weight loss (83%), and dyspnoea (60%). Transnasal fibre-optic bronchoscopy (with bronchoalveolar lavage, bronchial brushings and transbronchial lung biopsies) was performed on 35 patients, twice on 3 patients. 'Tru-cut' lung biopsies were obtained from 2 patients who died before bronchoscopy. Pulmonary tuberculosis was the commonest disease, being found in one-third of the patients (12 of 37). Mycobacterium tuberculosis was cultured from 4; the remainder of the plates were contaminated. Pneumocystis carinii was present in 8 patients: as the sole pathogen in 3, with Streptococcus pneumoniae in 4, Staphylococcus aureus in 2, and one also had tuberculous lymphadenitis. Endobronchial Kaposi's sarcoma was seen in 6 of 7 patients with skin nodules. Bacterial pathogens isolated included Staph. aureus (5), S. pneumoniae (5), Klebsiella pneumoniae (2), Haemophilus influenzae (2), H. parainfluenzae (1) and Pseudomonas aeruginosa (1). Invading Aspergillus fumigatus was diagnosed by lung biopsy in one. No diagnosis was reached for 8 patients. It is concluded that in Central Africa pulmonary complications in AIDS patients are similar to those in Europe and North America but the incidence of different pathogens depends on the prevalence of pathogens in the community. M. tuberculosis is probably the commonest pathogen. This study has confirmed that P. carinii pneumonia does occur, but occurs less frequently.

  3. Research of transport and deposition of aerosol in human airway replica

    Directory of Open Access Journals (Sweden)

    Mravec Filip

    2012-04-01

    Full Text Available Growing concern about knowledge of aerosol transport in human lungs is caused by great potential of use of inhaled pharmaceuticals. Second substantial motive for the research is an effort to minimize adverse effects of particular matter emitted by traffic and industry on human health. We created model geometry of human lungs to 7th generation of branching. This model geometry was used for fabrication of two physical models. The first one is made from thin walled transparent silicone and it allows a measurement of velocity and size of aerosol particles by Phase Doppler Anemometry (PDA. The second one is fabricated by stereolithographic method and it is designed for aerosol deposition measurements. We provided a series of measurements of aerosol transport in the transparent model and we ascertained remarkable phenomena linked with lung flow. The results are presented in brief. To gather how this phenomena affects aerosol deposition in human lungs we used the second model and we developed a technique for deposition fraction and deposition efficiency assessment. The results confirmed that non-symmetric and complicated shape of human airways essentially affects transport and deposition of aerosol. The research will now focus on deeper insight in aerosol deposition.

  4. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

    Science.gov (United States)

    Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

    2002-11-01

    Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

  5. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    Science.gov (United States)

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

  6. Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs).

    Science.gov (United States)

    Sharma, Monita; Nikota, Jake; Halappanavar, Sabina; Castranova, Vincent; Rothen-Rutishauser, Barbara; Clippinger, Amy J

    2016-07-01

    The increased production and use of multi-walled carbon nanotubes (MWCNTs) in a diverse array of consumer, medical, and industrial applications have raised concerns about potential human exposure to these materials in the workplace and ambient environments. Inhalation is a primary route of exposure to MWCNTs, and the existing data indicate that they are potentially hazardous to human health. While a 90-day rodent inhalation test (e.g., OECD Test No. 413: subchronic inhalation toxicity: 90-day study or EPA Health Effects Test Guidelines OPPTS 870.3465 90-day inhalation toxicity) is recommended by the U.S. Environmental Protection Agency Office of Pollution Prevention and Toxics for MWCNTs (and other CNTs) if they are to be commercially produced (Godwin et al. in ACS Nano 9:3409-3417, 2015), this test is time and cost-intensive and subject to scientific and ethical concerns. As a result, there has been much interest in transitioning away from studies on animals and moving toward human-based in vitro and in silico models. However, given the multiple mechanisms of toxicity associated with subchronic exposure to inhaled MWCNTs, a battery of non-animal tests will likely be needed to evaluate the key endpoints assessed by the 90-day rodent study. Pulmonary fibrosis is an important adverse outcome related to inhalation exposure to MWCNTs and one that the non-animal approach should be able to assess. This review summarizes the state-of-the-science regarding in vivo and in vitro toxicological methods for predicting MWCNT-induced pulmonary fibrosis.

  7. Indomethacin pretreatment reduces ozone-induced pulmonary function decrements in human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Schelegle, E.S.; Adams, W.C.; Siefkin, A.D.

    1987-12-01

    We studied whether O/sub 3/-induced pulmonary function decrements could be inhibited by the prostaglandin synthetase inhibitor, indomethacin, in healthy human subjects. Fourteen college-age males completed six 1-h exposure protocols consisting of no drug, placebo, and indomethacin (Indocin SR 75 mg every 12 h for 5 days) pretreatments, with filtered air and O/sub 3/ (0.35 ppm) exposures within each pretreatment. Pretreatments were delivered weekly in random order in a double-blind fashion. Ozone and filtered air exposures, separated by 72 h, were delivered in random order in a single-blind fashion. Exposures consisted of 1-h exercise on a bicycle ergometer with work loads set to elicit a mean minute ventilation of 60 L/min. Statistical analysis revealed significant (p less than 0.05) across pretreatment effects for FVC and FEV1, with no drug versus indomethacin and placebo versus indomethacin comparisons being significant. These findings suggest that cyclooxygenase products of arachidonic acid, which are sensitive to indomethacin inhibition, play a prominent role in the development of pulmonary function decrements consequent to acute O/sub 3/ exposure.

  8. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

  9. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...

  10. Impairment of cell cycle progression by sterigmatocystin in human pulmonary cells in vitro.

    Science.gov (United States)

    Huang, Shujuan; Wang, Juan; Xing, Lingxiao; Shen, Haitao; Yan, Xia; Wang, Junling; Zhang, Xianghong

    2014-04-01

    Sterigmatocystin (ST) is a carcinogenic mycotoxin that is commonly found in human food, animal feed and in the indoor environment. Although the correlation between ST exposure and lung cancer has been widely reported in many studies, the cytotoxicity of ST on human pulmonary cells is not yet fully understood. In the current study, we found that ST could induce DNA double-strand breaks in a human immortalized bronchial epithelial cell line (BEAS-2B cells) and a human lung cancer cell line (A549 cells). In addition, the effects of ST on cell cycle arrest were complex and dependent on the tested ST concentration and cell type. Low concentrations of ST arrested cells in the G2/M phase in BEAS-2B cells and in the S phase in A549 cells, while at high concentration both cells lines were arrested in S and G2/M phases. Furthermore, we observed that the modulation of cyclins and CDK expression showed concomitant changes with cell cycle arrest upon ST exposure in BEAS-2B and A549 cells. In conclusion, ST induced DNA damage and affected key proteins involved in cell cycle regulation to trigger genomic instability, which may be a potential mechanism underlying the developmental basis of lung carcinogenesis.

  11. [Expression of aquaporins and its significance in human pulmonary adenocarcinoma cell line SPC-A-1].

    Science.gov (United States)

    Chen, Jie; Bai, Chunxue; Zhang, Min; Ren, Zhenyi; Hu, Jie

    2004-06-20

    To investigate the expression of aquaporins in human pulmonary adenocarcinoma cell line SPC-A-1. The expressions of aquaporin 1, aquaporin 3, aquaporin 4, and aquaporin 5 in mRNA level and their locations were determined in cell line SPC-A-1 respectively by RT-PCR and immunohistochemistry. The immunohistochemical stain showed aquaporin 3 and aquaporin 5 located on the membrane of SPC-A-1 cell, but no positive stain of aquaporin 1 and aquaporin 4 was observed. Both aquaporin 3 and aquaporin 5 mRNA expressed in SPC-A-1 cell line, and the expression level of aquaporin 5 mRNA was significantly higher than that of aquaporin 3 mRNA ( P SPC-A-1 cell line. Aquaporin 3 and aquaporin 5 express in SPC-A-1 cell, and their roles in water transport of SPC-A-1 cell should be further investigated.

  12. PET Imaging of Tau Deposition in the Aging Human Brain.

    Science.gov (United States)

    Schöll, Michael; Lockhart, Samuel N; Schonhaut, Daniel R; O'Neil, James P; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L; Vogel, Jacob W; Faria, Jamie; Schwimmer, Henry D; Rabinovici, Gil D; Jagust, William J

    2016-03-02

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  13. Physicochemical characterization of mineral deposits in human ligamenta flava.

    Science.gov (United States)

    Orzechowska, Sylwia; Wróbel, Andrzej; Kozieł, Marcin; Łasocha, Wiesław; Rokita, Eugeniusz

    2017-04-07

    The aim of our study was the detailed characterization of calcium deposits in ligamenta flava. The use of microcomputed tomography allowed extending the routine medical investigations to characterize mineral grains in the microscopic scale. A possible connection between spinal stenosis and ligament mineralization was investigated. The studies were carried out on 24 surgically removed ligamentum flavum samples divided into control and stenosis groups. Physicochemical characterization of the inorganic material was performed using X-ray fluorescence, X-ray diffraction, and Fourier transform infrared spectroscopy. The minerals were present in 14 of 24 ligament samples, both in stenosis and control groups. The inorganic substance constitutes on average ~0.1% of the sample volume. The minerals are scattered in the soft tissue matrix without any regular pattern. It was confirmed that minerals possess an internal structure and consist of the organic material and small inorganic grains mixture. The physicochemical analyses show that the predominant crystalline phase was hydroxyapatite (HAP). In the stenosis group calcium pyrophosphate dehydrate (CPPD) was identified. Both structures were never present in a single sample. Two different crystal structures suggest two independent processes of mineralization. The formation of CPPD may be treated as a more intense process since CPPD minerals are characterized by bigger values of the structural parameters and higher density than HAP deposits. The formation of HAP minerals is a soft tissue degeneration process that begins, in some cases, at early age or may not occur at all. Various density and volume of mineral grains indicate that the mineralization process does not occur in a constant environment and proceeds with various speeds. The formation of minerals in ligamenta flava is not directly associated with diagnosed spinal canal stenosis.

  14. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

  15. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    Science.gov (United States)

    Purushotham, A D; McCulloch, P; George, W D

    1991-09-01

    Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

  16. Mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: A prospective, cohort study

    Directory of Open Access Journals (Sweden)

    Afessa Bekele

    2001-09-01

    Full Text Available Abstract Background A prospective observational study was done to describe nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus (HIV infection. Methods The study included 1,225 consecutive hospital admissions of 599 HIV-infected patients treated from April 1995 through March 1998. Data included demographics, risk factors for HIV infection, Acute Physiology and Chronic Health Evaluation (APACHE II score, pulmonary complications, CD4+ lymphocyte count, hospital stay and case-fatality rate. Results Patient age (mean ± SD was 38.2 ± 8.9 years, 62% were men, and 84% were African American. The median APACHE II score was 14, and median CD4+ lymphocyte count was 60/μL. Pulmonary complications were Pneumocystis carinii pneumonia (85 in 78 patients, Mycobacterium avium complex (51 in 38, Mycobacterium tuberculosis (40 in 35, Mycobacterium gordonae (11 in 11, Mycobacterium kansasii (10 in 9, Cytomegalovirus (10 in 10, Nocardia asteroides (3 in 3, fungus ball (2 in 2, respiratory syncytial virus (1, herpes simplex virus (1, Histoplasma capsulatum (1, lymphoma (3 in 3, bronchogenic carcinoma (2 in 2, and Kaposi sarcoma (1. The case-fatality rate of patients was 11% with Pneumocystis carinii pneumonia; 5%, Mycobacterium tuberculosis; 6%, Mycobacterium avium complex; and 7%, noninfectious pulmonary complications. Conclusion Most pulmonary complications in hospitalized patients with HIV are from Pneumocystis and mycobacterial infection.

  17. Protective effect of. cap alpha. -human atrial natriuretic polypeptide (. cap alpha. -hANP) on chemical-induced pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, T.; Ohnuma, N.; Iwasa, F.; Furuya, M.; Hayashi, Y.; Inomata, N.; Ishihara, T.; Noguchi, T.

    1988-01-01

    It has been established that ..cap alpha..-hANP, the newly discovered peptide extracted from human cardiac atria, has potent natriuretic and hypotensive actions. The authors present investigation is the first to demonstrate that ..cap alpha..-hANP is capable of protecting against pulmonary edema caused by various chemicals, using isolated perfused guinea pig lung system. Lungs were perfused via pulmonary artery with Krebs-Ringer bicarbonate buffer at 5.0 ml/min, and wet weight of lungs and perfusion pressure of pulmonary artery (Pa) were monitored. Bolus injection of Triton-X or CHAPS into cannulated pulmonary artery produced enema as indicated by a massive increase in wet weight and a slight increase in Pa. Constant infusion of ..cap alpha..-hANP through pulmonary artery at 200 ng/ml was effective in causing decrease in wet weight of lung. Perfusion of lung with paraquat or PGF/sub 2..cap alpha..'/, and repeated bolus injection of arachidonic acid or PGE/sub 2/ caused elevation in both wet weight of lung and Pa.

  18. A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents

    Science.gov (United States)

    Tu, Ly; De Man, Frances; Girerd, Barbara; Huertas, Alice; Chaumais, Marie-Camille; Lecerf, Florence; François, Charlène; Perros, Frédéric; Dorfmüller, Peter; Fadel, Elie; Montani, David; Eddahibi, Saadia; Humbert, Marc; Guignabert, Christophe

    2012-01-01

    Rationale Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary arterial muscularization due to excessive pulmonary vascular cell proliferation and migration, a phenotype dependent upon growth factors and activation of receptor tyrosine kinases (RTKs). p130Cas is an adaptor protein involved in several cellular signaling pathways that control cell migration, proliferation and survival. Objectives We hypothesized that in experimental and human PAH p130Cas signaling is over-activated, thereby facilitating the intracellular transmission of signal induced by fibroblast growth factor (FGF)-2, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). Measurements and Main Results In PAH patients, levels of p130Cas protein and/or activity are higher in the serum, in walls of distal pulmonary arteries, in cultured smooth muscle (PA-SMCs) and pulmonary endothelial cells (P-ECs) than controls. These abnormalities in the p130Cas signaling were also found to be in the chronically hypoxic mice and monocrotaline-injected rats as models of human PAH. We next obtained evidence for convergence and amplification of the growth-stimulating effect of EGF, FGF2 and PDGF signaling pathways via p130Cas signaling pathway. Finally, we found that daily treatment with each of the EGF-R inhibitor gefitinib, the FGF-R inhibitor dovitinib and the PDGF-R inhibitor imatinib started 2 weeks after a subcutaneous monocrotaline injection substantially attenuate the abnormal increase in p130cas and ERK1/2 activation and regress established PH. Conclusions Our findings demonstrate that p130Cas signaling plays a critical role in experimental and iPAH by modulating pulmonary vascular cell migration, proliferation and by acting as an amplifier of RTKs downstream signals. PMID:22798315

  19. Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Mingxia YANG; Zhengxia LIU; Shu ZHANG; Yu JING; Shijiang ZHANG; Weiping XIE; Lei MA; Changliang ZHU; Hong WANG

    2009-01-01

    Aim:To investigate the anti-proliferative effect of iptakalim (Ipt),a newly selective KATP channel opener,in endothelin-1 (ET-1)-induced human pulmonary arterial smooth muscle cells (PASMCs) using proteomic analysis.Methods: Human PASMCs were incubated with ET-1 (10-8 mol/L) and ETA (10-8 mol/L) plus iptaklim (10-5 mol/L) for 24 h.Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of whole-cell protein from cultures of control,ET-1 treatment alone,and treatment with ET-1 and iptaklim combined.Real time RT-PCR and Western blot analysis were used to confirm the proteomic analysis.Results: When iptakalim inhibited the proliferative effect of ET-1 in human PASMCs by opening the KATP channels,the expression of different groups of cellular proteins was changed,including cytoskeleton-associated proteins,plasma mem-brane proteins and receptors,chaperone proteins,ion transport-associated proteins,and glycolytic and metabolism-associ-ated proteins.We found that iptakalim could inhibit the proliferation of human PASMCs partly by affecting the expression of Hsp60,vimentin,nucleoporin P54 (NUP54) and Bcl-XL by opening the KATP channel.Conclusion: The data suggest that a wide range of signaling pathways may be involved in abolishing ET-1-induced prolif-eration of human PASMCs following iptakalim treatment.

  20. MCPIP1 mediates silica-induced cell migration in human pulmonary fibroblasts.

    Science.gov (United States)

    Liu, Haijun; Dai, Xiaoniu; Cheng, Yusi; Fang, Shencun; Zhang, Yingming; Wang, Xingang; Zhang, Wei; Liao, Hong; Yao, Honghong; Chao, Jie

    2016-01-15

    Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lungs initiates an inflammatory cascade that results in fibroblast proliferation and migration followed by fibrosis. According to previous data from our laboratory, monocyte chemotactic protein-1 (MCP-1) plays a critical role in fibroblast proliferation and migration in conventional two-dimensional (2D) monolayer cultures. The present study aimed to explore the downstream cascade of MCP-1 in both 2D and three-dimensional (3D) cell culture models of silicosis. Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following: 1) SiO2 treatment induces expression of MCP-1-induced protein (MCPIP1) in a time- and dose-dependent manner in both 2D and 3D cultures; 2) the MAPK and phosphatidylinositol-3-kinase (PI3K)/Akt pathways are involved in SiO2-induced MCPIP1 expression; and 3) MCPIP1 induction mediates the SiO2-induced increase in cell migration in both 2D and 3D cultures. The effect of MCP-1 in silicosis occurs mainly through MCPIP1, which, in turn, mediates the observed SiO2-induced increase in pulmonary fibroblast migration. However, the time frame for MCPIP1 induction differed between 2D and 3D cultures, indicating that, compared with conventional 2D cell culture systems, 3D culture may be useful for analyses of fibroblast physiology under conditions that more closely resemble in vivo environments. Our study determined the link between fibroblast-derived MCPIP1 and SiO2-induced cell migration, and this finding provides novel evidence of the potential of MCPIP1 in the development of novel therapeutic strategies for silicosis.

  1. Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans.

    Science.gov (United States)

    Bartko, Johann; Stiebellehner, Leopold; Derhaschnig, Ulla; Schoergenhofer, Christian; Schwameis, Michael; Prosch, Helmut; Jilma, Bernd

    2016-05-01

    The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL-6 were only 18% lower and levels of IL-8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. The present study demonstrated a remarkable dissociation between the systemic anti-inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other. © 2015 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  2. [Pulmonary hypertension in human immunodeficiency virus-infected patients: the role of antiretroviral therapy].

    Science.gov (United States)

    Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis

    2014-03-20

    Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  4. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsu-Chi; Swift, D.L. [John Hopkins Univ., Baltimore, MD (United States); Simpson, S.Q. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  5. Deposition pattern of inhaled radon progeny size distribution in human lung

    Directory of Open Access Journals (Sweden)

    Amer Mohamed

    2014-07-01

    Full Text Available One of the important factors controlling the distribution of radiation dose to the different portions of the human respiratory tract is the deposition pattern of radon progeny containing aerosol. Based on the activity size distribution parameters of radon progeny, which were measured in Minia University, the deposition behavior of radon progeny (attached and unattached has been studied by using a stochastic deposition model. The attached fraction was collected using a low pressure Berner cascade impactor technique. A screen diffusion battery was used for collecting the unattached fraction. Most of the attached activities for 222Rn progeny were associated with aerosol particles of the accumulation mode. The bronchial deposition fraction of particles in the size range of attached radon progeny was found to be lower than those of unattached progeny. The effect of radon progeny deposition by adult male has been also studied for various levels of physical exertion. An increase in the breathing rate was found to decrease the fraction with which inhaled progeny were deposited in the bronchi. As the ventilation rate increases from 0.54 to 1.5 m3 h−1, the average deposition fraction of airway generation 1 through 8 are expected to decrease by 22% for 1.4 nm particles and by 38% for 150 nm particles.

  6. Ultrafine Particles in Residential Indoors and Doses Deposited in the Human Respiratory System

    Directory of Open Access Journals (Sweden)

    Maurizio Manigrasso

    2015-09-01

    Full Text Available Indoor aerosol sources may significantly contribute to the daily dose of particles deposited into the human respiratory system. Therefore, it is important to characterize the aerosols deriving from the operations currently performed in an indoor environment and also to estimate the relevant particle respiratory doses. For this aim, aerosols from indoor combustive and non-combustive sources were characterized in terms of aerosol size distributions, and the relevant deposition doses were estimated as a function of time, particle diameter and deposition site in the respiratory system. Ultrafine particles almost entirely made up the doses estimated. The maximum contribution was due to particles deposited in the alveolar region between the 18th and the 21st airway generation. When cooking operations were performed, respiratory doses per unit time were about ten-fold higher than the relevant indoor background dose. Such doses were even higher than those associated with outdoor traffic aerosol.

  7. Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?

    DEFF Research Database (Denmark)

    Sørensen, Peter G; Rømer, F K; Cortes, Dina

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical...... or radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S-ACE...... was unchanged within each treatment course but increased significantly (P less than 0.05) from the initial value to the last treatment course. Two months after cessation of treatment S-ACE returned to pretreatment values. Although the changes were modest they might mirror treatment-associated endothelial damage....

  8. Variations in alveolar partial pressure for carbon dioxide and oxygen have additive not synergistic acute effects on human pulmonary vasoconstriction.

    Directory of Open Access Journals (Sweden)

    Quentin P P Croft

    Full Text Available The human pulmonary vasculature constricts in response to hypercapnia and hypoxia, with important consequences for homeostasis and adaptation. One function of these responses is to direct blood flow away from poorly-ventilated regions of the lung. In humans it is not known whether the stimuli of hypercapnia and hypoxia constrict the pulmonary blood vessels independently of each other or whether they act synergistically, such that the combination of hypercapnia and hypoxia is more effective than the sum of the responses to each stimulus on its own. We independently controlled the alveolar partial pressures of carbon dioxide (Paco 2 and oxygen (Pao 2 to examine their possible interaction on human pulmonary vasoconstriction. Nine volunteers each experienced sixteen possible combinations of four levels of Paco 2 (+6, +1, -4 and -9 mmHg, relative to baseline with four levels of Pao 2 (175, 100, 75 and 50 mmHg. During each of these sixteen protocols Doppler echocardiography was used to evaluate cardiac output and systolic tricuspid pressure gradient, an index of pulmonary vasoconstriction. The degree of constriction varied linearly with both Paco 2 and the calculated haemoglobin oxygen desaturation (1-So2. Mixed effects modelling delivered coefficients defining the interdependence of cardiac output, systolic tricuspid pressure gradient, ventilation, Paco 2 and So2. No interaction was observed in the effects on pulmonary vasoconstriction of carbon dioxide and oxygen (p>0.64. Direct effects of the alveolar gases on systolic tricuspid pressure gradient greatly exceeded indirect effects arising from concurrent changes in cardiac output.

  9. Cardiogenic mixing increases aerosol deposition in the human lung in the absence of gravity

    Science.gov (United States)

    Prisk, G. Kim; Sá, Rui Carlos; Darquenne, Chantal

    2012-01-01

    Rationale Exposure to extraterrestrial dusts is an almost inevitable consequence of any proposed planetary exploration. Previous studies in humans showed reduced deposition in low-gravity compared with normal gravity (1G). However, the reduced sedimentation means that fewer particles deposit in the airways, increasing the number of particles transported to the lung periphery where they eventually deposit albeit at a smaller rate than in 1G. In this study, we determined the role that gravity and other mechanisms such as cardiogenic mixing play in peripheral lung deposition during breath holds. Methods Eight healthy subjects inhaled boluses of 0.5 μm-diameter particles to penetration volumes (Vp) of 300 and 1200ml that were followed by breath holds of up to 10 sec. Tests were performed in 1G and during short periods of microgravity (μG) aboard the NASA Microgravity Research Aircraft. Aerosol deposition and dispersion were calculated from these data. Results Results show that, for both Vp, deposition in 1G was significantly higher than in μG. In contrast, while dispersion was significantly higher in 1G compared to μG at Vp=1200ml, there was no significant gravitational effect on dispersion at Vp=300ml. Finally, for each G level and Vp, deposition and dispersion significantly increased with increasing breath-hold time. Conclusion The most important finding of this study is that, even in the absence of gravity, aerosol deposition in the lung periphery increased with increasing residence time. Because the particles used in this study were too large to be significantly affected by Brownian diffusion, the increase in deposition is likely due to cardiogenic motion effects. PMID:23976801

  10. Modeling of deposition and clearance of inhaled Ni compounds in the human lung.

    Science.gov (United States)

    Hsieh, T H; Yu, C P; Oberdörster, G

    1999-08-01

    By extrapolation from the rat study, a mathematical model of deposition, clearance, and retention kinetics for inhaled Ni compounds (high-temperature (green) NiO, Ni(3)S(2), and NiSO(4). 6H(2)O) in the alveolar region of the human lung has been developed. For human deposition, an updated version of an earlier model (C. P. Yu and C. K. Diu, 1982, Am. Ind. Hyg. Assoc. J.) was used in this study. Because of the profound differences in physiological and ventilation conditions between humans and rats, humans were found to have a higher alveolar deposition fraction than rats when exposed to the same Ni compounds. However, when normalized to the lung weight, the deposition rate per gram of lung in humans is much smaller than in rats. In the development of a clearance model, a single-compartment model in the lung was used and a general assumption was made that the clearance of the insoluble and moderately soluble nickel compounds (high-temperature (green) NiO and Ni(3)S(2), respectively) depends highly on the volume of retained particles in the lungs. As for the highly soluble nickel compound (NiSO(4). 6H(2)O), the clearance rate coefficient was assumed to depend on the retained particle mass and total alveolar surface. These clearance rate coefficients were extrapolated from the rat data. The retention half-times for high temperature (green) NiO and Ni(3)S(2) particles in humans were found to be much longer than in rats, whereas the retention half-time for NiSO(4). 6H(2)O particles was about the same for both species. The lung burden results in humans for various exposure conditions are predicted and the equivalent exposure concentrations for humans which lead to the same lung burdens found in rats were calculated.

  11. TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS

    Science.gov (United States)

    TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS. Zhe Zhang*, Huawei Shi, Clement Kleinstreuer, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910; Chong S. Kim, National Health and En...

  12. Regional deposition of thoron progeny in models of the human tracheobronchial tree

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S.M.; Cheng, Yung-Sung; Yeh, Hsu-Chi

    1995-12-01

    Models of the human tracheobronchial tree have been used to determine total and regional aerosol deposition of inhaled particles. Particle sizes measured in these studies have all been > 40 nm in diameter. The deposition of aerosols < 40 nm in diameter has not been measured. Particles in the ultrafine aerosol size range include some combustion aerosols and indoor radon progeny. Also, the influence of reduced lung size and airflow rates on particle deposition in young children has not been determined. With their smaller lung size and smaller minute volumes, children may be at increased risk from ultrafine pollutants. In order to accurately determine dose of inhaled aerosols, the effects of particle size, minute volume, and age at exposure must be quantified. The purpose of this study was to determine the deposition efficiency of ultrafine aerosols smaller than 40 nm in diameter in models of the human tracheobronchia tree. This study demonstrates that the deposition efficiency of aerosols in the model of the child`s tracheobronchial tree may be slightly higher than in the adult models.

  13. Comparison of methods for evaluation of aerosol deposition in the model of human lungs

    Directory of Open Access Journals (Sweden)

    Belka Miloslav

    2014-03-01

    Full Text Available It seems to be very convenient to receive a medicine by inhalation instead of injection. Unfortunately transport of particles and targeted delivery of a drug in human respiratory airways is very complicated task. Therefore we carried out experiments and tested different methods for evaluation of particle deposition in a model of human lungs. The model included respiratory airways from oral cavity to 7th generation of branching. Particles were dispersed by TSI Small-scale Powder Disperser 3433 and delivered to the model. The model was disassembled into segments after the deposition of the particles and local deposition was measured. Two methods were used to analyse the samples, fluorescence spectroscopy and optical microscopy. The first method was based on measuring the intensity of luminescence, which represented the particle deposition. The second method used the optical microscope with phase-contrast objective. A dispersion of isopropanol and particles was filtrated using a vacuum filtration unit, a filter was placed on glass slide and made transparent. The particles on the filter were counted manually and the deposition was calculated afterwards. The results of the methods were compared and both methods proved to be useful.

  14. Human papillomavirus type 16 DNA detected in pulmonary metastases from a penile squamous cell carcinoma: a case study.

    Science.gov (United States)

    Lorenzon, Laura; Benevolo, Maria; Visca, Paolo; Venturo, Irene; Filippetti, Massimo; Piro, Francesca Romana; Rollo, Francesca; Vocaturo, Amina

    2013-02-01

    This report describe the case of a patient presenting with pulmonary metastases from a penile cancer, where the presence of the human papillomavirus (HPV) type 16 DNA both in the primary tumor and in the distant metastases confirmed the spreading of the disease, ruling out a possible primary lung squamous cell carcinoma. Indeed, according to the findings, the HPV genotyping test might help in the identification of metastatic disease from anogenital malignancies or other HPV-related cancers.

  15. [Pulmonary arterial hypertension associated with human immunodeficiency virus infection: study of 4 cases].

    Science.gov (United States)

    Pousada, Guillermo; Baloira, Adolfo; Castro-Añón, Olalla; Valverde, Diana

    2016-04-15

    Pulmonary arterial hypertension (PAH) is a rare and progressive disease that can be inherited as autosomal dominant form. The BMPR2, ACVRL1 and ENG genes are main genes involved in the pathology. PAH associated to human immunodeficiency virus (HIV) is another rare disease with a low incidence, prevalence and survival. The main objective of this analysis was to study the clinical and molecular characteristics of PAH associated to HIV patients. We present 4 cases of HIV patients who developed PAH and have been treated with ambrisentan. Pathogenic mutations have been identify in analyzed genes in 3 of the four analyzed patients. In addition, these patients present other changes classified as benign after a thorough in silico analysis. We identified some changes in genetic modifiers that predispose to these patients to more severe phenotype. The clinical analysis can help to define monitoring for these patients and the administration of appropriate treatment. These patients also have shown several pathogenic mutations. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. Pulmonary bacterial and fungal infections in human immunodeficiency virus patients: A study from India

    Directory of Open Access Journals (Sweden)

    K Shreevidya

    2012-01-01

    Full Text Available Background: Human Immunodeficiency Virus (HIV-reactive patients are more prone to infections. The morbidity and mortality in HIV-reactive patients is due to opportunistic infections. Most of the infections seen in Acquired Immunodeficiency Syndrome are endemic to that geographical region. Hence, this study was undertaken to document the occurrence of pulmonary bacterial and fungal infections in HIV patients. Materials and Methods: Expectorated and induced sputum samples were collected from 100 HIV-reactive patients and processed for bacterial and fungal pathogens including Pneumocystis carinii. Results: Of 100 samples, 66 were culture positive. Among the isolates, Mycobacterium tuberculosis constituted the highest number, 55 (83.3%, followed by other bacterial infections, 11 (16.6%, and fungi, 2 (3.03%. Tuberculosis patients had a CD4 count of less than 250 cells/μl with a mean count of 186 cells/μl and those with bacterial infections had a CD4 count of more than 300 cells/μl. The study showed that males were infected with HIV more than females and most of them belonged to the adult age group in the prime of their working life. Weight loss followed by fever and cough were the most common symptoms. Conclusion: M. tuberculosis is the most common opportunistic pathogen followed by bacterial pathogens infecting the lung in HIV. Low CD4 count is a dangerous signal of decreased immune status and higher chances of opportunistic infections and high mortality.

  17. Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy.

    Science.gov (United States)

    van den Blink, Bernt; Dillingh, Marlous R; Ginns, Leo C; Morrison, Lake D; Moerland, Matthijs; Wijsenbeek, Marlies; Trehu, Elizabeth G; Bartholmai, Brian J; Burggraaf, Jacobus

    2016-03-01

    Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM-151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study.A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients. Subjects in three successive cohorts (1, 5, or 10 mg·kg(-1) versus placebo) received intravenous study drug on days 1, 3, 5, 8 and 15, and were followed-up to day 57.PRM-151 was well tolerated at all dose levels, with no serious adverse reactions. Administration of PRM-151 resulted in two- to eight-fold dose-dependent increases in circulating pentraxin-2 levels. Forced vital capacity and 6-min walk test showed trends towards improvement in the combined PRM-151 dose groups. On high-resolution computed tomography scans, stable or improved lung volume unoccupied by interstitial lung abnormality was noted in some PRM-151 subjects compared to placebo subjects on day 57.The efficacy of PRM-151 in IPF remains to be investigated in dedicated future trials. Copyright ©ERS 2016.

  18. Effect of pulmonary vein isolation on the distribution of complex fractionated electrograms in humans.

    Science.gov (United States)

    Roux, Jean-François; Gojraty, Sattar; Bala, Rupa; Liu, Christopher F; Dixit, Sanjay; Hutchinson, Mathew D; Garcia, Fermin; Lin, David; Callans, David J; Riley, Michael; Marchlinski, Francis; Gerstenfeld, Edward P

    2009-02-01

    Targeting of complex fractionated electrograms (CFEs) has been used as an adjunctive strategy to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). However, it is unclear whether CFEs should be targeted before or after PVI. The purpose of this study was to examine the effect of PVI on CFE distribution in humans. We compared left atrial (LA) CFE maps acquired using the NavX system before and after PVI in patients with persistent AF. CFE maps were constructed from bipolar electrograms acquired from a circular mapping catheter. At each point, the mean AF cycle length (CL) was calculated automatically by averaging the intervals between deflections over a 4-second window. Sites with mean CL CFE+. A total of 22 consecutive patients (82% male, age 58 +/- 9 years) were studied. At baseline, 47% of the LA was encompassed by electrograms with CL CFE characteristics, with an increase in mean LA AF CL (144 ms pre-PVI vs. 214 ms post-PVI; P CFE+ LA surface area (47% vs 23%; P CFE burden after PVI in both PV (50% vs. 6%; P CFE. To limit extensive LA ablation, PVI should be performed before targeting CFE when a combined approach is pursued.

  19. The use of EDTA and DTPA for accelerating the removal of deposited transuranic elements from humans

    CERN Document Server

    Spoor, N L

    1977-01-01

    EDTA and DTPA have been prominent among the chelating agents used to increase the rate of excretion of certain deposited heavy metals from the human body. Since 1959, DTPA, administered either by intravenous injection or by aerosol inhalation, has been widely used to treat workers contaminated by plutonium or a higher actinide. In this report, an attempt is made to assess the toxicities of EDTA and DTPA and to evaluate the effectiveness and safety of DTPA as a drug for removing deposited transuranic elements.

  20. Human pulmonary dirofilariasis: a review Dirofilaríase humana pulmonar: revisão

    Directory of Open Access Journals (Sweden)

    Rosângela Rodrigues-Silva

    1995-12-01

    Full Text Available The authors presented a detailed summary of the geographical distribution, clinical and pathological aspects of human pulmonary dirofilariasis. Although benign, this zoonosis, of which Dirofilaria immitis is the major etiological agent, represents a medical problem since it produces symptoms which may be confused with neoplasia and thus may subject patients to unnecessary thoracic surgery. Of 229 cases cited in the literature, only 17 were reported in Brazil, despite the existence of highly favorable conditions for the transmission of this infection in man. Thus it may well be that this parasitic infection remains underdiagnosed. Finally, the importance of a differential diagnosis between dirofilariasis and pulmonary neoplasia is emphasized in cases where there is a solitary subpleural nodule ("coin lesion" present. In addition, the development and improvement of modern immunological diagnostic techniques are essential to distinguish this benign disease from other pathological conditions and thus avoid unneccessary surgery. These techniques may reveal the true prevalence of this parasitic infection in our environment.Os autores realizaram minuciosa revisão sobre a distribuição geográfica, a clínica, a patologia e o diagnóstico da dirofilaríase pulmonar humana. Esta zoonose, que tem como principal agente etiológico a Dirofilaria immitis, é um problema médico porque produz um quadro clínico, embora benigno, que se confunde com neoplasia e, assim interpretado, pode conduzir o paciente à cirurgia do tórax. Dos 229 casos citados na literatura, apenas 17 foram descritos no Brasil, apesar da existência de condições muito favoráveis à transmissão da infecção para o homem, admitindo-se portanto, que é uma parasitose subdiagnosticada. Finalmente, a importância do diagnóstico diferencial entre dirofilaríase e neoplasias pulmonares nos casos de presença de nódulo solitário subpleural ("coin lesion" é destacada, além do que o

  1. CXCL1 Regulation in Human Pulmonary Epithelial Cells by Tumor Necrosis Factor

    Directory of Open Access Journals (Sweden)

    Jiunn-Min Shieh

    2014-10-01

    Full Text Available Background/Aims: The chemokine CXCL1 has been reported to be expressed in lung airway epithelium and non-small cell lung cancer biopsy specimens. In this study, we investigated the effects of TNF-α, an abundant cytokine detected in inflammation and various cancers, on CXCL1 release by human A549 lung carcinoma epithelial cells. Methods: CXCL1 expression was determined by ELISA and RT-PCR. TNF-α signaling was examined by western blotting. Monocyte migration was assayed by a Transwell migration system. Results: TNF-α stimulated CXCL1 release and mRNA expression, and this release was inhibited by inhibitors of JNK, p38 MAPK, PI-3K/Akt and AP-1 transcription factor. TNF-α treatment was followed by JNK, p38 MAPK and PI3K/Akt activation. However, only the JNK inhibitor could reduce the CXCL1 mRNA level, suggesting that JNK is required mainly for CXCL1 mRNA synthesis, whereas p38 MAPK and PI-3K/Akt might be responsible for CXCL1 secretion. Dexamethasone (dex and TGF-β reduced CXCL1 secretion, with dex upregulating the expression of MAP kinase phosphatase-1 and TGF-β causing smad2/3 activation and nuclear translocation. A functional analysis showed that the released CXCL1 enhanced monocyte migration and could be abolished by a CXCL1 neutralizing antibody and CXCR antagonist. Conclusion: We demonstrate that TNF-α induces CXCL1 expression through the JNK, p38 MAPK and PI-3K/Akt signaling pathways in human pulmonary epithelial cells.

  2. Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung. METHODS AND FINDINGS: Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients. To study the fibrosis-relevant effects of osteopontin we stimulated primary human lung fibroblasts and alveolar epithelial cells (A549 with recombinant osteopontin. Osteopontin induced a significant increase of migration and proliferation in both fibroblasts and epithelial cells. Epithelial growth was inhibited by the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS and antibody to CD44, while fibroproliferation was inhibited by GRGDS and antibody to alphavbeta3 integrin. Fibroblast and epithelial cell migration were inhibited by GRGDS, anti-CD44, and anti-alphavbeta3. In fibroblasts, osteopontin up-regulated tissue inhibitor of metalloprotease-1 and type I collagen, and down-regulated matrix metalloprotease-1 (MMP-1 expression, while in A549 cells it caused up-regulation of MMP-7. In human IPF lungs, osteopontin colocalized with MMP-7 in alveolar epithelial cells, and application of weakest link statistical models to microarray data suggested a significant interaction between osteopontin and MMP-7. CONCLUSIONS: Our results provide a potential mechanism by which osteopontin secreted from the alveolar epithelium may exert a profibrotic effect in IPF lungs and highlight osteopontin as a potential target for therapeutic intervention in this incurable disease.

  3. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  4. Pulmonary edema

    Science.gov (United States)

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

  5. In vivo Measurement of Unattached Radon Progeny Deposited in the Human Respiratory Tract

    Energy Technology Data Exchange (ETDEWEB)

    Butterweck, G.; Vezzu, G.; Schuler, Ch.; Mueller, R.; Marsh, J.W.; Thrift, S.; Birchall, A

    2001-07-01

    Seven nose breathing and seven mouth breathing volunteers were exposed to atmospheres enriched with unattached radon progeny ({sup 218}Po, {sup 214}Pb and {sup 214}Bi). The activity of these radionuclides deposited in the respiratory track was measured in vivo after the exposures. The results of these measurements are in agreement with predictions calculated with the ICRP Publication 66 Human Respiratory Tract Model. Temporal analysis of the activity deposited in the heads of the volunteers leads to the conclusion that a significant amount of the deposited activity associated with particle diameters of about 1 nm is not subject to a fast transport to the gastrointestinal tract as generally reported for larger aerosol particles. (author)

  6. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Han, Miaojun [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Wang, Hailun [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Zhang, Hua-Tang [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Han, Zhaozhong, E-mail: zhaozhong.han@vanderbilt.edu [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. Black-Right-Pointing-Pointer Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  7. Acute Meteorite Dust Exposure and Pulmonary Inflammation - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary

  8. Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative

  9. Activation of endothelial and epithelial KCa2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm

    2012-01-01

    BACKGROUND AND PURPOSE: Small (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we...... investigated the expression of K(Ca) 2.3 and K(Ca) 3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries. EXPERIMENTAL APPROACH: Channel expression and functional studies were conducted in human isolated small pulmonary arteries.......1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the K(Ca) 2 channel blocker apamin, while the K(Ca) 3.1 channel blocker, charybdotoxin failed to reduce...

  10. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review.

  11. Scorched earth: how will changes in ozone deposition caused by drought affect human health and ecosystems?

    Science.gov (United States)

    Emberson, L. D.; Kitwiroon, N.; Beevers, S.; Büker, P.; Cinderby, S.

    2012-10-01

    This unique study investigates the effect of ozone (O3) deposition on ground level O3 concentrations and subsequent human health and ecosystem risk under hot summer "heat wave" type meteorological events. Under such conditions, extended drought can effectively "turn off" the O3 vegetation sink leading to a substantial increase in ground level O3 concentrations. Two models that have been used for human health (the CMAQ chemical transport model) and ecosystem (the DO3SE O3 deposition model) risk assessment are combined to provide a powerful policy tool capable of novel integrated assessments of O3 risk using methods endorsed by the UNECE Convention on Long-Range Transboundary Air Pollution. This study investigates 2006, a particularly hot and dry year during which a heat wave occurred during the summer across much of the UK and Europe. To understand the influence of variable O3 dry deposition three different simulations were investigated during June and July: (i) actual conditions in 2006; (ii) conditions that assume a perfect vegetation sink for O3 deposition and (iii) conditions that assume an extended drought period that reduces the vegetation sink to a minimum. The risk of O3 to human health, assessed by estimating the number of days during which running 8-h mean O3 concentrations exceeded 100 μg m-3, show that on average across the UK, there is a difference of 16 days exceedance of the threshold between the perfect sink and drought conditions. These average results hide local variation with exceedances reaching as high as 20 days in the East Midlands and Eastern UK. Estimates of acute exposure effects show that O3 removed from the atmosphere through dry deposition during the June and July period would have been responsible for approximately 460 premature deaths. Conversely, reduced O3 dry deposition will decrease the amount of O3 taken up by vegetation and, according to flux-based assessments of vegetation damage, will lead to protection from O3 across the UK

  12. Proteoglycan and proteome profiling of central human pulmonary fibrotic tissue utilizing miniaturized sample preparation: a feasibility study

    DEFF Research Database (Denmark)

    Malmström, Johan; Larsen, Kristoffer; Hansson, Lennart;

    2002-01-01

    The objective of this study was to isolate fibrotic cells from human lung biopsies taken from different central pulmonary locations. A comparison was made of cell morphology, proteoglycan- and protein-expression in mesenchymal cell cultures obtained from human bronchial biopsies from patients...... tissue; one of contractile type with lamellipodia that facilitate migration and a second cell type with an increased cell size, which most likely is of a synthetic phenotype. This is the first evidence of alterations in the proteoglycan expression pattern of versican, perlecan, biglycan and decorin which...

  13. The Effects of High Frequency Oscillatory Flow on Particles' Deposition in Upper Human Lung Airways

    Science.gov (United States)

    Bonifacio, Jeremy; Rahai, Hamid; Taherian, Shahab

    2016-11-01

    The effects of oscillatory inspiration on particles' deposition in upper airways of a human lung during inhalation/exhalation have been numerically investigated and results of flow characteristics, and particles' deposition pattern have been compared with the corresponding results without oscillation. The objective of the investigation was to develop an improved method for drug delivery for Asthma and COPD patients. Previous clinical investigations of using oral airway oscillations have shown enhanced expectoration in cystic fibrosis (CF) patients, when the frequency of oscillation was at 8 Hz with 9:1 inspiratory/expiratory (I:E) ratio. Other investigations on oscillatory ventilation had frequency range of 0.5 Hz to 2.5 Hz. In the present investigations, the frequency of oscillation was changed between 2 Hz to 10 Hz. The particles were injected at the inlet and particle velocity was equal to the inlet air velocity. One-way coupling of air and particles was assumed. Lagrangian phase model was used for transport and depositions of solid 2.5 micron diameter round particles with 1200 kg/m3 density. Preliminary results have shown enhanced PM deposition with oscillatory flow with lower frequency having a higher deposition rate Graduate Assistant.

  14. Prediction of localized aerosol deposition in a realistic replica of human airways using experimental data and numerical simulation

    Science.gov (United States)

    Lizal, Frantisek; Elcner, Jakub; Belka, Miloslav; Jedelsky, Jan; Jicha, Miroslav

    2016-11-01

    The presence of aerosol deposition hot-spots in human airways presumably contributes to development of various diseases. The overall aerosol deposition in human lungs can be predicted with sufficient accuracy nowadays. However, the prediction of localized aerosol deposition poses arduous challenge, namely in diseased lungs. Numerical simulation is considered to be a promising tool for the successful prediction. Yet, the validation of such simulations is difficult to perform, as not enough experimental data acquired using realistic airway replicas is available. This paper presents a first comparison of localized deposition measurement and simulation performed on the identical realistic geometry. The analysis indicates that both approaches yield similar results for low Reynolds number flows.

  15. Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model.

    Science.gov (United States)

    Murray, Lynne A; Zhang, Huilan; Oak, Sameer R; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R; Lee, Joyce; Bell, Matt; Knight, Darryl A; Martinez, Fernando J; Sleeman, Matthew A; Herzog, Erica L; Hogaboam, Cory M

    2014-05-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung.

  16. Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma. Efficacy and pulmonary deposition

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, M.A.; Newman, S.P.; Bloom, R.; Talaee, N.; Clarke, S.W.

    1989-07-01

    Bronchodilator responses to both nebulized albuterol (salbutamol) and ipratropium bromide and aerosol delivery to the tracheobronchial tree have been assessed in eight patients with chronic stable asthma (mean baseline FEV1, 50 percent; reversibility greater than 20 percent). Two commercially available nebulizer systems were used, namely, a Turret nebulizer operated at a compressed gas flow rate of 12 L/min (droplet MMD, 3.3 mu) and an Inspiron nebulizer driven at 6 L/min (MMD, 7.7 mu). Albuterol was given as doses of 250 micrograms, 250 micrograms, 500 micrograms, and 1,000 micrograms (cumulative dose, 2 mg) and ipratropium bromide as doses of 50 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms (cumulative dose, 400 micrograms) at intervals of 35 minutes. For albuterol, bronchodilatation was significantly (p less than 0.05) greater at all dosage levels with the Turret. For ipratropium, bronchodilatation was similar for both nebulizers. Measurements of aerosol deposition using /sup 99m/Tc-labelled pentetic acid (diethylenetriamine pentaacetic acid; DTPA) showed that 9.1 +/- 1.1 percent and 2.7 +/- 0.2 percent of the dose reached the lungs during nebulization to dryness for Turret and Inspiron, respectively (p less than 0.01); distribution within the lungs was similar for the two aerosols. Selection of nebulizer apparatus can influence delivery of aerosol and subsequent bronchodilator response to albuterol in patients with chronic stable asthma but is less important for aerosol delivery of ipratropium bromide in these patients.

  17. Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China

    Institute of Scientific and Technical Information of China (English)

    LAI Yu Ji; LIU Er Yong; WANG Li Ming; Jamie P MORANO; WANG Ning; Kaveh KHOSHNOOD; ZHOU Lin; CHENG Shi Ming

    2015-01-01

    Objective To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus (HIV) infection epidemics. Methods A prospective cohort study of newly registered patients in tuberculosis (TB) dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis. Results Of 19,103 newly registered pulmonary TB patients, 925 (4.8%) were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322 (1.7%) deaths that occurred during TB treatment, 85 (26%) of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio (aOR) 7.86]. Other significant mortality risk factors included presentation with miliary TB (aOR 4.10; 95% confidence interval: 2.14-7.88), ≥35 years of age (aOR 3.04), non-Han ethnicity (aOR 1.67), and farming as an occupation (aOR 1.59). For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death (aOR 5.48). A low CD4 count (≤200 cells/µL) (aOR 3.27) at the time of TB treatment initiation and a lack of antiretroviral therapy (ART) administration (aOR 3.78) were also correlated with an increased risk of death. Conclusion Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.

  18. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Science.gov (United States)

    Kumar, Akash; Dougherty, Max; Findlay, Gregory M; Geisheker, Madeleine; Klein, Jason; Lazar, John; Machkovech, Heather; Resnick, Jesse; Resnick, Rebecca; Salter, Alexander I; Talebi-Liasi, Faezeh; Arakawa, Christopher; Baudin, Jacob; Bogaard, Andrew; Salesky, Rebecca; Zhou, Qian; Smith, Kelly; Clark, John I; Shendure, Jay; Horwitz, Marshall S

    2014-01-01

    Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  19. Human pentraxin 3 (PTX3 as a novel biomarker for the diagnosis of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yuichi Tamura

    Full Text Available BACKGROUND: Although inflammation is an important feature of pulmonary arterial hypertension (PAH, the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3, a local inflammatory marker, would be a useful biomarker for detecting PAH. METHODS: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH, and six with congenital heart disease, 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP and C-reactive protein (CRP were also determined. RESULTS: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001. Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001. There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866 is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%. CONCLUSION: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

  20. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Directory of Open Access Journals (Sweden)

    Akash Kumar

    Full Text Available Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF. Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP, as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP, rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  1. Predictive models for deposition of inhaled diesel exhaust particles in humans and laboratory species. Research report, July 1984-January 1987

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C.P.; Xu, G.B.

    1987-07-01

    A deposition model for diesel-exhaust particles was formulated mathematically from available scientific data, and was used to predict the deposition of particles in the airways of laboratory animals and of humans of different ages. In addition, a lung-growth model was formulated for humans, from infancy to adulthood, to predict the effect of age on deposition. The investigators predicted from their models that: (1) deposition in the alveoli is markedly affected by changes in the size distribution of particles; (2) nose- versus mouth-breathing had little effect on deposition in the alveoli; (3) increased minute ventilation substantially increased the rate of particle deposition; and (4) age (in humans) influenced the levels of deposition observed in the unciliated regions of the airways (the highest levels of deposition occurred in infants under two years, decreased in children over two years, and decreased again in adults aged 25 years or older); and (5) the deposition rate in laboratory animals was higher than in humans of all ages.

  2. Extrapolation modeling of aerosol deposition in human and laboratory rat lungs

    Energy Technology Data Exchange (ETDEWEB)

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    Laboratory test animals are often used as surrogates in exposure studies to assess the potential threat to human health following inhalation of airborne contaminants. To aid in the interpretation and extrapolation of data to man, dosimetric considerations need to be addressed. Therefore, a mathematical model describing the behavior and fate of inhaled particulate matter within the respiratory tracts of man and rats has been developed. In the computer simulations, the CO2 concentrations of inhalation exposure chamber atmospheres are controlled to produce desired breathing patterns in the rat which mimic human breathing patterns as functions of physical activity levels. Herein, deposition patterns in human and rat lung airways are specifically examined as functions of respiratory intensities and particle parameters. The model provides a basis for the re-evaluation of data from past experiments, and, perhaps most importantly, permits new inhalation exposure tests to be designed and conducted in a sound scientific manner regarding this endpoint: the extrapolation of results to human conditions.

  3. Time-course of ventilation, arterial and pulmonary CO(2) tension during CO (2) increase in humans.

    Science.gov (United States)

    Satoh, Toru; Okada, Yasumasa; Hara, Yasushi; Sakamaki, Fumio; Kyotani, Shingo; Tomita, Takeshi; Nagaya, Noritoshi; Nakanishi, Norifumi

    2012-01-01

    A change of ventilation (VE), PaCO( 2 ) (arterial CO( 2 ) tension) and PvCO( 2 ) (pulmonary arterial CO( 2 ) tension) with time was not evaluated precisely during exercise or CO( 2 ) rebreathing in humans. In this study, changes of these variables with time were fitted to exponential curves {y = Exp ( x/ T + A ) + k} and compared. When exercise pulmonary hemodynamics was examined in 15 cardiac patients to decide therapies, we asked the patients to undergo CO( 2 ) rebreathing using air with supplementation of consumed O( 2 ). Arterial and pulmonary blood was drawn every minute. During exercise, T was 28.2 ± 8.4 and 26.8 ± 12.4, and A was 0.80 ± 0.50 and 0.50 ± 0.90 in VE and PvCO( 2 ), respectively, with no statistical differences. During CO( 2 ) rebreathing, T was 18.6 ± 5.8, 41.8 ± 38.0 and 21.6 ± 9.7 and A was 0.39 ± 0.67, 1.64 ± 1.35 and 0.17 ± 0.83 in VE, PaCO( 2 ) and PvCO( 2 ), respectively, with statistical difference of PaCO( 2 ) from other variables, suggesting that VE and PvCO( 2 ) showed same mode of change according to time but PaCO( 2 ) did not.

  4. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers.

    Science.gov (United States)

    Ungaro, Francesca; d'Angelo, Ivana; Coletta, Ciro; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Perfetto, Brunella; Tufano, Maria Antonietta; Miro, Agnese; La Rotonda, Maria Immacolata; Quaglia, Fabiana

    2012-01-10

    Although few experimental studies have been handled so far to exploit the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the production of dry powders for antibiotic inhalation, there has been no comprehensive study on the role played by NP composition. In this work, we try to shed light on this aspect by designing and developing a pulmonary delivery system for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM). At nanosize level, helper hydrophilic polymers were used to impart the desired surface, bulk and release properties to PLGA NPs prepared by a modified emulsion-solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and chitosan (CS) are essential to optimise the size and modulate the surface properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows efficient Tb entrapment within NPs and its release up to one month. Optimized formulations display good in vitro antimicrobial activity against P. aeruginosa planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM with peculiar but promising flow and aerosolization properties, while preserving the peculiar NP features. Nonetheless, in vivo biodistribution studies showed that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were found in great amounts in the upper airways, lining lung epithelial surfaces. In conclusion, PLGA NP composition appears to play a crucial role in determining not only the technological features of NPs but, once processed in the form of NEM, also their in vitro/in vivo deposition pattern.

  5. Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge.

    Science.gov (United States)

    Koullapis, P G; Kassinos, S C; Bivolarova, M P; Melikov, A K

    2016-07-26

    Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200kg/m(3)). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5μm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0μm, the DF was largely independent of particle size; it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth-throat. Moreover, significant enhancement in deposition was found in the left and right lung sub-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp<2.5μm, impaction prevailed over

  6. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Goncharova Elena A

    2012-11-01

    Full Text Available Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH. The long-acting β2-adrenergic receptor (β2AR agonist formoterol, a racemate comprised of (R,R- and (S,S-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD. PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recent studies demonstrate that formoterol has anti-proliferative effects on airway smooth muscle cells and bronchial fibroblasts. The effects of formoterol and its enantiomers on PAVSM cell proliferation are not determined. The goals of this study were to examine effects of racemic formoterol and its enantiomers on PAVSM cell proliferation as it relates to COPD-associated PH. Methods Basal, thrombin-, PDGF- and chronic hypoxia-induced proliferation of primary human PAVSM cells was examined by DNA synthesis analysis using BrdU incorporation assay. ERK1/2, mTORC1 and mTORC2 activation were determined by phosphorylation levels of ERK1/2, ribosomal protein S6 and S473-Akt using immunoblot analysis. Results We found that (R,R and racemic formoterol inhibited basal, thrombin- and chronic hypoxia-induced proliferation of human PAVSM cells while (S,S formoterol had lesser inhibitory effect. The β2AR blocker propranolol abrogated the growth inhibitory effect of formoterol. (R,R, but not (S,S formoterol attenuated basal, thrombin- and chronic hypoxia-induced ERK1/2 phosphorylation, but had little effect on Akt and S6 phosphorylation levels. Formoterol and its enantiomers did not significantly affect PDGF-induced DNA synthesis and PDGF-dependent ERK1/2, S473-Akt and S6 phosphorylation in human PAVSM cells. Conclusions Formoterol inhibits basal, thrombin-, and chronic hypoxia-, but not PDGF-induced human PAVSM cell proliferation and ERK1/2, but has little effect on

  7. The adrenal gland and the patient with pulmonary tuberculosis infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Ifedayo Adeola Odeniyi

    2017-01-01

    Full Text Available Background: The adrenal gland is not spared from the involvement by tuberculosis. One of the recognized causes of adrenal insufficiency (AI is tuberculosis. AI, mostly at the subclinical level, is common in persons with pulmonary tuberculosis (PTB infection, occurring in about 23% of patients. Coinfection with PTB and human immunodeficiency virus (HIV may compromise adrenocortical function and produce significant adrenocortical insufficiency. Objective: To determine if coinfection with tuberculosis and HIV have a compound effect on adrenocortical function in persons with HIV and PTB coinfection. Materials and Methods: Persons with sputum-positive PTB, treatment naive, who met our inclusion criteria, were selected. All the recruited patients were screened for HIV and those positive for HIV infection had confirmatory test. A baseline blood samples for cortisol, fasting plasma glucose, full blood count, and electrolytes were collected between 8.00 h and 9.00 h immediately before administration of adrenocorticotropic hormone (ACTH. The persons received an intravenous bolus injection of 1 μg ACTH (Alliance Pharmaceuticals Ltd., Chippenham, Wiltshire SN15 2BB and blood sample was drawn for cortisol level at 30 min. Results: Forty-four people with PTB infection and forty people with PTB and HIV coinfection met the inclusion criteria of the study. The adrenal response to 1 μg ACTH stimulation in participants with PTB and PTB and HIV coinfection showed that the mean basal cortisol level in the 2 groups was not statistically significant; however, 30-min post-ACTH stimulation cortisol level was 630.84 ± 372.17 and 980.36 ± 344.82 nmol/L (P < 0.001 and increment was 367.79 ± 334.87 and 740.77 ± 317.97 nmol/L (P < 0.001, respectively. Fourteen persons (31.8% with PTB has subnormal adrenal response to ACTH stimulation while only 2 (5% persons with PTB and HIV coinfection has subnormal response. Conclusion: AI, at subclinical level, was less frequent in

  8. RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension.

    Science.gov (United States)

    Jia, Daile; He, Yuhu; Zhu, Qian; Liu, Huan; Zuo, Caojian; Chen, Guilin; Yu, Ying; Lu, Ankang

    2017-05-01

    Extracellular matrix (ECM) proteins accumulation contributes to the progression of pulmonary arterial hypertension (PAH), a rare and fatal cardiovascular condition defined by high pulmonary arterial pressure, whether primary, idiopathic, or secondary to other causes. The receptor for advanced glycation end products (RAGE) is constitutively expressed in the lungs and plays an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE mediates ECM deposition/formation in pulmonary arteries and its roles in PAH progression remain unclear. Expression of RAGE and its activating ligands, S100/calgranulins and high mobility group box 1 (HMGB1), were increased in both human and mouse pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions and were also strikingly upregulated in pulmonary arteries in hypoxia plus SU5416 (HySu)-induced PAH in mice. RAGE deletion alleviated pulmonary arterial pressure and restrained extracellular matrix accumulation in pulmonary arteries in HySu-induced PAH murine model. Moreover, blocking RAGE activity with a neutralizing antibody in human PASMCs, or RAGE deficiency in mouse PASMCs exposed to hypoxia, suppressed the expression of fibrotic proteins by reducing TGF-β1 expression. RAGE reconstitution in deficient mouse PASMCs restored hypoxia-stimulated TGF-β1 production via ERK1/2 and p38 MAPK pathway activation and subsequently increased ECM protein expression. Interestingly, HMGB1 acting on RAGE, not toll-like receptor 4 (TLR4), induced ECM deposition in PASMCs. Finally, in both idiopathic PAH patients and HySu-induced PAH mice, soluble RAGE (sRAGE) levels in serum were significantly elevated compared to those in controls. Activation of RAGE facilitates the development of hypoxia-induced pulmonary hypertension by increase of ECM deposition in pulmonary arteries. Our results indicate that sRAGE may be a potential biomarker for PAH diagnosis and disease severity, and that RAGE may be a promising target for

  9. Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension

    NARCIS (Netherlands)

    van der Feen, Diederik E; Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Sietsma, Hannie; Lévy, Marilyne; Berger, Rolf M F

    BACKGROUND: Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated

  10. Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension

    NARCIS (Netherlands)

    van der Feen, Diederik E; Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Sietsma, Hannie; Lévy, Marilyne; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated w

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Ficolins serve as soluble recognition molecules in the lectin pathway of complement. They are known to participate in the systemic host-response to infection but their role in local pulmonary defence is still incompletely understood. The purpose of this study was to clarify whether...

  12. Rate of angiotensin II generation within the human pulmonary vascular bed

    DEFF Research Database (Denmark)

    Giese, Jacob; Kappelgaard, A M; Tønnesen, K H

    1980-01-01

    Plasma angiotensin II concentration gradients across the pulmonary vascular bed were measured during diagnostic renal venous/right heart catheterization in twenty-seven hypertensive patients with renal or renovascular disease. There was a linear correlation between the plasma angiotensin II...... vascular bed varied from 0.7 to 1.71/min, i.e. within a fairly narrow range....

  13. Pulmonary function testing in HTLV-I and HTLV-II infected humans: a cohort study

    Directory of Open Access Journals (Sweden)

    Garratty George

    2003-07-01

    Full Text Available Abstract Background HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function. Methods We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST, including vital capacity (VC, forced expiratory volume in one second (FEV1, and diffusing lung capacity for carbon monoxide (DLCO corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history. Results Mean (standard deviation pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89 L, FEV1 = 2.93 (0.67 L, DLCOcorr = 23.82 (5.89 ml/min/mmHg, alveolar ventilation (VA = 5.25 (1.20 L and DLCOcorr/VA = 4.54 (0.87 ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCOcorr/VA by HTLV status. For DLCOcorr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding. Conclusions There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.

  14. The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

    Science.gov (United States)

    Ghimire, Anukul; Andersen, Mads J; Burrowes, Lindsay M; Bouwmeester, J Christopher; Grant, Andrew D; Belenkie, Israel; Fine, Nowell M; Borlaug, Barry A; Tyberg, John V

    2016-12-01

    Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

  15. Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Korfhagen, T.R.; Glasser, S.W.; Wert, S.E.; Bruno, M.D.; Daugherty, C.C.; McNeish, J.D.; Stock, J.L.; Potter, S.S.; Whitsett, J.A. (Cincinnati College of Medicine, OH (USA))

    1990-08-01

    Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5{prime}-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

  16. Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro.

    Science.gov (United States)

    Amitani, R; Murayama, T; Nawada, R; Lee, W J; Niimi, A; Suzuki, K; Tanaka, E; Kuze, F

    1995-10-01

    Aspergillus species frequently colonize lower respiratory tracts and lungs with localized underlying conditions (healed tuberculous cavity, cystic fibrosis, bronchiectasis, etc.) even in subjects without systemic predisposing factors. We investigated the in vitro effects of culture filtrates of Aspergillus species and sputum sols from patients with pulmonary aspergillosis on ciliary beat frequency (CBF) and epithelial integrity of human respiratory ciliated epithelium. Culture filtrates of 25 clinically isolated fungi (16 Aspergillus fumigatus, three Aspergillus niger, one Aspergillus flavus, three Candida albicans, and two Cryptococcus neoformans) were obtained by culturing the fungi in Medium-199 at 37 degrees C for 7 days, and five sputum sols were obtained from patients with pulmonary aspergillosis infected by A. fumigatus. During 6 h experiments using a photometric technique, 14 out of 16 A. fumigatus culture filtrates caused progressive and significant reduction in CBF associated with marked epithelial disruption, whilst the culture filtrates of A. niger and A. flavus caused minor epithelial damage without slowing of CBF, and Medium-199 alone (Control) showed neither epithelial damage nor slowing of CBF. All of the sputum sols also caused significant slowing of CBF as well as epithelial disruption. Culture filtrates of C. albicans and Cr. neoformans had no effects on human respiratory epithelium. We conclude that Aspergillus species, especially A. fumigatus release a factor (or factors) which causes damage to respiratory epithelium and slows CBF, and that these factors may contribute to the colonization of the lower respiratory tracts by the Aspergillus species and may possibly contribute to the further proliferation and spread of the lesions in pulmonary aspergillosis.

  17. Aldosterone and mineralocorticoid receptor antagonists modulate elastin and collagen deposition in human skin.

    Science.gov (United States)

    Mitts, Thomas F; Bunda, Severa; Wang, Yanting; Hinek, Aleksander

    2010-10-01

    We have shown that the steroid hormone aldosterone, recognized for its action on the kidney and the cardiovascular system, also modulates deposition of extracellular matrix in human skin. We have shown that treatment of primary cultures of normal skin fibroblasts with aldosterone (10 n-1 μM), in addition to stimulation of collagen type I expression, induces elastin gene expression and elastic fiber deposition. We have further shown that the elastogenic effect of aldosterone, which can be enhanced in the presence of mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone, is executed in a MR-independent manner via amplification of IGF-I receptor-mediated signaling. Because aldosterone applied alone stimulates both collagen and elastin deposition in cultures of fibroblasts and in cultures of skin explants derived from dermal stretch marks, we postulate that this steroid should be used in the treatment of damaged skin that loses its volume and elasticity. Moreover, aldosterone applied in conjunction with spironolactone or eplerenone induces matrix remodeling and exclusively enhances elastogenesis in cultures of fibroblasts and explants derived from dermal scars and keloids. We therefore propose that intra-lesional injection of these factors should be considered in therapy for disfiguring dermal lesions and especially in prevention of their recurrence after surgical excision.

  18. The morphology of fecal and regurgitation artifacts deposited by the blow fly Lucilia cuprina fed a diet of human blood.

    Science.gov (United States)

    Durdle, Annalisa; van Oorschot, Roland A H; Mitchell, R John

    2013-07-01

    Fly feces and regurgitation deposits may be mistaken for bloodstain patterns at a crime scene, potentially compromising event reconstruction and/or misdirecting police resources. In some instances, these artifacts contain sufficient human biological material to generate a full DNA profile, sometimes 2 years after deposition. Clearly, it is important that investigators can make the distinction between artifacts and bloodstains. This study examined 6645 artifacts deposited on a smooth, nonporous surface after Lucilia cuprina were fed human blood. Artifacts were also compared with bloodstains on a variety of other surfaces. Both similarities and differences were found between artifacts and bloodstains, highlighting the need for an identification system to assist personnel with little training in bloodstain pattern analysis. The morphology of the artifacts has been described so that these deposits may be more clearly distinguished from bloodstains, targeted by crime scene personnel as potential sources of human DNA, and/or identified as potential evidence contaminants. Flowcharts have been devised to facilitate the analysis.

  19. Pulmonary embolus

    Science.gov (United States)

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

  20. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    Science.gov (United States)

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  1. Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure

    Directory of Open Access Journals (Sweden)

    Arne Andersson

    2008-01-01

    Full Text Available Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.

  2. Lung scintigraphy with nonspecific human immunoglobulin G ({sup 99m}Tc-HIG) in the evaluation of pulmonary involvement in connective tissue diseases: correlation with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT)

    Energy Technology Data Exchange (ETDEWEB)

    Kostopoulos, C.; Toubanakis, C.; Mamoulakis, C.; Gialafos, E.; Mavrikakis, M. [Alexandra University Hospital, Department of Clinical Therapeutics, Athens (Greece); Koutsikos, J.; Zerva, C.; Leondi, A. [Alexandra University Hospital, Department of Nuclear Medicine, Athens (Greece); Moulopoulos, L.A. [Areteion University Hospital, Department of Radiology, Athens (Greece); Sfikakis, P.P. [Laikon University Hospital, Department of Propaedeutic Medicine, Athens (Greece)

    2008-02-15

    In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients. Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs - abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained. Significant difference was found between HIG scores in the two groups (0.6 {+-} 0.07 vs 0.51 {+-} 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity. HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved. (orig.)

  3. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

    Science.gov (United States)

    Iino, Nozomi; Matsunaga, Toshiyuki; Harada, Tsuyoshi; Igarashi, Seiji; Koyama, Iwao; Komoda, Tsugikazu

    2007-05-01

    Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

  4. Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP-C)

    DEFF Research Database (Denmark)

    Lukovic, Dunja; Plasencia, Inés; Taberner, Francisco J

    2006-01-01

    Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich alpha helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component...... of various surfactant preparations of animal origin currently used to treat neonatal respiratory distress syndrome (NRDS) in preterm infants. The limited supply of this material and the risk of transmission of infectious agents and immunological reactions have prompted the development of synthetic SP...

  5. [Pulmonary hypertension in patients infected with human immunodeficiency virus: current situation].

    Science.gov (United States)

    Soto-Abánades, Clara Itzíar; Alcolea-Batres, Sergio; Ríos-Blanco, Juan José

    2013-01-01

    The increase in survival that has been achieved with the new treatments in the era of highly active antiretroviral therapy, has enabled clinicians and researchers to analyze issues that emerge in the long term in patients with HIV infection. Although the majority of cardiovascular complications have been widely described, the pathogenesis of pulmonary arterial hypertension is still poorly understood, and is one of the more complex and feared complications as it worsens the prognosis and quality of life of these patients This article reviews newer aspects related to the aetiology, symptoms, diagnosis and treatment of this disease. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  6. [Pulmonary strongyloidiasis].

    Science.gov (United States)

    Lozada, Heiler; Daza, Jorge E

    2016-10-01

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

  7. Muscular and pulmonary O2 uptake kinetics during moderate- and high-intensity sub-maximal knee-extensor exercise in humans

    DEFF Research Database (Denmark)

    Krustrup, Peter; Jones, Andrew M.; Wilkerson, Daryl P.;

    2009-01-01

    The purpose of this investigation was to determine the contribution of muscle O2 consumption (m O2) to pulmonary O2 uptake (p O2) during both low-intensity (LI) and high-intensity (HI) knee extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years...

  8. Microstructural characterization of CPPD and hydroxyapatite crystal depositions on human menisci

    Energy Technology Data Exchange (ETDEWEB)

    Katsamenis, Orestis L. [Bioengineering Research Group, University of Southampton, Southampton, SO17 1BJ (United Kingdom); Department of Materials Science, University of Patras, 26504 Rio, Patras (Greece); Karoutsos, Vagelis [Department of Materials Science, University of Patras, 26504 Rio, Patras (Greece); Kontostanos, Konstantinos; Panagiotopoulos, Elias C. [Department of Orthopaedics, School of Medicine, University of Patras, 26500 Rio, Patras (Greece); Papadaki, Helen [Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, 26500 Rio, Patras (Greece); Bouropoulos, Nikolaos [Department of Materials Science, University of Patras, 26504 Rio, Patras (Greece); Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature Chemical Processes - FORTH/ICE-HT, P.O. Box 1414, GR-26504 Patras (Greece)

    2012-11-15

    Meniscus is a fibrocartilaginous tissue composed mainly of water and a dense elaborate collagen network with a predominantly circumferential alignment. Crystal formation and accumulation on meniscal tissue is frequently observed especially in elderly. In this study, we used X-ray diffraction (XRD), FTIR and FT-Raman for the structural identification of the depositions and Optical microscopy, Scanning Electron microscopy (SEM/EDX) and Atomic Force microscopy (AFM), in order to investigate the structural relationship between the crystal deposits and the collagen fibers of human meniscal tissues. We are reporting on the formation of intercalary ''colonies'' of Calcium Pyrophosphate Dihydrate (CPPD) crystals with two distinct morphologies corresponding to the monoclinic and the triclinic phase, as well as the formation of micro-aggregations composed of nano-crystalline HAP aggregations which are developed along the longitudinal axis of collagen fibers without extensively disturbing the collagens arrangement. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Determining postmortem interval using glycoproteinous adhesion deposits by Balanus improvisus on human skeletal and dental remains.

    Science.gov (United States)

    Bytheway, Joan A; Pustilnik, Stephen M

    2013-01-01

    An anthropological analysis was conducted on skeletal and dental remains brought to the Galveston County Medical Examiner's office. The skeletal remains were dry, fragmented, and absent of typical fluvial characteristics. During microscopic examination, semitransparent, circular objects were discovered on the dentition, the mandible, tibial plateau, and distal femur. The objects were glycoproteinous adhesions deposited by the acorn barnacle, Balanus improvisus. B. improvisus is an intertidal barnacle found in estuaries in Galveston Bay. Basal diameter of the adhesions on the dentition were significantly smaller than those found on the postcranial bones (p = 0.010), indicating two consecutive cohorts adhered to the bone and dentition. As settlement typically occurs once a year, this would indicate that the remains were in the fluvial environment for at least 375-410 days. It is important in geographic areas that have prevalent fluvial environments that human remains, particularly dentition, are microscopically examined for marine life evidence. © 2012 American Academy of Forensic Sciences.

  10. VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema

    Science.gov (United States)

    Schaffartzik, W.; Poole, D. C.; Derion, T.; Tsukimoto, K.; Hogan, M. C.; Arcos, J. P.; Bebout, D. E.; Wagner, P. D.

    1992-01-01

    Ventilation-perfusion (VA/Q) inequality has been shown to increase with exercise. Potential mechanisms for this increase include nonuniform pulmonary vasoconstriction, ventilatory time constant inequality, reduced large airway gas mixing, and development of interstitial pulmonary edema. We hypothesized that persistence of VA/Q mismatch after ventilation and cardiac output subside during recovery would be consistent with edema; however, rapid resolution would suggest mechanisms related to changes in ventilation and blood flow per se. Thirteen healthy males performed near-maximal cycle ergometry at an inspiratory PO2 of 91 Torr (because hypoxia accentuates VA/Q mismatch on exercise). Cardiorespiratory variables and inert gas elimination patterns were measured at rest, during exercise, and between 2 and 30 min of recovery. Two profiles of VA/Q distribution behavior emerged during heavy exercise: in group 1 an increase in VA/Q mismatch (log SDQ of 0.35 +/- 0.02 at rest and 0.44 +/- 0.02 at exercise; P less than 0.05, n = 7) and in group 2 no change in VA/Q mismatch (n = 6). There were no differences in anthropometric data, work rate, O2 uptake, or ventilation during heavy exercise between groups. Group 1 demonstrated significantly greater VA/Q inequality, lower vital capacity, and higher forced expiratory flow at 25-75% of forced vital capacity for the first 20 min during recovery than group 2. Cardiac index was higher in group 1 both during heavy exercise and 4 and 6 min postexercise. However, both ventilation and cardiac output returned toward baseline values more rapidly than did VA/Q relationships. Arterial pH was lower in group 1 during exercise and recovery. We conclude that greater VA/Q inequality in group 1 and its persistence during recovery are consistent with the hypothesis that edema occurs and contributes to the increase in VA/Q inequality during exercise. This is supported by observation of greater blood flows and acidosis and, presumably therefore

  11. Phosphodiesterase 5 inhibitors augment UT-15C-stimulated ATP release from erythrocytes of humans with pulmonary arterial hypertension.

    Science.gov (United States)

    Bowles, Elizabeth A; Moody, Gina N; Yeragunta, Yashaswini; Stephenson, Alan H; Ellsworth, Mary L; Sprague, Randy S

    2015-01-01

    Both prostacyclin analogs and phosphodiesterase 5 (PDE5) inhibitors are effective treatments for pulmonary arterial hypertension (PAH). In addition to direct effects on vascular smooth muscle, prostacyclin analogs increase cAMP levels and ATP release from healthy human erythrocytes. We hypothesized that UT-15C, an orally available form of the prostacyclin analog, treprostinil, would stimulate ATP release from erythrocytes of humans with PAH and that this release would be augmented by PDE5 inhibitors. Erythrocytes were isolated and the effect of UT-15C on cAMP levels and ATP release were measured in the presence and absence of the PDE5 inhibitors, zaprinast or tadalafil. In addition, the ability of a soluble guanylyl cyclase inhibitor to prevent the effects of tadalafil was determined. Erythrocytes of healthy humans and humans with PAH respond to UT-15C with increases in cAMP levels and ATP release. In both groups, UT-15C-induced ATP release was potentiated by zaprinast and tadalafil. The effect of tadalafil was prevented by pre-treatment with an inhibitor of soluble guanylyl cyclase in healthy human erythrocytes. Importantly, UT-15C-induced ATP release was greater in PAH erythrocytes than in healthy human erythrocytes in both the presence and the absence of PDE5 inhibitors. The finding that prostacyclin analogs and PDE5 inhibitors work synergistically to enhance release of the potent vasodilator ATP from PAH erythrocytes provides a new rationale for the co-administration of these drugs in this disease. Moreover, these results suggest that the erythrocyte is a novel target for future drug development for the treatment of PAH.

  12. Polyvinylpyrrolidone-Capped Silver Nanoparticle Inhibits Infection of Carbapenem-Resistant Strain of Acinetobacter baumannii in the Human Pulmonary Epithelial Cell

    Directory of Open Access Journals (Sweden)

    Vishvanath Tiwari

    2017-08-01

    Full Text Available Acinetobacter baumannii, an opportunistic ESKAPE pathogen, causes respiratory and urinary tract infections. Its prevalence increases gradually in the clinical setup. Pathogenicity of Acinetobacter is significantly influenced by its ability to infect and survive in human pulmonary cells. Therefore, it is important to study the infection of A. baumannii in human pulmonary host cell (A-549, monitoring surface interacting and internalized bacteria. It was found that during infection of A. baumannii, about 40% bacteria adhered to A-549, whereas 20% got internalized inside pulmonary cell and induces threefold increase in the reactive oxygen species production. We have synthesized polyvinylpyrrolidone (PVP-capped AgNPs using chemical methods and tested its efficacy against carbapenem-resistant strain of A. baumannii. PVP-capped silver nanoparticles (PVP-AgNPs (30 µM have shown antibacterial activity against carbapenem-resistant strain of A. baumannii and this concentration does not have any cytotoxic effect on the human pulmonary cell line (IC50 is 130 µM. Similarly, PVP-AgNPs treatment decreases 80% viability of intracellular bacteria, decreases adherence of A. baumannii to A-549 (40 to 2.2%, and decreases intracellular concentration (20 to 1.3% of A. baumannii. This concludes that PVP-AgNPs can be developed as a substitute for carbapenem to control the infection caused by carbapenem-resistant A. baumannii.

  13. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice.

    Science.gov (United States)

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

    Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo.

    Science.gov (United States)

    Zhang, L; Ji, Y X; Jiang, W L; Lv, C J

    2015-06-01

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  15. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.; Ji, Y.X.; Jiang, W.L.; Lv, C.J. [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai (China)

    2015-05-08

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC{sub 50} of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  16. Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

    Science.gov (United States)

    Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

    2006-01-01

    Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

  17. DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome.

    Science.gov (United States)

    Hooper, Jay W; Brocato, Rebecca L; Kwilas, Steven A; Hammerbeck, Christopher D; Josleyn, Matthew D; Royals, Michael; Ballantyne, John; Wu, Hua; Jiao, Jin-an; Matsushita, Hiroaki; Sullivan, Eddie J

    2014-11-26

    Polyclonal immunoglobulin-based medical products have been used successfully to treat diseases caused by viruses for more than a century. We demonstrate the use of DNA vaccine technology and transchromosomal bovines (TcBs) to produce fully human polyclonal immunoglobulins (IgG) with potent antiviral neutralizing activity. Specifically, two hantavirus DNA vaccines [Andes virus (ANDV) DNA vaccine and Sin Nombre virus (SNV) DNA vaccine] were used to produce a candidate immunoglobulin product for the prevention and treatment of hantavirus pulmonary syndrome (HPS). A needle-free jet injection device was used to vaccinate TcB, and high-titer neutralizing antibodies (titers >1000) against both viruses were produced within 1 month. Plasma collected at day 10 after the fourth vaccination was used to produce purified α-HPS TcB human IgG. Treatment with 20,000 neutralizing antibody units (NAU)/kg starting 5 days after challenge with ANDV protected seven of eight animals, whereas zero of eight animals treated with the same dose of normal TcB human IgG survived. Likewise, treatment with 20,000 NAU/kg starting 5 days after challenge with SNV protected immunocompromised hamsters from lethal HPS, protecting five of eight animals. Our findings that the α-HPS TcB human IgG is capable of protecting in animal models of lethal HPS when administered after exposure provides proof of concept that this approach can be used to develop candidate next-generation polyclonal immunoglobulin-based medical products without the need for human donors, despeciation protocols, or inactivated/attenuated vaccine antigen. Copyright © 2014, American Association for the Advancement of Science.

  18. Extract from Nandina domestica inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in human pulmonary epithelial A549 cells.

    Science.gov (United States)

    Ueki, Takuro; Akaishi, Tatsuhiro; Okumura, Hidenobu; Abe, Kazuho

    2012-01-01

    Extract from fruits of Nandina domestica THUNBERG (NDE) has been used to improve cough and breathing difficulty in Japan for many years. To explore whether NDE may alleviate respiratory inflammation, we investigated its effect on expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E₂ (PGE₂) in human pulmonary epithelial A549 cells in culture. Treatment with lipopolysaccharide (LPS; 6 µg/mL) resulted in an increase of COX-2 expression and PGE₂ production in A549 cells. Both the LPS-induced COX-2 expression and PGE₂ production were significantly inhibited by NDE (1-10 µg/mL) in a concentration-dependent manner. NDE did not affect COX-1 expression nor COX activity. These results suggest that NDE downregulates LPS-induced COX-2 expression and inhibits PGE₂ production in pulmonary epithelial cells. Furthermore, higenamine and nantenine, two major constituents responsible for tracheal relaxing effect of NDE, did not mimic the inhibitory effect of NDE on LPS-induced COX-2 expression in A549 cells. To identify active constituent(s) of NDE responsible for the anti-inflammatory effect, NDE was introduced in a polyaromatic absorbent resin column and stepwise eluted to yield water fraction, 20% methanol fraction, 40% methanol fraction, 99.8% methanol fraction, and 99.5% acetone fraction. However, none of these five fractions alone inhibited LPS-induced COX-2 expression. On the other hand, exclusion of water fraction from NDE abolished the inhibitory effect of NDE on LPS-induced COX-2 expression. These results suggest that constituent(s) present in water fraction is required but not sufficient for the anti-inflammatory activity of NDE, which may result from interactions among multiple constituents.

  19. Titanium dioxide nanoparticles induce matrix metalloprotease 1 in human pulmonary fibroblasts partly via an interleukin-1β-dependent mechanism.

    Science.gov (United States)

    Armand, Lucie; Dagouassat, Maylis; Belade, Esther; Simon-Deckers, Angélique; Le Gouvello, Sabine; Tharabat, Chantal; Duprez, Corinne; Andujar, Pascal; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2013-03-01

    Exposure to titanium dioxide (TiO2) nanoparticles (NPs) is associated with lung remodeling, but the underlying mechanisms are unknown. Matrix metalloprotease (MMP)-1 is an important actor in matrix homeostasis and could therefore participate in TiO2 NP effects. Our aim was to evaluate the effects of TiO2 NPs on MMP-1 expression and activity in lung pulmonary fibroblasts and to understand the underlying mechanisms and assess the importance of the physicochemical characteristics of the particles in these effects. Human pulmonary fibroblasts (MRC-5 cell line and primary cells) were exposed to 10 or 100 μg/cm(2) TiO2 (two anatases, two anatase/rutile mix, one rutile NP, and one micrometric) and carbon black (CB) NPs for 6 to 48 hours. We examined cell viability, MMP-1 expression and activity, and the implication of oxidative stress, transforming growth factor (TGF)-β, extracellular MMP inducer, and IL-1β in MMP-1 expression. All TiO2 NPs induced MMP-1 (mRNA and protein expression), repression of procollagen-1, and α-actin expression, but only the two anatase/rutile mix induced MMP-1 activity. Micrometric TiO2 had smaller effects than TiO2 NPs, and CB NPs did not induce MMP-1. MMP-1 induction by TiO2 NPs was not related to TGF-β, oxidative stress, or EMPRIN expression but was related to IL-1β expression, which partly drives MMP-1 induction by two TiO2 NPs (one anatase/rutile mix and the rutile one). Taken together, our results show that TiO2 NPs are potent inducers and regulators of MMP-1 expression and activity, partly via an IL-1β-dependent mechanism. This may explain TiO2 lung remodeling effects.

  20. Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, J. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China); Xiao, F. [Department of Osteology, Pu Ai Hospital, Huazhong University of Science and Technology, Wuhan, Hubei (China); Zhang, Z.Z.; Wang, Y.P.; Chen, K.; Wang, Y.L. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China)

    2013-12-02

    β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M{sub 3} receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.

  1. Interspecies modeling of inhaled particle deposition patterns

    Energy Technology Data Exchange (ETDEWEB)

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    To evaluate the potential toxic effects of ambient contaminants or therapeutic effects of airborne drugs, inhalation exposure experiments can be performed with surrogate laboratory animals. Herein, an interspecies particle deposition theory is presented for physiologically based pharmacokinetic modeling. It is derived to improve animal testing protocols. The computer code describes the behavior and fate of particles in the lungs of human subjects and a selected surrogate, the laboratory rat. In the simulations CO2 is integrated with exposure chamber atmospheres, and its concentrations regulated to produce rat breathing profiles corresponding to selected levels of human physical activity. The dosimetric model is used to calculate total, compartmental (i.e., tracheobronchial and pulmonary), and localized distribution patterns of inhaled particles in rats and humans for comparable ventilatory conditions. It is demonstrated that the model can be used to predetermine the exposure conditions necessary to produce deposition patterns in rats that are equivalent to those in humans at prescribed physical activities.

  2. Sensitive and simultaneous quantification of zinc pyrithione and climbazole deposition from anti-dandruff shampoos onto human scalp

    NARCIS (Netherlands)

    Chen, G.; Miao, M.; Hoptroff, M.; Fei, X.; Collins, L.Z.; Jones, A.; Janssen, H.G.

    2015-01-01

    A sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for simultaneous quantification of zinc pyrithione (ZPT) and climbazole (CBZ) deposited onto human scalp from anti-dandruff (AD) shampoos. Scrubbing with a buffer so

  3. Sensitive and simultaneous quantification of zinc pyrithione and climbazole deposition from anti-dandruff shampoos onto human scalp

    NARCIS (Netherlands)

    G. Chen; M. Miao; M. Hoptroff; X. Fei; L.Z. Collins; A. Jones; H.G. Janssen

    2015-01-01

    A sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for simultaneous quantification of zinc pyrithione (ZPT) and climbazole (CBZ) deposited onto human scalp from anti-dandruff (AD) shampoos. Scrubbing with a buffer so

  4. Pulmonary hypertension

    Science.gov (United States)

    ... clots in the lung ( pulmonary embolism ) Heart failure Heart valve disease HIV infection Low oxygen levels in the blood for a long time (chronic) Lung disease, such as COPD or pulmonary fibrosis Medicines (for example, certain diet drugs) Obstructive sleep ...

  5. Pulmonary Edema

    Science.gov (United States)

    ... Accessed March 13, 2014. Pinto DS, et al. Pathophysiology of cardiogenic pulmonary edema. http://www.uptodate.com/ ... hvd/. Accessed March 10, 2014. What is pulmonary hypertension? National Heart, Lung, and Blood Institute. http://www. ...

  6. Pulmonary Fibrosis

    Science.gov (United States)

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

  7. Pulmonary Rehabilitation

    Science.gov (United States)

    ... shortness of breath and increase your ability to exercise. You may have heard that pulmonary rehabilitation is only for people with COPD (chronic obstructive pulmonary disease). We now know that ...

  8. Numerical simulation of micro-particle deposition in a realistic human upper respiratory tract model during transient breathing cycle

    Institute of Scientific and Technical Information of China (English)

    Jian hua Huang; Lian zhong Zhang

    2011-01-01

    An more reliable human upper respiratory tract model that consisted of an oropharynx and four generations of asymmetric tracheo-bronchial (TB) airways has been constructed to investigate the micro-particle deposition pattern and mass distribution in five lobes under steady inspiratory condition in former work by Huang and Zhang (2011 ).In the present work,transient airflow patterns and particle deposition during both inspiratory and expiratory processes were numerically simulated in the realistic human upper respiratory tract model with 14 cartilaginous rings (CRs) in the tracheal tube.The present model was validated under steady inspiratory flow rates by comparing current results with the theoretical models and published experimental data.The transient deposition fraction was found to strongly depend on breathing flow rate and particle diameter but slightly on turbulence intensity.Particles were mainly distributed in the high axial speed zones and traveled basically following the secondary flow.“Hot spots” of deposition were found in the lower portion of mouth cavity and posterior wall of pharynx/larynx during inspiration,but transferred to upper portion of mouth and interior wall of pharynx/larynx during expiration.The deposition fraction in the trachea during expiration was found to be much higher than that during inspiration because of the stronger secondary flow.

  9. Estimation of the Human Extrathoracic Deposition Fraction of Inhaled Particles Using a Polyurethane Foam Collection Substrate in an IOM Sampler.

    Science.gov (United States)

    Sleeth, Darrah K; Balthaser, Susan A; Collingwood, Scott; Larson, Rodney R

    2016-03-07

    Extrathoracic deposition of inhaled particles (i.e., in the head and throat) is an important exposure route for many hazardous materials. Current best practices for exposure assessment of aerosols in the workplace involve particle size selective sampling methods based on particle penetration into the human respiratory tract (i.e., inhalable or respirable sampling). However, the International Organization for Standardization (ISO) has recently adopted particle deposition sampling conventions (ISO 13138), including conventions for extrathoracic (ET) deposition into the anterior nasal passage (ET₁) and the posterior nasal and oral passages (ET₂). For this study, polyurethane foam was used as a collection substrate inside an inhalable aerosol sampler to provide an estimate of extrathoracic particle deposition. Aerosols of fused aluminum oxide (five sizes, 4.9 µm-44.3 µm) were used as a test dust in a low speed (0.2 m/s) wind tunnel. Samplers were placed on a rotating mannequin inside the wind tunnel to simulate orientation-averaged personal sampling. Collection efficiency data for the foam insert matched well to the extrathoracic deposition convention for the particle sizes tested. The concept of using a foam insert to match a particle deposition sampling convention was explored in this study and shows promise for future use as a sampling device.

  10. Estimation of the Human Extrathoracic Deposition Fraction of Inhaled Particles Using a Polyurethane Foam Collection Substrate in an IOM Sampler

    Directory of Open Access Journals (Sweden)

    Darrah K. Sleeth

    2016-03-01

    Full Text Available Extrathoracic deposition of inhaled particles (i.e., in the head and throat is an important exposure route for many hazardous materials. Current best practices for exposure assessment of aerosols in the workplace involve particle size selective sampling methods based on particle penetration into the human respiratory tract (i.e., inhalable or respirable sampling. However, the International Organization for Standardization (ISO has recently adopted particle deposition sampling conventions (ISO 13138, including conventions for extrathoracic (ET deposition into the anterior nasal passage (ET1 and the posterior nasal and oral passages (ET2. For this study, polyurethane foam was used as a collection substrate inside an inhalable aerosol sampler to provide an estimate of extrathoracic particle deposition. Aerosols of fused aluminum oxide (five sizes, 4.9 µm–44.3 µm were used as a test dust in a low speed (0.2 m/s wind tunnel. Samplers were placed on a rotating mannequin inside the wind tunnel to simulate orientation-averaged personal sampling. Collection efficiency data for the foam insert matched well to the extrathoracic deposition convention for the particle sizes tested. The concept of using a foam insert to match a particle deposition sampling convention was explored in this study and shows promise for future use as a sampling device.

  11. Modern muddy deposit along the Zhejiang coast in the East China Sea: Response to large-scale human projects

    Science.gov (United States)

    Xu, Gang; Liu, Jian; Liu, Shengfa; Wang, Zhongbo; Hu, Gang; Kong, Xianghuai

    2016-11-01

    Grain size and clay minerals in the surface sediment off Zhejiang Province, China, of the East China Sea were analyzed to study changes in grain size, muddy deposit boundary, and major riverine and other derived matters transport paths in the Zhejiang coastal muddy deposit since the impoundment of the Three Gorges Dam and after other large-scale human projects. The results show that the sediment types are mainly silt and mud in the muddy deposit, divided based on the 10% isoline of the sand-sized component. The sources of sediment in the muddy deposit are mainly the Yangtze River and simultaneously supplies from the Qiantang Jiang, Ou Jiang, relict fine-grain matter, and hydrolyzed volcanic rocks around the Zhoushan Islands. The transport and dispersal of sediments in the study area are largely controlled by the Zhejiang-Fujian coastal current and the Taiwan Warm Current and appear seasonally. The contributions from the Ou Jiang, relict matter, local hydrolyzed matter, and the Qiantang Jiang are enlarged owing to the decline of Yangtze suspended matter and the constructions of major human projects in the Hangzhou Bay, respectively. In addition, the sediment grain size exhibits a fining trend because of the influence of the Three Gorges Dam. The boundary of the muddy deposit is relatively stable after the Three Gorges Dam impoundment north of the city of Zhoushan. In contrast, south of the city of Zhoushan the boundary of the muddy deposit lies toward the east because the sediment supply from the relict fine-grained matters resuspended by the Taiwan Warm Current east of the study area. The changes in the grain size and contributions from smaller rivers and other derived matter as well as the boundary of the muddy deposit there will probably become more pronounced in the future.

  12. RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Hoban PR

    2006-06-01

    Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. Methods Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. Results Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p Conclusion These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.

  13. Human mesenchymal stem cell osteoblast differentiation, ECM deposition, and biomineralization on PAH/PAA polyelectrolyte multilayers.

    Science.gov (United States)

    Pattabhi, Sudhakara Rao; Lehaf, Ali M; Schlenoff, Joseph B; Keller, Thomas C S

    2015-05-01

    Polyelectrolyte multilayer (PEMU) coatings built layer by layer with alternating pairs of polyelectrolytes can be tuned to improve cell interactions with surfaces and may be useful as biocompatible coatings to improve fixation between implants and tissues. Here, we show that human mesenchymal stromal cells (hMSCs) induced with bone differentiation medium (BDM) to become osteoblasts biomineralize crosslinked PEMUs built with the polycation poly(allylamine hydrochloride) (PAH) and the polyanion poly(acrylic acid) (PAA). Degrees of hMSC osteoblast differentiation and surface biomineralization on the smooth PAH-terminated PEMUs (PAH-PEMUs) and microstructured PAA-terminated PEMUs (PAA-PEMUs) reflect differences in cell-deposited extracellular matrix (ECM). BDM-induced hMSCs expressed higher levels of the early osteoblast differentiation marker alkaline phosphatase and collagen 1 (COL1) sooner on PAA-PEMUs than on PAH-PEMUs. Cells on both types of PEMUs proceeded to express the later stage osteoblast differentiation marker bone sialoprotein (BSP), but the BDM-induced cells organized a more amorphous Collagen I and denser BSP localization on PAA-PEMUs than on PAH-PEMUs. These ECM properties correlated with greater biomineralization on the PAA-PEMUs than on PAH-PEMUs. Together, these results confirm the suitability of PAH/PAA PEMUs as a substrate for hMSC osteogenesis and highlight the importance of substrate effects on ECM organization and BSP presentation on biomineralization. © 2014 Wiley Periodicals, Inc.

  14. Communication across 300 generations: deterring human interference with waste deposit sites

    Energy Technology Data Exchange (ETDEWEB)

    Tannenbaum, P.H.

    1984-04-01

    The conditions attendant on the deep land burial of nuclear waste products raise a number of possible scenarios to cover the necessary 10,000 years of burial. However, no matter what kind of futuristic scenario obtains, it is desirable to develop an information system indicating the locale and nature of the deposit site and the types of materials stored, along with forewarnings not to interefere with the sites. A variety of such informational sites are suggested. Attention then turns to the recipients of such messages, recognizing from the outset that the psychological/perceptual makeup of individuals across the next 300 or so generations is virtually impossible to predict, particularly since new technologies may well alter that makeup in the furture. Nevertheless, current evidence suggests that certain human characteristics may be considered universal, and that these suggest the incorporation of selected sign signification into the message system. There are other such characteristics that, while probably not intrinsic, can probably be acquired with a minimum of formal training. That still leaves much of the message content to be deliberately created and, hence, learned. The common trefoil or other developed biohazardous signs emerge as the best candidates for a generic base symbol for the buried material.

  15. Simulated changes in dissolved Iron deposition to the global ocean driven by human activity

    Science.gov (United States)

    Myriokefalitakis, Stelios; Daskalakis, Nikos; Mihalopoulos, Nikos; Baker, Alex R.; Nenes, Athanassios; Kanakidou, Maria

    2015-04-01

    The global 3-d chemistry transport atmospheric model TM4-ECPL is used to simulate the atmospheric cycle of iron (Fe) and evaluate its atmospheric deposition to the ocean by accounting for both Fe natural and anthropogenic sources as well as of the proton and ligand promoted iron mobilisation from dust aerosol. Model evaluation is performed by comparison to available observations. Present day dissolved Fe deposition presents strong spatial and temporal variability with an annual deposition flux about 0.489 Tg(Fe)/yr from which about 25% are deposited over the ocean. The model simulates past, present and future iron deposition accounting for changes in anthropogenic emissions. We show that dissolved iron deposition has significantly increased since 1850 while it is expected to decrease in the future due to air pollution regulations. These changes affect the atmospheric dissolved Fe supply to High-Nutrient-Low-Chlorophyll oceanic areas characterized by Fe scarcity.

  16. Particle Deposition in Human Lungs due to Varying Cross-Sectional Ellipticity of Left and Right Main Bronchi

    Science.gov (United States)

    Roth, Steven; Oakes, Jessica; Shadden, Shawn

    2015-11-01

    Particle deposition in the human lungs can occur with every breathe. Airbourne particles can range from toxic constituents (e.g. tobacco smoke and air pollution) to aerosolized particles designed for drug treatment (e.g. insulin to treat diabetes). The effect of various realistic airway geometries on complex flow structures, and thus particle deposition sites, has yet to be extensively investigated using computational fluid dynamics (CFD). In this work, we created an image-based geometric airway model of the human lung and performed CFD simulations by employing multi-domain methods. Following the flow simulations, Lagrangian particle tracking was used to study the effect of cross-sectional shape on deposition sites in the conducting airways. From a single human lung model, the cross-sectional ellipticity (the ratio of major and minor diameters) of the left and right main bronchi was varied systematically from 2:1 to 1:1. The influence of the airway ellipticity on the surrounding flow field and particle deposition was determined.

  17. Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review.

    Science.gov (United States)

    Srour, Nadim; Thébaud, Bernard

    2015-12-01

    Idiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much enthusiasm for the treatment of several conditions, including lung diseases. Human trials of mesenchymal stromal cell (MSC) therapy for pulmonary fibrosis are under way. To shed light on the potential usefulness of MSCs for human disease, we aimed to systematically review the preclinical literature to determine if MSCs are beneficial in animal bleomycin pulmonary fibrosis models. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal bleomycin models of pulmonary fibrosis. Studies using embryonic stem cells or induced pluripotent stem cells were excluded. Seventeen studies were selected, all of which used MSCs in rodents. MSC therapy led to an improvement in bleomycin-induced lung collagen deposition in animal lungs and in the pulmonary fibrosis Ashcroft score in most studies. MSC therapy improved histopathology in almost all studies in which it was evaluated qualitatively. Furthermore, MSC therapy was found to improve 14-day survival in animals with bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage total and neutrophil counts, as well as transforming growth factor-β levels, were also reduced by MSCs. MSCs are beneficial in rodent bleomycin pulmonary fibrosis models. Since most studies examined the initial inflammatory phase rather than the chronic fibrotic phase, preclinical data offer better support for human trials of MSCs in acute exacerbations of pulmonary fibrosis rather than the chronic phase of the disease. There has been increased interest in mesenchymal stromal cell therapy for lung diseases. A few small clinical trials are under way in idiopathic pulmonary fibrosis. Preclinical evidence was assessed in a systematic review, as is often done for clinical studies. The existing studies offer better support for efficacy in the initial

  18. Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi.

    NARCIS (Netherlands)

    Lettow, M.H.E. van; West, C.E.; Meer, J.W.M. van der; Wieringa, F.; Semba, R.D.

    2005-01-01

    BACKGROUND: Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. OBJECTIVE: To characterize the antioxidant micronutrient status, inter

  19. Pulmonary vasculitis.

    Science.gov (United States)

    Lally, Lindsay; Spiera, Robert F

    2015-05-01

    Pulmonary vasculitis encompasses inflammation in the pulmonary vasculature with involved vessels varying in caliber from large elastic arteries to capillaries. Small pulmonary capillaries are the vessels most commonly involved in vasculitis affecting the lung. The antineutrophil cytoplasmic antibody-associated vasculitides, which include granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), are the small vessel vasculitides in which pulmonary vasculitis is most frequently observed and are the major focus of this review. Vasculitic involvement of the large pulmonary vessels as may occur in Behçet syndrome and Takayasu arteritis is also discussed.

  20. Human CD56+ cytotoxic lung lymphocytes kill autologous lung cells in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Christine M Freeman

    Full Text Available CD56+ natural killer (NK and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD are more cytotoxic to highly susceptible NK targets than those from control subjects. Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown. To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60. First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44 on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+ cells. Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining. Lung NK cells (CD56+ CD3- and CD56+ T cells (CD56+ CD3+ were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD. Lung NK cells had a predominantly "cytotoxic" CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased. Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted. Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation. Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery. These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their

  1. Pulmonary artery haemodynamic properties in patients with pulmonary hypertension secondary to rheumatic mitral stenosis.

    Science.gov (United States)

    Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin

    2012-12-01

    We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.

  2. Mycobacterium bovis bacille Calmette-Guérin (BCG) enhances human β-defensin-1 gene transcription in human pulmonary gland epithelial cells

    Institute of Scientific and Technical Information of China (English)

    ZHUBing-Dong; FENGYun; HUANGNing,; WUQi; WANGBo-Yao

    2003-01-01

    AIM: To examine the stimulatory effect of bacille Calmette-Guérin (BCG) cell wall components on human [β-defensin-1 (hBD-1)gene expression and analyze the response element in the 5'-flanking region of the gene. METHODS:BCG cell wall proteins were fractionated by Sephadex G-150 chromatography. Using reverse-transcription polymerase chain reaction (RT-PCR) and Northern hybridization analysis, hBD-1 mRNA expression was detected in ahuman pulmonary gland epithelial cell line SPC-A-1 cells. Progressive deletions of 5'-flanking region of hBD-1 genewere produced by PCR and ligated into promoterless chloramphenicol acetyltransferase (CAT) expression plasmidto construct pCAT reporter plasmids. Reporter gene expression was determined by ELISA. RESULTS: Therewas an obvious enhancement of hBD-1 mRNA expression after stimulation with heat-inactivated BCG whole cells(50mg/L), or the cell wall components with a molecular weight of 18-30 kDa (3mg/L) for 8 h. The upstreamsequence between -314 bp and +54 bp had the inducible activity by BCG, which contained CCAAT/enhancerbinding protein-β (C/EBPβ), activator protein-1 (AP-1), and CP2 cis element. CONCLUSION: BCG cell wallcomponents (18-30 kDa) can stimulate hBD-1 mRNA expression in pulmonary gland epithelial cells. The sequence(-314/+54) containing C/EBPβ, AP-1, and CP2 binding sites in the upstream of hBD-1 is involved in this induction.

  3. Modeling the deposition of bioaerosols with variable size and shape in the human respiratory tract – A review

    Directory of Open Access Journals (Sweden)

    R. Sturm

    2012-10-01

    Full Text Available The behavior of bioaerosol particles with various size and shape in the human respiratory tract was simulated by using a probabilistic model of the lung and an almost realistic mathematical approach to particle deposition. Results obtained from the theoretical computations clearly show that biogenic particle deposition in different lung compartments does not only depend on physical particle properties, but also on breathing mode (nose or mouth breathing and inhalative flow rate (=tidal volume × breathing frequency/30. Whilst ultrafine (5 μm particles tend to accumulate in the extrathoracic region and the uppermost airways of the tracheobronchial tree, particles with intermediate size are characterized by higher penetration depth, leading to their possible accumulation in the lung alveoli. Due to their deposition in deep lung regions and insufficient clearance, some bioaerosol particles may induce severe lung diseases ranging from infections, allergies, and toxic reactions to cancer.

  4. Correlates of Delayed Diagnosis among Human Immunodeficiency Virus-Infected Pulmonary Tuberculosis Suspects in a Rural HIV Clinic, South Africa

    Directory of Open Access Journals (Sweden)

    Respicious Boniface

    2012-01-01

    Full Text Available Background. Delay in pulmonary tuberculosis (PTB diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV infected individuals. Methods. A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA between January 2006 and December 2007. Using routine clinic registers, 480 records were identified. Results. PTB diagnosis delay was found among 77/176 (43.8% of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1–30 days in 27 (35.1% patients, 31–180 days in 24 (33.8% patients; 24 (31.2% patients remained undiagnosed for ≥180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR 3.43, 95% CI 1.45–8.08 and virological failure (OR 2.72, 95% CI 1.09–6.74. Conclusion. There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised.

  5. 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.

  6. Reperfusion pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. (Harvard Medical School, Boston, MA (USA))

    1989-02-17

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

  7. Assessment of Pulmonary Fibrogenic Potential of Multiwalled Carbon Nanotubes in Human Lung Cells

    Directory of Open Access Journals (Sweden)

    Anurag Mishra

    2012-01-01

    Full Text Available Multiwalled carbon nanotubes have been shown to possess unusual fibrogenic activity in vivo and are currently the focus of intense toxicological investigations. This study further determines the fibrogenic potential of well-dispersed MWCNT in human lung cell culture models and to develop a novel platform for understanding the cellular mechanisms of MWCNT-induced lung fibrosis. Survanta, a natural lung surfactant, showed effectiveness in dispersing agglomerates of MWCNT to fine structures similar in size to aerosolized one. At relevant low doses (0.002–0.2 μg/cm2, MWCNT exhibited a dose-dependent bio-effect on the human lung epithelial cells which is more pronounced in dispersed-MWCNT compared to non-dispersed form. Significantly elevated levels of fibrogenic mediators, such as transforming growth factor-β1 and matrix metalloprotienases-9 were observed in the dispersed-MWCNT treated lung epithelial cells. Based on previous in vivo studies showing that dispersed-MWCNT penetrated the interstitium and caused rapid interstitial fibrosis, we evaluated the potential direct interaction between lung fibroblasts and MWCNT. Direct stimulation of human lung fibroblast cell proliferation, collagen expression and fibroblast growth factor-2 were observed which suggests novel mechanisms of MWCNT-induced lung fibrosis. Our results indicate that the dispersion status of MWCNT determines their fibrogenic activity which is consistent with in vivo findings.

  8. Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts.

    Science.gov (United States)

    Radu, Mihaela; Dinu, Diana; Sima, Cornelia; Burlacu, Radu; Hermenean, Anca; Ardelean, Aurel; Dinischiotu, Anca

    2015-10-01

    Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications.

  9. Pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Lauro Martins Júnior

    2014-12-01

    Full Text Available Pulmonary hypertension is a pathological condition associated with various diseases, which must be remembered by the physicians, since early diagnosis may anticipate and avoid dangerous complications and even death if appropriate measures were not taken. The relationship with chronic obstructive pulmonary disease (COPD, important pathological process that is in increasing prevalence in developing countries, and leading position as cause of death, emphasizes its importance. Here are presented the classifications, pathophysiology, and general rules of treatment of pulmonary hypertension.

  10. Intestinal parasite co-infection among pulmonary tuberculosis cases without human immunodeficiency virus infection in a rural county in China.

    Science.gov (United States)

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2014-01-01

    Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01-4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47-6.20), and anemia (AOR = 2.43, 95% CI = 1.17-5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03-10.00). In addition, there was no significant trend between rates of infection with

  11. Pulmonary trichomoniasis and Trichomonas tenax.

    Science.gov (United States)

    Hersh, S M

    1985-08-01

    Pulmonary trichomoniasis is usually caused by aspirated Trichomonas tenax. Adult men with chronic purulent or necrotic pulmonary disease are usually affected. Sixty-eight patients were previously described. A Russian study demonstrated pulmonary trichomoniasis in 19 of 112 patients (17%), mostly in patients with lung cancer, lung abscess, or bronchiectasis. Rarely, pulmonary trichomoniasis may be caused by an intra-abdominal (T. hominis) or genitourinary (T. vaginalis) infection. T. tenax is usually regarded as a harmless commensal of the human mouth. Its prevalence ranges from 4% to 53% and may exceed that of vaginal infection with T. vaginalis in adult females. It is frequently found in patients with poor oral hygiene. Cultural identification is superior to microscopic examination of wet-smear, gram-stained and Papanicolaou-stained preparations. Aspirated pulmonary trichomoniasis is an opportunistic infection. Until the question of possible pathogenicity is resolved, metronidazole should be given. The underlying pulmonary disease should be vigorously treated.

  12. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Stahlhofen, W.; Gebhart, J.; Heyder, J.

    1980-06-01

    The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with /sup 198/Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 ..mu..m. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(Tl)-dectors. Characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest is found to be much slower for the material deposited in the alveolar region than for the amount deposited in the tracheobronchial tree. This allows the intrathoracic deposition to be divided into tracheolbronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention functions are presented and analyzed with respect to their different elimination rats belonging to the tracheobronchial and alveolar region. Total, tracheobronchial, alveolar and extrathoracic deposition data are reported in the aerodynamic diameter range between 1 and 10 ..mu..m.

  13. Biological characterization of low-energy ions with high-energy deposition on human cells.

    Science.gov (United States)

    Saha, Janapriya; Wilson, Paul; Thieberger, Peter; Lowenstein, Derek; Wang, Minli; Cucinotta, Francis A

    2014-09-01

    During space travel, astronauts are exposed to cosmic radiation that is comprised of high-energy nuclear particles. Cancer patients are also exposed to high-energy nuclear particles when treated with proton and carbon beams. Nuclear interactions from high-energy particles traversing shielding materials and tissue produce low-energy (energy (HZE) particles and low-energy secondary ions of similar LET will have distinct biological effects for cellular and tissue damage endpoints. We investigated the biological effects of low-energy ions of high LET utilizing the Tandem Van de Graaff accelerator at the Brookhaven National Laboratory (BNL), and compared these to experiments with HZE particles, that mimic the space environment produced at NASA Space Radiation Laboratory (NSRL) at BNL. Immunostaining for DNA damage response proteins was carried out after irradiation with 5.6 MeV/n boron (LET 205 keV/μm), 5.3 MeV/n silicon (LET 1241 keV/μm), 600 MeV/n Fe (LET 180 keV/μm) and 77 MeV/n oxygen (LET 58 keV/μm) particles. Low-energy ions caused more persistent DNA damage response (DDR) protein foci in irradiated human fibroblasts and esophageal epithelial cells compared to HZE particles. More detailed studies comparing boron ions to Fe particles, showed that boron-ion radiation resulted in a stronger G2 delay compared to Fe-particle exposure, and boron ions also showed an early recruitment of Rad51 at double-strand break (DSB) sites, which suggests a preference of homologous recombination for DSB repair in low-energy albeit high-LET particles. Our experiments suggest that the very high-energy radiation deposition by low-energy ions, representative of galactic cosmic radiation and solar particle event secondary radiation, generates massive but localized DNA damage leading to delayed DSB repair, and distinct cellular responses from HZE particles. Thus, low-energy heavy ions provide a valuable probe for studies of homologous recombination repair in radiation responses.

  14. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  15. Electrostatic Charge Effects on Pharmaceutical Aerosol Deposition in Human Nasal–Laryngeal Airways

    Directory of Open Access Journals (Sweden)

    Jinxiang Xi

    2014-01-01

    Full Text Available Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges.

  16. PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

    Science.gov (United States)

    Liang, Shoulei; Ren, Zhiwu; Han, Xiuxin; Yang, Jilong; Shan, Luling; Li, Lin; Wang, Binying; Zhang, Qianyi; Mu, Tianyang; Chen, Kexin; Xiong, Shunbin; Wang, Guowen

    2015-01-01

    Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis. Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors. Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P valuesmetastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values metastasis-free survival (both P values osteosarcoma patients for predicting the development of metastases and poor survival.

  17. PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

    Directory of Open Access Journals (Sweden)

    Shoulei Liang

    Full Text Available Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases, and immunohistochemistry (IHC staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05 than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02. Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03.This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.

  18. 25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Quint Jennifer K

    2012-06-01

    Full Text Available Abstract Background 25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population. Methods We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV exacerbations than those with insufficient and normal levels. We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR polymorphisms differed between frequent and infrequent exacerbators. Results There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1nmol/L (29.1 – 68.0 and 39.4nmol/L (22.3 – 59.2 or winter; medians 24.9nmol/L (14.3 – 43.1 and 27.1nmol/L (19.9 – 37.6. Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02. Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02. There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2nmol/L (IQR 22.4-59.4 and 33.3nmol/L (23.0-49.7; p = 0.43. HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0nmol/L (20.4 – 57.8 and 30.6nmol/L (19.4 – 48.7. There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05. Conclusions Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations. Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

  19. Aression of TLR9 in human pulmonary adenocarcinoma cell line A549%TLR9在人肺腺癌细胞A549中的表达

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Tiecheng Pan; Xiang Wei; Ligang Liu; Min Hu; Fang Yuan; Jiaduo Li

    2009-01-01

    Objective: Being considered as a bridge between the innate immunity and acquired immunity, Toll-like receptors (TRLs) are very important innate immunity moleculars. Recent researchs on the innate immunity have focused on the relation- ship between TLRs and human tumor. This paper investgated the expression and significance of TLR9 in human pulmonary adenocarcinoma cell (A549 cell) and human bronchial epithelial cell (HBE cell). Methods: After culturing A549 cell and HBE cell in vitro, the expression of TLR9 mRNA and protein in both cells were detected by immunocytochemistry, Real-time Quantitative Reverse Transcriptase-Polymerase Chain Reaction (Real-time Quantitative PCR) and Western blot, respectively. Results: By immunocytochemistry staining, TLR9 was mainly expressed in both cells' cell membrane and endochylema as brown-yellow material. It showed that the expressions of TLR9 mRNA and protein in A549 cell were stronger than those in HBE cell (P < 0.01). Conclusion: The results suggest TLR9 might cause the progression of human pulmonary adenocaroinoma, and the mechanism needs to be further investgatied.

  20. Physics, chemistry and pulmonary sequelae of thermodegradation events in long-mission space flight

    Science.gov (United States)

    Todd, Paul; Sklar, Michael; Ramirez, W. Fred; Smith, Gerald J.; Morgenthaler, George W.; Oberdoerster, Guenter

    1993-01-01

    An event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom is considered experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity enviroment impacts various stages of event simulation. Vapor-phase and particulate thermodegradation products were considered as potential spacecraft contaminants. A potential pathway for the production of ultrafine particles was identified. Different approaches to the simulation and prediction of contaminant transport were studied and used to predict the distribution of generic vapor-phase products in a Space Station model. A lung transport model was used to assess the pulmonary distribution of inhaled particles, and, finally, the impact of adaptation to low gravity on the human response to this inhalation risk was explored on the basis of known physiological modifications of the immune, endocrine, musculoskeletal and pulmonary systems that accompany space flight.

  1. Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro

    Science.gov (United States)

    Svegliati, Silvia; Amico, Donatella; Spadoni, Tatiana; Fischetti, Colomba; Finke, Doreen; Moroncini, Gianluca; Paolini, Chiara; Tonnini, Cecilia; Grieco, Antonella; Rovinelli, Marina; Gabrielli, Armando

    2017-01-01

    One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia. PMID:28228756

  2. Human mesenchymal cells from adipose tissue deposit laminin and promote regeneration of injured spinal cord in rats.

    Science.gov (United States)

    Menezes, Karla; Nascimento, Marcos Assis; Gonçalves, Juliana Pena; Cruz, Aline Silva; Lopes, Daiana Vieira; Curzio, Bianca; Bonamino, Martin; de Menezes, João Ricardo Lacerda; Borojevic, Radovan; Rossi, Maria Isabel Doria; Coelho-Sampaio, Tatiana

    2014-01-01

    Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a description of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.

  3. Resolution of human immunodeficiency virus type 1 infection-related severe pulmonary hypertension in a very low-birth-weight infant.

    Science.gov (United States)

    Feiterna-Sperling, Cornelia; Hüseman, Dieter; Timme, Jens; Bührer, Christoph; Obladen, Michael

    2008-06-01

    Pulmonary arterial hypertension (PAH) affects approximately 0.5% of human immunodeficiency virus (HIV)-infected adults with poor prognosis. The effectiveness of highly active antiretroviral therapy for treatment of HIV-related PAH (HIV-PAH) remains controversial. Little is known about the incidence, clinical course, and therapy options for PAH in HIV-1-infected pediatric patients. Here, we report the case of a preterm infant with HIV-related life-threatening PAH, which resolved after initiation of highly active antiretroviral therapy.

  4. Dirofilariose pulmonar humana, adquirida no Brasil: comunicação de um caso Case report: human pulmonary dirofilariasis acquired in Brazil

    OpenAIRE

    Vicente Amato Neto; Valdir Sabbaga Amato; Antonio Carlos Pedroso de Moraes Júnior; Giovanni Guido Cerri

    1993-01-01

    É comunicado caso de dirofilariose humana, adquirida no Brasil. Trata-se do segundo acometimento dessa natureza publicado em literatura científica. Como expressão clínica, foram evidenciados dois nódulos pulmonares, através de exame radiológico convencional e de tomografia computadorizada. O diagnóstico decorreu de análise histopatológica de uma das lesões.We report the second published case of human dirofilariasis acquired in Brazil. The patient had two pulmonary coin lesions seen in convent...

  5. Scorched Earth: how will changes in the strength of the vegetation sink to ozone deposition affect human health and ecosystems?

    Science.gov (United States)

    Emberson, L. D.; Kitwiroon, N.; Beevers, S.; Büker, P.; Cinderby, S.

    2013-07-01

    This study investigates the effect of ozone (O3) deposition on ground level O3 concentrations and subsequent human health and ecosystem risk under hot summer "heat wave" type meteorological events. Under such conditions, extended drought can effectively "turn off" the O3 vegetation sink leading to a substantial increase in ground level O3 concentrations. Two models that have been used for human health (the CMAQ chemical transport model) and ecosystem (the DO3SE O3 deposition model) risk assessment are combined to provide a powerful policy tool capable of novel integrated assessments of O3 risk using methods endorsed by the UNECE Convention on Long-Range Transboundary Air Pollution. This study investigates 2006, a particularly hot and dry year during which a heat wave occurred over the summer across much of the UK and Europe. To understand the influence of variable O3 dry deposition three different simulations were investigated during June and July: (i) actual conditions in 2006, (ii) conditions that assume a perfect vegetation sink for O3 deposition and (iii) conditions that assume an extended drought period that reduces the vegetation sink to a minimum. The risks of O3 to human health, assessed by estimating the number of days during which running 8 h mean O3 concentrations exceeded 100 μg m-3, show that on average across the UK, there is a difference of 16 days exceedance of the threshold between the perfect sink and drought conditions. These average results hide local variation with exceedances between these two scenarios reaching as high as 20 days in the East Midlands and eastern UK. Estimates of acute exposure effects show that O3 removed from the atmosphere through dry deposition during the June and July period would have been responsible for approximately 460 premature deaths. Conversely, reduced O3 dry deposition will decrease the amount of O3 taken up by vegetation and, according to flux-based assessments of vegetation damage, will lead to a reduction in

  6. Scorched Earth: how will changes in the strength of the vegetation sink to ozone deposition affect human health and ecosystems?

    Directory of Open Access Journals (Sweden)

    L. D. Emberson

    2013-07-01

    Full Text Available This study investigates the effect of ozone (O3 deposition on ground level O3 concentrations and subsequent human health and ecosystem risk under hot summer "heat wave" type meteorological events. Under such conditions, extended drought can effectively "turn off" the O3 vegetation sink leading to a substantial increase in ground level O3 concentrations. Two models that have been used for human health (the CMAQ chemical transport model and ecosystem (the DO3SE O3 deposition model risk assessment are combined to provide a powerful policy tool capable of novel integrated assessments of O3 risk using methods endorsed by the UNECE Convention on Long-Range Transboundary Air Pollution. This study investigates 2006, a particularly hot and dry year during which a heat wave occurred over the summer across much of the UK and Europe. To understand the influence of variable O3 dry deposition three different simulations were investigated during June and July: (i actual conditions in 2006, (ii conditions that assume a perfect vegetation sink for O3 deposition and (iii conditions that assume an extended drought period that reduces the vegetation sink to a minimum. The risks of O3 to human health, assessed by estimating the number of days during which running 8 h mean O3 concentrations exceeded 100 μg m−3, show that on average across the UK, there is a difference of 16 days exceedance of the threshold between the perfect sink and drought conditions. These average results hide local variation with exceedances between these two scenarios reaching as high as 20 days in the East Midlands and eastern UK. Estimates of acute exposure effects show that O3 removed from the atmosphere through dry deposition during the June and July period would have been responsible for approximately 460 premature deaths. Conversely, reduced O3 dry deposition will decrease the amount of O3 taken up by vegetation and, according to flux-based assessments of vegetation damage, will lead

  7. Intercellular deposits of basement membrane material in active human pituitary adenomas detected by immunostaining for laminin and electron microscopy

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R

    1986-01-01

    Thirty-eight human pituitary adenomas (24 endocrine active and 14 endocrine inactive tumors) were studied immunohistochemically for the presence of the basement membrane component, laminin, and ultrastructurally for the presence of basement membrane. Immunoreactivity of laminin delineated staining...... and one patient with Cushing's syndrome). Concurrently, at the ultrastructural level, bunches of basement membrane-like material intermingled between the adenoma cells were demonstrated in seven of these ten active adenomas. Furthermore, secretory granules were entrapped occasionally in this intercellular...... matrix, indicating a mutual dependence between excessive hormone extrusion and an increase of "misplaced" deposits of basement membrane components, e.g., laminin....

  8. Influência da variação dos decúbitos laterais na deposição pulmonar de aerossol Influence of change in lateral decubitus on pulmonary aerosol deposition

    Directory of Open Access Journals (Sweden)

    Luciana Alcoforado

    2011-08-01

    Full Text Available CONTEXTUALIZAÇÃO: O decúbito lateral apresenta as maiores mudanças em relação à ventilação pulmonar regional e é utilizado na rotina da fisioterapia respiratória. OBJETIVOS: Avaliar a influência do decúbito lateral na deposição pulmonar de radioaerossol durante a inalação em indivíduos jovens e relacionar os efeitos desse decúbito na rotina terapêutica. MÉTODOS: Em estudo randomizado em duas fases, foram incluídos oito homens voluntários saudáveis, com média de idade de 23,6±2,5 anos. Na primeira fase, inalou-se aerossol durante nove minutos no decúbito lateral sorteado e, após intervalo de cinco a sete dias, realizou-se a segunda fase. Para a cintilografia, inalou-se uma dose média de ácido dietilnotriaminopentacético marcado com tecnécio (DTPA - TC99m, com uma atividade radioativa em média de 25 milicuries (mCi. Ao final da inalação, as imagens foram adquiridas em câmaras de cintilação e analisadas por meio da divisão longitudinal e transversal dos pulmões em regiões de interesse (ROI. Para análise estatística, utilizou-se o teste t de Student pareado, considerando significativo pBACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of

  9. A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

    Science.gov (United States)

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have ...

  10. Sensitive and simultaneous quantification of zinc pyrithione and climbazole deposition from anti-dandruff shampoos onto human scalp.

    Science.gov (United States)

    Chen, Guoqiang; Miao, Miao; Hoptroff, Michael; Fei, Xiaoqing; Collins, Luisa Z; Jones, Andrew; Janssen, Hans-Gerd

    2015-10-15

    A sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for simultaneous quantification of zinc pyrithione (ZPT) and climbazole (CBZ) deposited onto human scalp from anti-dandruff (AD) shampoos. Scrubbing with a buffer solution was used as the sampling method for the extraction of ZPT and CBZ from scalp. Derivatization of ZPT was carried out prior to UHPLC-MS/MS analysis. The identification of ZPT and CBZ was performed by examining ratios of selected multiple reaction monitoring (MRM) transitions in combination with UHPLC retention times. The limit of detection for ZPT and CBZ was established to be 1 and 2ng/mL, respectively. This sensitivity enables the quantification of ZPT and CBZ at deposition levels in the low ng/cm(2) range. The method was successfully applied for the analysis of scalp buffer scrub samples from an in vivo study. The levels of ZPT and CBZ deposited on the scalp at different time points after application of the AD shampoo were measured. The results revealed that dual-active AD shampoo delivered more ZPT onto the scalp in a single wash than single active shampoo did. The amount of ZPT and CBZ retained on the scalp after AD shampoo application declined over 72h. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Atypical Radiological Manifestation of Pulmonary Metastatic Calcification

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Hae; Kim, Eun Sun; Kim, Chul Hwan; Ham, Soo Youn; Oh, Yu Whan [Korea University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Metastatic pulmonary calcification is a condition of calcium deposition in the normal pulmonary parenchyma, and this is secondary to abnormal calcium metabolism without any prior soft tissue damage. The predisposing factors for this condition include chronic renal failure, hypercalcemia and increased tissue alkalinity. The most common radiologic manifestation consists of poorly defined nodular opacities in the upper lung zone. These opacities reflect the deposition of calcium salts in the pulmonary interstitium. We present here a case of metastatic pulmonary calcification in a patient who recovered from pneumonia with sepsis and whose high-resolution CT (HRCT) images demonstrated localized parenchymal airspace calcification that was limited to the bilateral lower lobes. These lower lobes had been involved with pneumonic consolidation without calcification, as seen on the previous CT scan. In summary, we report here on an atypical presentation of metastatic pulmonary calcification that showed dense airspace consolidation localized to the bilateral lower lobes in a patient with primary hyperparathyroidism and pneumonia.

  12. Pulmonary Kaposi Sarcoma with Osseous Metastases in an Human Immunodeficiency Virus (HIV) Patient: A Remarkable Response to Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Dirweesh, Ahmed; Khan, Muhammad Yasir; Hamiz, Shaikh Fawad; Karabulut, Nigahus

    2017-01-01

    Patient: Male, 34 Final Diagnosis: Pulmonary Kaposi’s sarcoma with bony metastatses Symptoms: Cough • weight loss Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Kaposi sarcoma (KS) is known to involve the mucocutaneous tissues and the aero-digestive tracts. In acquired immune deficiency syndrome (AIDS) patients, KS has an aggressive course and carries poor prognosis. We present a case of pulmonary KS with osseous metastases as the first presentation of human immunodeficiency virus (HIV) infection in a young male. The lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (HAART). Case Report: A 34-year-old heterosexual male presented with a one month history of cough and 15–20 pound weight loss within six months. Examination revealed oral thrush, decreased breath sounds and crackles on the right lower lung base. Imaging showed a large right perihilar mass with multiple lytic lesions involving thoracic and lumber vertebrae, ribs, sternum, and clavicles. Blood and sputum cultures, smears for acid fast bacilli, and a QUANTIferon gold test were all negative. He tested positive for HIV and his CD4 count was 7 cells/uL. Bronchoscopy with biopsy was unrevealing. Pathology of the right hilar mass was diagnostic of KS. Following initiation of antiretroviral therapy his condition dramatically improved; repeat chest CT scan showed marked regression of the bony and pulmonary lesions. Conclusions: The dual action of HAART on the recovery of the immune system and against human herpes virus 8 (HHV-8) may essentially cause regression of KS lesions. PMID:28216610

  13. Pulmonary aspergilloma

    Science.gov (United States)

    ... grows on dead leaves, stored grain, bird droppings, compost piles, and other decaying vegetation. Cavities in the ... Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 8/31/2014 Updated by: Jatin M. ...

  14. Pulmonary tuberculosis

    Science.gov (United States)

    ... ray Pulmonary nodule, solitary - CT scan Miliary tuberculosis Tuberculosis of the lungs Erythema nodosum associated with sarcoidosis Respiratory system Tuberculin skin test References Fitzgerald DW, Sterling TR, Haas DW. ...

  15. Pulmonary hypertension

    OpenAIRE

    2016-01-01

    In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summaris...

  16. Pulmonary Agenesis.

    Science.gov (United States)

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

    2015-01-01

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

  17. Pulmonary Edema

    OpenAIRE

    Tanser, Paul H.

    1981-01-01

    The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients.

  18. Proteomic expression profiling of Haemophilus influenzae grown in pooled human sputum from adults with chronic obstructive pulmonary disease reveal antioxidant and stress responses

    Directory of Open Access Journals (Sweden)

    Brauer Aimee L

    2010-06-01

    Full Text Available Abstract Background Nontypeable Haemophilus influenzae colonizes and infects the airways of adults with chronic obstructive pulmonary disease, the fourth most common cause of death worldwide.Thus, H. influenzae, an exclusively human pathogen, has adapted to survive in the hostile environment of the human airways.To characterize proteins expressed by H. influenzae in the airways, a prototype strain was grown in pooled human sputum to simulate conditions in the human respiratory tract.The proteins from whole bacterial cell lysates were solubilized with a strong buffer and then quantitatively cleaned with an optimized precipitation/on-pellet enzymatic digestion procedure.Proteomic profiling was accomplished by Nano-flow liquid chromatography/mass spectroscopy with low void volume and high separation efficiency with a shallow, long gradient. Results A total of 1402 proteins were identified with high confidence, including 170 proteins that were encoded by genes that are annotated as conserved hypothetical proteins.Thirty-one proteins were present in greater abundance in sputum-grown conditions at a ratio of > 1.5 compared to chemically defined media.These included 8 anti-oxidant and 5 stress-related proteins, suggesting that expression of antioxidant activity and stress responses is important for survival in the airways.Four proteins involved in uptake of divalent anions and 9 proteins that function in uptake of various molecules were present in greater abundance in sputum-grown conditions. Conclusions Proteomic expression profiling of H. influenzae grown in pooled human sputum revealed increased expression of antioxidant, stress-response proteins and cofactor and nutrient uptake systems compared to media grown cells.These observations suggest that H. influenzae adapts to the oxidative and nutritionally limited conditions of the airways in adults with chronic obstructive pulmonary disease by increasing expression of molecules necessary for survival

  19. Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers.

    Science.gov (United States)

    Manigrasso, Maurizio; Buonanno, Giorgio; Fuoco, Fernanda Carmen; Stabile, Luca; Avino, Pasquale

    2015-01-01

    Aerosols from eight e-cigarettes at different nicotine levels and flavoring were characterized as particle number size distributions in the range 5.6-560 nm by FMPS and CPC. Results were used to provided osimetry estimates applying the MMPD model.Particle number concentrations varied between 3.26 x 10(9) and 4.09 x 10(9) part cm(-3) for e-liquids without nicotine and between 5.08 x 10(9) and 5.29 x 10(9) part cm(-3) for e-liquids with nicotine. No flavor effects were detected on particle concentration data. Particle size distributions were unimodal with modes between 107-165 nm and 165-255 nm, for number and volume metrics, respectively. Averagely, 6.25 x 10(10) particles were deposited in respiratory tree after a single puff. Highest deposition densities and mean layer thickness of e-cigarette liquid on the lung epithelium were estimated at lobar bronchi. Our study shows that e-cigarette aerosol is source of high particle dose in respiratory system, from 23%to 35% of the daily dose of a no-smoking individual.

  20. Human-driven changes in dissolved phosphorus deposition to the ocean

    Science.gov (United States)

    Myriokefalitakis, Stelios; Nenes, Athanasios; Kanakidou, Maria

    2016-04-01

    The atmospheric cycle of phosphorus (P) is parameterized in a global 3-D chemistry-transport model by taking into account the primary emissions of total (TP) and dissolved P (PO4) associated with dust, sea-salt, bioaerosols and combustion particles of anthropogenic and natural sources. Mineral sources are calculated to contribute by roughly 80% to the TP emissions. The calculated annual deposition flux of PO4 presents strong spatial and temporal variability with about 30% occurring over the ocean. Sensitivity simulations using preindustrial (year 1850), present (year 2008) and future (year 2100) anthropogenic and biomass burning emission scenarios, indicate that an increase in dust-P dissolution flux may have occurred in the last 150 years due to increasing atmospheric acidity due to anthropogenic emissions. On the opposite, a decrease of dust-P containing dissolution flux is projected for near future, since air-quality regulations are expected to reduce atmospheric acidity compared to present-day. Present day simulations of atmospheric P aerosol concentrations and deposition fluxes compare satisfactorily with available observations, thus, providing confidence to the model results. This work has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program: ARISTEIA - PANOPLY (Pollution Alters Natural Aerosol Composition: implications for Ocean Productivity, cLimate and air qualitY) grant.

  1. Development and use of a pneumoconiosis database of human pulmonary inorganic particulate burden in over 400 lungs.

    Science.gov (United States)

    Abraham, J L; Burnett, B R; Hunt, A

    1991-03-01

    Over 400 cases with data from in situ electron microprobe quantitation of non-fibrous inorganic particles (e.g., silica, alumino-silicates, talc, metals) in pulmonary tissue sections, and data from quantitative digestion analyses for fiber content (e.g., asbestos, silica, alumino-silicates, man-made fibers, talc) comprise an extensive microcomputer data set of lung particle burden. When allied with demographic and histopathologic information the result is a comprehensive database of occupational pulmonary pathology. Examples of the kinds of information which can be extracted from the database include: 1) summary information on the types sizes and associations of particles in lungs with a variety of exposures, 2) concentrations of etiologic particle type in cases with recognized pneumoconioses, and 3) correlations between particle type, pathology, occupation and social history. The database provides a powerful tool for assessing such information on statistically meaningful sample sets.

  2. Combination Therapy of Advanced Invasive Pulmonary Aspergillosis in Transiently Neutropenic Rats Using Human Pharmacokinetic Equivalent Doses of Voriconazole and Anidulafungin▿

    OpenAIRE

    van de Sande, Wendy W. J.; Mathot, Ron A.A.; ten Kate, Marian T.; van Vianen, Wim; Tavakol, Mehri; Rijnders, Bart J. A.; Bakker-Woudenberg, Irma A. J. M.

    2009-01-01

    At present, voriconazole (VOR) is the drug of first choice for treating invasive pulmonary aspergillosis (IPA). However, particularly in advanced stages of disease and in the severely immunocompromised host, the mortality remains substantial. The combination of VOR with an echinocandin may improve the therapeutic outcome. We investigate here whether combining VOR and anidulafungin (ANI) in advanced IPA in transiently neutropenic rats results in a higher therapeutic efficacy. Since VOR is meta...

  3. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    OpenAIRE

    Purushotham, A D; McCulloch, P.; George, W. D.

    1991-01-01

    Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacr...

  4. Types of Pulmonary Hypertension

    Science.gov (United States)

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  5. Detection of platelet deposition in cases of arteriosclerosis obliterans (ASO) using indium-111 platelets and Tc-99m human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Kitagawa, Kazuo; Miyai, Motonobu; Etani, Hideki

    1987-02-01

    We evaluated platelet deposition in vivo in 10 patients with arteriosclerosis obliterans (ASO) of the lower limbs and 8 normal subjects with a dual-tracer technique using indium-111 platelets and Tc-99m human serum albumin. Each patient with ASO showed intermittent claudication and angiographically occlusive vascular lesions in either the aorta, common iliac artery, external iliac artery, internal iliac artery or femoral artery. Of the 8 patients who were not under antiplatelet medication, 5 showed positive platelet deposition at angiographically occlusive vascular sites, whereas none of the normal subjects showed in vivo platelet deposition. In three patients who showed platelet deposition without antiplatelet medication and thereafter received aspirin therapy (650 mg/day), platelet deposition at all occlusive vascular sites was resolved after aspirin therapy. This preliminary study indicated that platelet scintigraphy might be useful in evaluating thrombogenicity and the effect of antiplatelet medication in vivo, in patients with ASO.

  6. Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

    Science.gov (United States)

    Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

    2017-02-01

    A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described.

  7. Effect of pulmonary surfactant and phospholipid hexadecanol tyloxapol on recombinant human-insulin absorption from intratracheally administered dry powders in diabetic rats.

    Science.gov (United States)

    Zheng, Jianheng; Zhang, Ge; Lu, Yang; Fang, Fang; He, Jiake; Li, Ning; Talbi, Amer; Zhang, Ying; Tang, Yue; Zhu, Jiabi; Chen, Xijing

    2010-12-01

    The purpose of the present study was to evaluate the enhancement effect of the natural pulmonary surfactant (PS) or its artificial substitute, phospholipid hexadecanol tyloxapol (PHT) on the bioavailability and hypoglycemic activity of recombinant human insulin (rh-insulin) in a pulmonary delivery system. PS- or PHT-loaded insulin formulation was administered to streptozotocin induced diabetic rats, at doses of 5 U/kg, 10 U/kg and 20 U/kg insulin, respectively. The hypoglycemic effect caused by PS or PHT containing rh-insulin was analyzed and the area above the curves (AAC) of serum glucose levels versus time, the minimum glucose concentration (C(min)), the time to C(min) (T(min)) and the pharmacological availability (PA%) were derived from the serum glucose profiles. Results showed that PS and PHT caused significantly decrease in serum glucose levels. The decrease in plasma glucose levels continued for about 5 h after the nadir. The highest AAC value was obtained when 20 U/kg rh-insulin with PS or PHT as absorption enhancer was administered to rats. AAC(0-360 min) of PS- or PHT-loaded rh-insulin was 2-3 times as much as that without PS or PHT and PA% increased by 1.3-2 fold. Thus, the extent of oral absorption of insulin from PS- or PHT-loaded particles was significantly greater when compared with that without them. In addition, PHT as well as PS did not change the lactate dehydrogenase (LDH) activity, alkaline phosphatase (AKP) activity and N-acetyl-β-D-glucoaminidase (NAG) activity in bronch fluid which are sensitive indicators of acute toxicity to lung cells in bronchoalveolar lavage (BAL). It is concluded that PS and PHT is a promising absorption enhancer for pulmonary delivery systems of large molecule drugs as rh-insulin.

  8. Treatment of Hantavirus Pulmonary Syndrome

    Science.gov (United States)

    2007-10-14

    Clinical syndrome Hantaviruses cause a spectrum of vascular-leak syndromes n humans ranging from proteinuria to pulmonary edema and rank hemorrhage...of fatal illness. The illness is haracterized by fever and vascular leakage resulting in noncar- iogenic pulmonary edema followed in severe cases by...cardiopulmonary syndrome (HCPS) o emphasize the important role of cardiogenic shock; among ospitalized patients, death almost invariably results from

  9. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    Science.gov (United States)

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Palaeoloxodon and human interaction: depositional setting, chronology and archaeology at the Middle Pleistocene Ficoncella site (Tarquinia, Italy.

    Directory of Open Access Journals (Sweden)

    Daniele Aureli

    Full Text Available The Ficoncella site in northern Latium (Italy represents a unique opportunity to investigate the modalities of a short occupation in an alluvial setting during the Lower Palaeolithic. The small excavation area yielded a lithic assemblage, a carcass of Palaeoloxodon antiquus, and some other faunal remains. The main objectives of the study are to better characterize the depositional context where the Palaeoloxodon and the lithic assemblage occur, and to evaluate with greater precision the occupation dynamics. A 25 m-long well was drilled just above the top of the terrace of the Ficoncella site and faunal and lithic remains were analyzed with current and innovative techniques. The archaeological site contains floodplain deposits as it is located next to a small incised valley that feeds into a larger valley of the Mignone River. A tephra layer capping the site is 40Ar/39Ar dated to 441± 8 ka. Collectively, the geochronologic, tephrochronologic and geologic data, suggest the site was occupied during MIS 13. The new results should prompt further research at Ficoncella in order to improve our understanding of the dynamics of human settlement in Europe during the Early to Middle Pleistocene.

  11. Palaeoloxodon and Human Interaction: Depositional Setting, Chronology and Archaeology at the Middle Pleistocene Ficoncella Site (Tarquinia, Italy)

    Science.gov (United States)

    Aureli, Daniele; Contardi, Antonio; Giaccio, Biagio; Jicha, Brian; Lemorini, Cristina; Madonna, Sergio; Magri, Donatella; Marano, Federica; Milli, Salvatore; Modesti, Valerio; Palombo, Maria Rita; Rocca, Roxane

    2015-01-01

    The Ficoncella site in northern Latium (Italy) represents a unique opportunity to investigate the modalities of a short occupation in an alluvial setting during the Lower Palaeolithic. The small excavation area yielded a lithic assemblage, a carcass of Palaeoloxodon antiquus, and some other faunal remains. The main objectives of the study are to better characterize the depositional context where the Palaeoloxodon and the lithic assemblage occur, and to evaluate with greater precision the occupation dynamics. A 25 m-long well was drilled just above the top of the terrace of the Ficoncella site and faunal and lithic remains were analyzed with current and innovative techniques. The archaeological site contains floodplain deposits as it is located next to a small incised valley that feeds into a larger valley of the Mignone River. A tephra layer capping the site is 40Ar/39Ar dated to 441± 8 ka. Collectively, the geochronologic, tephrochronologic and geologic data, suggest the site was occupied during MIS 13. The new results should prompt further research at Ficoncella in order to improve our understanding of the dynamics of human settlement in Europe during the Early to Middle Pleistocene. PMID:25898322

  12. Palaeoloxodon and human interaction: depositional setting, chronology and archaeology at the Middle Pleistocene Ficoncella site (Tarquinia, Italy).

    Science.gov (United States)

    Aureli, Daniele; Contardi, Antonio; Giaccio, Biagio; Jicha, Brian; Lemorini, Cristina; Madonna, Sergio; Magri, Donatella; Marano, Federica; Milli, Salvatore; Modesti, Valerio; Palombo, Maria Rita; Rocca, Roxane

    2015-01-01

    The Ficoncella site in northern Latium (Italy) represents a unique opportunity to investigate the modalities of a short occupation in an alluvial setting during the Lower Palaeolithic. The small excavation area yielded a lithic assemblage, a carcass of Palaeoloxodon antiquus, and some other faunal remains. The main objectives of the study are to better characterize the depositional context where the Palaeoloxodon and the lithic assemblage occur, and to evaluate with greater precision the occupation dynamics. A 25 m-long well was drilled just above the top of the terrace of the Ficoncella site and faunal and lithic remains were analyzed with current and innovative techniques. The archaeological site contains floodplain deposits as it is located next to a small incised valley that feeds into a larger valley of the Mignone River. A tephra layer capping the site is 40Ar/39Ar dated to 441± 8 ka. Collectively, the geochronologic, tephrochronologic and geologic data, suggest the site was occupied during MIS 13. The new results should prompt further research at Ficoncella in order to improve our understanding of the dynamics of human settlement in Europe during the Early to Middle Pleistocene.

  13. RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement

    NARCIS (Netherlands)

    A. Cieslak (Agata); S. le Noir (Sandrine); A. Trinquand (Amélie); L. Lhermitte; D.-M. Franchini (Don-Marc); P. Villarese (Patrick); S. Gon (Stéphanie); J. Bond (Jonathan); M. Simonin (Mathieu); L. Vanhile (Laurent); C. Reimann (Christian); E. Verhoeyen (Els); J. Larghero (Jerome); E. Six (Emmanuelle); S. Spicuglia (Salvatore); I. André-Schmutz (Isabelle); A.W. Langerak (Anton); B. Nadel (Bertrand); E.A. Macintyre (Elizabeth); D. Payet-Bornet (Dominique); V. Asnafi (Vahid)

    2014-01-01

    textabstractV(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2 proteins, rendering RAG1/2 targeting a potentially important regulator of lymphoid differentiation. We show that within the human TCR-α/δ locus, Dδ2-Dδ3 rearrangements occur at a very immature thymic,

  14. The Hominin Sites and Paleolakes Drilling Project: inferring the environmental context of human evolution from eastern African rift lake deposits

    Science.gov (United States)

    Cohen, A.; Campisano, C.; Arrowsmith, R.; Asrat, A.; Behrensmeyer, A. K.; Deino, A.; Feibel, C.; Hill, A.; Johnson, R.; Kingston, J.; Lamb, H.; Lowenstein, T.; Noren, A.; Olago, D.; Owen, R. B.; Potts, R.; Reed, K.; Renaut, R.; Schäbitz, F.; Tiercelin, J.-J.; Trauth, M. H.; Wynn, J.; Ivory, S.; Brady, K.; O'Grady, R.; Rodysill, J.; Githiri, J.; Russell, J.; Foerster, V.; Dommain, R.; Rucina, S.; Deocampo, D.; Russell, J.; Billingsley, A.; Beck, C.; Dorenbeck, G.; Dullo, L.; Feary, D.; Garello, D.; Gromig, R.; Johnson, T.; Junginger, A.; Karanja, M.; Kimburi, E.; Mbuthia, A.; McCartney, T.; McNulty, E.; Muiruri, V.; Nambiro, E.; Negash, E. W.; Njagi, D.; Wilson, J. N.; Rabideaux, N.; Raub, T.; Sier, M. J.; Smith, P.; Urban, J.; Warren, M.; Yadeta, M.; Yost, C.; Zinaye, B.

    2016-02-01

    The role that climate and environmental history may have played in influencing human evolution has been the focus of considerable interest and controversy among paleoanthropologists for decades. Prior attempts to understand the environmental history side of this equation have centered around the study of outcrop sediments and fossils adjacent to where fossil hominins (ancestors or close relatives of modern humans) are found, or from the study of deep sea drill cores. However, outcrop sediments are often highly weathered and thus are unsuitable for some types of paleoclimatic records, and deep sea core records come from long distances away from the actual fossil and stone tool remains. The Hominin Sites and Paleolakes Drilling Project (HSPDP) was developed to address these issues. The project has focused its efforts on the eastern African Rift Valley, where much of the evidence for early hominins has been recovered. We have collected about 2 km of sediment drill core from six basins in Kenya and Ethiopia, in lake deposits immediately adjacent to important fossil hominin and archaeological sites. Collectively these cores cover in time many of the key transitions and critical intervals in human evolutionary history over the last 4 Ma, such as the earliest stone tools, the origin of our own genus Homo, and the earliest anatomically modern Homo sapiens. Here we document the initial field, physical property, and core description results of the 2012-2014 HSPDP coring campaign.

  15. Paraquat induces epithelial-mesenchymal transition-like cellular response resulting in fibrogenesis and the prevention of apoptosis in human pulmonary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamada

    Full Text Available The aim of this study is to investigate the molecular mechanisms underlying delayed progressive pulmonary fibrosis, a characteristic of subacute paraquat (PQ poisoning. Epithelial-mesenchymal transition (EMT has been proposed as a cause of organ fibrosis, and transforming growth factor-β (TGF-β is suggested to be a powerful mediator of EMT. We thus examined the possibility that EMT is involved in pulmonary fibrosis during PQ poisoning using A549 human alveolar epithelial cells in vitro. The cells were treated with various concentrations of PQ (0-500 μM for 2-12 days. Short-term (2 days high-dose (>100 μM treatments with PQ induced cell death accompanied by the activation of caspase9 as well as a decrease in E-cadherin (an epithelial cell marker, suggesting apoptotic cell death with the features of anoikis (cell death due to the loss of cell-cell adhesion. In contrast, long-term (6-12 days low-dose (30 μM treatments with PQ resulted in a transformation into spindle-shaped mesenchymal-like cells with a decrease of E-cadherin as well as an increase of α-smooth muscle actin (α-SMA. The mesenchymal-like cells also secreted the extracellular matrix (ECM protein fibronectin into the culture medium. The administration of a TGF-β1 receptor antagonist, SB431542, almost completely attenuated the mesenchymal transformation as well as fibronectin secretion, suggesting a crucial role of TGF-β1 in EMT-like cellular response and subsequent fibrogenesis. It is noteworthy that despite the suppression of EMT-fibrogenesis, apoptotic death was observed in cells treated with PQ+SB431542. EMT-like cellular response and subsequent fibrogenesis were also observed in normal human bronchial epithelial (NHBE cells exposed to PQ in a TGF-β1-dependent manner. Taken together, our experimental model reflects well the etiology of PQ poisoning in human and shows the involvement of EMT-like cellular response in both fibrogenesis and resistance to cell death during

  16. Edema pulmonar de altura: Modelo de estudio de la fisiopatología del edema pulmonar y de la hipertensión pulmonar hipóxica en humanos High altitude pulmonary edema: An experiment of Nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans

    Directory of Open Access Journals (Sweden)

    Marcos Schwab

    2007-02-01

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

  17. Donor smoking is associated with pulmonary edema, inflammation and epithelial dysfunction in ex vivo human donor lungs

    Science.gov (United States)

    Ware, Lorraine B.; Lee, Jae W.; Wickersham, Nancy; Nguyen, John; Matthay, Michael A.; Calfee, Carolyn S.

    2014-01-01

    Although recipients of donor lungs from smokers have worse clinical outcomes, the underlying mechanisms are unknown. We tested the association between donor smoking and the degree of pulmonary edema (as estimated by lung weight), the rate of alveolar fluid clearance (measured by airspace instillation of 5% albumin) and biomarkers of lung epithelial injury and inflammation (bronchoalveolar lavage surfactant protein-D and IL-8) in ex vivo lungs recovered from 298 organ donors. The extent of pulmonary edema was higher in current smokers (n=127) compared to non-smokers (median 408g, IQR 364-500 vs. 385g, IQR 340 - 460, p=0.009). Oxygenation at study enrollment was worse in current smokers versus non-smokers (median PaO2/FiO2 214 mmHg, IQR 126-323 vs. 266 mmHg, IQR 154-370, p=0.02). Current smokers with the highest exposure (≥20 pack-years) had significantly lower rates of alveolar fluid clearance, suggesting that the effects of cigarette smoke on alveolar epithelial fluid transport function may be dose related. BAL IL-8 was significantly higher in smokers while surfactant protein-D was lower. These findings indicate that chronic exposure to cigarette smoke has important effects on inflammation, gas exchange, lung epithelial function and lung fluid balance in the organ donor that could influence lung function in the lung transplant recipient. PMID:25146497

  18. Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi

    NARCIS (Netherlands)

    Lettow, van M.; West, C.E.; Meer, van der J.W.M.; Wieringa, F.T.; Semba, R.D.

    2005-01-01

    Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. Objective: To characterize the antioxidant micronutrient status, interleukin-6 (IL

  19. Dirofilariose pulmonar humana, adquirida no Brasil: comunicação de um caso Case report: human pulmonary dirofilariasis acquired in Brazil

    Directory of Open Access Journals (Sweden)

    Vicente Amato Neto

    1993-10-01

    Full Text Available É comunicado caso de dirofilariose humana, adquirida no Brasil. Trata-se do segundo acometimento dessa natureza publicado em literatura científica. Como expressão clínica, foram evidenciados dois nódulos pulmonares, através de exame radiológico convencional e de tomografia computadorizada. O diagnóstico decorreu de análise histopatológica de uma das lesões.We report the second published case of human dirofilariasis acquired in Brazil. The patient had two pulmonary coin lesions seen in conventional chest roentgenogram and confirmed as solid round nodules by computherized X-ray chest scan. Diagnosis was done by surgical removal of one of the lesions and anatomopathological study of tissue removed.

  20. Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

    Science.gov (United States)

    Peng, Zhanglong; Pati, Shibani; Fontaine, Magali J; Hall, Kelly; Herrera, Anthony V; Kozar, Rosemary A

    2016-11-01

    Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic

  1. Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo.

    Directory of Open Access Journals (Sweden)

    Alexia J Taylor

    Full Text Available BACKGROUND: Multi-walled carbon nanotubes (MWCNTs pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL-1β, IL-6, tumor necrosis factor (TNF-α, and osteopontin (OPN. Atomic layer deposition (ALD is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. METHODS: The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3 would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U-MWCNTs or ALD-coated (A-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. RESULTS: ALD coating of MWCNTs with Al2O3 enhanced IL-1β secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1β but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. CONCLUSION: These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of

  2. Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo.

    Science.gov (United States)

    Taylor, Alexia J; McClure, Christina D; Shipkowski, Kelly A; Thompson, Elizabeth A; Hussain, Salik; Garantziotis, Stavros; Parsons, Gregory N; Bonner, James C

    2014-01-01

    Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. ALD coating of MWCNTs with Al2O3 enhanced IL-1β secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1β but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1β, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

  3. 人体上呼吸道内气溶胶沉积的实验研究%Experimental Study of Aerosol Deposition in Human Upper Respiratory Tract

    Institute of Scientific and Technical Information of China (English)

    赵秀国; 徐新喜; 孙栋; 刘亚军; 谭树林

    2011-01-01

    It is important to examine aerosol deposition in human upper respiratory tract for understanding the impact of toxic aerosol on human health and therapy effect of medicine aerosol. A replica of human upper respiratory tract for experiment was constructed using stereolithography ( SL). The test-bed for measuring aerosol deposition in upper respiratory tract was set up and the experiment for aerosol deposition was performed. The deposition efficiencies of different aerosol with aerosol diameter of d = 0. 3 , 6. 5 μm at breathing intensity of Q = 30 L/min was measured. The results showed that the aerosol deposition efficiencies were high in pharynx, larynx and trachea. Aerosol diameter has little impact on aerosol deposition pattern with almost same aerosol deposition efficiencies at aerosol diameter of d = 0. 3, 6. 5 μm while aerosol diameters influence aerosol deposition efficiencies in the human upper respiratory tract. Inertial impact and dispersion are main deposition mechanism of aerosol. The increases of inertial parameter improve aerosol deposition efficiencies.%研究人体呼吸道内气溶胶沉积规律,对于认识有毒气溶胶对人体健康的影响和提高治疗药物气溶胶的治疗效果具有重要意义.采用激光快速成型技术制作人体上呼吸道的实验模型,在呼吸流量为30 L/min的状态下,分别对粒径为0.3和6.5 μm的气溶胶在人体上呼吸道内的沉积进行实验研究,分析气溶胶在上呼吸道内的沉积规律.研究结果表明;气溶胶在咽、喉和气管位置存留较多;气溶胶粒径对其在上呼吸道内的沉积模式影响较小,两种粒径气溶胶的沉积模式很相似,仅对其在呼吸道内不同部位的沉积率影响较大;惯性碰撞和湍流扩散是气溶胶的主要沉积机制,气溶胶在人体呼吸道内不同部位的沉积率均随惯性参数值的增加而升高.

  4. Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells.

    Science.gov (United States)

    Devailly, Guillaume; Grandin, Mélodie; Perriaud, Laury; Mathot, Pauline; Delcros, Jean-Guy; Bidet, Yannick; Morel, Anne-Pierre; Bignon, Jean-Yves; Puisieux, Alain; Mehlen, Patrick; Dante, Robert

    2015-07-13

    DNA methylation is thought to induce transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators unable to bind their target sites when methylated, and the recruitment of transcriptional repressors with specific affinity for methylated DNA. The Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. Here, we present MBD2 ChIPseq data obtained from the endogenous MBD2 in an isogenic cellular model of oncogenic transformation of human mammary cells. In immortalized (HMEC-hTERT) or transformed (HMLER) cells, MBD2 was found in a large proportion of methylated regions and associated with transcriptional silencing. A redistribution of MBD2 on methylated DNA occurred during oncogenic transformation, frequently independently of local DNA methylation changes. Genes downregulated during HMEC-hTERT transformation preferentially gained MBD2 on their promoter. Furthermore, depletion of MBD2 induced an upregulation of MBD2-bound genes methylated at their promoter regions, in HMLER cells. Among the 3,160 genes downregulated in transformed cells, 380 genes were methylated at their promoter regions in both cell lines, specifically associated by MBD2 in HMLER cells, and upregulated upon MBD2 depletion in HMLER. The transcriptional MBD2-dependent downregulation occurring during oncogenic transformation was also observed in two additional models of mammary cell transformation. Thus, the dynamics of MBD2 deposition across methylated DNA regions was associated with the oncogenic transformation of human mammary cells.

  5. Pulmonary hypertension complicating pulmonary sarcoidosis

    NARCIS (Netherlands)

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should

  6. Pulmonary hypertension complicating pulmonary sarcoidosis

    NARCIS (Netherlands)

    Huitema, M P; Grutters, J C; Rensing, B J W M; Reesink, H J; Post, M C

    2016-01-01

    Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should

  7. Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones around a lead source

    DEFF Research Database (Denmark)

    Moseholm, L.; Larsen, Erik Huusfeldt; Andersen, B.

    1992-01-01

    The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones...

  8. Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.

    NARCIS (Netherlands)

    Groen, T. van; Kiliaan, A.J.; Kadish, I.

    2006-01-01

    The deposition of amyloid beta (Abeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e., h

  9. Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.

    NARCIS (Netherlands)

    Groen, T. van; Kiliaan, A.J.; Kadish, I.

    2006-01-01

    The deposition of amyloid beta (Abeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e.,

  10. Possible role of WT1 in a human fetus with evolving bronchial atresia, pulmonary malformation and renal agenesis.

    Science.gov (United States)

    Loo, Christine K C; Algar, Elizabeth M; Payton, Diane J; Perry-Keene, Joanna; Pereira, Tamara N; Ramm, Grant A

    2012-01-01

    The association of peripheral bronchial atresia and congenital pulmonary airway malformation (CPAM) has recently been recognised, but the pathology of the lesions evolving together has not been described. We present autopsy findings in a 20 week fetus showing areas of peripheral bronchial destruction and airway malformation consistent with developing CPAM in the right lung supporting a causal relationship between these lesions. This fetus also had congenital heart defect, bilateral renal agenesis and syndactyly. We identified another fetus from our autopsy files, with bilateral renal agenesis, similar right sided pulmonary malformation and cardiac defects. Similar bilateral renal agenesis and defects of the heart and lungs are found in wt1(-/-) mice and we have investigated the expression of WT1 in these fetuses. We hypothesise that the cardiac, liver, renal and possibly lung lesions in these two cases may arise due to mesenchymal defects consequent to WT1 misexpression and discuss evidence for this from the scientific literature. We used immunoperoxidase stains to analyse WT1 expression in autopsy hepatic tissue in both fetuses. We also investigated the expression of α-smooth muscle actin (α-SMA), a marker of activated hepatic stellate cells/myofibroblasts, and desmin in hepatic mesenchyme and compare these findings with control fetuses, without congenital malformations. We found reduced WT1 expression in hepatic mesothelium in both fetuses with malformations. There was also increased expression of α-SMA in liver perisinusoidal cells, as seen in the wt1(-/-) mouse model. We therefore propose that abnormality of WT1 signalling may be an underlying factor, as WT1 is expressed in coelomic lining cells from which mesenchyme is derived in many organs.

  11. The effect of heat- or ultra violet ozone-treatment of titanium on complement deposition from human blood plasma.

    Science.gov (United States)

    Linderbäck, Paula; Harmankaya, Necati; Askendal, Agneta; Areva, Sami; Lausmaa, Jukka; Tengvall, Pentti

    2010-06-01

    Titanium (Ti) is a well known metallic biomaterial extensively used in dental, orthopaedic-, and occasionally also in blood contacting applications. It integrates well to bone and soft tissues, and is shown upon blood plasma contact to activate the intrinsic pathway of coagulation and bind complement factor 3b. The material properties depend largely on those of the nm-thick dense layer of TiO(2) that becomes rapidly formed upon contact with air and water. The spontaneously formed amorphous Ti-oxide has a pzc approximately 5-6 and its water solubility is at the order of 1-2 micromolar. It is often subjected to chemical- and heat treatments in order to increase the anatase- and rutile crystallinity, to modify the surface topography and to decrease the water solubility. In this work, we prepared sol-gel derived titanium and smooth PVD titanium surfaces, and analysed their oxide and protein deposition properties in human blood plasma before and after annealing at 100-500 degrees C or upon UVO-treatment for up to 96 hours. The blood plasma results show that complement deposition vanished irreversibly after heat treatment at 250-300 degrees C for 30 minutes or after UVO exposure for 24 hours or longer. XPS and infrared spectroscopy indicated change of surface water/hydroxyl binding upon the heat- and UVO treatments, and increased Ti oxidation. XRD analysis confirmed an increased crystallinity and both control (untreated) and annealed smooth titanium displayed low XRD-signals indicating some nanocrystallinity, with predominantly anatase phase. The current results show that the behaviour of titanium dioxide in blood contact can be controlled through relatively simple means, such as mild heating and illumination in UV-light, which both likely irreversibly change the stoichiometry and structure of the outmost layers of titanium dioxide and its OH/H(2)O binding characteristics.

  12. Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts.

    Science.gov (United States)

    Newman, Donna R; Sills, W Shane; Hanrahan, Katherine; Ziegler, Amanda; Tidd, Kathleen McGinnis; Cook, Elizabeth; Sannes, Philip L

    2016-02-01

    The wingless (Wnt) family of signaling ligands contributes significantly to lung development and is highly expressed in patients with usual interstitial pneumonia (UIP). We sought to define the cellular distribution of Wnt5A in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and the signaling ligands that control its expression in human lung fibroblasts and IPF myofibroblasts. Tissue sections from 40 patients diagnosed with IPF or UIP were probed for the immunolocalization of Wnt5A. Further, isolated lung fibroblasts from normal or IPF human lungs, adenovirally transduced for the overexpression or silencing of Wnt7B or treated with TGF-β1 or its inhibitor, were analyzed for Wnt5A protein expression. Wnt5A was expressed in IPF lungs by airway and alveolar epithelium, smooth muscle cells, endothelium, and myofibroblasts of fibroblastic foci and throughout the interstitium. Forced overexpression of Wnt7B with or without TGF-β1 treatment significantly increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in IPF myofibroblasts where Wnt5A was already highly expressed. The results demonstrate a wide distribution of Wnt5A expression in cells of the IPF lung and reveal that it is significantly increased by Wnt7B and TGF-β1, which, in combination, could represent key signaling pathways that modulate the pathogenesis of IPF.

  13. First in human experience of a new self-expandable percutaneous pulmonary valve implantation using knitted nitinol-wire and tri-leaflet porcine pericardial valve in the native right ventricular outflow tract.

    Science.gov (United States)

    Kim, Gi Beom; Kwon, Bo Sang; Lim, Hong Gook

    2017-04-01

    Balloon-expandable percutaneous pulmonary valve systems using the Melody and Edwards SAPIEN transcatheter heart valves have been increasingly used instead of surgically implantable pulmonary valves. However, limited patients with right ventricular outflow tract (RVOT) lesions are suitable candidates for percutaneous pulmonary valve implantation (PPVI) using these systems after surgical correction of tetralogy of Fallot. Therefore, larger self-expandable valved-stents are being developed for native RVOT lesions. We report the first-in-human case of a new self-expandable PPVI in a patient with a native RVOT lesion using a newly made knitted nitinol-wire stent mounted with a tri-leaflet porcine pericardial valve developed in South Korea. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Zhou, Yue

    2016-09-01

    Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle dia- meters ranging from 0.5 to 24 mm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71 m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.

  15. Differential responses of healthy and chronic obstructive pulmonary diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM4.

    Science.gov (United States)

    Leclercq, B; Happillon, M; Antherieu, S; Hardy, E M; Alleman, L Y; Grova, N; Perdrix, E; Appenzeller, B M; Lo Guidice, J-M; Coddeville, P; Garçon, G

    2016-11-01

    While the knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects is still incomplete, detailed in vitro studies are highly needed. With the aim of getting closer to the human in vivo conditions and better integrating a number of factors related to pre-existing chronic pulmonary inflammatory, we sought to develop primary cultures of normal human bronchial epithelial (NHBE) cells and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells, grown at the air-liquid interface. Pan-cytokeratin and MUC5AC immunostaining confirmed the specific cell-types of both these healthy and diseased cell models and showed they are closed to human bronchial epithelia. Thereafter, healthy and diseased cells were repeatedly exposed to air pollution-derived PM4 at the non-cytotoxic concentration of 5 μg/cm(2). The differences between the oxidative and inflammatory states in non-exposed NHBE and COPD-DHBE cells indicated that diseased cells conserved their specific physiopathological characteristics. Increases in both oxidative damage and cytokine secretion were reported in repeatedly exposed NHBE cells and particularly in COPD-DHBE cells. Diseased cells repeatedly exposed had lower capacities to metabolize the organic chemicals-coated onto the air-pollution-derived PM4, such as benzo[a]pyrene (B[a]P), but showed higher sensibility to the formation of OH-B[a]P DNA adducts, because their diseased state possibly affected their defenses. Differential profiles of epigenetic hallmarks (i.e., global DNA hypomethylation, P16 promoter hypermethylation, telomere length shortening, telomerase activation, and histone H3 modifications) occurred in repeatedly exposed NHBE and particularly in COPD-DHBE cells. Taken together, these results closely supported the highest responsiveness of COPD-DHBE cells to a repeated exposure to air pollution-derived PM4. The use of these innovative in

  16. Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement of climbazole deposition from hair care products onto artificial skin and human scalp

    NARCIS (Netherlands)

    G. Chen; M. Hoptroff; X. Fei; Y. Su; H.-G. Janssen

    2013-01-01

    A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal st

  17. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

    NARCIS (Netherlands)

    Van Ly, David; Burgess, Janette K.; Brock, Thomas G.; Lee, Tak H.; Black, Judith L.; Oliver, Brian G. G.

    2012-01-01

    Van Ly D, Burgess JK, Brock TG, Lee TH, Black JL, Oliver BG. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol 303: L239-L250, 2012. First published Ma

  18. Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement of climbazole deposition from hair care products onto artificial skin and human scalp

    NARCIS (Netherlands)

    Chen, G.; Hoptroff, M.; Fei, X.; Su, Y.; Janssen, H.-G.

    2013-01-01

    A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal st

  19. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

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

    Science.gov (United States)

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

    2014-11-01

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

  1. The influence of glancing angle deposited nano-rough platinum surfaces on the adsorption of fibrinogen and the proliferation of primary human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Dolatshahi-Pirouz, A; Foss, M; Chevallier, J; Besenbacher, F [Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus (Denmark); Pennisi, C P; Yoshida, K [Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg (Denmark); Skeldal, S; Andreasen, P [Department of Molecular Biology, Aarhus University, Aarhus (Denmark); Zachar, V [Laboratory for Stem Cell Research, Aalborg University (Denmark)], E-mail: foss@inano.au.dk

    2009-03-04

    We have used the glancing angle deposition (GLAD) method as a simple and fast method to generate nano-rough surfaces for protein adsorption experiments and cell assays. The surface roughness and the detailed geometrical surface morphology of the thin films were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). As the GLAD deposition angle approaches grazing incidence, sharp and whisker-like columnar protrusions are formed. Smaller and less sharp surface features appear for the thin films synthesized at higher deposition angles. By changing the GLAD deposition angle together with the total amount of mass deposited per area on the respective surfaces, the size of the surface features can be varied on the nanoscale. Using the GLAD topographies as model surfaces, we have investigated the influence of the nano-roughness on fibrinogen adsorption and on the proliferation of primary human fibroblasts. It is found that fibrinogen, an important blood protein, preferentially adheres on the whisker-like nano-rough substrates in comparison to a flat surface. Furthermore, the proliferation of the human fibroblasts is significantly reduced on the nano-rough substrates. These results demonstrate that the GLAD technique can be used to fabricate nano-rough surface morphologies that significantly influence both protein and cellular adhesion to surfaces and are therefore well suited for biological assays.

  2. Pulmonary Arterial Hypertension

    Science.gov (United States)

    Pulmonary Arterial Hypertension What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout your body. While the heart is one organ, it ...

  3. Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities.

    Science.gov (United States)

    Mangal, Sharad; Gao, Wei; Li, Tonglei; Zhou, Qi Tony

    2017-06-01

    Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers.

  4. Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer.

    Science.gov (United States)

    Shaykhiev, Renat; Sackrowitz, Rachel; Fukui, Tomoya; Zuo, Wu-Lin; Chao, Ion Wa; Strulovici-Barel, Yael; Downey, Robert J; Crystal, Ronald G

    2013-09-01

    CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 up-regulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of genes was linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer.

  5. Active Expression of Human Tissue Plasminogen Activator (t-PA) c-DNA from Pulmonary Metastases in the Methylotrophic Yeast Pichia Pastoris KM71H Strain

    Science.gov (United States)

    Mohseni, Amir Hossein; Soleimani, Mohammad; Majidzadeh-A, Keivan; Taghinezhad-S, Sedigheh; Keyvani, Hossein

    2017-08-27

    Background: Human tissue-type plasminogen activator (t-PA) is a key protease of the trypsin family. It catalyzes the activation of zymogen plasminogen to the fibrin-degrading proteinase, plasmin, leading to digestion of fibrin clots. The recombinant enzyme produced by recombinant technology issued to dissolve blood clots in treatment of various human diseases such as coronary artery thrombosis, pulmonary embolism, acute ischemic stroke (AIS). Pichia pastoris expression system is a unique system for the production of high level of recombinant proteins. GS115 and KM71H are two kinds of Pichia pastoris strains whilst production of recombinant proteins in these strains is not predictable. The aim of the study was evaluation of t-PA expression in KM71H strains. Methods: In this study, the cDNA of the t-PA gene was amplified by PCR, sequenced and cloned into Pichia pastoris KM71H host strain using pPICZalphaA expression vector that allows methanol-induced expression and secretion of the protein. Results: Dot blotting results confirmed the presence oft-PA in the cell supernatant. Western blotting test revealed the approximate size of 70 KDa for recombinant t-PA. Quantitative ELISA experiment showed 810 μg/L of t-PA in the supernatant samples. Zymography analysis confirmed the proteolytic activity and biological function of the expressed recombinant t-PA. Conclusions: Correspondingly, Pichia pastoris KM71H is an appropriate strain for production of active recombinant protein. Creative Commons Attribution License

  6. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Shao, Dongmin; Perros, Frédéric; Caramori, Gaetano; Meng, Chao; Dormuller, Peter; Chou, Pai-Chien; Church, Colin; Papi, Alberto; Casolari, Paolo; Welsh, David; Peacock, Andrew; Humbert, Marc; Adcock, Ian M; Wort, Stephen J

    2014-08-15

    Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the "alarmin" family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  7. Interaction of New-Developed TiO2-Based Photocatalytic Nanoparticles with Pathogenic Microorganisms and Human Dermal and Pulmonary Fibroblasts

    Science.gov (United States)

    Nica, Ionela Cristina; Stan, Miruna Silvia; Popa, Marcela; Chifiriuc, Mariana Carmen; Lazar, Veronica; Pircalabioru, Gratiela G.; Dumitrescu, Iuliana; Ignat, Madalina; Feder, Marcel; Tanase, Liviu Cristian; Mercioniu, Ionel; Diamandescu, Lucian; Dinischiotu, Anca

    2017-01-01

    TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe–N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe–N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields. PMID:28125053

  8. How Is Pulmonary Hypertension Treated?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Treated? Pulmonary hypertension (PH) has no cure. However, ... Types of Pulmonary Hypertension." ) Group 1 Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension (PAH) includes PH ...

  9. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  10. Simple pulmonary eosinophilia

    Science.gov (United States)

    Pulmonary infiltrates with eosinophilia; Loffler syndrome; Eosinophilic pneumonia; Pneumonia - eosinophilic ... A rare complication of simple pulmonary eosinophilia is a severe type of pneumonia called acute idiopathic eosinophilic pneumonia.

  11. The beneficial effect of suramin on monocrotaline-induced pulmonary hypertension in rats.

    Directory of Open Access Journals (Sweden)

    Mohamed Izikki

    Full Text Available BACKGROUND: Pulmonary hypertension (PH is a progressive disorder characterized by an increase in pulmonary artery pressure and structural changes in the pulmonary vasculature. Several observations indicate that growth factors play a key role in PH by modulating pulmonary artery smooth muscle cell (PA-SMC function. In rats, established monocrotaline-induced PH (MCT-PH can be reversed by blocking platelet-derived growth factor receptors (PDGF-R, epidermal growth factor receptors (EGF-R, or fibroblast growth factor receptors (FGF-R. All these receptors belong to the receptor tyrosine kinase (RTK family. METHODS AND RESULTS: We evaluated whether RTK blockade by the nonspecific growth factor inhibitor, suramin, reversed advanced MCT-PH in rats via its effects on growth-factor signaling pathways. We found that suramin inhibited RTK and ERK1/2 phosphorylation in cultured human PA-SMCs. Suramin inhibited PA-SMC proliferation induced by serum, PDGF, FGF2, or EGF in vitro and ex vivo. Treatment with suramin from day 1 to day 21 after monocrotaline injection attenuated PH development, as shown by lower values for pulmonary artery pressure, right ventricular hypertrophy, and distal vessel muscularization on day 21 compared to control rats. Treatment with suramin from day 21 to day 42 after monocrotaline injection reversed established PH, thereby normalizing the pulmonary artery pressure values and vessel structure. Suramin treatment suppressed PA-SMC proliferation and attenuated both the inflammatory response and the deposition of collagen. CONCLUSIONS: RTK blockade by suramin can prevent MCT-PH and reverse established MCT-PH in rats. This study suggests that an anti-RTK strategy that targets multiple RTKs could be useful in the treatment of pulmonary hypertension.

  12. The Beneficial Effect of Suramin on Monocrotaline-Induced Pulmonary Hypertension in Rats

    Science.gov (United States)

    Izikki, Mohamed; Mercier, Olaf; Lecerf, Florence; Lubert Guin, Lauriane; Hoang, Eric; Dorfmüller, Peter; Perros, Frédéric; Humbert, Marc; Simonneau, Gerald; Dartevelle, Philippe; Fadel, Elie; Eddahibi, Saadia

    2013-01-01

    Background Pulmonary hypertension (PH) is a progressive disorder characterized by an increase in pulmonary artery pressure and structural changes in the pulmonary vasculature. Several observations indicate that growth factors play a key role in PH by modulating pulmonary artery smooth muscle cell (PA-SMC) function. In rats, established monocrotaline-induced PH (MCT-PH) can be reversed by blocking platelet-derived growth factor receptors (PDGF-R), epidermal growth factor receptors (EGF-R), or fibroblast growth factor receptors (FGF-R). All these receptors belong to the receptor tyrosine kinase (RTK) family. Methods and Results We evaluated whether RTK blockade by the nonspecific growth factor inhibitor, suramin, reversed advanced MCT-PH in rats via its effects on growth-factor signaling pathways. We found that suramin inhibited RTK and ERK1/2 phosphorylation in cultured human PA-SMCs. Suramin inhibited PA-SMC proliferation induced by serum, PDGF, FGF2, or EGF in vitro and ex vivo. Treatment with suramin from day 1 to day 21 after monocrotaline injection attenuated PH development, as shown by lower values for pulmonary artery pressure, right ventricular hypertrophy, and distal vessel muscularization on day 21 compared to control rats. Treatment with suramin from day 21 to day 42 after monocrotaline injection reversed established PH, thereby normalizing the pulmonary artery pressure values and vessel structure. Suramin treatment suppressed PA-SMC proliferation and attenuated both the inflammatory response and the deposition of collagen. Conclusions RTK blockade by suramin can prevent MCT-PH and reverse established MCT-PH in rats. This study suggests that an anti-RTK strategy that targets multiple RTKs could be useful in the treatment of pulmonary hypertension. PMID:24143201

  13. Pulmonary alveolar microlithiasis

    Directory of Open Access Journals (Sweden)

    Surender Kashyap

    2013-01-01

    Full Text Available Pulmonary alveolar microlithiasis (PAM is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation.

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

    Science.gov (United States)

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

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

  15. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

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

    2006-01-01

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

  16. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  17. Measurement of the deposited activity of the short-lived radon progeny in the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Vezzu, G.; Butterweck-Dempewolf, G.; Schuler, C. [Paul Scherrer Inst., Villigen (Switzerland). Div. for Radiation Protection and Waste Management

    1998-12-31

    Volunteers were exposed in the radon chamber at Paul Scherrer Institut to an atmosphere enriched with highly unattached radon progeny. The deposited radon progeny activity in the respiratory tract of the volunteers was determined using a low level in-vivo counter. The detector arrangement and its calibration for the measurement of deposited radon progeny activity is described and the results for a mouth and a nose breathing volunteer are presented. For the nose breathing volunteer 55% of the deposited radon progeny activity was located in the head and the remaining 45% in the chest whereas for the mouth breathing volunteer 25% was located in the head and the remaining 75% in the chest. A mean clearance half-life for the deposited radon progeny from the respiratory tract of (2{+-}1) h was obtained from the analyses of the temporal behaviour of the deposited radon progeny activity in the head. (orig.)

  18. Seasonal size distribution of airborne culturable bacteria and fungi and preliminary estimation of their deposition in human lungs during non-haze and haze days

    Science.gov (United States)

    Gao, Min; Jia, Ruizhi; Qiu, Tianlei; Han, Meilin; Song, Yuan; Wang, Xuming

    2015-10-01

    In recent years, haze events in Beijing have significantly increased in frequency. On haze days, airborne microorganisms are considered to be a potential risk factor for various health concerns. However, limited information on bioaerosols has prevented our proper understanding of the possible threat to human health due to these bioaerosols. In this study, we used a six-stage impactor for sampling culturable bioaerosols and the LUDEP 2.07 computer-based model for calculating their deposition on human lungs to investigate seasonal concentration, size distribution, and corresponding deposition efficiency and flux in the human respiratory tract during different haze-level events. The current results of the analysis of 398 samples over four seasons indicate that the concentration of culturable airborne bacteria decreased with increasing haze severity. The bioaerosol concentration ratio was skewed towards larger particle sizes on heavy haze days leading to larger bioaerosol aerodynamic diameters than on non-haze days. During nasal breathing by an adult male engaged in light exercise in an outdoor environment, the total deposition efficiency of culturable bioaerosols is 80-90% including approximately 70% in the upper respiratory tract, 5-7% in the alveoli, and about 3% in the bronchial couple with bronchiolar regions. Although the difference in culturable bioaerosol aerodynamic diameters at different haze levels was not large enough to cause obvious differences in lung deposition efficiency, the deposition fluxes clearly varied with the degree of haze owing to the varied concentration of culturable airborne bacteria and fungi. The results here could improve our understanding of the seasonal health threat due to culturable bioaerosols during non-haze and haze days.

  19. The sGC activator inhibits the proliferation and migration, promotes the apoptosis of human pulmonary arterial smooth muscle cells via the up regulation of plasminogen activator inhibitor-2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shuai [Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing (China); Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing (China); Zou, Lihui [Institute of Geriatrics, Beijing Hospital, 1 Dahua Rd, Beijing (China); National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing (China); Yang, Ting; Yang, Yuanhua; Zhai, Zhenguo [Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing (China); Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing (China); Xiao, Fei [Institute of Geriatrics, Beijing Hospital, 1 Dahua Rd, Beijing (China); National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing (China); Wang, Chen, E-mail: chenwangcjfh@163.com [Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing (China); Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing (China); National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing (China)

    2015-03-15

    Background: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. Objectives: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. Methods: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured human PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. Results: BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. Conclusions: PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2. - Highlights: • sGC activator BAY41-2272 up regulated PAI-2 in PASMCs, on the mRNA and protein level. • PAI-2 overexpression inhibits the proliferation and migration of human PASMCs. • PAI-2 overexpression promotes the apoptosis of human PASMCs. • sGC activator might alleviate the vascular remodeling in pulmonary hypertension.

  20. Effects of herpes simplex virus thymidine kinase/acyclovir system on growth of human pulmonary adenocarcinoma A549 cell line in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    HE Xiang-liang; HE Dong-hua; GUO Xian-jian; QIAN Gui-sheng; HUANG Gui-jun; CHEN Wei-zhong; LI Shu-ping

    2002-01-01

    Objective: To observe the effect of anciclovir (ACV) treatment on tumors induced by inoculation of TK gene-transfected human pulmonary adenocarcinoma A549 cells in nude mice. Methods: A recombinant plasmid containing TK gene was constructed and transfected into A549 cells by electroporation. The sensitivity of the transgenic cells (A549-TK) to ACV was examined by MTT assay in vitro and for in vivo observation, inoculation of A549-TK and A-549 cells into nude mice was separately performed to induce tumor growth, the response of which to ACV treatment was observed, and the tumor tissues were pathologically examined. Results: A recombinant plasmid containing TK gene was successfully constructed and transfected into A549 cells. The sensitivity of A549-TK cells to ACV was 43 times higher than that of A549 cells. The tumors induced by A549-TK cells showed no significant increase in size after ACV treatment (P>0. 05), and light microscopy revealed local tissue necrosis, karyoklasis, and nuclei disappearance. Conclusion: A549-TK cells acquires sensitivity to ACV both in vitro and in vivo, and ACV can inhibit the growth of tumors induced by A549-TK cell inoculation in nude mice.

  1. Chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B E; Snijder, R J; Mager, J J; van Es, H W; Plokker, H W M; Reesink, H J; Morshuis, W J; Post, M C

    2014-12-01

    Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

  2. Association of individual-level concentrations and human respiratory tract deposited doses of fine particulate matter with alternation in blood pressure.

    Science.gov (United States)

    Yin, Wenjun; Hou, Jian; Xu, Tian; Cheng, Juan; Wang, Xiaoying; Jiao, Shilin; Wang, Lin; Huang, Cheng; Zhang, Youjian; Yuan, Jing

    2017-11-01

    Fine particulate matter (PM2.5) contributes to the risk of cardiovascular events, partially owing to its deposition in the human respiratory tract. To investigate short-term effects of ambient PM2.5 exposure on alternation of blood pressure (BP), this study was conducted during the winter-summer period between 2014 and 2015. The study included 106 community residents in Wuhan city, China. We repeatedly monitored the household and outdoor PM2.5 concentrations as well as individual-level PM2.5 in each season, and then assessed personal PM2.5 exposure (including deposited doses of PM2.5 in the human respiratory tract) by using different methodology (such as using a dosimetry model). All participants took part in the physical examination, including the inflammatory indicators, BP and lung function parameters measurements. Subsequently, we assessed the health damage of exposure to PM2.5 using generalized additive models. We observed increased BP at 2-day lag for an interquartile range increase in ambient fixed-site, households, individual-level PM2.5 exposure and the corresponding lung deposited doses of each exposure concentration (p < 0.05), decreased BP at 3-day lag for an interquartile range increase in ambient fixed-site, households PM2.5 and the corresponding lung deposited doses of each exposure concentration (p < 0.05). The estimated deposited doses of PM2.5 by the deposition fractions in this study and the referenced deposition fractions by previous reported method were equivalent associated with alternation in BP. In conclusion, lung deposited dose of PM2.5 as a quantitative indicator may be used to assess adverse cardiovascular effects following the systemic inflammation. However, we require careful assessment of acute adverse cardiovascular effects using ambient fixed-site PM2.5 after short-term PM2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1.

    Science.gov (United States)

    Wu, Zhiyong; Dai, Feifeng; Ren, Wei; Liu, Huagang; Li, Bowen; Chang, Jinxing

    2016-01-01

    Patients with acute aortic dissection (AAD) usually showed acute lung injury (ALI). However, its pathogenesis is still not well defined. Apoptosis of pulmonary microvascular endothelial cells (PMVECs) is closely related to the alveolus-capillary barrier injury and the increased vascular permeability. In this study, we aim to investigate the human PMVECs (hPMVECs) apoptosis induced by angiotensin II (AngII) and monocyte chemoattractant protein-1 (MCP-1) and their potential interaction in the pathogenesis of AAD complicated with ALI. Fifty-eight newly diagnosed AAD, 12 matched healthy individuals were included. Pulmonary tissues of AAD complicated with lung injury were obtained from 2 cadavers to determine the levels of AngII type 1 receptor (AT1-R) and MCP-1. Serum AngII was measured using commercial ELISA kit. H&E staining and immunohistostaining were performed to determine the expression of AT1-R and MCP-1. For the in vitro experiment, hPMVECs were divided into control, AngII group, AngII+Bindarit group and Bindarit group, respectively. Flow cytometry was performed to analyze the apoptosis in each group. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of MCP-1. Western blot analysis was performed to evaluate the expression of MCP-1 and apoptosis related protein. Apoptosis of hPMVECs was observed in the lung tissues in the cadavers with AAD complicated with ALI. Besides, the expression of AT1-R and MCP-1 was remarkably elevated. Compared with normal individuals and the non-lung injury AAD patients, the expression of serum AngII was remarkably elevated in AAD patients complicated with ALI. In vitro experiments showed AngII contributed to the apoptosis and elevation of MCP1 in hPMVECs. Besides, it involved in the down-regulation of Bcl-2 protein, and up-regulation of Bax and Caspase-3. Such phenomenon was completely reversed after administration of MCP-1 inhibitor (Bindarit). The production of MCP-1 and cellular

  4. Relationship between human LTA4H polymorphisms and extra-pulmonary tuberculosis in an ethnic Han Chinese population in Eastern China.

    Science.gov (United States)

    Yang, Jinghui; Chen, Jin; Yue, Jun; Liu, Lirong; Han, Min; Wang, Hongxiu

    2014-12-01

    Two single nucleotide polymorphisms in Leukotriene A4 hydrolase (LTA4H) gene were reported to be associated with protection from pulmonary tuberculosis in Vietnamese population. But these associations were not found in the Russians. To investigate the association of LTA4H polymorphisms with tuberculosis in a Han Chinese population in Eastern China, we genotyped 5 SNPs of LTA4H gene in 743 of pulmonary tuberculosis patients, 372 of extra-pulmonary tuberculosis patients and 888 of healthy controls individuals. The CC and TT homozygotes of rs1978331 and rs2540474 were identified to have higher rates (P tuberculosis (OR = 1.412; 95% CI = 1.104-1.804 and(OR = 1.380; 95% CI = 1.080-1.764). However, no significant association was found between any of the SNPs and pulmonary tuberculosis. In the extra-pulmonary tuberculosis subgroups. LTA4H gene were significantly associated with tuberculous meningitis, lymph node tuberculosis, bone tuberculosis and other extra-pulmonary tuberculosis except for pleural tuberculosis. The present findings suggest that polymorphisms in the LTA4H gene may affect susceptibility to extra-pulmonary tuberculosis and change the risk of developing the disease in the Han nationality in the East China.

  5. Apelin and pulmonary hypertension

    DEFF Research Database (Denmark)

    Andersen, Charlotte Uggerhøj; Hilberg, Ole; Mellemkjær, Søren;

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin...... vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting...

  6. Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones around a lead source

    DEFF Research Database (Denmark)

    Moseholm, L.; Larsen, Erik Huusfeldt; Andersen, B.

    1992-01-01

    The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones...... were identified by a multivariate statistical analysis. Within each zone, the total dietary intake of lead was estimated for adults and children as a percentage of the provisional tolerably weekly intake (PTWI), and as a result recommendation on restrictions in use of locally grown fruit and vegetables...... were given to the public. The pattern of lead deposition in the area during the period 1981-1988 was monitored and the amount of lead ingested via vegetables was toxically evaluated. Lead emission reduction measures introduced in the factory and in the traffic during the period produced significant...

  7. Rock magnetic investigation of loess deposits in the Eastern Qingling Mountains (central China) and its implications for the environment of early humans

    Science.gov (United States)

    Wang, Xiaoyong; Lu, Huayu; Zhang, Weiguo; Hu, Pengxiang; Zhang, Hongyan; Han, Zhiyong; Wang, Shejiang; Li, Baoguo

    2016-11-01

    The Luonan Basin, located in the transitional zone between temperate and subtropical China, is an important locality for human evolution during the early to middle Pleistocene. The loess deposits in the Luonan Basin contain numerous in situ lithic artefacts; the deposits also constitute suitable material for dating the artefacts and are potentially useful for reconstructing the climatic fluctuations which is important for studying the adaptation and occupation of the area by early humans. We carried out a combined rock magnetic and geochemical investigation of a loess sequence from the Liuwan Palaeolithic site in the Luonan Basin. The results indicate a mixture of magnetic minerals, including magnetite/maghemite and hematite/goethite. Magnetic susceptibility was used as a palaeoclimate proxy on the Chinese Loess Plateau; however, its application to the Luonan Basin may be problematic because the provenance of the loess parent material, as well as the depositional environment, differs from that of the Chinese Loess Plateau. We found that rock magnetic parameters related to the grain size of magnetic minerals, such as SIRM/χ and χARM/SIRM, are better palaeoclimatic indicators than magnetic susceptibility. Overall, the magnetic results, together with the results of bulk grain-size and chemical index of alteration, indicate that the interglacial environment of early humans in Luonan Basin was warmer and more humid than the coeval environment of the Chinese Loess Plateau.

  8. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  9. Aryl hydrocarbon Receptor is Necessary to Protect Fetal Human Pulmonary Microvascular Endothelial Cells against Hyperoxic Injury: Mechanistic Roles of Antioxidant Enzymes and RelB

    Science.gov (United States)

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly (ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. PMID:25831079

  10. Inhibiting effect of Fasudil on human pulmonary artery smooth muscle cell proliferation%法舒地尔对人肺动脉平滑肌细胞增殖抑制作用研究

    Institute of Scientific and Technical Information of China (English)

    刘爱军; 王栋; 朱耀斌; 凌锋; 李晓峰; 史强; 刘迎龙

    2011-01-01

    Objective To investigate the inhibiting effect of Fasudil on platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation and its mechanism. Methods Human pulmonary artery smooth muscle cells were cultured with the stimulation of platelet-derived growth factor-BB, and Fasudil in different concentrations was added before the addition of mitogen.Cell number and cell viability were determined with a hemocytometer and MTT assay respectively.The expressions of PCNA and p27kipl protein were measured with Western blot analysis. Results Compared with control group, platelet-derived growth factor markedly induced human pulmonary artery smooth muscle cell proliferation, increased the percentage of cells in S phase and PCNA expression, but deceased p27kipl expression. Pretreatment with Fasudil, however, significantly reversed the above effect induced by platelet-derived growth factor. Conclusion Fasudil can effectively inhibit the platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation and cell-cycle progression by up-regulating p27kipl.%目的:探讨法舒地尔对血小板源性生长因子(platelet-derived growth factor,PDGF)诱导的人肺动脉平滑肌细胞(human pulmonary artery smooth muscle cell,HPASMC)增殖的抑制作用及机制.方法:以体外培养的HPASMC为研究对象,PDGF-BB诱导增殖,法舒地尔进行预处理,MTT法检测细胞增殖;流式细胞仪检测细胞周期,Western blot检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和p27k1p1蛋白的表达.结果:细胞培养24 h后与空白组比较,PDGF组HPASMC细胞增殖比例,S期细胞比例和PCNA蛋白表达明显增加,p27k1p1蛋白表达则明显降低;用法舒地尔预处理后,与PDGF组比较.细胞增殖比例,S期细胞比例和PCNA蛋白表达明显下降,p27k1p1蛋白表达则明显增加.结论:法舒地尔可通过上调p27k1p1蛋白表达来抑制PDGF诱导的HPASMC增殖和细胞周期进程.

  11. Deposição pulmonar de tobramicina inalatória antes e após fisioterapia respiratória e uso de salbutamol inalatório em pacientes com fibrose cística colonizados por Pseudomonas aeruginosa Pulmonary deposition of inhaled tobramycin prior to and after respiratory therapy and use of inhaled albuterol in cystic fibrosis patients colonized with Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Milena Baptistella Grotta

    2009-01-01

    Full Text Available OBJETIVO: Avaliar se a fisioterapia respiratória seguida do uso de salbutamol inalatório modifica a deposição pulmonar de tobramicina inalatória em pacientes com fibrose cística (FC e se a deposição pulmonar apresenta correlação com a gravidade da doença ou com o genótipo. MÉTODOS: Um estudo prospectivo foi realizado com pacientes com FC maiores de 6 anos e colonizados por Pseudomonas aeruginosa. Os critérios de exclusão foram exacerbação pulmonar, mudança terapêutica entre as fases do estudo e FEV1 OBJECTIVE: To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF and whether pulmonary deposition correlates with disease severity or genotype. METHODS: A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aeruginosa. Exclusion criteria were pulmonary exacerbation, changes in therapy between the study phases and FEV1 < 25%. All patients were submitted to pulmonary scintigraphy by means of a scintillation camera equipped with a low energy all purpose collimator in order to evaluate drug penetration following the administration of inhaled 99mTc-tobramycin, as well as to pulmonary perfusion with 99mTc-macroaggregated albumin (phase 1. One month later, the same procedure was performed following respiratory therapy and administration of inhaled albuterol (phase 2. RESULTS: We included 24 patients (12 males aged 5-27 years (mean ± SD: 12.85 ± 6.64 years. The Shwachman score (SS was excellent/good in 8 patients, moderate/fair in 16 and poor in 0. Genotyping revealed that 7 patients were ΔF508 homozygotes, 13 were ΔF508 heterozygotes; and 4 presented other mutations. In all patients, lung deposition of tobramycin decreased in phase 2, especially in those with moderate/fair SS (p = 0.017 and in heterozygotes (p = 0.043. CONCLUSIONS: The use of a

  12. The Impact of Immunosenescence on Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Michelle A. Murray

    2015-01-01

    Full Text Available The global population is aging with significant gains in life expectancy particularly in the developed world. Consequently, greater focus on understanding the processes that underlie physiological aging has occurred. Key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. Immunosenescence and its associated chronic low grade systemic “inflamm-aging” contribute to the development and progression of pulmonary disease in older individuals. These physiological processes predispose to pulmonary infection and confer specific and unique clinical phenotypes observed in chronic respiratory disease including late-onset asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. Emerging concepts of the gut and airway microbiome further complicate the interrelationship between host and microorganism particularly from an immunological perspective and especially so in the setting of immunosenescence. This review focuses on our current understanding of the aging process, immunosenescence, and how it can potentially impact on various pulmonary diseases and the human microbiome.

  13. The Impact of Immunosenescence on Pulmonary Disease.

    LENUS (Irish Health Repository)

    Murray, Michelle A

    2015-08-01

    The global population is aging with significant gains in life expectancy particularly in the developed world. Consequently, greater focus on understanding the processes that underlie physiological aging has occurred. Key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. Immunosenescence and its associated chronic low grade systemic "inflamm-aging" contribute to the development and progression of pulmonary disease in older individuals. These physiological processes predispose to pulmonary infection and confer specific and unique clinical phenotypes observed in chronic respiratory disease including late-onset asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. Emerging concepts of the gut and airway microbiome further complicate the interrelationship between host and microorganism particularly from an immunological perspective and especially so in the setting of immunosenescence. This review focuses on our current understanding of the aging process, immunosenescence, and how it can potentially impact on various pulmonary diseases and the human microbiome.

  14. Measurement of pulmonary flow reserve and pulmonary index of microcirculatory resistance for detection of pulmonary microvascular obstruction.

    Directory of Open Access Journals (Sweden)

    Rahn Ilsar

    Full Text Available BACKGROUND: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic/(basal flow] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressurex(maximum hyperemic T(mn]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. METHODS AND RESULTS: Temperature- and pressure-sensor guidewires (TPSG were placed in segmental pulmonary arteries (SPA of 13 baboons and intravascular temperature measured. T(mn and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min and papaverine (3-24 mg. Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1, supporting T(mn use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min & papaverine (to 24 mg induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn reductions v baseline, respectively; p<0.0001. PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4, 10(5 & 10(6 microspheres; p

  15. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  16. IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Kovacs, J A; Mathiesen, Lars Reinhardt

    1993-01-01

    95. Four of the 5 patients with IgM antibodies also had IgG antibodies to gp95 and microbiologically proven P. carinii pneumonia (PCP). In 76/128 patients for whom serial samples were available, changes in antibody response were determined. In 3 patients we demonstrated an increase in IgM antibody...... response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major...... human P. carinii surface antigen. The increase in IgM response during the course of PCP observed in 3 patients suggests either reinfection with a new strain, or antigenic drift of an already acquired strain of P. carinii....

  17. Aryl hydrocarbon receptor is necessary to protect fetal human pulmonary microvascular endothelial cells against hyperoxic injury: Mechanistic roles of antioxidant enzymes and RelB

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-07-15

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly(ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. - Highlights: • AhR deficiency potentiates oxygen toxicity in human fetal lung cells. • Deficient AhR signaling increases hyperoxia-induced cell death. • AhR deficiency increases hyperoxia-induced ROS generation and inflammation. • Anti-oxidant enzyme levels are attenuated in AhR-deficient lung cells

  18. Giant infantile pulmonary hemangioma

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, Rajul; Tummala, Venkat [Hurley Medical Center One Hurley Plaza, Department of Radiology, Flint, MI (United States)

    2010-12-15

    We present a very unusual case of giant infantile pulmonary hemangioma presenting as a large solitary pulmonary mass. This was successfully managed with surgical resection. Histological examination revealed that the mass was positive for GLUT-1 receptor, a marker for infantile hemangioma. To our knowledge only a few cases of pulmonary hemangioma have been described previously in the literature. Pulmonary hemangiomas are very rare lesions, most of them presenting as a pulmonary mass. This case emphasizes the fact that this rare lesion should be considered in the differential of an enhancing pulmonary mass in an infant. (orig.)

  19. Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Walters Dianne M

    2011-08-01

    Full Text Available Abstract Background Multi-walled carbon nanotubes (MWCNTs are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis. Methods MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA. Results Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33, chemokine (Ccl3 and Ccl11, and protease production (Mmp13 that promoted the inflammatory and fibrotic changes observed within the lung. Conclusions These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.

  20. Effect of Nuclear Factor-kappa B on Vascular Endothelial Growth Factor mRNA Expression of Human Pulmonary Artery Smooth Muscle Cells in Hypoxia

    Institute of Scientific and Technical Information of China (English)

    张焕萍; 徐永健; 张珍祥; 许淑云; 倪望; 陈士新

    2004-01-01

    Summary: In order to investigate the effect of nuclear factor-kappa B (NF-κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. The NF-κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBa protein expression was measured by Western blot.RT-PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF-κB p65 nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but the levels of NF-κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups (P<0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h-24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups (P<0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration-dependent manner in hypoxia. In conclusion, NF-κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF-κB activation can decrease the VEGF mRNA expression. h is suggested that the activation of NF-κB is involved in the VEGFmRNA expression of HPASMCs under hypoxia.

  1. FGF9 and FGF18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts in vitro.

    Science.gov (United States)

    Joannes, Audrey; Brayer, Stéphanie; Besnard, Valérie; Marchal-Sommé, Joëlle; Jaillet, Madeleine; Mordant, Pierre; Mal, Hervé; Borie, Raphael; Crestani, Bruno; Mailleux, Arnaud A

    2016-04-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix proteins and fibroblasts in the distal airways. Key developmental lung signaling pathways are reactivated in IPF. For instance, fibroblast growth factor 9 (FGF9) and FGF18, involved in epithelial-mesenchymal interactions, are critical for lung development. We evaluated the expression of FGF9, FGF18, and FGF receptors (FGFRs) in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration, and differentiation of control and IPF human lung fibroblasts (HLFs). FGF9, FGF18, and all FGFRs were present in the remodeled alveolar epithelium close to the fibroblast foci in IPF lungs. FGFR3 was generally detected in fibroblast foci by immunohistochemistry. In vitro, HLFs mainly expressed mesenchyme-associated FGFR isoforms (FGFR1c and FGFR3c) and FGFR4. FGF9 did not affect fibroblast proliferation, whereas FGF18 inhibited cell growth in control fibroblasts. FGF9 and FGF18 decreased Fas-ligand-induced apoptosis in control but not in IPF fibroblasts. FGF9 prevented transforming growth factor β1-induced myofibroblast differentiation. FGF9 and FGF18 increased the migratory capacities of HLF, and FGF9 actively modulated matrix metalloproteinase activity. In addition, FGFR3 inhibition by small interfering RNA impacted p-ERK activation by FGF9 and FGF18 and their effects on differentiation and migration. These results identify FGF9 as an antiapoptotic and promigratory growth factor on HLF, maintaining fibroblasts in an undifferentiated state. The biological effects of FGF9 and FGF18 were partially driven by FGFR3. FGF18 was a less potent molecule. Both growth factors likely contribute to the fibrotic process in vivo.

  2. The Src family tyrosine kinases src and yes have differential effects on inflammation-induced apoptosis in human pulmonary microvascular endothelial cells.

    Science.gov (United States)

    Nelin, Leif D; White, Hilary A; Jin, Yi; Trittmann, Jennifer K; Chen, Bernadette; Liu, Yusen

    2016-05-01

    Endothelial cells are essential for normal lung function: they sense and respond to circulating factors and hemodynamic alterations. In inflammatory lung diseases such as acute respiratory distress syndrome, endothelial cell apoptosis is an inciting event in pathogenesis and a prominent pathological feature. Endothelial cell apoptosis is mediated by circulating inflammatory factors, which bind to receptors on the cell surface, activating signal transduction pathways, leading to caspase-3-mediated apoptosis. We hypothesized that yes and src have differential effects on caspase-3 activation in human pulmonary microvascular endothelial cells (hPMVEC) due to differential downstream signaling effects. To test this hypothesis, hPMVEC were treated with siRNA against src (siRNAsrc), siRNA against yes (siRNAyes), or their respective scramble controls. After recovery, the hPMVEC were treated with cytomix (LPS, IL-1β, TNF-α, and IFN-γ). Treatment with cytomix induced activation of the extracellular signal-regulated kinase (ERK) pathway and caspase-3-mediated apoptosis. Treatment with siRNAsrc blunted cytomix-induced ERK activation and enhanced cleaved caspase-3 levels, while treatment with siRNAyes enhanced cytomix-induced ERK activation and attenuated levels of cleaved caspase-3. Inhibition of the ERK pathway using U0126 enhanced cytomix-induced caspase-3 activity. Treatment of hPMVEC with cytomix induced Akt activation, which was inhibited by siRNAsrc. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway using LY294002 prevented cytomix-induced ERK activation and augmented cytomix-induced caspase-3 cleavage. Together, our data demonstrate that, in hPMVEC, yes activation blunts the ERK cascade in response to cytomix, resulting in greater apoptosis, while cytomix-induced src activation induces the phosphatidylinositol 3-kinase pathway, which leads to activation of Akt and ERK and attenuation of apoptosis.

  3. Pulmonary Complications due to Esophagectomy

    Directory of Open Access Journals (Sweden)

    Yashar Talebi

    2011-08-01

    Full Text Available Introduction: Esophageal carcinoma is the scourge of human beings. Pulmonary compli-cations in patients who have undergone operation are common (20-30% of cases and there are no suitable tools and ways to predict these complications. Methods: During a period of 10 years, from March 1998 to February 2007, 200 patients (150 male and 50 female underwent Esophagectomy due to esophageal carcinoma in thoracic surgery ward retrospectively. Complications include the length of hospitalization, mechanical ventilation, morbidity and mortality. Patients’ risk factors include age, preoperative chemo-radiotherapy, stage of the disease and preoperative spirometry condition. Results: We grouped our patients into three categories: Normal (FEV1 ≥ 80% predicted, mildly impaired (FEV1 65% to 79% predicted, more severely impaired (FEV1 < 65% predicted.Although almost all patients had radiographic pulmonary abnormalities, significant pulmonary complications occurred in 40 patients (20% which underwent Esophagectomy. Pleural effusion and atelectasia in 160 patients (80%. 24 patients needed chest-tube insertion. 20 patients (10% developed ARDS. 14 patients (7% developed chylothorax. 20 patients (10% of patients died during their postoperative hospital stay. 30 patients (15% required mechanical ventilation for greater than 48 hours. Conclusion: We reviewed a number of preoperative clinical variables to determine whether they contributed to postoperative pulmonary complications as well as other outcomes. In general, age, impaired pulmonary function especially in those patients with FEV1 less than 65% predicted was associated with prolonged hospital length of stay (LOS. In fact pulmonary complications rate after Esophagectomy are high and there was associated mortality and morbidity.

  4. Silica nanoparticles are less toxic to human lung cells when deposited at the air–liquid interface compared to conventional submerged exposure

    Directory of Open Access Journals (Sweden)

    Alicja Panas

    2014-09-01

    Full Text Available Background: Investigations on adverse biological effects of nanoparticles (NPs in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air–liquid interface.Results: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air–liquid interphase (ALI by using the ALI deposition apparatus (ALIDA. The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stöber method. Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence

  5. Pulmonary Hemorrhage in Cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    G Kirkpatrick

    2015-01-01

    Full Text Available Pulmonary manifestations of cryoglobulinemia are uncommon and their clinical behaviour is unpredictable, ranging from mild dyspnea to life-threatening presentations. A patient with cryoglobulinemia who presented with hypoxic respiratory failure attributed to pulmonary hemorrhage is reported.

  6. Pregnancy and pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, Petronella G.; Lameijer, Heleen; Hoendermis, Elke S.

    Pulmonary hypertension during pregnancy is associated with considerable risks of maternal mortality and morbidity. Our systematic review of the literature on the use of targeted treatments for pulmonary arterial hypertension during pregnancy indicates a considerable decrease of mortality since a

  7. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... 03-13T18:29:11+00:00 PH and HIV Print PH and HIV Brochure (PDF) Order Copies ... to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and HIV are two separate ...

  8. Miliary pulmonary cryptococcosis

    Directory of Open Access Journals (Sweden)

    Shane Kelly

    2014-10-01

    Imaging features of pulmonary cryptococcosis are generally of well-defined pleural-based nodules and less commonly alveolar infiltrates, lymphadenopathy, pleural effusions or cavitating lesions. Miliary pulmonary infiltrates are an exceptionally rare presentation.

  9. Pulmonary arteriovenous fistula

    Science.gov (United States)

    ... medlineplus.gov/ency/article/001090.htm Pulmonary arteriovenous fistula To use the sharing features on this page, please enable JavaScript. Pulmonary arteriovenous fistula is an abnormal connection between an artery and ...

  10. Histoplasmosis - acute (primary) pulmonary

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000098.htm Histoplasmosis - acute (primary) pulmonary To use the sharing features on this page, please enable JavaScript. Acute pulmonary histoplasmosis is a respiratory infection that is caused by ...

  11. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>20070291 Gong Ping (Northern Fujian Geological Party, Shaozou 354000) Discussion on Geological Characteristics and Control Factors of the Shimen Au-polymetallic Deposit in Zhenghe County, Fujian Province (Geology of Fujian, ISSN1001-3970, CN38-1080/P, 25(1), 2006, p.18-24, 2 illus., 2 tables, 1 ref.) Key words: gold deposits, polymetallic deposits, Fujian Province

  12. [Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro].

    Science.gov (United States)

    Ignashkova, T I; Mesitov, M V; Rybakov, A S; Moskovtsev, A A; Sokolovskaia, A A; Kubatiev, A A

    2012-01-01

    Von Willebrand factor (vWF) is an adhesive glycoprotein synthesized and secreted by endothelial cells and megakaryocytes. Violation of vWF secretion by endothelial cells is a characteristic feature of endothelial dysfunction in hyperhomocysteinemia. In our study we examined to clarify the concentration-dependent effect of homocysteine (Hcy) on the expression of vWF. Our studies have shown that homocysteine excess induces changes in the intracellular deposition of von Willebrand factor in cultured human endothelial cells in vitro. Primary cultures of human umbilical vein endothelial cells (HUVEC) were incubated with the various concentrations of D,L-homocysteine (0.025 - 5 mM). Homocysteine at a concentration of 0.025 and 0.25 mM after 18 h incubation caused an increase in the intracellular fraction of vWF in HUVEC cells. High concentrations of homocysteine induced a dose-dependent decrease in the intracellular fraction of vWF. These dose-dependent variations may indicate the modulation by homocysteine of different mechanisms of the deposition, the constitutive secretion and the degradation of vWF in human endothelial cells. We proposed that Endoplasmic reticulum stress, in HUVEC cells by the action of an excess of homocysteine associated with increased intracellular levels of vWF at a relatively low concentration of the inducer. We found decline in intracellular vWF at the same duration but higher concentrations of inducer, which may be due to the ER-associated protein degradation.

  13. Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement of climbazole deposition from hair care products onto artificial skin and human scalp.

    Science.gov (United States)

    Chen, Guoqiang; Hoptroff, Michael; Fei, Xiaoqing; Su, Ya; Janssen, Hans-Gerd

    2013-11-22

    A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal standard. Atmospheric pressure chemical ionization (APCI) in positive mode was applied for the detection of climbazole. For quantification, multiple reaction monitoring (MRM) transition 293.0>69.0 was monitored for climbazole, and MRM transition 296.0>225.1 for the deuterated climbazole. The linear range ran from 4 to 2000 ng mL(-1). The limit of detection (LOD) and the limit of quantification (LOQ) were 1 ng mL(-1) and 4 ng mL(-1), respectively, which enabled quantification of climbazole on artificial skin and human scalp at ppb level (corresponding to 16 ng cm(-2)). For the sampling of climbazole from human scalp the buffer scrub method using a surfactant-modified phosphate buffered saline (PBS) solution was selected based on a performance comparison of tape stripping, the buffer scrub method and solvent extraction in in vitro studies. Using this method, climbazole deposition in in vitro and in vivo studies was successfully quantified. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing...... a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes......) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand...

  15. Pulmonary Hypertension Overview

    Science.gov (United States)

    ... chest X-ray, a breathing test called a pulmonary function test and an echocardiogram (sometimes called an “echo”). Your doctor may also need to do other tests to find out whether another medical condition is causing your pulmonary hypertension. TreatmentHow is pulmonary hypertension treated?If the ...

  16. Pulmonary Hypertension Association

    Science.gov (United States)

    ... at www.AHeartCures.org . Help Kickoff November’s Pulmonary Hypertension Awareness Month Want to help raise awareness for ... Heart2CurePH | Help promote Awareness Month Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Awareness Chronic thromboembolic pulmonary hypertension (CTEPH) is ...

  17. Pharmacotherapy in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Gaurav Acharya

    2014-10-01

    Full Text Available Idiopathic pulmonary fibrosis or cryptogenic fibrosing alveolitis is a form of chronic, progressive interstitial lung disease causing scarring of lung tissue and usually affect adults. Treatment is usually aimed at controlling inflammation and thus slowing the process of fibrosis. With only few patients responding to treatment and the disease being ultimately fatal with poor progression, the underlying lesion was considered to be fibrotic rather than inflammatory. Fibrotic foci, deposition of collagen, and lack of inflammatory cells are a predominant finding. Pirfenidone and N-acetyl cysteine are the only effective pharmacotherapy available till date. Interim results of PANTHER Trial clearly indicate more risk with triple therapy. However, in Indian patients, trial of steroid therapy may be tried when there is doubt of chronic hypersensitivity pneumonitis. BIBF 1120 has also shown positive results in Phase II clinical trial and shows a positive response in deteriorating lung function. Supplemental oxygen, education of patient, pulmonary rehabilitation, and Streptococcus pneumoniae and influenza vaccine are the most important supportive care. Pulmonary rehabilitation should be used as a treatment in the majority of patients. [Int J Basic Clin Pharmacol 2014; 3(5.000: 761-763

  18. Detailed diesel exhaust characteristics including particle surface area and lung deposited dose for better understanding of health effects in human chamber exposure studies

    Science.gov (United States)

    Wierzbicka, Aneta; Nilsson, Patrik T.; Rissler, Jenny; Sallsten, Gerd; Xu, Yiyi; Pagels, Joakim H.; Albin, Maria; Österberg, Kai; Strandberg, Bo; Eriksson, Axel; Bohgard, Mats; Bergemalm-Rynell, Kerstin; Gudmundsson, Anders

    2014-04-01

    Several diesel exhaust (DE) characteristics, comprising both particle and gas phase, recognized as important when linking with health effects, are not reported in human chamber exposure studies. In order to understand effects of DE on humans there is a need for better characterization of DE when performing exposure studies. The aim of this study was to determine and quantify detailed DE characteristics during human chamber exposure. Additionally to compare to reported DE properties in conducted human exposures. A wide battery of particle and gas phase measurement techniques have been used to provide detailed DE characteristics including the DE particles (DEP) surface area, fraction and dose deposited in the lungs, chemical composition of both particle and gas phase such as NO, NO2, CO, CO2, volatile organic compounds (including aldehydes, benzene, toluene) and polycyclic aromatic hydrocarbons (PAHs). Eyes, nose and throat irritation effects were determined. Exposure conditions with PM1 (<1 μm) mass concentration 280 μg m-3, number concentration 4 × 105 cm-3 and elemental to total carbon fraction of 82% were generated from a diesel vehicle at idling. When estimating the lung deposited dose it was found that using the size dependent effective density (in contrast to assuming unity density) reduced the estimated respiratory dose by 132% by mass. Accounting for agglomerated structure of DEP prevented underestimation of lung deposited dose by surface area by 37% in comparison to assuming spherical particles. Comparison of DE characteristics reported in conducted chamber exposures showed that DE properties vary to a great extent under the same DEP mass concentration and engine load. This highlights the need for detailed and standardized approach for measuring and reporting of DE properties. Eyes irritation effects, most probably caused by aldehydes in the gas phase, as well as nose irritation were observed at exposure levels below current occupational exposure limit

  19. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    DEFF Research Database (Denmark)

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous ...... of MAC formation was also found to be highly pathway dependent, with the AP being about 15-fold more efficient at initiating this process than the CP. A model accounting for the effectiveness of the AP in both preserving C3 fragment integrity and initiating MAC is presented....

  20. Changes in dissolved iron deposition to the oceans driven by human activity: a 3-D global modelling study

    Directory of Open Access Journals (Sweden)

    S. Myriokefalitakis

    2015-03-01

    Full Text Available The global atmospheric iron (Fe cycle is parameterized in the global 3-D chemical transport model TM4-ECPL to simulate the proton- and the organic ligand-promoted mineral Fe dissolution as well as the aqueous-phase photochemical reactions between the oxidative states of Fe(III/II. Primary emissions of total (TFe and dissolved (DFe Fe associated with dust and combustion processes are also taken into account. TFe emissions are calculated to amount to ~35 Tg Fe yr−1. The model reasonably simulates the available Fe observations, supporting the reliability of the results of this study. Accounting for proton- and organic ligand-promoted Fe-dissolution in present-day TM4-ECPL simulations, the total Fe-dissolution is calculated to be ~0.163 Tg Fe yr−1 that accounts for up to ~50% of the calculated total DFe emissions. The atmospheric burden of DFe is calculated to be ~0.012 Tg Fe. DFe deposition presents strong spatial and temporal variability with an annual deposition flux ~0.489 Tg Fe yr−1 from which about 25% (~0.124 Tg Fe yr−1 are deposited over the ocean. The impact of air-quality on Fe deposition is studied by performing sensitivity simulations using preindustrial (year 1850, present (year 2008 and future (year 2100 emission scenarios. These simulations indicate that an increase (~2 times in Fe-dissolution may have occurred in the past 150 years due to increasing anthropogenic emissions and thus atmospheric acidity. On the opposite, a decrease (~2 times of Fe-dissolution is projected for near future, since atmospheric acidity is expected to be lower than present-day due to air-quality regulations of anthropogenic emissions. The organic ligand contribution to Fe dissolution shows inverse relationship to the atmospheric acidity thus its importance has decreased since the preindustrial period but is projected to increase in the future. The calculated changes also show that the atmospheric DFe supply to High-Nutrient-Low-Chlorophyll oceanic

  1. Pulmonary involvement in patients presenting with extra-pulmonary tuberculosis: thinking beyond a normal chest x-ray

    Directory of Open Access Journals (Sweden)

    Herath S

    2014-03-01

    Full Text Available INTRODUCTION: Recognition of pulmonary involvement in extra-pulmonary tuberculosis (TB may be an important public health issue, as smear-negative pulmonary TB is responsible for about 17% of new infections. Pulmonary TB can be present despite a normal chest x-ray (CXR, even in human immunodeficiency virus (HIV–negative patients. In this retrospective clinical audit, we reviewed a case series of HIV-negative patients with extra-pulmonary tuberculosis to identify the proportion with concurrent pulmonary TB despite an unremarkable CXR. METHODS: Clinical notes, microbiology results and CXR reports were reviewed from consecutive patients treated at Auckland City Hospital for extra-pulmonary TB from January 2007 to July 2010. RESULTS: Of the sample of 103 patients with extra-pulmonary TB, the majority of patients were born in an Asian country (n=70; 68%. The commonest presentation of extra-pulmonary TB was lymphadenopathy (n=51; 50%, followed by pleural (n=24; 23% and bone (n=6; 6% disease. Extra-pulmonary TB was diagnosed by biopsy or excision of the extra-pulmonary site in the majority (n=74; 72%, and by sputum testing alone in 26 (25%. The majority had CXR abnormalities (n=76; 74%. In the group with a normal CXR (n=27, 55% (n=15 had sputum cultures performed. In total, 18% (n=5 of patients with extra-pulmonary TB and a normal CXR had pulmonary TB, of whom two were smear positive. DISCUSSION: In patients with extra-pulmonary TB, sputum testing should be considered to detect concurrent pulmonary TB even if a CXR is normal, especially in immunosuppressed or symptomatic patients. This may aid diagnosis and determine infectivity and consequent public health action.

  2. Characterization and estimation of human airway deposition of size-resolved particulate-bound trace elements during a recent haze episode in Southeast Asia.

    Science.gov (United States)

    Behera, Sailesh N; Betha, Raghu; Huang, Xian; Balasubramanian, Rajasekhar

    2015-03-01

    Toxic elements present in airborne particulate matter (PM) are associated with human health effects; however, their toxic characteristics depend on the source of their origins and their concentrations in ambient air. Twenty four elements (Al, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, K, Li, Mg, Mn, Na, Ni, Pb, Se, Sr, Te, Tl, and Zn) in 12 different size fractions of PM ranging from 10 nm to 10 μm were characterized in Singapore during two different atmospheric conditions (smoke haze and non-haze periods) in 2012 for the first time. In addition, their possible sources were identified based on backward air trajectory analysis and principal component analysis (PCA). The health implications of inhalable particles were assessed using a human airway deposition model, the Multiple-Path Particle Dosimetry model (MPPD). The results concerning particle-bound trace elements are interpreted in terms of coarse (PM2.5-10), fine (PM2.5), ultrafine (PM0.01-0.1, 0.01 μm haze episode and the non-haze period in coarse, fine, ultrafine, and nano particles varied from 1.2 (Bi) to 6.6 (Co). Both the PCA and backward trajectory analysis revealed that trans-boundary biomass-burning emissions from Indonesia were primarily responsible for enhanced concentrations of particulate-bound elements during the smoke haze episode. The particle depositions in the respiratory system were higher during the smoke haze episode compared to the non-haze period. The study finds that ultrafine and nano particles present in the atmosphere have higher tendencies to be deposited into the deeper parts of the respiratory system, compared to coarse and fine particles.

  3. Multidetector computed tomography pulmonary angiography in childhood acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Schoepf, U.J. [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Department of Pediatrics, Charleston, SC (United States); Chowdhury, Shahryar M. [Medical University of South Carolina, Department of Pediatrics, Charleston, SC (United States); Fox, Mary A. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States)

    2015-09-15

    Pulmonary embolism is a life-threatening condition affecting people of all ages. Multidetector row CT pulmonary angiography has improved the imaging of pulmonary embolism in both adults and children and is now regarded as the routine modality for detection of pulmonary embolism. Advanced CT pulmonary angiography techniques developed in recent years, such as dual-energy CT, have been applied as a one-stop modality for pulmonary embolism diagnosis in children, as they can simultaneously provide anatomical and functional information. We discuss CT pulmonary angiography techniques, common and uncommon findings of pulmonary embolism in both conventional and dual-energy CT pulmonary angiography, and radiation dose considerations. (orig.)

  4. Changes in dissolved iron deposition to the oceans driven by human activity: a 3-D global modelling study

    Science.gov (United States)

    Myriokefalitakis, S.; Daskalakis, N.; Mihalopoulos, N.; Baker, A. R.; Nenes, A.; Kanakidou, M.

    2015-07-01

    The global atmospheric iron (Fe) cycle is parameterized in the global 3-D chemical transport model TM4-ECPL to simulate the proton- and the organic ligand-promoted mineral-Fe dissolution as well as the aqueous-phase photochemical reactions between the oxidative states of Fe (III/II). Primary emissions of total (TFe) and dissolved (DFe) Fe associated with dust and combustion processes are also taken into account, with TFe mineral emissions calculated to amount to ~ 35 Tg-Fe yr-1 and TFe emissions from combustion sources of ~ 2 Tg-Fe yr-1. The model reasonably simulates the available Fe observations, supporting the reliability of the results of this study. Proton- and organic ligand-promoted Fe dissolution in present-day TM4-ECPL simulations is calculated to be ~ 0.175 Tg-Fe yr-1, approximately half of the calculated total primary DFe emissions from mineral and combustion sources in the model (~ 0.322 Tg-Fe yr-1). The atmospheric burden of DFe is calculated to be ~ 0.024 Tg-Fe. DFe deposition presents strong spatial and temporal variability with an annual flux of ~ 0.496 Tg-Fe yr-1, from which about 40 % (~ 0.191 Tg-Fe yr-1) is deposited over the ocean. The impact of air quality on Fe deposition is studied by performing sensitivity simulations using preindustrial (year 1850), present (year 2008) and future (year 2100) emission scenarios. These simulations indicate that about a 3 times increase in Fe dissolution may have occurred in the past 150 years due to increasing anthropogenic emissions and thus atmospheric acidity. Air-quality regulations of anthropogenic emissions are projected to decrease atmospheric acidity in the near future, reducing to about half the dust-Fe dissolution relative to the present day. The organic ligand contribution to Fe dissolution shows an inverse relationship to the atmospheric acidity, thus its importance has decreased since the preindustrial period but is projected to increase in the future. The calculated changes also show that the

  5. Dry powder platform for pulmonary drug delivery

    Institute of Scientific and Technical Information of China (English)

    Derek Ivan Daniher; Jesse Zhu

    2008-01-01

    The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1-5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van tier Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.

  6. Landscapes, depositional environments and human occupation at Middle Paleolithic open-air sites in the southern Levant, with new insights from Nesher Ramla, Israel

    Science.gov (United States)

    Zaidner, Yossi; Frumkin, Amos; Friesem, David; Tsatskin, Alexander; Shahack-Gross, Ruth

    2016-04-01

    Middle Paleolithic human occupation in the Levant (250-50 ka ago) has been recorded in roofed (cave and rockshelter) and open-air sites. Research at these different types of sites yielded different perspectives on the Middle Paleolithic human behavior and evolution. Until recently, open-air Middle Paleolithic sites in the Levant were found in three major sedimentary environments: fluvial, lake-margin and spring. Here we describe a unique depositional environment and formation processes at the recently discovered open-air site of Nesher Ramla (Israel) and discuss their contribution to understanding site formation processes in open-air sites in the Levant. The site is 8-m-thick Middle Paleolithic sequence (OSL dated to 170-80 ka) that is located in a karst sinkhole formed by gravitational deformation and sagging into underground voids. The sedimentary sequence was shaped by gravitational collapse, cyclic colluviation of soil and gravel into the depression, waterlogging, in situ pedogenesis and human occupation. Original bedding and combustion features are well-preserved in the Lower archaeological sequence, a rare occurrence in comparison to other open-air archaeological sites. This phenomenon coincides with episodes of fast sedimentation/burial, which also allowed better preservation of microscopic remains such as ash. The Upper archaeological sequence does not exhibit bedding or preservation of ash, despite presence of heat-affected lithic artifacts, which makes it similar to other open-air sites in the Levant. We suggest that rate of burial is the major factor that caused the difference between the Upper and Lower sequences. The differences in the burial rate may be connected to environmental and vegetation changes at the end of MIS 6. We also identified an interplay between sediment in-wash and density of human activity remains, i.e. during episodes of low natural sediment input the density of artifacts is higher relative to episodes with high rate of sediment in

  7. Pulmonary hemorrhage resulting from leptospirosis

    Directory of Open Access Journals (Sweden)

    Mauro Razuk Filho

    2016-07-01

    Full Text Available Leptospirosis is one of the most widespread zoonoses in the world, although the mechanisms responsible for the pathogenesis of spirochetes of the genus Leptospira are largely unknown. Human infection occurs either by direct contact with infected animals or indirectly, through contact with water or soil contaminated with urine, as the spirochetes easily penetrate human skin. The present report exposes the case of a female patient, diagnosed with leptospirosis after having had contact with a dog infected by Leptospira sp. that developed pulmonary hemorrhage, acute respiratory distress syndrome and acute renal failure.

  8. A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pulmonary arteries.

    Science.gov (United States)

    Fuchikami, Chiaki; Murakami, Kohji; Tajima, Koyuki; Homan, Junko; Kosugi, Keiji; Kuramoto, Kazuya; Oka, Michiko; Kuwano, Keiichi

    2017-01-15

    Selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension (PAH). We examined the effect of the active metabolite of selexipag, MRE-269, and IP receptor agonists that are currently available as PAH therapeutic drugs on the relaxation of rat, porcine and human pulmonary artery. cAMP formation in human pulmonary artery smooth muscle cells was induced by all test compounds (MRE-269, epoprostenol, iloprost, treprostinil and beraprost sodium) and suppressed by IP receptor antagonists (CAY10441 and 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid). MRE-269 induced endothelium-independent vasodilation of rat extralobar pulmonary artery (EPA). In contrast, endothelial denudation or the addition of a nitric oxide synthase inhibitor markedly attenuated the vasodilation of EPA induced by epoprostenol, treprostinil and beraprost sodium but not iloprost. The vasorelaxant effects of MRE-269 on rat small intralobar pulmonary artery (SIPA) and EPA were the same, while the other IP receptor agonists induced less vasodilation in SIPA than in EPA. Furthermore, a prostaglandin E receptor 3 antagonist enhanced the vasodilation induced by all IP receptor agonists tested except MRE-269. We also investigated the relaxation induced by IP receptor agonists in pulmonary arteries from non-rodent species and found similar vasodilation modes in porcine and human as in rat preparations. These results suggest that MRE-269, in contrast to other IP receptor agonists, works as a selective IP receptor agonist, thus leading to pronounced vasorelaxation of rat, porcine and human pulmonary artery.

  9. Physical and Biological Characterization of Ferromagnetic Fiber Networks: Effect of Fibrin Deposition on Short-Term In Vitro Responses of Human Osteoblasts

    Science.gov (United States)

    Spear, Rose L.; Srigengan, Brajith; Neelakantan, Suresh; Bosbach, Wolfram; Brooks, Roger A.

    2015-01-01

    Ferromagnetic fiber networks have the potential to deform in vivo imparting therapeutic levels of strain on in-growing periprosthetic bone tissue. 444 Ferritic stainless steel provides a suitable material for this application due to its ability to support cultures of human osteoblasts (HObs) without eliciting undue inflammatory responses from monocytes in vitro. In the present article, a 444 fiber network, containing 17 vol% fibers, has been investigated. The network architecture was obtained by applying a skeletonization algorithm to three-dimensional tomographic reconstructions of the fiber networks. Elastic properties were measured using low-frequency vibration testing, providing globally averaged properties as opposed to mechanical methods that yield only local properties. The optimal region for transduction of strain to cells lies between the ferromagnetic fibers. However, cell attachment, at early time points, occurs primarily on fiber surfaces. Deposition of fibrin, a fibrous protein involved in acute inflammatory responses, can facilitate cell attachment within this optimal region at early time points. The current work compared physiological (3 and 5 g·L−1) and supraphysiological fibrinogen concentrations (10 g·L−1), using static in vitro seeding of HObs, to determine the effect of fibrin deposition on cell responses during the first week of cell culture. Early cell attachment within the interfiber spaces was observed in all fibrin-containing samples, supported by fibrin nanofibers. Fibrin deposition influenced the seeding, metabolic activity, and early stage differentiation of HObs cultured in the fibrin-containing fiber networks in a concentration-dependant manner. While initial cell attachment for networks with fibrin deposited from low physiological concentrations was similar to control samples without fibrin deposition, significantly higher HObs attached onto high physiological and supraphysiological concentrations. Despite higher cell

  10. Mechanisms responsible for pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH).

  11. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance a

  12. IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies.

    Science.gov (United States)

    Klang, Andrea; Schmidt, Peter; Kneissl, Sibylle; Bagó, Zoltán; Vincent, Angela; Lang, Bethan; Moloney, Teresa; Bien, Christian G; Halász, Péter; Bauer, Jan; Pákozdy, Akos

    2014-05-01

    Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

  13. Pulmonary drug delivery by powder aerosols.

    Science.gov (United States)

    Yang, Michael Yifei; Chan, John Gar Yan; Chan, Hak-Kim

    2014-11-10

    The efficacy of pharmaceutical aerosols relates to its deposition in the clinically relevant regions of the lungs, which can be assessed by in vivo lung deposition studies. Dry powder formulations are popular as devices are portable and aerosolisation does not require a propellant. Over the years, key advancements in dry powder formulation, device design and our understanding on the mechanics of inhaled pharmaceutical aerosol have opened up new opportunities in treatment of diseases through pulmonary drug delivery. This review covers these advancements and future directions for inhaled dry powder aerosols.

  14. Pulmonary candidiasis presenting as mycetoma

    Directory of Open Access Journals (Sweden)

    Bachh Arshad

    2008-01-01

    Full Text Available Candida is a saprophytic yeast that is frequently recovered from the respiratory tract. Most mycetoma lesions are due to Aspergillus species growing inside an existing cavity. The saprophytic nature of the Candida species in the human respiratory tract obscures diagnosis of Candida pulmonary infections. Only a few cases of mycetoma due to Can-dida have been reported. We report a case of mycetoma caused by Candida albicans in a diabetic immunocompromised tuberculous patient. Diagnosis was confirmed by biopsy and certain points strongly favoured the diagnosis. The patient was immunocompromised due to uncontrolled diabetes mellitus. Candida albicans was grown from bronchial and repeatedly from sputum samples and Candida antigen was positive from blood in high titre. There was a good clinical as well as radiological response to antifungal therapy and Candida antigen became negative. We emphasize that in the immunosuppressed host, a mycetoma-like lesion may be caused by Candida pulmonary infection.

  15. Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration.

    Science.gov (United States)

    Horiguchi, Michiko; Oiso, Yuki; Sakai, Hitomi; Motomura, Tomoki; Yamashita, Chikamasa

    2015-09-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causing widespread and irreversible alveoli collapse. The discovery of a low-molecular-weight compound that induces regeneration of pulmonary alveoli is of utmost urgency to cure intractable pulmonary diseases such as COPD. However, a practically useful compound for regenerating pulmonary alveoli is yet to be reported. Previously, we have elucidated that Akt phosphorylation is involved in a differentiation-inducing molecular mechanism of human alveolar epithelial stem cells, which play a role in regenerating pulmonary alveoli. In the present study, we directed our attention to phosphoinositide 3-kinase (PI3K)-Akt signaling and examined whether PI3K inhibitors display the pulmonary alveolus regeneration. Three PI3K inhibitors with different PI3K subtype specificities (Wortmannin, AS605240, PIK-75 hydrochloride) were tested for the differentiation-inducing effect on human alveolar epithelial stem cells, and Wortmannin demonstrated the most potent differentiation-inducing activity. We evaluated Akt phosphorylation in pulmonary tissues of an elastase-induced murine COPD model and found that Akt phosphorylation in the pulmonary tissue was enhanced in the murine COPD model compared with normal mice. Then, the alveolus-repairing effect of pulmonary administration of Wortmannin to murine COPD model was evaluated using X-ray CT analysis and hematoxylin-eosin staining. As a result, alveolar damages were repaired in the Wortmannin-administered group to a similar level of normal mice. Furthermore, pulmonary administration of Wortmannin induced a significant recovery of the respiratory function, compared to the control group. These results indicate that Wortmannin is capable of inducing differentiation of human alveolar epithelial stem cells and represents a promising drug candidate for curative treatment of pulmonary alveolar destruction in COPD.

  16. Handbook of pulmonary emergencies

    Energy Technology Data Exchange (ETDEWEB)

    Spaquolo, S.V.; Medinger, A

    1986-01-01

    This book presents information on the following topics: clinical assessment of the patient with pulmonary disease; interpretation of arterial blood gases in the emergency patient; life-threatening pneumonia; extrapulmonic ventilatory failure; acute inhalation lung disease; pulmonary edema; near drowning; chest trauma; upper airway emergencies; chronic lung disease with acute respiratory decompensation; acute respiratory failure in the patient with chronic airflow obstruction; asthma; hemoptysis; embolic pulmonary disease; superior vena cava syndrome; catastrophic pleural disease; ventilatory assistance and its complications; and ventilator emergencies.

  17. Capsule influences the deposition of critical complement C3 levels required for the killing of Burkholderia pseudomallei via NADPH-oxidase induction by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Michael E Woodman

    Full Text Available Burkholderia pseudomallei is the causative agent of melioidosis and is a major mediator of sepsis in its endemic areas. Because of the low LD(50 via aerosols and resistance to multiple antibiotics, it is considered a Tier 1 select agent by the CDC and APHIS. B. pseudomallei is an encapsulated bacterium that can infect, multiply, and persist within a variety of host cell types. In vivo studies suggest that macrophages and neutrophils are important for controlling B. pseudomallei infections, however few details are known regarding how neutrophils respond to these bacteria. Our goal is to describe the capacity of human neutrophils to control highly virulent B. pseudomallei compared to the relatively avirulent, acapsular B. thailandensis using in vitro analyses. B. thailandensis was more readily phagocytosed than B. pseudomallei, but both displayed similar rates of persistence within neutrophils, indicating they possess similar inherent abilities to escape neutrophil clearance. Serum opsonization studies showed that both were resistant to direct killing by complement, although B. thailandensis acquired significantly more C3 on its surface than B. pseudomallei, whose polysaccharide capsule significantly decreased the levels of complement deposition on the bacterial surface. Both Burkholderia species showed significantly enhanced uptake and killing by neutrophils after critical levels of C3 were deposited. Serum-opsonized Burkholderia induced a significant respiratory burst by neutrophils compared to unopsonized bacteria, and neutrophil killing was prevented by inhibiting NADPH-oxidase. In summary, neutrophils can efficiently kill B. pseudomallei and B. thailandensis that possess a critical threshold of complement deposition, and the relative differences in their ability to resist surface opsonization may contribute to the distinct virulence phenotypes observed in vivo.

  18. Capsule influences the deposition of critical complement C3 levels required for the killing of Burkholderia pseudomallei via NADPH-oxidase induction by human neutrophils.

    Science.gov (United States)

    Woodman, Michael E; Worth, Randall G; Wooten, R Mark

    2012-01-01

    Burkholderia pseudomallei is the causative agent of melioidosis and is a major mediator of sepsis in its endemic areas. Because of the low LD(50) via aerosols and resistance to multiple antibiotics, it is considered a Tier 1 select agent by the CDC and APHIS. B. pseudomallei is an encapsulated bacterium that can infect, multiply, and persist within a variety of host cell types. In vivo studies suggest that macrophages and neutrophils are important for controlling B. pseudomallei infections, however few details are known regarding how neutrophils respond to these bacteria. Our goal is to describe the capacity of human neutrophils to control highly virulent B. pseudomallei compared to the relatively avirulent, acapsular B. thailandensis using in vitro analyses. B. thailandensis was more readily phagocytosed than B. pseudomallei, but both displayed similar rates of persistence within neutrophils, indicating they possess similar inherent abilities to escape neutrophil clearance. Serum opsonization studies showed that both were resistant to direct killing by complement, although B. thailandensis acquired significantly more C3 on its surface than B. pseudomallei, whose polysaccharide capsule significantly decreased the levels of complement deposition on the bacterial surface. Both Burkholderia species showed significantly enhanced uptake and killing by neutrophils after critical levels of C3 were deposited. Serum-opsonized Burkholderia induced a significant respiratory burst by neutrophils compared to unopsonized bacteria, and neutrophil killing was prevented by inhibiting NADPH-oxidase. In summary, neutrophils can efficiently kill B. pseudomallei and B. thailandensis that possess a critical threshold of complement deposition, and the relative differences in their ability to resist surface opsonization may contribute to the distinct virulence phenotypes observed in vivo.

  19. Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation.

    Science.gov (United States)

    Ortiz, Manoel; Jornada, Denise Soledade; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski

    2015-10-01

    Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatment of PCP. In this context, microencapsulation for pulmonary administration can offer an alternative to increase the bioavailability of dapsone, reducing its adverse effects. The aim of this work was to develop novel dapsone-loaded chitosan microcapsules intended for deep-lung aerosolized drug delivery. The geometric particle size (D 4,3) was approximately 7 μm, the calculated aerodynamic diameter (d aero) was approximately 4.5 μm, and the mass median aerodynamic diameter from an Andersen cascade impactor was 4.7 μm. The in vitro dissolution profile showed an efficient dapsone encapsulation, demonstrating the sustained release of the drug. The in vitro deposition (measured by the Andersen cascade impactor) showed an adequate distribution and a high fine particles fraction (FPF = 50%). Scanning electron microscopy of the pulmonary tissues demonstrated an adequate deposition of these particles in the deepest part of the lung. An in vivo toxicity experiment showed the low toxicity of the drug-loaded microcapsules, indicating a protective effect of the microencapsulation process when the particles are microencapsulated. In conclusion, the pulmonary administration of the novel dapsone-loaded microcapsules could be a promising alternative for PCP treatment.

  20. Miliary pulmonary cryptococcosis

    Science.gov (United States)

    Kelly, Shane; Marriott, Deborah

    2014-01-01

    A 32-year-old HIV positive male presents with fevers and a non-productive cough. Initial X-ray and subsequent computerised tomography of the chest shows a bilateral miliary pattern of pulmonary infiltration highly suggestive of disseminated tuberculosis. However subsequent results were consistent with disseminated cryptococcosis, including pulmonary involvement, with cryptococcus identified on transbronchial tissue biopsy, and on blood and cerebrospinal fluid cultures. Imaging features of pulmonary cryptococcosis are generally of well-defined pleural-based nodules and less commonly alveolar infiltrates, lymphadenopathy, pleural effusions or cavitating lesions. Miliary pulmonary infiltrates are an exceptionally rare presentation. PMID:25379393

  1. Idiopathic pulmonary artery aneurysm.

    Science.gov (United States)

    Kotwica, Tomasz; Szumarska, Joanna; Staniszewska-Marszalek, Edyta; Mazurek, Walentyna; Kosmala, Wojciech

    2009-05-01

    Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.

  2. 75 FR 8377 - Pulmonary-Allergy Drugs Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2010-02-24

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Amendment of... Administration (FDA) is announcing an amendment to the notice of a meeting of the Pulmonary-Allergy Drugs... meeting of the Pulmonary-Allergy Drugs Advisory Committee would be held on March 10 and 11, 2010. On...

  3. 78 FR 17413 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-21

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of..., Pulmonary-Allergy Drugs Advisory Committee meeting due to unanticipated weather conditions. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the Committee: To provide...

  4. The regional lung deposition of thoron progeny attached to the particulate phase of environmental tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Strong, J.C.; Black, A.; Knight, D.A.; Dickens, C.J.; McAughey, J. (AEA Technology, Harwell (United Kingdom))

    1994-01-01

    The [gamma] emitting isotope of lead (([sup 212]Pb), a decay product of thoron ([sup 220]Rn)), has been used to radiolabel the particulate phase of aged and diluted sidestream tobacco smoke in situ. The radiolabelled aerosol is suitable for studies with human volunteers and as a marker for lung deposition and clearance of the attached fraction of thoron progeny, as well as environmental tobacco smoke (ETS) in a variety of environmental situations. Total mean deposition values for nine male volunteers varied from 22% to 59% under different breathing conditions, including nasal as against mouth breathing. These data are higher than previously reported values for environmental tobacco smoke but are consistent with models of particle deposition in the lung. Data for regional deposition and clearance show deposition principally in the pulmonary region of the lung. Preliminary studies using radon ([sup 222]Rn) to determine the degree of association of progeny in the presence of ambient particulate or environmental tobacco smoke confirm that the degree of attachment rises with increasing particle concentration, and is therefore likely to influence both the magnitude and site of deposition in the lung. (author).

  5. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    <正>20102406 Chen Gang(China University of Geosciences,Beijing 100083,China);Li Fengming Discussion on Geological Characteristics and Genesis of Yuquanshan Graphite Deposit of Xinjiang(Xinjiang Geology,ISSN1000-8845,CN65-1092/P,27(4),2009,p.325-329,4 illus.,4 tables,5 refs.)Key words:graphite deposit,XinjiangYuquanshan graphite deposit of Xinjiang occurs in mica-quartz schist of Xingeer Information which belongs to Xinditate Group of Lower Pt in Kuluketage Block of Tarim paleo-continent,and experiences two mineralizing periods of

  6. Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety

    Directory of Open Access Journals (Sweden)

    Cássio C. Ibiapina

    2004-12-01

    Full Text Available OBJETIVO: Rever a literatura sobre o hidrofluoralcano como propelente dos inaladores de dose medida contendo medicamentos empregados na asma. FONTES DOS DADOS: O levantamento bibliográfico foi realizado em bancos de dados eletrônicos - MEDLINE, MDConsult, HighWire, Medscape e LILACS - e por pesquisa direta - referentes aos últimos 15 anos -, utilizando-se as seguintes palavras-chaves: hidrofluoralcano, asma e infância. SÍNTESE DOS DADOS: Foram selecionados 43 artigos originais abordando a questão da substituição do clorofluorcarbono pelo hidrofluoralcano. Este gás mostrou-se como uma alternativa de propelente segura, com deposição pulmonar de 50 a 60% e eficácia significativa quando comparado com placebo (p OBJECTIVE: To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs. SOURCES OF DATA: Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out. SUMMARY OF THE FINDINGS: 43 original articles on the replacement of clorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < 0.003 in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers. CONCLUSIONS: Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced

  7. Ultra-pure soft water ameliorates atopic skin disease by preventing metallic soap deposition in NC/Tnd mice and reduces skin dryness in humans.

    Science.gov (United States)

    Tanaka, Akane; Matsuda, Akira; Jung, Kyungsook; Jang, Hyosun; Ahn, Ginnae; Ishizaka, Saori; Amagai, Yosuke; Oida, Kumiko; Arkwright, Peter D; Matsuda, Hiroshi

    2015-09-01

    Mineral ions in tap water react with fatty acids in soap, leading to the formation of insoluble precipitate (metallic soap) on skin during washing. We hypothesised that metallic soap might negatively alter skin conditions. Application of metallic soap onto the skin of NC/Tnd mice with allergic dermatitis further induced inflammation with elevation of plasma immunoglobulin E and proinflammatory cytokine expression. Pruritus and dryness were ameliorated when the back of mice was washed with soap in Ca2+- and Mg2+-free ultra-pure soft water (UPSW). Washing in UPSW, but not tap water, also protected the skin of healthy volunteers from the soap deposition. Furthermore, 4 weeks of showering with UPSW reduced dryness and pruritus of human subjects with dry skin. Washing with UPSW may be therapeutically beneficial in patients with skin troubles.

  8. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Jackson, Petra; Kling, Kirsten

    2016-01-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commerci...

  9. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Jackson, Petra; Kling, Kirsten;

    2016-01-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial...

  10. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

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

    2014-01-01

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

  11. Pulmonary arterial hypertension in pregnancy.

    Science.gov (United States)

    Običan, Sarah G; Cleary, Kirsten L

    2014-08-01

    Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving.

  12. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>20140876 Gao Junbo(College of Resources and Environmental Engineering,Guizhou University,Guiyang 550025,China);Yang Ruidong Study on the Strontium Isotopic Composition of Large Devonian Barite Deposits from Zhenning,Guizhou Province(Geochimica,

  13. Age, gender, and hemispheric differences in iron deposition in the human brain: an in vivo MRI study.

    Science.gov (United States)

    Xu, Xiaojun; Wang, Qidong; Zhang, Minming

    2008-03-01

    It is well known that iron accumulates in the brains of patients with various neurodegenerative diseases. To better understand disease-related iron changes, it is necessary to know the physiological distribution and accumulation of iron in the human brain. Studies have shown that brain iron levels increase with aging. However, the effects of gender and hemispheric laterality on iron accumulation and distribution are not well established. In this study, we estimated the brain iron levels in vivo in 78 healthy adults ranging in age 22 to 78 years using magnetic susceptibility-weighted phase imaging. The effects of age, gender, and hemispheric location on brain iron levels were evaluated within the framework of a general linear model. We found that the left hemisphere had higher iron levels than the right in the putamen, globus pallidus, substantia nigra, thalamus, and frontal white matter. We argue that the hemispheric asymmetry of iron content may underlie that of the dopaminergic system and may be related to motor lateralization in humans. In addition, significant age-related iron accumulation occurred in the putamen, red nucleus, and frontal white matter, but no gender-related differences in iron levels were detected. The results of this study extend our knowledge of the physiological distribution and accumulation of iron in the human brain.

  14. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>20122457 Cai Jianshe ( Fujian Institute of Geological Survey and Drawing,Fuzhou 350011,China ) On the Geologic Characteristics and Genesis of the Longtangsi Fluorite Deposit in Pucheng County,Fujian Province ( Geology of Fujian,ISSN1001-3970,CN35-1080 / P,30 ( 4 ), 2011,p.301-306,3illus.,1table,6 refs.,with English abstract ) Key words:fluorspar deposit,Fujian Province

  15. Treatment considerations in pulmonary coccidioidomycosis.

    Science.gov (United States)

    Hartmann, Carlos A; Aye, Wint T; Blair, Janis E

    2016-10-01

    Coccidioidomycosis is an endemic fungal infection caused by the soil-dwelling fungi, Coccidioides species. Coccidioidal infections may be asymptomatic in up to two-thirds of infected persons. Pulmonary coccidioidomycosis is the most common form of symptomatic infection. Fluconazole is the antifungal agent typically used to treat pulmonary coccidioidomycosis. Other azoles and amphotericin B products may be prescribed to treat nuanced aspects of coccidioidomycosis. This review discusses current literature regarding medical treatment options, including the various triazoles and amphotericin B products. In addition, we discuss uncomplicated and complicated pulmonary infections and their sequelae and the approach to managing coccidioidomycosis in certain populations of patients, such as pregnant women, transplant recipients, individuals infected with human immunodeficiency virus, and recipients of tumor necrosis factor-α inhibitors. Expert commentary: Symptomatic coccidioidomycosis can present physicians with a number of challenges, including the lack of sensitivity and specificity of diagnostic tests and lack of a standard treatment approach for all patients with the infection. Ongoing and future clinical trials will determine the optimal diagnostic, therapeutic, and prophylactic approaches, particularly for patients with comorbid conditions.

  16. Unilateral pulmonary hypoplasia

    Directory of Open Access Journals (Sweden)

    Albay S

    2008-10-01

    Full Text Available Pulmonary hypoplasia represents a broad range of malformations characterized by incomplete development of lung tissue. The severity of the lesion depends on the appearance time of the malformation during the timeline of lung development, and the presence of further anatomic anomalies. In this report, we present a case of pulmonary hypoplasia in a 27-year old woman.

  17. Pregnancy and pulmonary hypertension

    NARCIS (Netherlands)

    Pieper, Petronella G.; Lameijer, Heleen; Hoendermis, Elke S.

    2014-01-01

    Pulmonary hypertension during pregnancy is associated with considerable risks of maternal mortality and morbidity. Our systematic review of the literature on the use of targeted treatments for pulmonary arterial hypertension during pregnancy indicates a considerable decrease of mortality since a pre

  18. Pulmonary Hypertension in Scleroderma

    Science.gov (United States)

    ... is a reduced diffusing capacity (DL CO ) on pulmonary function tests (PFTs). The DL CO measures the ability of ... catheterization to measure the actual pressure in the pulmonary ... the PH; to assess the function of the left side of the heart; and ...

  19. Pulmonary Function Tests

    OpenAIRE

    Ranu, H; Wilde, M.; Madden, B

    2011-01-01

    Pulmonary function tests are valuable investigations in the management of patients with suspected or previously diagnosed respiratory disease. They aid diagnosis, help monitor response to treatment and can guide decisions regarding further treatment and intervention. The interpretation of pulmonary functions tests requires knowledge of respiratory physiology. In this review we describe investigations routinely used and discuss their clinical implications.

  20. [Mediastino-pulmonary sarcoidosis].

    Science.gov (United States)

    Delaval, P; Desrues, B; Quinquenel, M L; Lineau, C; Lena, H

    1993-01-01

    Sarcoidosis is diffuse granulomatosis disease. The aetiology and pathogenesis are unknown. Many different localizations have been described together with immunological disturbances. Generally, the prognosis is favourable. Here we describe the pulmonary manifestations and their staging. Extra-pulmonary manifestations are then presented. Finally, the principle elements of the diagnosis and the treatment of sarcoidosis are discussed.

  1. Molecular identification of a causative parasite species using formalin-fixed paraffin embedded (FFPE) tissues of a complicated human pulmonary sparganosis case without decisive clinical diagnosis.

    Science.gov (United States)

    Koonmee, Supinda; Intapan, Pewpan M; Yamasaki, Hiroshi; Sugiyama, Hiromu; Muto, Maki; Kuramochi, Toshiaki; Kularbkeaw, Jurairat; Kanpittaya, Jaturat; Maleewong, Wanchai; Nawa, Yukifumi

    2011-12-01

    PCR-based molecular diagnosis was made for the identification of causative agents of the clinically suspected pulmonary proliferative sparganosis case found in Thailand using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. As a reference, FFPE biopsy specimen from a typical cutaneous sparganosis case was examined together. DNA samples were extracted from tissues and two partial fragments of cytochrome c oxidase subunit 1 (cox1) gene were amplified for the detection of Spirometra DNA. Two cox1 fragments were amplified successfully for both specimens. After alignment of nucleotide sequences of the PCR-amplicons, the causative agents of both cases were identified as Spirometra erinaceieuropaei.

  2. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    Science.gov (United States)

    Abstract Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  3. Clinical characteristics and epidemiology of pulmonary pseudallescheriasis

    NARCIS (Netherlands)

    Kantarcioglu, A.S.; de Hoog, G.S.; Guarro, J.

    2012-01-01

    Background: Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections.

  4. Clinical characteristics and epidemiology of pulmonary pseudallescheriasis

    NARCIS (Netherlands)

    Kantarcioglu, A.S.; de Hoog, G.S.; Guarro, J.

    2012-01-01

    Background: Some members of the Pseudallescheria (anamorph Scedosporium) have emerged as an important cause of life-threatening infections in humans. These fungi may reach the lungs and bronchial tree causing a wide range of manifestations, from colonization of airways to deep pulmonary infections.

  5. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20110947 Chen Xinglong(Guizhou Bureau of Nonferrous Metal and Nuclear Geology,Guiyang 550005,China);Gong Heqiang Endowment Factors and Development & Utilization Strategy of Bauxite Resource in North Guizhou Province(Guizhou Geology,ISSN1000-5943,CN52-1059/P,27(2),2010,p.106-110,6 refs.,with English abstract)Key words:bauxite deposit,Guizhou Province20110948 Dang Yanxia(Mineral Resource & Reservoir Evaluation Center,Urumiq 830000,China);Fan Wenjun Geological Features and a Primary Study of Metallogenesis of the Wucaiwang Zeolite Deposit,Fuyun County(Xinjiang Geology,ISSN1000-8845,CN65-1092/P,28(2),2010,p.167-170,2 illus.,1 table,5 refs.)Key words:zeolite deposit,Xinjiang Nearly all zeolite deposits in the world result from low-temperature-alteration of glass-bearing volcanic rocks.The southern slope of the Kalamali Mountain is one of the regions where medium to acid volcanics are major lithological type,thus it is a preferred area to look for zeolite deposit.The Wucaiwang zeolite ore district consists of mainly acid volcanic-clastic rocks.

  6. Inflammation and pulmonary hypertension.

    Science.gov (United States)

    Mathew, Rajamma

    2010-01-01

    Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. Evidence is accumulating to suggest that inflammation plays a significant role in the pathogenesis of PH. Endothelial cells play an important role in inflammation and immune reactions, and inflammatory cytokines cause endothelial dysfunction. Endothelial dysfunction is a hallmark of PH, consisting of reduced availability of vasodilators and antiproliferative factors and increased production of vasoconstrictors and vascular proliferative factors. Up-regulation of inflammatory cytokines and perivascular inflammatory cell infiltration have been detected in the lungs of patients with idiopathic PH. Prevalence of PH in patients with systemic inflammatory diseases is well documented. Interestingly, a significant loss of endothelial caveolin-1, a potent immunomodulator and an inhibitor of cell proliferation, has been reported in human and experimental forms of PH. Reduction in the expression of caveolin-1 is known to result in the removal of antiproliferative activities, thus, leading to deregulated vascular cell proliferation. This article summarizes the roles of inflammation and endothelial caveolin-1 and their possible interrelationship in PH.

  7. Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

    Science.gov (United States)

    Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

  8. Pulmonary malakoplakia associated with immunodeficiency by HTLV-1 and HIV

    Directory of Open Access Journals (Sweden)

    Manuela Madruga

    2014-08-01

    Full Text Available Malakoplakia is a rare chronic inflammatory disease often confused with neoplasia. In this paper we report two cases of pulmonary Malakoplakia, both with typical clinical diagnosis of tuberculosis and lung cancer. A patient with human T-lymphotropic virus type I (HTLV-1 and diagnosis of adult T-cell leukemia/lymphoma, and another patient with human immunodeficiency virus (HIV, which was treated for tuberculosis, but, after pulmonary lobectomy, was evidenced Rodococosis equi, progressed to death.

  9. Pulmonary mycoses among the clinically suspected cases of pulmonary tuberculosis

    OpenAIRE

    Tshering Ongmu Bhutia; Luna Adhikari

    2015-01-01

    Background: This study was carried with the main objectives: (1) to find out the occurrence of pulmonary mycoses in clinically suspected pulmonary tuberculosis cases at central referral hospital, Tadong, Sikkim. (2) To find out the various fungi causing pulmonary mycoses in clinically suspected pulmonary tuberculosis cases. Methods: 200 clinically suspected pulmonary tuberculosis cases who visited the department of microbiology for the diagnostic microscopic examination of sputum sample f...

  10. Computational modeling of aerosol deposition in respiratory tract: a review.

    Science.gov (United States)

    Rostami, Ali A

    2009-02-01

    This review article is intended to serve as an overview of the current status of the computational tools and approaches available for predicting respiratory-tract dosimetry of inhaled particulate matter. There are two groups of computational models available, depending on the intended use. The whole-lung models are designed to provide deposition prediction for the whole lung, from the oronasal cavities to the pulmonary region. The whole-lung models are generally semi-empirical and hence provide more reliable results but within the range of parameters used for empirical correlations. The local deposition or computational fluid dynamics (CFD)-based models, on the other hand, utilize comprehensive theoretical and computational approaches but are often limited to upper respiratory tracts. They are based on theoretical principles and are applicable to a wider range of parameters, but less accurate. One of the difficulties with modeling of aerosol deposition in human lung is related to the complexity of the airways geometry and the limited morphometric data available. Another difficulty corresponds to simulation of the realistic physiological conditions of lung environment. Furthermore, complex physical and chemical phenomena associated with dense and multicomponent aerosols complicate the modeling tasks. All of these issues are addressed in this review. The progress made in each area in the last three decades and the challenges ahead are discussed along with some suggestions for future direction. The following subjects are covered in this review: introduction, aerosol deposition mechanisms, elements of a computational model, respiratory-tract geometry models, whole-lung models, CFD based models, cigarette smoke deposition models, and conclusion.

  11. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>20091594 Bao Yafan(The Third Geologic Survey of Jilin Province,Siping 136000,China);Liu Yanjun Relations between Bashenerxi Granite,West Dongkunlun and Baiganhu Tungsten-Tin Deposit(Jilin Geology,ISSN1001-2427,CN22-1099/P,27(3),2008,p.56-59,67,5 illus.,2 tables,7 refs.,with English abstract)Key words:tungsten ores,tin ores,monzogranite,Kunlun Mountains20091595 Chen Fuwen(Yichang Institute of Geology and Mineral Resources,China Geological Survey,Yichang 443003,China);Dai Pingyun Metallogenetic and Isotopic Chronological Study on the Shenjiaya Gold Deposit in Xuefeng Mountains,Hunan Province(Acta Geologica Sinica,ISSN0001-5717,CN11-1951/P,82(7),2008,p.906-911,3 illus.,2 tables,30 refs.)Key words:gold ores,HunanThe Shenjiaya gold deposit is a representative one

  12. Prostaglandin E2 inhibits in-vitro mineral deposition by human periodontal ligament cells via modulating the expression of TWIST1 and RUNX2.

    Science.gov (United States)

    Manokawinchoke, J; Pimkhaokhum, A; Everts, V; Pavasant, P

    2014-12-01

    Prostaglandin E2 (PGE2) has been shown to be able to influence both bone formation and resorption. The purpose of this study was to investigate the effect of PGE2 on the osteogenic differentiation of human periodontal ligament (HPDL) cells. HPDL cells were cultured with 0.001-1 μm PGE2 in osteogenic medium. In-vitro mineral deposition was determined by Alizarin Red S staining, and gene expression was determined by real-time PCR. PGE2 inhibited in-vitro mineral deposition by HPDL cells in a dose-dependent manner. PCR analyses showed that PGE2 upregulated the expression of Runt-related transcription factor 2 (RUNX2), but had no effect on osteocalcin expression. Upregulation of TWIST-related protein1 (TWIST1), a functional antagonist of RUNX2, was also observed. In addition, increased levels of RUNX2 and TWIST1 proteins, induced by PGE2, were detected by western blot analysis. Using a chemical activator of E prostanoid (EP) receptors as well as small interfering RNA against an EP receptor, it was shown that PGE2 regulated RUNX2 and TWIST1 via the EP2 receptor. The role of protein kinase A in the inductive effect of PGE2 was also demonstrated. The results of this study revealed that PGE2 modulates the osteogenic differentiation of HPDL cells via regulating the expression of RUNX2 and TWIST1. The results suggest a possible role for PGE2 in regulating the homeostasis of periodontal ligament tissue. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20111705 An Junbo(Team 603,Bureau of Nonferrous Metals Geological Exploration of Jilin Province,Hunchun 133300,China);Xu Renjie Geological Features and Ore Genesis of Baishilazi Scheelite Deposit in Yanbian Area(Jilin Geology,ISSN1001-2427,CN22-1099/P,29(3),2010,p.39-43,2 illus.,2 tables,7 refs.)Key words:tungsten ores,Jilin ProvinceThe Baishilazi scheelite deposit is located in contacting zone between the marble of the Late Palaeozoic Qinglongcun Group and the Hercynian biotite granite.The vein and lenticular major ore body is obviously controlled by NE-extending faults and con

  14. Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

    Directory of Open Access Journals (Sweden)

    Weingartner R.

    1999-01-01

    Full Text Available To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05, systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05 and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05 from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05. Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05 after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05 after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05 after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock

  15. Characterization of particle deposition in a lung model using an individual path

    Directory of Open Access Journals (Sweden)

    Ferrera C.

    2013-04-01

    Full Text Available Suspended particles can cause a wide range of chronic respiratory illnesses such as asthma and chronic obstructive pulmonary diseases, as well as worsening heart conditions and other conditions. To know the particle depositions in realistic models of the human respiratory system is fundamental to prevent these diseases. The main objective of this work is to study the lung deposition of inhaled particles through a numerical model using UDF (User Defined Function to impose the boundary conditions in the truncated airways. For each generation, this UDF puts the values of velocity profile of the flow path to symmetrical truncated outlet. The flow rates tested were 10, 30 and 60 ℓ/min, with a range of particles between 0.1 µm and 20 µm.

  16. The Role of Hyperglycemia and Insulin Resistance in the Development and Progression of Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Daniel Grinnan

    2016-01-01

    Full Text Available Pulmonary hypertension is a progressive disorder which often leads to right ventricular failure and death. While the existing classification system for pulmonary hypertension does not account for the impact of diabetes mellitus, evidence is emerging that suggests that diabetes is associated with pulmonary hypertension and that diabetes modifies the course of pulmonary hypertension. There is also growing radiographic, hemodynamic, biochemical, and pathologic data supporting an association between diabetes and pulmonary hypertension. More robust epidemiologic studies are needed to confirm an association between diabetes and pulmonary hypertension and to show that diabetes is a disease modifier in pulmonary hypertension. In addition, evaluating the effects of glucose control in animals with pulmonary hypertension and diabetes (as well as in humans is warranted.

  17. Pulmonary manifestations of leptospirosis

    Directory of Open Access Journals (Sweden)

    Sameer Gulati

    2012-01-01

    Full Text Available Leptospirosis has a spectrum of presentation which ranges from mild disease to a severe form comprising of jaundice and renal failure. Involvement of the lung can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome. Of late, it has been identified that leptospirosis can present atypically with predominant pulmonary manifestations. This can delay diagnosis making and hence optimum treatment. The purpose of this review is to bring together all the reported pulmonary manifestations of leptospirosis and the recent trends in the management.

  18. Anesthesia and pulmonary hypertension.

    Science.gov (United States)

    McGlothlin, Dana; Ivascu, Natalia; Heerdt, Paul M

    2012-01-01

    Anesthesia and surgery are associated with significantly increased morbidity and mortality in patients with pulmonary hypertension due mainly to right ventricular failure, arrhythmias, postoperative hypoxemia, and myocardial ischemia. Preoperative risk assessment and successful management of patients with pulmonary hypertension undergoing cardiac surgery involve an understanding of the pathophysiology of the disease, screening of patients at-risk for pulmonary arterial hypertension, analysis of preoperative and operative risk factors, thorough multidisciplinary planning, careful intraoperative management, and early recognition and treatment of postoperative complications. This article will cover each of these aspects with particular focus on the anesthetic approach for non-cardiothoracic surgeries.

  19. Isolated pulmonary Goodpasture syndrome.

    Science.gov (United States)

    Harrity, P; Gilbert-Barness, E; Cabalka, A; Hong, R; Zimmerman, J

    1991-01-01

    The case of a 13-year-old girl with Goodpasture syndrome is reported. The presentation at this age with only pulmonary hemorrhage is unusual among Goodpasture syndrome patients. The case illustrates well the diagnostic difficulties in Goodpasture syndrome. The choices of treatment modalities available for this disease and the results and risks of such treatment options are reviewed. A discussion and classification of diffuse pulmonary hemorrhage is presented. The case emphasizes that Goodpasture syndrome should be considered in the differential diagnosis of diffuse pulmonary hemorrhage in spite of a lack of renal abnormalities and that serum anti-glomerular basement membrane antibody testing can be of great help in confirming the diagnosis.

  20. Simultaneous determination of five naphthoylindole-based synthetic cannabinoids and metabolites and their deposition in human and rat hair.

    Science.gov (United States)

    Kim, Jihyun; Park, Yuran; Park, Meejung; Kim, Eunmi; Yang, Wonkyung; Baeck, Seungkyung; Lee, Sooyeun; Han, Sangbeom

    2015-01-01

    The continuing appearance of new synthetic cannabinoids has been a major issue in the field of forensic and clinical toxicology. In response to that, analytical methods for synthetic cannabinoids have been increasingly established in a variety of biological matrices. Since most of synthetic cannabinoids with structure similarity share some enzymatic metabolites, making the interpretation of analytical results and the discovery of the parent drug actually ingested very complicated, the investigation on metabolites of the first generation of synthetic cannabinoids with their relatively short side chains in chemical structure could be more important. Therefore, in the present study, we developed the analytical method for AM-2201, JWH-122 and MAM-2201 with JWH-018 as a precursor and their monohydroxylated metabolites in hair matrix. Also, using a rat model, AM-2201 and its monohydroxylated metabolites were identified and then the ratios of metabolite-to-parent drug were estimated to be used as criteria on external contamination. All analytes were extracted with methanol from washed and cut hair samples and the extracts were injected into LC-MS/MS with electrospray ion source in the positive ionization mode. Matrix effect and recovery were evaluated in hair matrices and no significant variations were observed. The validation results for precision and accuracy were satisfactory in both human and rat hair. The LOD and LOQ were 0.5 pg/10mg and 1.0 pg/10mg in human hair and 0.5 pg/20mg and 1.0 pg/20mg in pigmented and non-pigmented rat hair, respectively. Additionally, as a result of the animal study, there were not significant differences in the effect of pigmentation on the distribution of AM-2201 and its monohydroxylated metabolites in hair. Wide variations were observed for the concentrations of the naphthoylindole-based synthetic cannabinoids and metabolites in authentic hair samples from nine cases; those were 0.4-59.2 pg/mg for JWH-018, 0.1-0.8 pg/mg for JWH-073, 1

  1. Fluvial deposits as an archive of early human activity: Progress during the 20 years of the Fluvial Archives Group

    Science.gov (United States)

    Chauhan, Parth R.; Bridgland, David R.; Moncel, Marie-Hélène; Antoine, Pierre; Bahain, Jean-Jacques; Briant, Rebecca; Cunha, Pedro P.; Despriée, Jackie; Limondin-Lozouet, Nicole; Locht, Jean-Luc; Martins, Antonio A.; Schreve, Danielle C.; Shaw, Andrew D.; Voinchet, Pierre; Westaway, Rob; White, Mark J.; White, Tom S.

    2017-06-01

    Fluvial sedimentary archives are important repositories for Lower and Middle Palaeolithic artefacts throughout the 'Old World', especially in Europe, where the beginning of their study coincided with the realisation that early humans were of great antiquity. Now that many river terrace sequences can be reliably dated and correlated with the globally valid marine isotope record, potentially useful patterns can be recognized in the distribution of the find-spots of the artefacts that constitute the large collections that were assembled during the years of manual gravel extraction. This paper reviews the advances during the past two decades in knowledge of hominin occupation based on artefact occurrences in fluvial contexts, in Europe, Asia and Africa. As such it is an update of a comparable review in 2007, at the end of IGCP Project no. 449, which had instigated the compilation of fluvial records from around the world during 2000-2004, under the auspices of the Fluvial Archives Group. An overarching finding is the confirmation of the well-established view that in Europe there is a demarcation between handaxe making in the west and flake-core industries in the east, although on a wider scale that pattern is undermined by the increased numbers of Lower Palaeolithic bifaces now recognized in East Asia. It is also apparent that, although it seems to have appeared at different places and at different times in the later Lower Palaeolithic, the arrival of Levallois technology as a global phenomenon was similarly timed across the area occupied by Middle Pleistocene hominins, at around 0.3 Ma.

  2. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>20090243 Chen Zhibin (Hebei Institute of Geological Survey, Shijiazhuang 050081, China) Ore-Controlling Factors of the Beichagoumen Ag-Polymetallic Deposits in Northern Hebei Province (Geological Survey and Research, ISSN1672-4135, CN12-1353/P, 31(1), 2008, p.1-5, 3 illus., 10 refs.)

  3. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>20131565 Cai Lianyou(No.332 Geological Team,Bureau of Geology and Mineral Resources Exploration of Anhui Province,Huangshan 245000,China);Weng Wangfei Geological Characteristics and Genesis Analysis of Guocun Navajoite Deposit in South Anhui Province(Mineral Resources and Geology,

  4. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    <正>20102341 Bao Peisheng(Institute of Geology,Chinese Academy of Geological Science,Beijing 100037,China)Further Discussion on the Genesis of the Podiform Chromite Deposits in the Ophiolites-Questioning about the Rock:Melt Interaction Metallogeny(Geological Bulletin of China,ISSN1671-2552,CN11-4648/P,28(12),2009,p.1741-1761

  5. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>20131601 Gao Junbo(College of Resources and Environmental Engineering,Guizhou University,Guiyang 550003,China);Yang Ruidong Hydrothermal Venting-Flowing Sedimentation Characteristics of Devonian Barite Deposits from Leji,Zhenning County,Guizhou Province(Acta Sedimentologica Sinica,ISSN1000-0550,CN62-1038/P,30(3),

  6. [Novel immunopathological approaches to pulmonary arterial hypertension].

    Science.gov (United States)

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.

  7. Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis.

    Science.gov (United States)

    Mehrad, Borna; Burdick, Marie D; Strieter, Robert M

    2009-01-01

    Fibrotic interstitial lung diseases are characterized by progressive decline in lung function and premature death from respiratory failure. Fibrocytes are circulating bone marrow-derived progenitor cells that traffic to the lungs and contribute to fibrosis and may represent novel therapeutic targets in these diseases. We have previously found the recruitment of fibrocytes to the lung to be dependent on the chemokine ligand CXCL12. Given that the expression of the CXCL12 receptor, CXCR4, can be modulated pharmacologically in other cell types, we tested the hypotheses that the regulation of CXCR4 expression on fibrocytes mediates their influx to the lung in the context of pulmonary fibrosis and that pharmacologic inhibition of this process results in attenuated disease severity. CXCR4 was the predominant chemokine receptor on human fibrocytes, and its expression on fibrocytes was enhanced by hypoxia and by growth factors including platelet-derived growth factor. Both hypoxia-induced and growth factor-induced CXCR4 expressions were attenuated by specific inhibition of PI3-kinase and mTOR. Finally, in the mouse model of bleomycin-induced pulmonary fibrosis, treatment with the mTOR inhibitor rapamycin resulted in reduced numbers of CXCR4-expressing fibrocytes in the peripheral blood and lung as well as reduced lung collagen deposition. Taken together, these experiments support the notion that pharmacologic inhibition of the CXCR4/CXCL12 biological axis is achievable in human fibrocytes and reduces the magnitude of pulmonary fibrosis in an animal model. This approach may hold promise in human fibrotic lung diseases.

  8. Dissociation between the time courses of femoral artery blood flow and pulmonary VO2 during repeated bouts of heavy knee extension exercise in humans.

    Science.gov (United States)

    Fukuba, Yoshiyuki; Ohe, Yukie; Miura, Akira; Kitano, Asami; Endo, Masako; Sato, Hironori; Miyachi, Motohiko; Koga, Shunsaku; Fukuda, Osamu

    2004-05-01

    It has frequently been demonstrated that prior heavy cycling exercise facilitates pulmonary O(2) kinetics at the onset of subsequent heavy exercise. This might be due to improved muscle perfusion via acidosis-induced vasodilating effects. However, it is difficult to measure the blood flow (BF) to the working muscles (via the femoral artery) during cycling exercise. We therefore selected supine knee extension (KE) exercise as an alternative, and investigated whether the faster O(2) kinetics in the 2nd bout was matched by proportionally faster BF kinetics to the exercising muscle. Nine healthy subjects (aged 21-44 years) volunteered to participate in this study. The protocol consisted of two consecutive 6-min KE exercise bouts in a supine position (work rate: 70-75% of peak power) separated by a 6-min baseline rest (EX1 to EX2). During the protocol, a pulsed Doppler ultrasound technique was utilized to continuously measure the BF in the right femoral artery. The protocol was repeated at least 6 times to characterize the precise kinetics. In agreement with previous studies using cycling exercise, the O(2) kinetics in the 2nd bout were facilitated compared with that in the 1st bout [mean +/-s.d. of the 'effective' time constant (tau): EX1, 68.6 +/- 15.9, versus EX2, 58.0 +/- 14.4 s. Phase II-tau: EX1, 48.7 +/- 9.0, versus EX2, 41.2 +/- 13.3 s. Empirical index of the slow component (Delta O(2(6-3))): EX1, 78 +/- 44, versus EX2, 57 +/- 36 ml min(-1) (P 0.05)]. It was concluded that the faster pulmonary O(2) kinetics during heavy KE exercise following prior heavy exercise was not associated with a similar modulation in the BF to the working muscles.

  9. Automatic Synthesis of Anthropomorphic Pulmonary CT Phantoms.

    Directory of Open Access Journals (Sweden)

    Daniel Jimenez-Carretero

    Full Text Available The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery-vein (AV separations. The design of synthetic computed tomography (CT images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen's d effect size and AUC values, supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field.

  10. Automatic Synthesis of Anthropomorphic Pulmonary CT Phantoms

    Science.gov (United States)

    Jimenez-Carretero, Daniel; San Jose Estepar, Raul; Diaz Cacio, Mario; Ledesma-Carbayo, Maria J.

    2016-01-01

    The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery–vein (AV) separations. The design of synthetic computed tomography (CT) images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen’s d effect size and AUC values), supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field. PMID:26731653

  11. Management of pulmonary aspiration

    NARCIS (Netherlands)

    Janda, Matthias; Scheeren, Thomas W L; Nöldge-Schomburg, Gabriele F E

    2006-01-01

    Pulmonary aspiration of gastric contents in the perioperative phase is associated with increased postoperative morbidity and mortality. For the management of aspiration, differentiation between acid-associated aspiration pneumonitis and aspiration pneumonia as a consequence of a secondary bacterial

  12. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...... of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs......, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however...

  13. Pulmonary valve stenosis

    Science.gov (United States)

    ... valvuloplasty - pulmonary Images Heart valves References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Saunders; 2016:chap 69. Otto CM, Bownow RO. Valvular heart disease. In: Mann DL, Zipes DP, Libby P, Bonow ...

  14. Pulmonary Arteriovenous Malformations

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Oxhøj, H; Andersen, P E

    1999-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM....

  15. Neonatal pulmonary artery thrombosis

    Directory of Open Access Journals (Sweden)

    Mangesh Jadhav

    2012-01-01

    Full Text Available Pulmonary artery thrombosis in neonates is a rare entity. We describe two neonates with this diagnosis; their presentation, evaluation, and management. These cases highlight the importance of this differential diagnosis when evaluating the cyanotic neonate.

  16. Pulmonary Valve Stenosis

    Science.gov (United States)

    ... growths called carcinoid tumors in the digestive system. Rheumatic fever. This complication of an infection caused by streptococcus ... valve stenosis later in life, including: Carcinoid syndrome Rheumatic fever Noonan's syndrome Mild to moderate pulmonary valve stenosis ...

  17. [Pulmonary Manifestations of Vasculitis].

    Science.gov (United States)

    von Vietinghoff, S

    2016-11-01

    The variable symptoms and signs of pulmonary vasculitis are a diagnostic and therapeutic challenge. Vasculitis should be considered in rapidly progressing, severe and unusual manifestations of pulmonary disease. Clinical examination of other organ systems typically affected by vasculitis such as skin and kidney and autoantibody measurements are complementary approaches to manage this situation. Pulmonary involvement is common in small vessel vasculitis including anti-GBM disease (Goodpasture syndrome) and the ANCA-associated vasculitides. Life threatening pulmonary hemorrhage and irreversible damage of other organs, frequently the kidney, are important complications necessitating rapid diagnosis of these conditions.Vasculitides are rare diseases of multiple organs and therapies including biologics are evolving rapidly, requiring cooperation of specialities and with specialized centres to achieve best patient care. All involved physicians should be aware of typical complications of immunosuppressive therapy. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Pulmonary mycosis in AIDS

    Energy Technology Data Exchange (ETDEWEB)

    Busi Rizzi, Elisa; Schinina, Vincenzo; Bellussi, Angelo; De Santis, Andrea; Mazzuoli, Giovanna; Giosue, Sandro; Bibbolino, Corrado

    2001-01-01

    We retrospectively reviewed our series of 35 pulmonary mycosis in patients with AIDS, observed from 1987 to 1999, to correlate the imaging and pathologic findings. We further evaluated the frequency of fungal pneumonia before and after the use of a highly active antiretroviral therapy (HAART). Early recognition of pulmonary mycosis is imperative in these patients and improved survival can be achieved with early CT detection and prompt institution of high-dose antifungal therapy.

  19. Chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008430 Effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease. WANG Haoyan(王浩彦), et al. Dept Respir Dis, Beijing Friendship Hosp, Capital Med Sci Univ, Beijing 100050. Chin J Tuberc Respir Dis 2008;31(6):414-416. Objective To investigate the effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease (COPD).

  20. Reexpansion pulmonary edema

    OpenAIRE

    Genofre Eduardo Henrique; Vargas Francisco S.; Teixeira Lisete R.; Vaz Marcelo Alexandre Costa; Marchi Evaldo

    2003-01-01

    Reexpansion pulmonary edema (RPE) is a rare, but frequently lethal, clinical condition. The precise pathophysiologic abnormalities associated with this disorder are still unknown, though decreased pulmonary surfactant levels and a pro-inflammatory status are putative mechanisms. Early diagnosis is crucial, since prognosis depends on early recognition and prompt treatment. Considering the high mortality rates related to RPE, preventive measures are still the best available strategy for patient...

  1. Traumatic pulmonary pseudocyst.

    Science.gov (United States)

    Gupta, Neeraj; George, Jacob; Gupta, Rakesh C; Dixit, Ramakant

    2013-04-01

    Blunt thoracic trauma manifests in various ways, depending on the structures injured and type of injury. Commonly manifested as parenchymal contusion, at times, pseudacavitation may also been seen on the chest X ray. They are to be differentiated from other causes of pulmonary cavitations which are often done based on history. The so called pulmonary pseudo cysts usually have a benign course and needs only observation.

  2. Traumatic pulmonary pseudocyst

    OpenAIRE

    Gupta, Neeraj; George, Jacob; Gupta, Rakesh C; Dixit, Ramakant

    2013-01-01

    Blunt thoracic trauma manifests in various ways, depending on the structures injured and type of injury. Commonly manifested as parenchymal contusion, at times, pseudacavitation may also been seen on the chest X ray. They are to be differentiated from other causes of pulmonary cavitations which are often done based on history. The so called pulmonary pseudo cysts usually have a benign course and needs only observation.

  3. Effects of niflumic acid on the pulmonary vasoconstriction of human in acute hypoxia conditions%尼氟灭酸对急性低氧人肺动脉收缩的影响

    Institute of Scientific and Technical Information of China (English)

    杨朝; 耑冰; 张丽萍; 张珍祥

    2011-01-01

    Aim To investigate the effects of nifiumic acid ( NFA ) , an inhibitor of calcium-activated chloride ( ClCa )channels, on pulmonary vasoconstriction of human in acute hypoxic conditions. Methods Acute hypoxia-induced contraction was observed in human pulmonary artery by using routine blood vascular perfusion in vitro; the fluorescence Ca2+ indicator Fura-2/AM was used to observe intracellular free Ca2+ concentration( [ Caz+ ]i ) in human pulmonary artery smooth muscle cells( PASMCs )through putting into ClCa channel blockers NFA and indaryloxyacetic acid( IAA-94 ) in normal( 37℃ ,5o% CO2 ,21% O2 ,74% N2 )and acute hypoxic( 37℃ ,5% CO2 ,2% O2 ,93% N2 )conditions. Results ① In acute hypoxic condition,[ Ca2+ ]i was increased: in normoxic condition,[ Ca2+ ]i was( 103. 26 ±4. 72 )nmol · L-1 , and in hypoxic condition,[ Caz+ ]i was( 253. 89 ± 9. 82 )nmol ·L-1( P < 0. 01 ); The NFA and IAA-94 decreased [ Ca2+ ]i from( 253. 89 ±9. 82 )nmol . L-1 to( 107. 18 ± 14. 99 )nmol · L-1( P < 0. 01 ). ②Acute hypoxia evoked pulmonary artery contractions from ( 4. 54 ± 0. 52 )g · g-1 to( 49. 51 ± 1. 30 )g · g-1( P < 0. 01 );The NFA and IAA-94 inhibited hypoxia-evoked contractions in the pulmonary artery from( 49. 51 ± 1. 30 )g · g-1 to( 4. 50 ± 0. 40 )g · g-1( P < 0. 01 ). Conclusions NFA can inhibit the contraction of human pulmonary artery in acute hypoxic condition, which may result from the inhibition of activity ClCa channels.%目的 研究钙激活氯离子(ClCa)通道阻滞剂尼氟灭酸(NFA)对急性低氧人肺动脉收缩的影响.方法 在常氧(37℃、5% CO2、21% O2、74% N2)和急性低氧 (37℃、5% CO2、2% O2、93% N2)条件下,采用荧光分光光度计法、离体血管灌流法,观察ClCa阻滞剂NFA和indaryloxyacetic acid(IAA-94)对急性低氧人肺动脉平滑肌细胞质内游离钙离子浓度([Ca2+]i)及肺动脉张力的影响.结果 ① 急性低氧引起[Ca2+]i升高,由常氧时的(103.26±4.72)nmol·L-1

  4. Biological characteristic effects of human dental pulp stem cells on poly-ε-caprolactone-biphasic calcium phosphate fabricated scaffolds using modified melt stretching and multilayer deposition.

    Science.gov (United States)

    Wongsupa, Natkrita; Nuntanaranont, Thongchai; Kamolmattayakul, Suttatip; Thuaksuban, Nuttawut

    2017-02-01

    Craniofacial bone defects such as alveolar cleft affect the esthetics and functions that need bone reconstruction. The advanced techniques of biomaterials combined with stem cells have been a challenging role for maxillofacial surgeons and scientists. PCL-coated biphasic calcium phosphate (PCL-BCP) scaffolds were created with the modified melt stretching and multilayer deposition (mMSMD) technique and merged with human dental pulp stem cells (hDPSCs) to fulfill the component of tissue engineering for bone substitution. In the present study, the objective was to test the biocompatibility and biofunctionalities that included cell proliferation, cell viability, alkaline phosphatase activity, osteocalcin, alizarin red staining for mineralization, and histological analysis. The results showed that mMSMD PCL-BCP scaffolds were suitable for hDPSCs viability since the cells attached and spread onto the scaffold. Furthermore, the constructs of induced hDPSCs and scaffolds performed ALP activity and produced osteocalcin and mineralized nodules. The results indicated that mMSMD PCL-BCP scaffolds with hDPSCs showed promise in bone regeneration for treatment of osseous defects.

  5. A regional record of expanded Holocene wetlands and prehistoric human occupation from paleowetland deposits of the western Yarlung Tsangpo valley, southern Tibetan Plateau

    Science.gov (United States)

    Hudson, Adam M.; Olsen, John W.; Quade, Jay; Lei, Guoliang; Huth, Tyler E.; Zhang, Hucai

    2016-07-01

    The Asian Monsoon, which brings ∼80% of annual precipitation to much of the Tibetan Plateau, provides runoff to major rivers across the Asian continent. Paleoclimate records indicate summer insolation and North Atlantic paleotemperature changes forced variations in monsoon rainfall through the Holocene, resulting in hydrologic and ecologic changes in plateau watersheds. We present a record of Holocene hydrologic variability in the Yarlung Tsangpo (YT) valley of the southern Tibetan Plateau, based on sedimentology and 14C dating of organic-rich 'black mats' in paleowetlands deposits, that shows changes in wetlands extent in response to changing monsoon intensity. Four sedimentary units indicate decreasing monsoon intensity since 10.4 ka BP. Wet conditions occurred at ∼10.4 ka BP, ∼9.6 ka BP and ∼7.9-4.8 ka BP, with similar-to-modern conditions from ∼4.6-2.0 ka BP, and drier-than-modern conditions from ∼2.0 ka BP to present. Wetland changes correlate with monsoon intensity changes identified in nearby records, with weak monsoon intervals corresponding to desiccation and erosion of wetlands. Dating of in situ ceramic and microlithic artifacts within the wetlands indicates Epipaleolithic human occupation of the YT valley after 6.6 ka BP, supporting evidence for widespread colonization of the Tibetan Plateau in the early and mid-Holocene during warm, wet post-glacial conditions.

  6. Mycobacterium Szulgai Pulmonary Infection: Case Report of an Uncommon Pathogen in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Jae; Lee, Jae Chun; Jeong, Sun Young [Jeju National University School of Medicine, Jeju (Korea, Republic of)

    2014-10-15

    Mycobacterium szulgai (M. szulgai) is an unusual pathogen in a human non-tuberculous mycobacterial infection. Pulmonary infection due to M. szulgai may be clinically and radiologically confused with active pulmonary tuberculosis. In contrast to other non-tuberculous mycobacteria, M. szulgai infection is well controlled by combination antimycobacterial therapy. Most of the previously reported cases of M. szulgai pulmonary infection showed cavitary upper lobe infiltrates. We herein describe a case of pulmonary M. szulgai infection that shows clinical and radiological presentations similar to active pulmonary tuberculosis.

  7. MS80,a novel sulfated oligosaccharide,inhibits pulmonary fibrosis by targeting TGF-β1 both in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Han-dong JIANG; Hua-shi GUAN

    2009-01-01

    Aim:The pro-fibrogenic cytokine transforming growth factor-beta 1 (TGF-131) has attracted much attention for its potential role in the etiology of idiopathic pulmonary fibrosis (IPF).Here,we demonstrate that MS80,a novel sulfated oligosaccharide extracted from seaweed,can bind TGF-β1.The aim of the present study was to determine whether MSSO is capable of combating TGF-β1-mediated pulmonary fibrotic events both in vitro and in vivo,and to investigate the possible underlying mechanisms.Methods:Surface plasmon resonance was used to uncover the binding profiles between the compound and TGF-β.MTT assay,flow cytometry,Western blot analysis,BCA protein assay and SDS-PAGE gelatin zymography were used to probe the antifibrotic mechanisms of MS80.The in vivo fibrotic efficacy was evaluated in a bleomycin instillation-induced rat model.Results:We report that MS80,a new kind of sulfated oligosaccharide extracted from seaweed,inhibits TGF-β1-induced pulmonary fibrosis in vitro and bleomycin-induced pulmonary fibrosis in vivo.Our results indicated that MS80 competitively inhibited heparin/HS-TGF-β1 interaction through its high binding affinity for TGF-β1.Moreover,MS80 arrested TGF-β1-induced human embryo pulmonary fibroblast (HEPF) cell proliferation,collagen deposition and matrix metalloproteinase (MMP) activity.Intriguingly,MS80 deactivated both the ERK and p38 signaling pathways.MS80 was also a potent suppressor of bleomycin-induced rat pulmonary fibrosis in vivo,as evidenced by improved pathological settings and decreased lung collagen contents.Conclusion:MS80 in particular,and perhaps oligosaccharide in general,offer better pharmacological profiles with appreciably few side effects and represent a promising class of drug candidates for IPF therapy.

  8. Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway.

    Science.gov (United States)

    Chen, Tian; Nie, Haiyu; Gao, Xin; Yang, Jinglin; Pu, Ji; Chen, Zhangjian; Cui, Xiaoxing; Wang, Yun; Wang, Haifang; Jia, Guang

    2014-04-21

    Multi-walled carbon nanotubes (MWCNT) are a typical nanomaterial with a wide spectrum of commercial applications. Inhalation exposure to MWCNT has been linked with lung fibrosis and mesothelioma-like lesions commonly seen with asbestos. In this study, we examined the pulmonary fibrosis response to different length of MWCNT including short MWCNT (S-MWCNT, length=350-700nm) and long MWCNT (L-MWCNT, length=5-15μm) and investigated whether the epithelial-mesenchymal transition (EMT) occurred during MWCNT-induced pulmonary fibrosis. C57Bl/6J male mice were intratracheally instilled with S-MWCNT or L-WCNT by a single dose of 60μg per mouse, and the progress of pulmonary fibrosis was evaluated at 7, 28 and 56 days post-exposure. The in vivo data showed that only L-MWCNT increased collagen deposition and pulmonary fibrosis significantly, and approximately 20% of pro-surfactant protein-C positive epithelial cells transdifferentiated to fibroblasts at 56 days, suggesting the occurrence of EMT. In order to understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-β/p-Smad2 signaling pathway in EMT. Our results showed that L-MWCNT downregulated E-cadherin and upregulated α-smooth muscle actin (α-SMA) protein expression in A549 cells. Taken together, both in vivo and in vitro study demonstrated that respiratory exposure to MWCNT induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-β/Smad pathway.

  9. NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Szema, Anthony M.; Forsyth, Edward; Ying, Benjamin; Hamidi, Sayyed A.; Chen, John J.; Hwang, Sonya; Li, Jonathan C.; Sabatini Dwyer, Debra; Ramiro-Diaz, Juan M.; Giermakowska, Wieslawa; Gonzalez Bosc, Laura V.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In

  10. H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension.

    Science.gov (United States)

    Feng, Shasha; Chen, Siyao; Yu, Wen; Zhang, Da; Zhang, Chunyu; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2017-03-01

    This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.

  11. CT findings of pulmonary aspergillosis

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Jung Eun; Im, Jung Gi; Goo, Jin Mo; Kim, Hong Dae; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-10-15

    The fungus aspergillus can cause a variety of pulmonary disorders. Aspergilloma is a noninvasive aspergillus colonization of virtually any type of preexisting pulmonary cavity or cystic space. Invasive pulmonary aspergillosis is serious, usually fatal infection in patients being treated with immunosuppressants or who have chronic debilitating disease. Allergic bronchopulmonary aspergillosis is characterized clinically by asthma, blood and sputum eosinophilia and positive immunologic reaction to aspergillus antigen. Awareness of the radiographic and CT findings of pulmonary aspergillosis is important in making the diagnosis of aspergillus-caused pulmonary disorders. In this pictorial essay, we illustrated various radiological findings of pulmonary aspergillosis focused on CT findings correlated with gross pathologic specimens.

  12. In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial cells by non-anticoagulant fraction of enoxaparin.

    Directory of Open Access Journals (Sweden)

    Madhur D Shastri

    Full Text Available Enoxaparin, a mixture of anticoagulant and non-anticoagulant fractions, is widely used as an anticoagulant agent. However, it is also reported to possess anti-inflammatory properties. Our study indicated that enoxaparin inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their release causes extensive lung tissue damage. The use of enoxaparin as an anti-inflammatory agent is hampered due to the risk of bleeding associated with its anticoagulant fractions. Therefore, we aimed to identify the fraction responsible for the observed anti-inflammatory effect of enoxaparin and to determine the relationship between its structure and biological activities.A549 pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells were measured by ELISA. The anticoagulant activity of the fraction responsible for the effect of enoxaparin was determined using an anti-factor-Xa assay. The fraction was structurally characterised using nuclear magnetic resonance. The fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups required for the inhibition of interleukins. High-performance size-exclusion chromatography was performed to rule out that the observed effect was due to the interaction between the fraction and trypsin or interleukins.Enoxaparin (60 μg/mL inhibited the release of IL-6 and IL-8 by >30%. The fraction responsible for this effect of enoxaparin was found to be a disaccharide composed of α-L-iduronic-acid and α-D-glucosamine-6-sulfate. It (15 μg/mL inhibited the release of interleukins by >70%. The 6-O sulphate groups were responsible for its anti-inflammatory effect. The fraction did not bind to trypsin or interleukins, suggesting the effect was not due to an artefact of the experimental model.The identified disaccharide has no anticoagulant activity and therefore eliminates the risk of bleeding

  13. Enhanced nitrogen deposition over China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xuejun; Zhang, Ying; Han, Wenxuan; Tang, Aohan; Shen, Jianlin; Cui, Zhenling; Christie, Peter; Zhang, Fusuo [College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193 (China); Vitousek, Peter [Department of Biology, Stanford University, Stanford, California 94305 (United States); Erisman, Jan Willem [VU University Amsterdam, 1081 HV Amsterdam (Netherlands); Goulding, Keith [The Sustainable Soils and Grassland Systems Department, Rothamsted Research, Harpenden AL5 2JQ (United Kingdom); Fangmeier, Andreas [Institute of Landscape and Plant Ecology, University of Hohenheim, 70593 Stuttgart (Germany)

    2013-02-28

    China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen. These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity. However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s, before the introduction of mitigation measures. Nitrogen from ammonium (NH4+) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3-), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized croplands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment.

  14. An image reconstruction algorithm of EIT based on pulmonary prior information

    Institute of Scientific and Technical Information of China (English)

    Huaxiang WANG; Li HU; ling WANG; Lu LI

    2009-01-01

    Using a CT scan of the pulmonary tissue, a human pulmonary model is established combined with the structure property of the human lung tissue using the software COMSOL. Combined with the conductivity contribution information of the human tissue and organ,an image reconstruction method of electrical impedance tomography based on pulmonary prior information is proposed using the conjugate gradient method. Simulation results show that the uniformity index of sensitivity distribution of the pulmonary model is 15.568, which is significantly reduced compared with 34.218 based on the round field. The proposed algorithm improves the uniformity of the sensing field, the image resolution of the conductivity distribution of pulmonary tissue and the quality of the reconstruction image based on pulmonary prior information.

  15. Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

    Science.gov (United States)

    Cerrada, Alejandro; de la Torre, Paz; Grande, Jesús; Haller, Thomas; Flores, Ana I; Pérez-Gil, Jesús

    2014-01-01

    Lung alveolar type II (ATII) cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs) have been differentiated into Alveolar Type II- Like Cells (ATII-LCs), which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

  16. Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

    Directory of Open Access Journals (Sweden)

    Alejandro Cerrada

    Full Text Available Lung alveolar type II (ATII cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs have been differentiated into Alveolar Type II- Like Cells (ATII-LCs, which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

  17. Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus-infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor

    Directory of Open Access Journals (Sweden)

    Pierangelo Chinello

    2015-03-01

    Full Text Available Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI. We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI.

  18. Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation—A Retrospective Multivariate Statistical Analysis

    Science.gov (United States)

    Almeida, Tiago P.; Chu, Gavin S.; Li, Xin; Dastagir, Nawshin; Tuan, Jiun H.; Stafford, Peter J.; Schlindwein, Fernando S.; Ng, G. André

    2017-01-01

    Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model. Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs. Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P PVI that remained fractionated after PVI (31% of the collected points); (ii) fractionated that converted to normal (39%); (iii) normal prior to PVI that became fractionated (9%) and; (iv) normal that remained normal (21%). Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination (P PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information. PMID:28883795

  19. Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation-A Retrospective Multivariate Statistical Analysis.

    Science.gov (United States)

    Almeida, Tiago P; Chu, Gavin S; Li, Xin; Dastagir, Nawshin; Tuan, Jiun H; Stafford, Peter J; Schlindwein, Fernando S; Ng, G André

    2017-01-01

    Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model. Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs. Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P multivariate statistical models were effective in their discrimination (P multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.

  20. 低氧对人肺腺癌A549细胞迁移和黏附的影响%Effect of hypoxia on migration, invasion and adhesion to endothelium of human pulmonary adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    Weigan Shen; Jun Zhu; Zhiyong Yu; Qingyu Xue

    2008-01-01

    Objective:To evaluate the effect of hypoxia on migration,invasion and adhesion to endothelium of human pulmonary adenocarcinoma A549 cells.Methods:Wound-healing and Transwell invasion assays were performed to study the effect of hypoxia on migration and invasion of A549 cells,and A549 cells were added to a monolayer of human umbilical vein endothelial cells (HUVECs) to test the ability to adhere to endothelium.Immunofluorescence assay and luciferase reporter gene assay were also used to evaluate the effect of hypoxia on distribution of E-cadherin,β-catenin,and actin,and hypoxia-inducible factor-1 (HIF-1)-dependent transcription,respectively.Results:Hypoxia facilitated A549 cell migration,invasion,and A549 cell-endothelial cells adhesion,and modulated the distribution of E-cadherin and β-catenin,and actin cytoskeleton rearrangement,and up-regulated HIF-1-dependent reporter gene expression in A549 cells.Conclusion:Promotion of A549 cell migration,invasion,and adhesion on endothelium by hypoxia might be modulated through its up-regulating HIF-l-dependent gene expression,which then induced the redistribution of E-cadherin and β-catenin,and the actin cytoskeletal reorganization.

  1. Pulmonary Tuberculosis in Children

    Directory of Open Access Journals (Sweden)

    Keshtkar Jahromi

    2014-09-01

    Full Text Available Tuberculosis (TB is the most common cause of infection-related death worldwide. Children represent 5 to 15% of all TB cases around the world and are more frequently infected and more easily affected by the most severe forms of the disease such as meningitis and disseminated form .Here, we reviewed TB in children with impact on the routes of transmission, clinical manifestations, treatment, control, and prophylaxis. Electronic databases (PubMed, Scopus were searched from June1995 to May 2014 by using key words (pulmonaryTB,epidemiology,transmission,clinical manifestations,treatment,control, and prophylaxis . Pulmonary tuberculosis may manifest in several forms, including endobronchial TB with focal lymphadenopathy, progressive pulmonary disease, pleural involvement, and reactivated pulmonary disease . Symptoms of primary pulmonary disease in the pediatric population are often insignificant. Gastric aspirates are used instead of sputum in children younger than 6 years. BCG vaccination is used in many parts of the world and the major role of vaccination is the prevention of life-threatening illness such as disseminated TB and meningitis in children.Treatment is the same as for adults. Most people infected with M .tuberculosis do not develop active disease. In healthy individuals, the lifetime risk of developing infection to disease is 5-10%. Reactivation of TB often occurs in older children and adolescent and is more common in patients who acquire TB at age 7 years and older.

  2. Pulmonary thromboembolism in children

    Energy Technology Data Exchange (ETDEWEB)

    Babyn, Paul S.; Gahunia, Harpal K. [Hospital for Sick Children, Department of Pediatric Diagnostic Imaging, Toronto, ON (Canada); Massicotte, Patricia [Stollery Children' s Hospital and University of Alberta, Departments of Pediatric Hematology and Cardiology, Edmonton, AB (Canada)

    2005-03-01

    Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions, malignancy, renal disease, foreign bodies or, uncommonly, intracranial venous sinus thrombosis, burns, or nonbacterial thrombotic endocarditis. Other types of embolism can occur uncommonly in childhood and need to be recognized, as the required treatment will vary. These include pulmonary cytolytic thrombi, foreign bodies, tumor and septic emboli, and post-traumatic fat emboli. No single noninvasive test for pulmonary embolism is both sensitive and specific. A combination of diagnostic procedures must be used to identify suspect or confirmed cases of PTE. This article reviews the risk factors, clinical presentation and treatment of pulmonary embolism in children. It also highlights the current diagnostic tools and protocols used to evaluate pulmonary embolism in pediatric patients. (orig.)

  3. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  4. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>20122389 Cai Lianyou ( No.332 Geological Team,Bureau of Geology and Mineral Resources Exploration of Anhui Province,Huangshan 245000,China );Weng Wangfei Geologic Characteristic and Ore-Control Factors of the Nanshan W-Mo Polymetallic Ore Deposit in South Anhui Province ( Geological Survey and Research,ISSN1672-4135,CN12-1353 / P,34 ( 4 ), 2011,p.290-298,3 illus.,1table,14refs. ) Key words:tungsten ores,molybdenum ores,ore guide of prospecting,Anhui Province

  5. METALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20110165 Chen Jiawei(The 3rd Geological Team,Henan Bureau of Geology and Mineral Resources,Xinyang 464000,China)Ore Control Conditions and Genetic Model for the Bodaoling Ag-Au Deposit in Guangshan,Henan Province(Acta Geologica Sichuan,ISSN1006-0995,CN51-1273/P,30(1),2010,p.28-30,5 illus.,1 ref.,with English abstract)Key words:gold ores,Henan Province20110166 Chen Mingquan(Geological Team 306,Yunnan Bureau of Nonferrous Geology,Kunming 650216,Ch

  6. Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis.

    Science.gov (United States)

    Tarantal, A F; Chen, H; Shi, T T; Lu, C-H; Fang, A B; Buckley, S; Kolb, M; Gauldie, J; Warburton, D; Shi, W

    2010-10-01

    Altered transforming growth factor (TGF)-β expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-β in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-β1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-β1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-β1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-β1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-β1 overexpression was no longer evident. Therefore, overexpression of TGF-β1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.

  7. Pulmonary Hypertension: Diagnosis and Treatment

    National Research Council Canada - National Science Library

    Dunlap, Beth; Weyer, George

    2016-01-01

    Pulmonary hypertension is a common, complex group of disorders that result from different pathophysiologic mechanisms but are all defined by a mean pulmonary arterial pressure of 25 mm Hg or greater...

  8. Update in pulmonary arterial hypertension.

    Science.gov (United States)

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.

  9. Lung Transplantation for Pulmonary Hypertension

    Science.gov (United States)

    ... the page. Answers about Lung Transplantation for PULMONARY HYPERTENSION Part One: Overview From the development of epoprostenol ... decades, expansion of medical treatment of pulmonary arterial hypertension (PAH) has improved survival and quality of life ...

  10. Pulmonary embolism; Lungenarterienembolie

    Energy Technology Data Exchange (ETDEWEB)

    Sudarski, Sonja; Henzler, Thomas [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Inst. fuer Klinische Radiologie und Nuklearmedizin

    2016-09-15

    Pulmonary embolism (PE) requires a quick diagnostic algorithm, as the untreated disease has a high mortality and morbidity. Crucial for the diagnostic assessment chosen is the initial clinical likelihood of PE and the individual risk profile of the patient. The overall goal is to diagnose or rule out PE as quickly and safely as possible or to initiate timely treatment if necessary. CT angiography of the pulmonary arteries (CTPA) with multi-slice CT scanner systems presents the actual diagnostic reference standard. With CTPA further important diagnoses can be made, like presence of right ventricular dysfunction. There are different scan and contrast application protocols that can be applied in order to gain diagnostic examinations with sufficient contrast material enhancement in the pulmonary arteries while avoiding all kinds of artifacts. This review article is meant to be a practical guide to examine patients with suspected PE according to the actual guidelines.

  11. Ultrastructural observation on pulmonary fibrosis in E9 rats treated with compoundCarapax trionycis formula

    Institute of Scientific and Technical Information of China (English)

    Jin Ren; Li-Xuan Wang; Xue-Cheng Ji; Jia-Ying Zhou; Man-Ying Zhang

    2013-01-01

    Objective:To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compoundCarapax trionycis(C. trionycis;Biejia inChinese) formula.Methods:Sixty maleSprague-Dawley rats were randomly divided into four groups(n=15): compoundC. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin.Five rats from each group weresacrificed on day 7,14 and28 of the drug treatment, respectively.The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy.TheSzapiel’s method was used to assess the degree of alveolitis and pulmonary fibrosis.Results:Compared with the model group, the compoundC. trionycis formula groups had slighter pulmonary alveolitis after the7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the14-day treatment.After the28-day treatment, the compoundC. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than51% of the whole lung area. Conclusions:The compoundC. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.

  12. Pulmonary manifestations of heartworm disease.

    Science.gov (United States)

    Calvert, C A; Rawlings, C A

    1985-09-01

    The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.

  13. Pulmonary artery sling: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Gil Hyun; Lee, Sun Wha; Cha, Sung Ho [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1993-09-15

    Aberrant left-sided pulmonary artery(pulmonary artery sling) is an uncommon anomaly,which may cause significant respiratory abnormality. We report a case of pulmonary artery sling which is combined with persistent left superior vena cava and dextrocardia. This case were identified by esophagogram and CT and confirmed by MRI and angiography. We consider that MRI is a valuable new method for the diagnosis of aberrant left-sided pulmonary artery.

  14. AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates

    National Research Council Canada - National Science Library

    Jeyanathan, Mangalakumari; Shao, Zhongqi; Yu, Xuefeng; Harkness, Robin; Jiang, Rong; Li, Junqiang; Xing, Zhou; Zhu, Tao

    2015-01-01

    Persisting high global tuberculosis (TB) morbidity and mortality and poor efficacy of BCG vaccine emphasizes an urgent need for developing effective novel boost vaccination strategies following parenteral BCG priming in humans...

  15. AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates: e0135009

    National Research Council Canada - National Science Library

    Mangalakumari Jeyanathan; Zhongqi Shao; Xuefeng Yu; Robin Harkness; Rong Jiang; Junqiang Li; Zhou Xing; Tao Zhu

    2015-01-01

      Persisting high global tuberculosis (TB) morbidity and mortality and poor efficacy of BCG vaccine emphasizes an urgent need for developing effective novel boost vaccination strategies following parenteral BCG priming in humans...

  16. Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation—A Retrospective Multivariate Statistical Analysis

    Directory of Open Access Journals (Sweden)

    Tiago P. Almeida

    2017-08-01

    Full Text Available Purpose: Complex fractionated atrial electrograms (CFAE-guided ablation after pulmonary vein isolation (PVI has been used for persistent atrial fibrillation (persAF therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model.Methods: 207 pairs of atrial electrograms (AEGs were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA and linear discriminant analysis (LDA have been used to characterize the atrial regions and AEGs.Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P < 0.0001. Four types of LA regions were identified, based on the AEGs characteristics: (i fractionated before PVI that remained fractionated after PVI (31% of the collected points; (ii fractionated that converted to normal (39%; (iii normal prior to PVI that became fractionated (9% and; (iv normal that remained normal (21%. Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination (P < 0.0001.Conclusion: Our results have unveiled that there are LA regions resistant to PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.

  17. Methamphetamine Use and Pulmonary Hypertension

    Science.gov (United States)

    ... other problems, diagnosing a case of pulmonary hyper- tension can be difficult and may require a specialist. Once pulmonary hyperten- sion is diagnosed, however, treatment can begin immediately. One form of PH is called pulmonary arterial hypertension (PAH). In PAH, the blood vessels that ...

  18. Pulmonary Artery Dissection: A Fatal Complication of Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Chuanchen Zhang

    2016-01-01

    Full Text Available Pulmonary artery dissection is extremely rare but it is a really life-threatening condition when it happens. Most patients die suddenly from major bleeding or tamponade caused by direct rupture into mediastinum or retrograde into the pericardial sac. What we are reporting is a rare case of a 46-year-old female patient whose pulmonary artery dissection involves both the pulmonary valve and right pulmonary artery. The patient had acute chest pain and severe dyspnea, and the diagnosis of pulmonary artery dissection was confirmed by ultrasonography and CT angiography. Moreover, its etiology, clinical manifestations, and management are also discussed in this article.

  19. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism

    Science.gov (United States)

    Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE. PMID:27798647

  20. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism.

    Science.gov (United States)

    Tang, Zhiyuan; Wang, Xudong; Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie; Ni, Songshi

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.

  1. NONMETALS DEPOSITS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>20111761 Chen Hua(115 Geological Party,Guizhou Bureau of Geology and Mineral Exploration & Development,Guiyang 551400,China);Deng Chao Analysis on the Metallogenic Environment of Maochang Bauxite in Guizhou Province(Guizhou Geology,ISSN1000-5943,CN52-1059/P,27(3),2010,p.198-201,2 illus.,1 table,8 refs.)Key words:bauxite deposit,Guizhou Province By long time physical and chemical process,the carbonate rock after Central Guizhou uplidft,becomes red clay,after further weathering,the red clay decomposed into the oxide,hydroxide of Al and Fe,in the dissolution hole and depression,it concentrates primary fragmentary tight and earthy karst bauxite ore.Because the variation of landform,it decomposes and cracks again,affords the material source

  2. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  3. Pulmonary eosinophilia due to Trichomonas tenax.

    Science.gov (United States)

    El Kamel, A; Rouetbi, N; Chakroun, M; Battikh, M

    1996-05-01

    A 39 year old woman was admitted with fever and an exacerbation of asthma. The chest radiograph showed extensive bilateral lung infiltrates, but transtracheal needle aspiration did not reveal any infectious organisms. The bronchoalveolar fluid lavage contained a large number of Trichomonas tenax and an increased percentage of eosinophils. Corticosteroids provided a dramatic response. Because of the relatively high frequency of colonisation of the human mouth by T tenax (about 20%), this organism should be considered in all cases of pulmonary eosinophilia.

  4. Imaging in pulmonary hydatid cysts

    Institute of Scientific and Technical Information of China (English)

    Mandeep K Garg; Madhurima Sharma; Ajay Gulati; Ujjwal Gorsi; Ashutosh N Aggarwal; Ritesh Agarwal; Niranjan Khandelwal

    2016-01-01

    Hydatid disease is a zoonosis that can involve almost any organ in the human body. After the liver, the lungs are the most common site for hydatid disease in adults. Imaging plays a pivotal role in the diagnosis of the disease, as clinical features are often nonspecific. Classical radiological signs of pulmonary hydatid cysts have been described in the literature, aiding in the diagnosis of the disease. However, complicated hydatid cysts can prove to be a diagnostic challenge at times due to their atypical imaging features. Radiography is the initial imaging modality. Computed tomography can provide a specific diagnosis in complicated cases. Ultrasound is particularly useful in peripheral lung lesions. The role of magnetic resonance imaging largely remains unexplored.

  5. Canine pulmonary angiostrongylosis

    DEFF Research Database (Denmark)

    Koch, Jørgen; Willesen, Jakob Lundgren

    2009-01-01

    Canine pulmonary angiostrongylosis is an emerging snail-borne disease causing verminous pnemonia and coagulopathy in dogs. The parasite is fund in Europe, North and South America and Africa, covering tropical, subtropical and temperate regions. Its distribution has been characterised by isolated ...

  6. Primary Pulmonary Hodgkin Lymphoma

    OpenAIRE

    Shumaila Tanveer; Ahmed El Damati; Ayman El Baz; Ahmed Alsayyah; Tarek ElSharkawy; Mohamed Regal

    2015-01-01

    Primary pulmonary Hodgkin lymphoma (PPHL) is a rare disease. Herein, we report a case of PPHL with diagnostic concerns encountered during initial evaluation which is of paramount importance to keep the differential diagnosis in cases with high index of sus- picion for this rare entity.

  7. Solitary pulmonary nodule

    Science.gov (United States)

    ... Chest x-ray Granulomatosis with polyangiitis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Skin nodules Valley fever Review Date 8/1/2015 Updated by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, ... Cancer Lung Diseases Browse the Encyclopedia A.D.A. ...

  8. An unexpected pulmonary bystander

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, M.; Vorm, van der P. A.; Koning, K. J.; van der Werf, T. S.

    2016-01-01

    A 30-year-old man from Eritrea was admitted with a pulmonary bacterial abscess. Unexpectedly, histopathology of the resected lobe also revealed an infection with Schistosoma mansoni with surrounding granulomatous tissue and fibrosis. Patients from endemic areas are often asymptomatic with blood eosi

  9. What Is Pulmonary Hypertension?

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pulmonary Hypertension - High Blood Pressure in the Heart-to-Lung System Updated:Sep ... Pressure" This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  10. Pulmonary function tests

    Science.gov (United States)

    ... or lung disease. Some lung diseases (such as emphysema, asthma, chronic bronchitis, and infections) can make the lungs ... A.M. Editorial team. Related MedlinePlus Health Topics Asthma Breathing Problems COPD Emphysema Interstitial Lung Diseases Lung Diseases Pulmonary Fibrosis Sarcoidosis ...

  11. Hantavirus Pulmonary Syndrome