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Sample records for repeated intratracheal instillations

  1. Biodistribution of gold nanoparticles following intratracheal instillation in mouse lung

    DEFF Research Database (Denmark)

    Sadauskas, Evaldas; Jacobsen, Nicklas R.; Danscher, Gorm

    2009-01-01

    plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA). The liver is the major site of deposition of circulating gold nanoparticles. Therefore the degree of translocation was determined by the hepatic deposition of gold. Mice were instilled with 5 intratracheal doses of gold...... repeatedly during 3 weeks, the load was substantial. Ultrastructurally, AMG silver enhanced gold nanoparticles were found in lysosome-/endosome-like organelles of the macrophages and analysis with AMG, ICP-MS and NAA of the liver revealed an almost total lack of translocation of nanoparticles. In mice given...... repeated instillations of 2 nm gold nanoparticles, 1.4‰ (by ICP-MS) to 1.9‰ (by NAA) of the instilled gold was detected in the liver. With the 40 nm gold, no gold was detected in the liver (detection level 2 ng, 0.1‰) except for one mouse in which 3‰ of the instilled gold was found in the liver. No gold...

  2. Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

    Science.gov (United States)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

    Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

  3. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies

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    Yamamoto Kazuhiro

    2010-03-01

    Full Text Available Abstract Background We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs were examined in rat lungs in both studies. Results In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group. Conclusion These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

  4. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

    2015-11-15

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  5. Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    International Nuclear Information System (INIS)

    Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Hashiba, Masayoshi; Kambara, Tatsunori; Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami; Tomonaga, Taisuke; Myojo, Toshihiko; Yamamoto, Kazuhiro; Kitajima, Shinichi; Horie, Masanori; Kuroda, Etsushi; Morimoto, Yasuo

    2015-01-01

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO 2 ) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO 2 nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO 2 nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO 2 may not lead to chronic, irreversible legions in the lung, and that TiO 2 nanoparticles may not have a high potential for lung disorder

  6. Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Yukiko, E-mail: y-yoshiura@med.uoeh-u.ac.jp; Izumi, Hiroto [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Oyabu, Takako [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Hashiba, Masayoshi; Kambara, Tatsunori [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Tomonaga, Taisuke [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Myojo, Toshihiko [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Horie, Masanori [National Institute of Advanced Industrial Science and Technology (AIST), Health Research Institute (HRI) (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Morimoto, Yasuo [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan)

    2015-06-15

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO{sub 2}) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO{sub 2} may not lead to chronic, irreversible legions in the lung, and that TiO{sub 2} nanoparticles may not have a high potential for lung disorder.

  7. Long-term effects of intratracheally instilled 253EsCl3 in rats

    International Nuclear Information System (INIS)

    Ballou, J.E.; Dagle, G.E.; Morrow, W.

    1975-01-01

    ts administered 253 EsCl 3 by intratracheal instillation developed more bone tumors and fewer lung tumors than similar rats administered 239 Pu(NO 3 ) 4 . In explanation, it is suggested that 253 Es may irradiatete bone surface cells more effectively while 239 Pu may irradiate a greater total number of cells in the lung. (U.S.)

  8. Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung

    Directory of Open Access Journals (Sweden)

    Masanori Horie

    2016-01-01

    Full Text Available NiO nanoparticles were administered to rat lungs via intratracheal instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both intratracheal instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress. The oxidative stress response protein, heme oxygenase-1 (HO-1, was induced by the administration of NiO nanoparticles at both the protein and gene expression level. Additionally, certain oxidative-stress markers in the lung, such as 8-iso-prostaglandin F2α, thioredoxin, and inducible nitric oxide synthase were increased. Furthermore, the concentration of myeloperoxidase (MPO in the lung was also increased by the administration of NiO nanoparticles. When the amount of NiO in the lung is similar, the responses against pulmonary oxidative stress of intratracheal instillation and inhalation are also similar. However, the state of pulmonary oxidative stress in the early phase was different between intratracheal instillation and inhalation, even if the amount of NiO in the lung was similar. Inhalation causes milder oxidative stress than that caused by intratracheal instillation. On evaluation of the nanoparticle-induced pulmonary oxidative stress in the early phase, we should understand the different states of oxidative stress induced by intratracheal instillation and inhalation.

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

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    Chia-Feng Yang

    2010-08-01

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

  10. Effect of intratracheally instilled depleted uranium on immunological function of rats

    International Nuclear Information System (INIS)

    You Hanhu; Yang Zhihua; Cao Zhenshan; Zhu Maoxiang; Liu Xingrong

    2004-01-01

    Objective: To study immunological effects of depleted uranium in rats. Methods: Wistar rats were exposed to depleted uranium by single intratracheal instillation. Body weight and peripheral blood cells were measured weekly and immunological functions were evaluated by weight coefficient of immune organs, plague forming cells of splenocytes, total and subpopulation counts of lymphocytes in thymus. Results: Early after administration, body weight decreased and red blood cells as well as platelets reduced while white blood cells increased, which returned to normal within 1 or 2 months. Immunological functions of splenocytes and thymocytes were affected dose-dependently by depleted uranium. Conclusion: Depleted uranium induces immunological dysfunction in rats. (authors)

  11. Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

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    Angela Maria Rizzo

    Full Text Available Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

  12. Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs

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    Peters Annette

    2010-09-01

    Full Text Available Abstract Rationale Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR, a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg. Methods 250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter 2.5-AB collected from an urban background site in Augsburg during September and October 2006 (PM2.5 18.2 μg/m3, 10,802 particles/cm3 were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF, blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed. Results Exposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP during 2nd-4th day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg and reduced heart rate (HR on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm. BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2 from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1, renin-angiotensin system (angiotensin converting enzyme and also coagulation system (tissue factor, plasminogen activator inhibitor-1 in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected. Conclusions Our data suggests that high concentrations of PM2.5-AB

  13. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

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    Nalabotu SK

    2011-10-01

    Full Text Available Siva K Nalabotu1,2, Madhukar B Kolli1,2, William E Triest3,4, Jane Y Ma5, Nandini DPK Manne2,6, Anjaiah Katta1,2, Hari S Addagarla2, Kevin M Rice2,6–8, Eric R Blough1,2,6,7,91Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C Edwards School of Medicine; 2Center for Diagnostic Nanosystems, Marshall University; 3Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center; 4Section of Pathology, Department of Anatomy and Pathology, Joan C Edwards School of Medicine, Marshall University, Huntington; 5Health Effects Laboratory Division, NIOSH, Morgantown; 6Department of Biological Sciences; 7School of Kinesiology, College of Health Professions, Marshall University; 8Biotechnology Department, West Virginia State University; 9Department of Cardiology, Joan C Edwards School of Medicine, Marshall University Huntington, WV, USABackground: Cerium oxide (CeO2 nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05. Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight (P < 0.05 and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO2 nanoparticles.Conclusion: Taken together, these data suggest that

  14. Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation

    International Nuclear Information System (INIS)

    He Xiao; Zhang Haifeng; Ma Yuhui; Bai Wei; Zhang Zhiyong; Ding Yayun; Zhao Yuliang; Chai Zhifang; Lu Kai

    2010-01-01

    The broad potential applications of manufactured nanomaterials call for urgent assessment of their environmental and biological safety. However, most of the previous work focused on the cell level performance; little was known about the consequences of nanomaterial exposure at the whole-body and organ levels. In the present paper, the radiotracer technique was employed to study the pulmonary deposition and the translocation to secondary target organs after ceria nanoparticles (nano-ceria) were intratracheally instilled into Wistar rats. It was found that 63.9 ± 8.2% of the instilled nano-ceria remained in the lung by 28 d postexposure and the elimination half-life was 103 d. At the end of the test period, only 1/8-1/3 of the daily elimination of nano-ceria from the lung was cleared via the gastrointestinal tract, suggesting that phagocytosis by alveolar macrophages (AMs) with subsequent removal towards the larynx was no longer the predominant route for the elimination of nano-ceria from the lung. The whole-body redistribution of nano-ceria demonstrated that the deposited nano-ceria could penetrate through the alveolar wall into the systemic circulation and accumulate in the extrapulmonary organs. In vitro study suggested that nano-ceria would agglomerate and form sediments in the bronchoalveolar aqueous surrounding while binding to protein would be conducive to the redispersion of nano-ceria. The decrease in the size of agglomerates might enhance the penetration of nano-ceria into the systemic circulation. Our findings suggested that the effect of nanomaterial exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanomaterials.

  15. Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate.

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    Rudolphus, A.; Stolk, J.; van Twisk, C.; van Noorden, C. J.; Dijkman, J. H.; Kramps, J. A.

    1992-01-01

    Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase-specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5-nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN-elastase is involved in the development of LPS-mediated emphysema. Images Figure 1 Figure 2 Figure 3 PMID:1632460

  16. Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use.

    Science.gov (United States)

    Pirela, Sandra V; Lu, Xiaoyan; Miousse, Isabelle; Sisler, Jennifer D; Qian, Yong; Guo, Nancy; Koturbash, Igor; Castranova, Vincent; Thomas, Treye; Godleski, John; Demokritou, Philip

    2016-01-01

    Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use "real world" printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 ( Rantes ), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery ( Dnmt3a ) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects.

  17. Acute and subacute pulmonary toxicity caused by a single intratracheal instillation of colloidal silver nanoparticles in mice: pathobiological changes and metallothionein responses.

    Science.gov (United States)

    Kaewamatawong, Theerayuth; Banlunara, Wijit; Maneewattanapinyo, Pattwat; Thammachareon, Chuchaat; Ekgasit, Sanong

    2014-01-01

    To study the acute and subacute pulmonary toxicity of colloidal silver nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alterations were determined 1, 3, 7, 15, and 30 days after instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF indices during the acute period; however, these changes gradually regressed in a time-dependent manner. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. Superoxide dismutase and metallothionein expression occurred in particle-laden macrophages and alveolar epithelial cells, which correlated to lung lesions in mice treated with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient moderate acute lung inflammation and tissue damage. Oxidative stress may underlie the induction of injury to lung tissue. Moreover, the expression of metallothionein in tissues indicated the protective response to exposure to Ag-NPs.

  18. Lung clearance and disposition of 63Ni in F344/N rats after intratracheal instillation of nickel sulfate solutions

    International Nuclear Information System (INIS)

    Medinsky, M.A.; Benson, J.M.; Hobbs, C.H.

    1987-01-01

    Epidemiology studies have indicated increased incidences of respiratory tract and renal cancer in nickel refinery workers. Since the most likely route of exposure to nickel in the workplace is via the respiratory tract, the objectives of the experiments described here were to determine the retention pattern of Ni in the lungs, identify the target organs for Ni absorbed from the respiratory tract, and determine rates for excretion of Ni. Male and female F344 rats were given 17, 190, or 1800 nmoles Ni (as a nickel sulfate solution) in saline, containing trace amounts of 63 Ni, by intratracheal instillation. Urine and feces were collected, and rats were necropsied at predetermined times up to 96 hr after instillation. At all times, lungs, trachea, larynx, kidney, and urinary bladder contained the highest concentrations of Ni as determined by liquid scintillation spectrometry. Urine was the major route for excretion of Ni, accounting for 50% of the dose after instillation of 17 or 190 nmoles Ni, and 80% of the dose after instillation of 1800 nmoles Ni. The half-time for urinary excretion of Ni increased from 4.6 hr at the highest dose to 23 hr at the lowest dose used. Fecal excretion accounted for 30% (17- and 190-nmole doses) or 13% (1800 nmoles) of the initial dose. Of the Ni remaining in the body at the end of 96 hr, over 50% was in the lungs. The long-term half-time for clearance of Ni from the lungs ranged from 21 hr at the highest dose to 36 hr at the lowest dose instilled. As the amount of instilled Ni decreased, the fraction of the instilled Ni associated with the long-term clearance component increased (from 24% at the highest dose to 40% at the lowest dose). Results suggest that, over the range of doses studied, both pulmonary clearance of Ni and routes for excretion of Ni were dependent on the instilled dose

  19. Dose-dependent pulmonary response of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    International Nuclear Information System (INIS)

    Oyabu, Takako; Morimoto, Yasuo; Hirohashi, Masami; Horie, Masanori; Kambara, Tatsunori; Lee, Byeong Woo; Hashiba, Masayoshi; Mizuguchi, Yohei; Myojo, Toshihiko; Kuroda, Etsushi

    2013-01-01

    In order to investigate the relationship between pulmonary inflammation and particle clearance of nanoparticles, and also their dose dependency, we performed an instillation study of well-dispersed TiO 2 nanoparticles and examined the pulmonary inflammations, the particle clearance rate and histopathological changes. Wistar rats were intratracheally administered 0.1 mg (0.33 mg/kg), 0.2 mg (0.66 mg/kg), 1 mg (3.3 mg/kg), and 3 mg (10 mg/kg) of well-dispersed TiO 2 nanoparticles (diameter of agglomerates: 25 nm), and the pulmonary inflammation response and the amount of TiO 2 in the lung were determined from 3 days up to 12 months sequentially after the instillation. There were no increases of total cell or neutrophil counts in bronchoalveolar lavage fluid (BALF) in the 0.1 and the 0.2 mg-administered groups. On the other hand, mild infiltration of neutrophils was observed in the 1 and 3 mg-administered groups. Histopathological findings showed infiltration of neutrophils in the 1 and 3 mg-administered groups. Of special note, a granulomatous lesion including a local accumulation of TiO 2 was observed in the bronchioli-alveolar space in the 3 mg-administered group. The biological half times of the TiO 2 in the lung were 4.2, 4.4, 6.7, and 10.8 months in the 0.1, 0.2, 1, and 3 mg-administered groups, respectively. Neutrophil infiltration was observed as the particle clearance was delayed, suggesting that an excessive dose of TiO 2 nanoparticles may induce pulmonary inflammation and clearance delay.

  20. Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

    Science.gov (United States)

    Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

    2011-02-28

    3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Pulmonary Toxicity, Distribution, and Clearance of Intratracheally Instilled Silicon Nanowires in Rats

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts

    2012-01-01

    Full Text Available Silicon nanowires (Si NWs are being manufactured for use as sensors and transistors for circuit applications. The goal was to assess pulmonary toxicity and fate of Si NW using an in vivo experimental model. Male Sprague-Dawley rats were intratracheally instilled with 10, 25, 50, 100, or 250 μg of Si NW (~20–30 nm diameter; ~2–15 μm length. Lung damage and the pulmonary distribution and clearance of Si NW were assessed at 1, 3, 7, 28, and 91 days after-treatment. Si NW treatment resulted in dose-dependent increases in lung injury and inflammation that resolved over time. At day 91 after treatment with the highest doses, lung collagen was increased. Approximately 70% of deposited Si NW was cleared by 28 days with most of the Si NW localized exclusively in macrophages. In conclusion, Si NW induced transient lung toxicity which may be associated with an early rapid particle clearance; however, persistence of Si NW over time related to dose or wire length may lead to increased collagen deposition in the lung.

  2. Functional ability and fate of pulmonary alveolar macrophages after intratracheal instillation into rats

    International Nuclear Information System (INIS)

    Snipes, M.B.; Feddersen, D.; Mueller, H.L.; Guilmette, R.A.; Haley, P.J.

    1988-01-01

    Pulmonary alveolar macrophages (PAM) from donor rats were intratracheally instilled into recipient rats to determine if donor macrophages were functionally similar to the recipient's own macrophages. Recipient and donor (extrinsic) PAM were equivalent in their ability to phagocytize 1.7 μm and 3.9 μm latex microspheres in vivo and sensitized sheep red blood cells in vitro. Also, the extrinsic PAM appeared functionally equivalent to recipient PAM with respect to ability to translocate into interstitial tissue and migrate to the lung-associated lymph nodes (LALN). The recipient PAN appeared to phagocytize the extrinsic PAM, but the extrinsic PAM did not appear to phagocytize the recipient PAM. This could represent a different degree of physiological coordination of intrinsic and extrinsic PAM activities in the lung. Overall, results indicated that extrinsic PAM can live and function in the lungs of recipient rats, and perform most or all of the functions ascribed to recipient PAM. Results also support the hypothesis that PAM are able to move into the pulmonary interstitium and translocate to the LALM without the involvement of other pulmonary macrophages. (author)

  3. Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Hong, Young-Shick [Division of Food and Nutrition, Chonnam National University, Yongbong-Ro, Buk-Gu, Gwangju 500-757 (Korea, Republic of); Lee, Byoung-Seok [Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Jeong, Uiseok; Kim, Younghun [Department of Chemical Engineering, Kwangwoon University, Seoul 139-701 (Korea, Republic of)

    2016-07-15

    Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200 μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200 μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes and increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries. - Highlights: • We evaluated local and systemic health effects following persistence of SWCNTs. • SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation. • Th1-polarized immune response was induced in the lung. • The expression of antigen presentation-related proteins was altered. • Immune and metabolic regulation function were disturbed.

  4. Dose-dependent pulmonary response of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Oyabu, Takako [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Hirohashi, Masami; Horie, Masanori; Kambara, Tatsunori [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Occupational Pneumology (Japan); Lee, Byeong Woo [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Hashiba, Masayoshi [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Occupational Pneumology (Japan); Mizuguchi, Yohei; Myojo, Toshihiko [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan)

    2013-04-15

    In order to investigate the relationship between pulmonary inflammation and particle clearance of nanoparticles, and also their dose dependency, we performed an instillation study of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammations, the particle clearance rate and histopathological changes. Wistar rats were intratracheally administered 0.1 mg (0.33 mg/kg), 0.2 mg (0.66 mg/kg), 1 mg (3.3 mg/kg), and 3 mg (10 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (diameter of agglomerates: 25 nm), and the pulmonary inflammation response and the amount of TiO{sub 2} in the lung were determined from 3 days up to 12 months sequentially after the instillation. There were no increases of total cell or neutrophil counts in bronchoalveolar lavage fluid (BALF) in the 0.1 and the 0.2 mg-administered groups. On the other hand, mild infiltration of neutrophils was observed in the 1 and 3 mg-administered groups. Histopathological findings showed infiltration of neutrophils in the 1 and 3 mg-administered groups. Of special note, a granulomatous lesion including a local accumulation of TiO{sub 2} was observed in the bronchioli-alveolar space in the 3 mg-administered group. The biological half times of the TiO{sub 2} in the lung were 4.2, 4.4, 6.7, and 10.8 months in the 0.1, 0.2, 1, and 3 mg-administered groups, respectively. Neutrophil infiltration was observed as the particle clearance was delayed, suggesting that an excessive dose of TiO{sub 2} nanoparticles may induce pulmonary inflammation and clearance delay.

  5. Cardiovascular effects in rats after intratracheal instillation of metal welding particles.

    Science.gov (United States)

    Zheng, Wen; Antonini, James M; Lin, Yen-Chang; Roberts, Jenny R; Kashon, Michael L; Castranova, Vincent; Kan, Hong

    2015-01-01

    Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max) at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

  6. Correlation of the octanol/water partition coefficient with clearance halftimes of intratracheally instilled aromatic hydrocarbons in rats

    International Nuclear Information System (INIS)

    Bond, J.A.; Baker, S.M.; Bechtold, W.E.

    1985-01-01

    Studies on the lung retention of polycyclic aromatic hydrocarbons (PAH) after inhalation have indicated that, in general, the PAH are rapidly cleared from the respiratory tract. Clearance of the PAH from the lungs is best described as bi-phasic, with the long-term component of the clearance curve having a half-time of greater than 24 h. The purpose of this study was to determine whether a relationship exists between the lipophilicity (as measured by the octanol/water partition coefficient, P) of various PAH and the short-term and long-term clearance half-times of PAH in rat lungs. Female F344/Crl rats were administered intratracheally 1 nmol of 14 C-labelled anthracene (AN), benz (a) anthracene (BA), 1-nitropyrene (NP), 6-nitrobenzo (a) pyrene (6-NBP), or dibenzo (c, g) carbazole (DBC). At various times after instillation rats were sacrificed and the amount of 14 C from rat lungs following instillation of the different PAH was biphasic. In all cases, greater than 85% of the initial dose instilled was cleared with a half-time of less than 1 h. The half-times for clearance of the residual 14 C (1-15% of the dose) were 26, 30, 36, 53 and 63 h for AN, NP, 6-NBP, BA and DCB, respectively. The log of the octanol-water partition coefficients for the different PAH examined ranged from 4.1 (AN) to 6.05 (DBC). Plots of the octanol/water coefficients vs. the long-term clearance half-time for the PAH indicated a linear correlation (p 2 =0.96). The results from this study indicate that the greater the lipophilicity of the PAH, the slower the long-term clearance of a small fraction (1-15%) of PAH from rat lungs. These data suggest that predictions of long-term lung clearance can be made for PAH with log octanol-water partition coefficients between 4 and 6. (author)

  7. ACCUMULATION AND TISSUE DISPOSITION OF PARTICLE ASSOCIATED ELEMENTS IN THE RAT AFTER REPEATED INTRATRACHAEL ADMINISTRATION OF SOURCE PARTICLES

    Science.gov (United States)

    The goal of this study was to determine the fate of source particle tracer elements following repeated intratracheal instillation (IT) to rats. PM samples comprised Mt. St. Helens ash (MSH) with no water-soluble metals, and oil flyash emission PM (EPM) with water-leachable solubl...

  8. Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice

    DEFF Research Database (Denmark)

    Husain, Mainul; Wu, Dongmei; Saber, Anne T.

    2015-01-01

    translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 mu g of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed...... of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following...... at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early...

  9. Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

    Energy Technology Data Exchange (ETDEWEB)

    Becak DP, Holland NA; Shannahan, Jonathan H.

    2015-01-01

    Background: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been previously reported. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of other nanomaterials. We hypothesized that pulmonary exposure to Ag core AgNP induces persistent increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and associated with altered coronary vessel reactivity. Methods: Male Sprague-Dawley rats were exposed to 200 µg of 20 nm citrate capped Ag core AgNP, or a citrate vehicle intratracheally (IT). One and 7 days following IT instillation lungs were evaluated for inflammation and silver presence, serum was analyzed for concentrations of selected cytokines, and cardiac I/R injury and coronary artery reactivity was assessed. Results: AgNP instillation resulted in modest pulmonary injury with detection of silver in lung tissue and infiltrating cells, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Seven days post IT instillation was associated with persistent detection of silver in lungs, elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. Conclusions: Based on these data, IT instillation of AgNP increases circulating levels of several cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.

  10. Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide

    DEFF Research Database (Denmark)

    Christophersen, Daniel Vest; Jacobsen, Nicklas Raun; Jensen, Ditte Marie

    2016-01-01

    Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular.......5% plasma extracted from CB-exposed ApoE-/- mice caused vasoconstriction in aorta rings isolated from naive mice; this effect was abolished by the treatment with the serotonin receptor antagonist Ketanserin. In conclusion, repeated pulmonary exposure to nanosized CB and LPS caused lung inflammation without...

  11. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    DEFF Research Database (Denmark)

    Husain, Mainul; Saber, Anne Thoustrup; Guo, Charles

    2013-01-01

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano-TiO2 via single intratracheal instillations of 18, 54, and 162......μg/mouse. Mice were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific q...

  12. Chronic intratracheal application of the soluble guanylyl cyclase stimulator BAY 41-8543 ameliorates experimental pulmonary hypertension.

    Science.gov (United States)

    Amirjanians, Matthieu; Egemnazarov, Bakytbek; Sydykov, Akylbek; Kojonazarov, Baktybek; Brandes, Ralf; Luitel, Himal; Pradhan, Kabita; Stasch, Johannes-Peter; Redlich, Gorden; Weissmann, Norbert; Grimminger, Friedrich; Seeger, Werner; Ghofrani, Hossein; Schermuly, Ralph

    2017-05-02

    Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats. Four weeks after a single injection of monocrotaline (MCT, 60 mg/kg s.c.), rats were randomized to a two-week treatment with either placebo, BAY 41-8543 (10 mg/kg per os (PO)) or intra-tracheal (IT) instillation (3 mg/kg or 1 mg/kg).Circulating concentrations of the drug 10 mg/kg PO and 3 mg/kg IT were comparable. BAY 41-8543 was detected in the lung tissue and broncho-alveolar fluid after IT delivery at higher concentrations than after PO administration. Systemic arterial pressure transiently decreased after oral BAY 41-8543 and was unaffected by intratracheal instillation of the drug. PO 10 mg/kg and IT 3 mg/kg regimens partially reversed pulmonary hypertension and improved heart function in MCT-injected rats. Minor efficacy was noted in rats treated IT with 1 mg/kg. The degree of pulmonary vascular remodeling was largely reversed in all treatment groups.Intratracheal administration of BAY 41-8543 reverses PAH and vascular structural remodeling in MCT-treated rats. Local lung delivery is not associated with systemic blood pressure lowering and represents thus a further development of PH treatment with sGC stimulators.

  13. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    DEFF Research Database (Denmark)

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Zenner

    2011-01-01

    cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation...... and lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring....

  14. Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice

    DEFF Research Database (Denmark)

    Roursgaard, Martin; Jensen, Keld A; Poulsen, Steen Seier

    2011-01-01

    This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compo...

  15. The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

    Directory of Open Access Journals (Sweden)

    Nemmar A

    2017-04-01

    Full Text Available Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Al-Khod, Sultanate of Oman Abstract: Cerium oxide nanoparticles (CeO2 NPs, used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours effect of intratracheal (IT instillation of either CeO2 NPs (0.1 or 0.5 mg/kg or saline (control on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice. CeO2 NPs induced a significant increase of neutrophils into the bronchoalveolar lavage (BAL fluid with an elevation of tumor necrosis factor α (TNFα and a decrease in the activity of the antioxidant catalase. Lung sections of mice exposed to CeO2 NPs showed a dose-dependent infiltration of inflammatory cells consisting of macrophages and neutrophils. Similarly, the plasma levels of C-reactive protein and TNFα were significantly increased, whereas the activities of catalase and total antioxidant were significantly decreased. Interestingly, CeO2 NPs significantly and dose dependently induced a shortening of the thrombotic occlusion time in pial arterioles and venules. Moreover, the plasma concentrations of fibrinogen and plasminogen activator inhibitor-1 were significantly elevated by CeO2 NPs. The direct addition of CeO2 NPs (1, 5, or 25 µg/mL to mouse whole blood, collected from the inferior vena cava, in vitro neither caused significant platelet aggregation nor affected prothrombin time or partial

  16. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    International Nuclear Information System (INIS)

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-01-01

    Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte–macrophage colony stimulating factor (GM-CSF), an upregulator of PPARγ. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPARγ plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPARγ or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

  17. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  18. Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant.

    Science.gov (United States)

    Porter, D W; Castranova, V; Robinson, V A; Hubbs, A F; Mercer, R R; Scabilloni, J; Goldsmith, T; Schwegler-Berry, D; Battelli, L; Washko, R; Burkhart, J; Piacitelli, C; Whitmer, M; Jones, W

    1999-05-14

    Several cases of interstitial lung disease have been diagnosed among workers at a nylon flock plant, but the etiologic agent for the disease outbreak was unknown. The results of a medical survey and industrial hygiene study indicated that the dust present in the plant may be responsible. Thus, airborne dust collected at the plant was examined for its inflammatory potential in rat lungs. The endpoints measured were: (1) breathing rates, (2) differential cell counts of bronchoalveolar lavage cells, (3) alveolar macrophage (AM) chemiluminescence, (4) albumin concentration and matrix metalloprotease activities in the acellular fluid from the initial bronchoalveolar lavage, and (5) pulmonary histopathology. In the first study, rats received a single dose of the airborne dust sample (10 mg/kg body weight) by intratracheal (IT) instillation. At 1 d post-IT, all inflammatory endpoints were significantly increased versus controls, but by 29 d post-IT they did not differ significantly from controls. Histopathology demonstrated mild to moderate, multifocal, suppurative pneumonia, usually centered around bronchioles, at 1 d post-IT. At 29 d post-IT, pulmonary inflammation was minimal to mild and characterized by alveolar histocytosis usually restricted to the immediate area of retained bire-fringent fibers. In subsequent experiments, airborne dust was extracted with water and the dust (washed airborne dust) and water extract (soluble fraction) were separated by centrifugation for further study. Nylon tow dust was prepared in the laboratory by milling uncut nylon strands (called tow) that had not been treated with the finish or dyes that are commonly used in the flock plants. Rats were administered a single dose of a dust sample (10 mg/kg body weight) or the soluble fraction (1.3 ml/kg body weight) by IT administration and the same endpoints were measured at 1 d post-IT. The dust samples caused significant increases in all of the inflammatory endpoints; however, the soluble

  19. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    International Nuclear Information System (INIS)

    Husain, Mainul; Saber, Anne T.; Guo, Charles; Jacobsen, Nicklas R.; Jensen, Keld A.; Yauk, Carole L.; Williams, Andrew; Vogel, Ulla; Wallin, Hakan; Halappanavar, Sabina

    2013-01-01

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO 2 ). Female C57BL/6 mice were exposed to rutile nano-TiO 2 via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO 2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO 2 in the lungs up to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p 2 in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO 2 were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose group

  20. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  1. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    Directory of Open Access Journals (Sweden)

    Milena V. Oliveira

    2016-10-01

    Full Text Available Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking the changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across 2 groups. Emphysema (ELA animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU with a 1-week interval between them. Controls (C received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma was increased compared to C (p = 0.0001. The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p=0.0197. Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways were increased, whereas static lung elastance was reduced compared to C (p=0.0094. After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1beta, keratinocyte-derived chemokine, hepatocyte growth factor, and vascular endothelial growth factor; and collagen fiber content in the pulmonary vessel wall were increased compared to C (p=0.0096. At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during controlled

  2. In vivo study with quartz-containing ceramic dusts: Inflammatory effects of two factory samples in lungs after intratracheal instillation in a 28-day study with rats

    Energy Technology Data Exchange (ETDEWEB)

    Creutzenberg, O; Ziemann, C; Hansen, T; Ernst, H [Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover (Germany); Jackson, P; Cartlidge, D [CERAM Research Ltd., Stoke-on-Trent (United Kingdom); Brown, R, E-mail: otto.creutzenberg@item.fraunhofer.d [TOXSERVICES, Stretton (United Kingdom)

    2009-02-01

    As various quartz polymorphs react differently in lungs, a differentiation of effects is needed while setting occupational exposure levels. The objective of this European Collective Research Project SILICERAM was to characterize differences in biological activity of four quartz species, i.) 2 quartz-containing materials collected at typical ceramic manufacturing sites (Tableware granulate, TG and Tableware cast, TC) versus ii.) a designed ceramic dust sample (Contrived Sample, CS) and iii.) ground quartz DQ12 (well-characterised standard quartz (Positive Control, PC) and TiO{sub 2} (negative control). TG and TC had been selected as the most promising two candidates based on a preceding in vitro screening of 5 factory samples. Total doses of 5 mg per rat of the TG and TC, 1.1 mg of the CS and 0.33 mg of the PC corresponding to 0.29, 0.16, 0.29 and 0.29 mg quartz per rat, respectively, were administered to rats by intratracheal instillation. After 3 days, bronchoalveolar lavagate (BAL) analysis resulted in polymorphonuclear neutrophil (PMN) levels of 15%, 25%, 0.6% and 25% in the TG, TC, CS and PC groups, respectively. At 28 days, the values were 29%, 20%, 7% and 45%. Histopathologically, the TG and TC groups showed very slight to slight effects, the PC group, however, stronger effects after the same period. In conclusion, the following ranking was found: PC > TG > TC > CS > TiO{sub 2} > Vehicle Control. Thus, a clear differentiation of effects for TG and TC, CS and PC was found. From a regulatory point of view, the substance-specific toxic potentials of TG and TC may need to be considered when devising occupational exposure limits.

  3. Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

    Science.gov (United States)

    Luo, Guanpingsheng; Gebremariam, Teclegiorgis; Lee, Hongkyu; French, Samuel W.; Wiederhold, Nathan P.; Patterson, Thomas F.; Filler, Scott G.

    2013-01-01

    Mucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation of Mucorales spores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates of Mucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threatening Mucorales infections. PMID:23650163

  4. Determination of the Tissue Distribution and Excretion by Accelerator Mass Spectrometry of the Nonadecapeptide 14C-Moli1901 in Beagle dogs after Intratracheal Instillation

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, D E; Dingley, K H; Ubick, E; Dix, K J; Molina, L

    2004-07-02

    Administration of {sup 14}C-Moli1901 (duramycin, 2622U90), a 19 amino acid polycyclic peptide by intratracheal instillation (approximately 100 {micro}g) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. In this study, we used accelerator mass spectrometry (AMS) to quantify Moli901 following administration of only 0.045 {micro}Ci of {sup 14}C-Moli901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Whole blood and plasma concentrations of {sup 14}C were <5ng/ml at all times after the dose. Concentrations of {sup 14}C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of {sup 14}C in whole blood, but after that time, plasma accounted for only 25-30% of the {sup 14}C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using {sup 14}C-Moli1901 and AMS.

  5. Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices

    International Nuclear Information System (INIS)

    Giri, S.N.

    1987-01-01

    Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of [ 14 C] acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on [ 14 C] acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of [ 14 C] acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production

  6. Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

    Directory of Open Access Journals (Sweden)

    Alexandre Robbe

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.

  7. Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles

    International Nuclear Information System (INIS)

    Wang Jiangxue; Liu Ying; Jiao Fang; Lao Fang; Li Wei; Gu Yiqun; Li Yufeng; Ge Cuicui; Zhou Guoqiang; Li Bai; Zhao Yuliang; Chai Zhifang; Chen Chunying

    2008-01-01

    Nanoparticles can be administered via nasal, oral, intraocular, intratracheal (pulmonary toxicity), tail vein and other routes. Here, we focus on the time-dependent translocation and potential damage of TiO 2 nanoparticles on central nervous system (CNS) through intranasal instillation. Size and structural properties are important to assess biological effects of TiO 2 nanoparticles. In present study, female mice were intranasally instilled with two types of well-characterized TiO 2 nanoparticles (i.e. 80 nm, rutile and 155 nm, anatase; purity > 99%) every other day. Pure water instilled mice were served as controls. The brain tissues were collected and evaluated for accumulation and distribution of TiO 2 , histopathology, oxidative stress, and inflammatory markers at post-instillation time points of 2, 10, 20 and 30 days. The titanium contents in the sub-brain regions including olfactory bulb, cerebral cortex, hippocampus, and cerebellum were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that the instilled TiO 2 directly entered the brain through olfactory bulb in the whole exposure period, especially deposited in the hippocampus region. After exposure for 30 days, the pathological changes were observed in the hippocampus and olfactory bulb using Nissl staining and transmission electron microscope. The oxidative damage expressed as lipid peroxidation increased significantly, in particular in the exposed group of anatase TiO 2 particles at 30 days postexposure. Exposure to anatase TiO 2 particles also produced higher inflammation responses, in association with the significantly increased tumor necrosis factor alpha (TNF-α) and interleukin (IL-1β) levels. We conclude that subtle differences in responses to anatase TiO 2 particles versus the rutile ones could be related to crystal structure. Thus, based on these results, rutile ultrafine-TiO 2 particles are expected to have a little lower risk potential for producing adverse

  8. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Husain, Mainul, E-mail: mainul.husain@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Saber, Anne T., E-mail: ats@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Guo, Charles, E-mail: charles.guo@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Jensen, Keld A., E-mail: kaj@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Vogel, Ulla, E-mail: ubv@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby DK-2800 (Denmark); Wallin, Hakan, E-mail: hwa@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Institute of Public Health, University of Copenhagen, Copenhagen DK-1014 (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada)

    2013-06-15

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO{sub 2}). Female C57BL/6 mice were exposed to rutile nano-TiO{sub 2} via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO{sub 2} in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO{sub 2} in the lungs up to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p < 0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO{sub 2} in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO{sub 2} were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose

  9. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

    Christiansen, Karen J; Moeslund, Niels; Lauridsen, Henrik

    2017-01-01

    . The device consisted of an intratracheal silicone seal disc fixated by a cord through the stoma to an external part. At day 14, computed tomography (CT) was performed before the device was extracted. With the pulling of a cord, the disc unraveled into a thin thread and was extracted through the stoma. At day...

  10. Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation

    International Nuclear Information System (INIS)

    Husain, Mainul; Kyjovska, Zdenka O.; Bourdon-Lacombe, Julie; Saber, Anne T.; Jensen, Keld A.; Jacobsen, Nicklas R.; Williams, Andrew; Wallin, Håkan; Halappanavar, Sabina; Vogel, Ulla; Yauk, Carole L.

    2015-01-01

    Inhalation of carbon black nanoparticles (CBNPs) causes pulmonary inflammation; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 mice were intratracheally instilled with 162 μg CBNPs alongside vehicle controls. Lung tissues were examined 3 h, and 1, 2, 3, 4, 5, 14, and 42 days (d) post-exposure. Global gene expression and pulmonary inflammation were assessed. DNA damage was evaluated in bronchoalveolar lavage (BAL) cells and lung tissue using the comet assay. Increased neutrophil influx was observed at all time-points. DNA strand breaks were increased in BAL cells 3 h post-exposure, and in lung tissues 2–5 d post-exposure. Approximately 2600 genes were differentially expressed (± 1.5 fold; p ≤ 0.05) across all time-points in the lungs of exposed mice. Altered transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3 h post-exposure declining to base-levels by 3 d, increasing again at 14 d, and then persisting to 42 d post-exposure. Thus, this single CBNP exposure that was equivalent to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42 d post-exposure, raising concern over the chronic effects of CBNP exposure. - Highlights: • A single exposure to CBNPs induced expression changes in over 2600 genes in mouse lungs. • Altered genes were associated with immune-inflammatory and acute phase responses. • Several genes were involved in DNA

  11. Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Husain, Mainul, E-mail: mainul.husain@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON (Canada); Kyjovska, Zdenka O., E-mail: zky@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Bourdon-Lacombe, Julie, E-mail: julie.bourdon-lacombe@hc-sc.gc.ca [Water and Air Quality Bureau, Safe Environments Directorate, HECSB, Health Canada, Ottawa, ON (Canada); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Jensen, Keld A., E-mail: kaj@arbejdsmiljoforskning.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Institute of Public Health, University of Copenhagen (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen (Denmark); Institute of Micro- and Nanotechnology, Technical University of Denmark, Lyngby (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON (Canada)

    2015-12-15

    Inhalation of carbon black nanoparticles (CBNPs) causes pulmonary inflammation; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 mice were intratracheally instilled with 162 μg CBNPs alongside vehicle controls. Lung tissues were examined 3 h, and 1, 2, 3, 4, 5, 14, and 42 days (d) post-exposure. Global gene expression and pulmonary inflammation were assessed. DNA damage was evaluated in bronchoalveolar lavage (BAL) cells and lung tissue using the comet assay. Increased neutrophil influx was observed at all time-points. DNA strand breaks were increased in BAL cells 3 h post-exposure, and in lung tissues 2–5 d post-exposure. Approximately 2600 genes were differentially expressed (± 1.5 fold; p ≤ 0.05) across all time-points in the lungs of exposed mice. Altered transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3 h post-exposure declining to base-levels by 3 d, increasing again at 14 d, and then persisting to 42 d post-exposure. Thus, this single CBNP exposure that was equivalent to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42 d post-exposure, raising concern over the chronic effects of CBNP exposure. - Highlights: • A single exposure to CBNPs induced expression changes in over 2600 genes in mouse lungs. • Altered genes were associated with immune-inflammatory and acute phase responses. • Several genes were involved in DNA

  12. Biological effects of nano-nickel in rat lungs after administration by inhalation and by intratracheal instillation

    International Nuclear Information System (INIS)

    Ogami, A; Morimoto, Y; Murakami, M; Myojo, T; Oyabu, T; Tanaka, I

    2009-01-01

    We examined the biological effects of the nickel oxide (NiO) nanoparticles by inhalation and instillation study. Wistar male rats were exposed to NiO nanoparticles (nNiOs) for 4 weeks (6 hrs/day). The nNiOs was black-colored NiO (99.8%) and average particle size (APS) was 20 nm. The geometric mean diameter of the particles in the chamber and the daily average exposure concentration were 139 ± 12 nm and 1.0 ± 0.5 x 105 particles/cc, respectively. The deposited amount of nNiOs in the rat lungs at 4 days after the inhalation exposure ended was 29 ± 4 μg. Although nNiOs exposure group showed temporal significant increase in the number of total cells in brochoalveolar lavage fluid (BALF) at 4 days after the exposure end, the difference were not seen at one month after an exposure end compared with control group. The histopathological change was not severe just after the inhalation nor throughout the observation time. Elemental mappings of nickel showed that nickel particles were located in agglomeration at the pulmonary macrophages.

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

    Science.gov (United States)

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

    2016-03-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    Science.gov (United States)

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  15. Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.

    Science.gov (United States)

    Park, Eun-Jung; Choi, Je; Kim, Jae-Ho; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-10-01

    Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs.

  16. The cardioprotective effect of vanillic acid on hemodynamic parameters, malondialdehyde, and infarct size in ischemia-reperfusion isolated rat heart exposed to PM10

    Directory of Open Access Journals (Sweden)

    Esmat Radmanesh

    2017-07-01

    Full Text Available Objective(s: Particulate matter (PM exposure can promote cardiac ischemia and myocardial damage. The effects of PM10 on hemodynamic parameters, lipid peroxidation, and infarct size induced by ischemia-reperfusion injury and the protective effects of vanillic acid (VA in isolated rat heart were investigated. Materials and Methods: Eighty male Wistar rats (250–300 g were divided into 8 groups (n=10: Control, Sham, VAc, VA, PMa (0.5 mg/kg PM, intratracheal instillation, PMb (2.5 mg/kg PM, intratracheal instillation, PMc (5 mg/kg PM, intratracheal instillation, and PMc + VA (5 mg/kg PM, intratracheal instillation; and 10 mg/kg vanillic acid, gavage for 10 days. PM10 was instilled into the trachea in two stages, within 48 hr. After isolating the hearts and transfer to a Langendorff apparatus, hearts were subjected to 30 min ischemia and 60 min reperfusion. Hemodynamic parameters (±dp/dt, LVSP, LVDP, and RPP, production of lipid peroxidation (MDA, and infarct size were assessed. Results: A significant decrease in ±dp/dt, LVSP, LVDP and RPP occurred in PM groups. A significant increase in MDA and myocardial infarct size occurred in PM groups. A significant increase in LVDP, LVSP, ±dp/dt, RPP and decrease in infarct size, MDA, and myocardial dysfunction was observed in groups that received vanillic acid after ischemia–reperfusion. Conclusion: It was demonstrated that PM10 increases MDA, as well as the percentage of cardiac infarct size, and has negative effects on hemodynamic parameters. This study suggests that vanillic acid may serve as an adjunctive treatment in delaying the progression of ischemic heart disease.

  17. Toxicological effects of multi-wall carbon nanotubes in rats

    International Nuclear Information System (INIS)

    Liu Aihong; Sun Kangning; Yang, Jiafeng; Zhao Dongmei

    2008-01-01

    The aim of this study was to evaluate the lung toxicity of multi-wall carbon nanotubes (MWCNTs). The present work exposed MWCNTs into the rats in intratracheal instillation administration modes. We systematically studied the distribution of nanoparticles in vivo, target organs and time-effects of nanotoxicity, dose-effects of nanotoxicity, etc. These results indicate that under the conditions of this test, pulmonary exposures to MWCNTs in rats by intratracheal instillation produced a series of multiple lesions in a dose-dependent and time-dependent manner, evidence of a foreign tissue body reaction.

  18. Toxicological effects of multi-wall carbon nanotubes in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu Aihong; Sun Kangning, E-mail: Sunkangning@sdu.edu.cn; Yang, Jiafeng [Engineering Ceramics Key Laboratory of Shandong Province, Material Science and Engineering Institute, Shandong University, Key Laboratory of Liquid Structure and Heredity of Materials ministry of Education (China); Zhao Dongmei [The Second Hospital of Shandong University (China)

    2008-12-15

    The aim of this study was to evaluate the lung toxicity of multi-wall carbon nanotubes (MWCNTs). The present work exposed MWCNTs into the rats in intratracheal instillation administration modes. We systematically studied the distribution of nanoparticles in vivo, target organs and time-effects of nanotoxicity, dose-effects of nanotoxicity, etc. These results indicate that under the conditions of this test, pulmonary exposures to MWCNTs in rats by intratracheal instillation produced a series of multiple lesions in a dose-dependent and time-dependent manner, evidence of a foreign tissue body reaction.

  19. Formation of DNA adducts in mouse tissues after 1-nitropyrene administration

    International Nuclear Information System (INIS)

    Mitchell, C.E.

    1986-01-01

    DNA adducts were isolated and characterized in mouse lung, liver and kidney after intratracheal instillation of [ 3 H]-1-nitropyrene (1-NP). HPLC analysis of the enzymatically digested DNA indicated the presence of multiple DNA adducts in mouse lung, liver and kidney. These results indicate that DNA adducts of 1-NP are formed in mouse lung, liver and kidney after intratracheal instillation of 1-NP; the HPLC profiles of the multiple adducts suggests that adducts may be formed via metabolic pathways that involve both nitroreduction and ring-oxidation. 6 references, 1 figure

  20. An Experimental Protocol for Maternal Pulmonary Exposure in Developmental Toxicology

    DEFF Research Database (Denmark)

    Jackson, Petra; Lund, Søren P.; Kristiansen, Gitte

    2011-01-01

    To establish a protocol for studying effects of pulmonary exposure in developmental toxicity studies, the effects of intratracheal sham instillation under short-term isoflurane anaesthesia were evaluated with a protocol including multiple instillations during gestation. Twelve time-mated mice (C5...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  2. Topical medication instillation techniques for glaucoma.

    Science.gov (United States)

    Xu, Li; Wang, Xuemei; Wu, Meijing

    2017-02-20

    Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops. To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication. Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane. We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We

  3. Late effects of inhaled 253Es(NO3)3 in rats

    International Nuclear Information System (INIS)

    Ballou, J.E.; Dagle, G.E.; Gies, R.A.; Smith, L.G.

    1979-01-01

    Einsteinium-253 nitrate was administered as an aerosol to male Wistar rats and the long-term biological effects were followed for the animals' life span. Lung was the major target organ for absorbed radiation dose and tumor induction, in agreement with results for other inhaled transuranic nitrates. The earlier finding of a high incidence of bone tumors following intratracheal instillation of 253 EsCl 3 was not confirmed in the present study with inhaled 253 Es(NO 3 ) 3 . The reason for the difference in bone tumor production is believed to be related to the different acute toxicities of intratracheally instilled and inhaled 253 Es. Intratracheally instilled 253 EsCl 3 was less acutely toxic (only a single lobe or one-half the lung was irradiated); thus, a larger more tumorigenic dose could be translocated to bone without shortening the life span to the extent that bone tumors could not be expressed. The radiation dose from inhaled 253 Es(NO 3 ) 3 was uniformly spread throughout both lungs and early death due to a generalized radiation pneumonitis precluded the development of long-term effects in bone. (author)

  4. Can vacuum-assisted closure and instillation therapy (VAC-Instill therapy) play a role in the treatment of the infected open abdomen?

    Science.gov (United States)

    D'Hondt, M; D'Haeninck, A; Dedrye, L; Penninckx, F; Aerts, R

    2011-03-01

    Severe superimposed infection during open abdomen treatment with development of intra-abdominal sepsis is a challenging complication associated with high mortality rates. We report our experience with VAC-Instill therapy (KCI, San Antonio, USA) used for treatment of an infected open abdomen following pancreatic surgery. A literature search revealed no analogous case reports using VAC-Instill therapy for treatment of an infected laparostomy. The encouraging result of the case presented seems to indicate that VAC-Instill therapy could be used as adjunctive treatment in the management of the infected open abdomen when traditional therapy fails to control the infection.

  5. Intratracheal administration of bacterial lipopolysaccharide elicits pulmonary hypertension in broilers with primed airways.

    Science.gov (United States)

    Lorenzoni, A G; Wideman, R F

    2008-04-01

    Broilers reared under commercial conditions inhale irritant gases and aerosolized particulates contaminated with gram-negative bacteria and bacterial lipopolysaccharide (LPS). Previous studies demonstrated that i.v. injections of LPS can trigger an increase in the pulmonary arterial pressure (PAP); however, the pulmonary hemodynamic response to aerosolized LPS entering via the most common route, the respiratory tract, had not been evaluated in broilers. In experiment 1, broilers reared on new wood shavings litter in clean environmental chambers either were not pretreated (control group) or were pretreated via aerosol inhalation of substances (food color dyes and propylene glycol) known to sensitize the airways. One day later, the broilers were anesthetized, catheterized to record the PAP, and an intratracheal aerosol spray of LPS (1 mL of 2 mg/mL of LPS) was administered. Broilers in the control group as well as broilers pretreated with aerosolized distilled water or yellow and blue food color dyes did not develop pulmonary hypertension (PH; an increase in PAP) after the intratracheal spray of LPS, whereas broilers that had been pretreated with red food color did develop PH in response to intratracheal LPS. In experiment 2, birds raised under commercial conditions on used wood shavings litter developed PH in response to intratracheal LPS regardless of whether they had been pretreated with aerosolized red food color dye. In experiment 3, broilers reared in clean environmental chambers on new wood shavings litter were used to demonstrate that Red Dye #3 and propylene glycol are capable of priming the responsiveness of the airways to a subsequent intratracheal LPS challenge. Common air contaminants such as LPS can result in PH leading to pulmonary hypertension syndrome (ascites) in broilers with appropriately primed airways.

  6. Evaluating Eye Drop Instillation Technique and Its Determinants in Glaucoma Patients

    Directory of Open Access Journals (Sweden)

    Xinbo Gao

    2018-01-01

    Full Text Available Aim. To evaluate eye drop instillation technique and to explore its determinants in glaucoma patients. Methods. One hundred and thirteen patients diagnosed with glaucoma and self-administering topical antiglaucoma eye drops for at least 1 month were evaluated. All patients instilled artificial tear solution in one eye as they would do at home. The whole process was evaluated by two study staff. A comprehensive score system associated with eye drop instillation techniques was used to quantify the instillation technique and explore its determinants such as demographic and clinical characteristics. Results. Half of the patients (48.67% finished the administration of eye drop on first attempt.1.7 eye drops were squeezed out on average. 43 patients (37.17% got contact with ocular surface or adnexa. Only 19.7% patients had eye drop instillation techniques being defined as well. 11 patients (9.7% had prior instruction regarding using eye drops, while only 4 patients knew to occlude the tear duct by pressing the dacryocyst area. Older age and worse visual acuity were found to be independent risk factors for worse instillation technique. Conclusions. Eye drop instillation technique in glaucoma patients deserves great attention from eye care practitioners during their lifelong follow-up, especially those aged older and have worse visual acuity.

  7. Single Silver Nanoparticle Instillation Induced Early and Persisting Moderate Cortical Damage in Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Elisa Roda

    2017-10-01

    Full Text Available The potential toxic effects of silver nanoparticles (AgNPs, administered by a single intratracheal instillation (i.t, was assessed in a rat model using commercial physico-chemical characterized nanosilver. Histopathological changes, overall toxic response and oxidative stress (kidney and plasma protein carbonylation, paralleled by ultrastructural observations (TEM, were evaluated to examine renal responses 7 and 28 days after i.t. application of a low AgNP dose (50 µg/rat, compared to an equivalent dose of ionic silver (7 µg AgNO3/rat. The AgNPs caused moderate renal histopathological and ultrastructural alteration, in a region-specific manner, being the cortex the most affected area. Notably, the bulk AgNO3, caused similar adverse effects with a slightly more marked extent, also triggering apoptotic phenomena. Specifically, 7 days after exposure to both AgNPs and AgNO3, dilatation of the intercapillary and peripheral Bowman’s space was observed, together with glomerular shrinkage. At day 28, these effects still persisted after both treatments, accompanied by an additional injury involving the vascular component of the mesangium, with interstitial micro-hemorrhages. Neither AgNPs nor AgNO3 induced oxidative stress effects in kidneys and plasma, at either time point. The AgNP-induced moderate renal effects indicate that, despite their benefits, novel AgNPs employed in consumer products need exhaustive investigation to ensure public health safety.

  8. Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model of pulmonary emphysema.

    Science.gov (United States)

    Tibboel, Jeroen; Keijzer, Richard; Reiss, Irwin; de Jongste, Johan C; Post, Martin

    2014-06-01

    The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters. Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema. MSCs were administered intratracheally or intravenously, before or after elastase injection. Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration. Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up. Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up. Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology. Intratracheal MSC treatment did not modify lung function or histology. In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema. Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function. Intratracheal MSC treatment had no effect on lung function or histology.

  9. Enhanced bioavailability of opiates after intratracheal administration

    International Nuclear Information System (INIS)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-01-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities [codeine (84%), ethylmorphine (100%), and morphine (87%)] of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability

  10. Pulmonary epithelial response in the rat lung to instilled Montserrat respirable dusts and their major mineral components.

    Science.gov (United States)

    Housley, D G; Bérubé, K A; Jones, T P; Anderson, S; Pooley, F D; Richards, R J

    2002-07-01

    The Soufriere Hills, a stratovolcano on Montserrat, started erupting in July 1995, producing volcanic ash, both from dome collapse pyroclastic flows and phreatic explosions. The eruptions/ash resuspension result in high concentrations of suspended particulate matter in the atmosphere, which includes cristobalite, a mineral implicated in respiratory disorders. To conduct toxicological studies on characterised samples of ash, together with major components of the dust mixture (anorthite, cristobalite), and a bioreactive mineral control (DQ12 quartz). Rats were challenged with a single mass (1 mg) dose of particles via intratracheal instillation and groups sacrificed at one, three, and nine weeks. Acute bioreactivity of the particles was assessed by increases in lung permeability and inflammation, changes in epithelial cell markers, and increase in the size of bronchothoracic lymph nodes. Data indicated that respirable ash derived from pyroclastic flows (20.1% cristobalite) or phreatic explosion (8.6% cristobalite) had minimal bioreactivity in the lung. Anorthite showed low bioreactivity, in contrast to pure cristobalite, which showed progressive increases in lung damage. Results suggests that either the percentage mass of cristobalite particles present in Montserrat ash was not sufficient as a catalyst in the lung environment, or its surface reactivity was masked by the non-reactive volcanic glass components during the process of ash formation.

  11. Polymer degradation and ultrafine particles - Potential inhalation hazards for astronauts

    Science.gov (United States)

    Ferin, J.; Oberdoerster, G.

    1992-01-01

    To test the hypothesis that exposure to ultrafine particles results in an increased interstiatilization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO2 particles access the pulmonary interstitium to a larger extent than fine particles and that they elicit an inflammatory response as indicated by PMN increase in lavaged cells. The release of ultrafine particles into the air of an enclosed environment from a thermodegradation event or from other sources is a potential hazard for astronauts. Knowing the mechanisms of action is a prerequisite for technical or medical countermeasures.

  12. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

    Science.gov (United States)

    Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

    2012-08-01

    While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, "omics" methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl2-treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl2. These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

  13. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

    International Nuclear Information System (INIS)

    Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

    2012-01-01

    While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, “omics” methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl 2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl 2 -treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl 2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl 2 . These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

  14. Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

    International Nuclear Information System (INIS)

    Coccini, T; Roda, E; Manzo, L; Barni, S

    2013-01-01

    Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl 2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl 2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

  15. Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

    Science.gov (United States)

    Coccini, T.; Roda, E.; Barni, S.; Manzo, L.

    2013-04-01

    Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

  16. EMISSION PARTICLE-INDUCED VENTILATORY ABNORMALITIES IN A RAT MODEL OF PULMONARY HYPERTENSION

    Science.gov (United States)

    AbstractPreexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation...

  17. Elastase-induced emphysema: retention of instilled proteinase in the rat

    International Nuclear Information System (INIS)

    Sandhaus, R.A.; Janoff, A.

    1982-01-01

    Airway instillation of proteinases with the ability to degrade elastin has been used to produce disease in the rat analogous to human pulmonary emphysema. This study examined the retention, localization, and fate of endotracheally instilled elastase using 125 I labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with 125 I was detected in rat lungs through 96 h after instillation; over half of the label was still present after 7 h. Similar results were obtained when elastase was reacted with a specific, catalytic site inactivator prior to instillation. Trypsin and denatured elastase, however, were cleared much more rapidly from the lung (less than half of the label present after 30 min). When lungs were homogenized after instillation of active elastase, the soluble fraction contained elastase bound to rat alpha1-antitrypsin. In addition, a small amount of label (less than 10%) appeared bound to insoluble components for extended periods of time. Using immunoperoxidase histochemistry, it was found that exogenous elastase was rapidly contained with pulmonary alveolar macrophages, as well as associated with alveolar septums and other parenchymal structures. Similar results were obtained with elastase from both porcine pancreas and human neutrophils. These results suggest that exogenous elastase in the rat, and perhaps endogenous elastolytic enzymes in humans, may have several fates in the lungs: complex formation with endogenous inhibitors, containment within the macrophage, and/or association with connective tissue targets

  18. Preliminary Experience with Instillation of Triamcinolone Acetonide into the Urethra for Idiopathic Urethritis: A Prospective Pilot Study.

    Science.gov (United States)

    Ashraf, Junaid; Radford, Anna R; Turner, Alexander; Subramaniam, Ramnath

    2017-11-01

    Idiopathic bulbar urethritis (IBU) is characterized by hematuria ± dysuria without infection. Symptoms result from inflammation of the bulbar urethra, distal to external sphincter. IBU is difficult to manage and there is no recommended therapy. To determine whether instillation of triamcinolone acetonide is a useful treatment of IBU and its associated complications. Data were prospectively collected, for 22 months, on 14 consecutive patients presenting with terminal hematuria or blood spotting ± dysuria to a pediatric urology unit. Median age was 12 years (range: 10-15). Mean symptom duration was 13 months (range: 8-24). Normal baseline laboratory blood tests, urine cultures, and ultrasound assessments were seen in all; therefore, none were excluded on the basis of a known pathology. Follow-up telephone interviews, to assess symptom persistence and side effects, were performed at 6 weeks postintervention. The mean follow-up period was 15 months (range: 4-20). Visual confirmation of IBU was obtained cystoscopically and 40 mg of triamcinolone was instilled to the inflamed area under direct vision using an open-ended ureteral catheter. Symptoms resolution was the primary outcome. Repeat cystoscopic assessment ± triamcinolone instillation was recorded, as was the occurrence of complications. Seven patients (50%) required at least one further treatment. Overall complete or partial resolution was reported in 12/14 patients (85.7%). No side effects were reported. This small prospective series demonstrates that intraurethral instillation of triamcinolone seems to be a promising treatment option to alleviate inflammatory symptoms in majority of cases of idiopathic urethritis. Patient Summary: Fourteen boys with inflammation of the urethra, with no identifiable cause, were treated by topically triamcinolone, directly to the inflamed area. We demonstrate an 85.7% complete/partial resolution of symptoms with no side effects seen.

  19. An in vitro liver model--assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Gaiser, Birgit K; Hutchison, Gary R

    2012-01-01

    Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...... titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbon nanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as a model for potential detrimental properties of nanomaterials on the liver.......Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five...

  20. Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation

    DEFF Research Database (Denmark)

    Husain, Mainul; Kyjovska, Zdenka O.; Bourdon-Lacombe, Julie

    2015-01-01

    Inhalation of carbon black nanoparticles (CBNPs) causes pulmonary inflammation; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 mice were intratracheally...... to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42d post-exposure, raising concern over the chronic effects of CBNP exposure....... transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also...... differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3h post-exposure declining to base-levels by 3d, increasing again at 14d, and then persisting to 42d post-exposure. Thus, this single CBNP exposure that was equivalent...

  1. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  2. Negative-pressure wound therapy with instillation: international consensus guidelines.

    Science.gov (United States)

    Kim, Paul J; Attinger, Christopher E; Steinberg, John S; Evans, Karen K; Lehner, Burkhard; Willy, Christian; Lavery, Larry; Wolvos, Tom; Orgill, Dennis; Ennis, William; Lantis, John; Gabriel, Allen; Schultz, Gregory

    2013-12-01

    Negative-pressure wound therapy with instillation is increasingly utilized as an adjunct therapy for a wide variety of wounds. Despite its growing popularity, there is a paucity of evidence and lack of guidance to provide effective use of this therapy. A panel of experts was convened to provide guidance regarding the appropriate use of negative-pressure wound therapy with instillation. A face-to-face meeting was held where the available evidence was discussed and individual clinical experience with this therapy was shared. Follow-up communication among the panelists continued until consensus was achieved. The final consensus recommendations were derived through more than 80 percent agreement among the panelists. Nine consensus statements were generated that address the appropriate use of negative-pressure wound therapy with instillation. The question of clinical effectiveness of this therapy was not directly addressed by the consensus panel. This document serves as preliminary guidelines until more robust evidence emerges that will support or modify these consensus recommendations.

  3. Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs.

    Science.gov (United States)

    Chen, Zhe; Chen, Hui; Chen, Fagui; Gu, Dachuan; Sun, Lejia; Zhang, Weitao; Fan, Linfeng; Lin, Yong; Dong, Rong; Lai, Kefang

    2017-12-20

    Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

  4. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    Science.gov (United States)

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  5. Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice

    NARCIS (Netherlands)

    Ruscitti, F. (Francesca); Ravanetti, F. (Francesca); J. Essers (Jeroen); Y. Ridwan (Yanto); Belenkov, S. (Sasha); W.G. Vos (Wim G.); Ferreira, F. (Francisca); A. Kleinjan (Alex); P.M. van Heijningen (Paula ); C. Van Holsbeke (Cedric); Cacchioli, A. (Antonio); Villetti, G. (Gino); Stellari, F.F. (Franco Fabio)

    2017-01-01

    textabstractBackground: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology

  6. Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

    Science.gov (United States)

    Nalabotu, Siva Krishna

    The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

  7. Reiter's syndrome postintravesical Bacillus Calmette–Guérin instillations

    Directory of Open Access Journals (Sweden)

    Keng Lim Ng

    2017-03-01

    Full Text Available Intravesical Bacillus Calmette–Guérin (BCG has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1, and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain and eye ointment (for conjunctivitis and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.

  8. Effects of Lignocaine Administered Intravenously or Intratracheally on Airway and Hemodynamic Responses during Emergence and Extubation in Patients Undergoing Elective Craniotomies in Supine Position.

    Science.gov (United States)

    Shabnum, Tabasum; Ali, Zulfiqar; Naqash, Imtiaz Ahmad; Mir, Aabid Hussain; Azhar, Khan; Zahoor, Syed Amer; Mir, Abdul Waheed

    2017-01-01

    Sympathoadrenergic responses during emergence and extubation can lead to an increase in heart rate (HR) and blood pressure whereas increased airway responses may lead to coughing and laryngospasm. The aim of our study was to compare the effects of lignocaine administered intravenously (IV) or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies. Sixty patients with physical status American Society of Anaesthesiologists Classes I and II aged 18-70 years, scheduled to undergo elective craniotomies were included. The patients were randomly divided into three groups of twenty patients; Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). The tolerance to the endotracheal tube was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were also recorded. There was a decrease of HR in both IV and intratracheal groups in comparison with placebo group ( P < 0.005). Rise in blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial pressure) was comparable in both Groups 1 and 2 but was lower in comparison with placebo group ( P < 0.005). Cough suppression was comparable in all the three groups. Grade III cough (15%) was documented only in placebo group. Both IV and intratracheal lignocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation. There was comparable cough suppression through intratracheal route and IV routes than the placebo group.

  9. Late sensory function after intraoperative capsaicin wound instillation

    DEFF Research Database (Denmark)

    Aasvang, E K; Hansen, J B; Kehlet, H

    2010-01-01

    is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. METHODS: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin after....... placebo group at the 1-week follow-up (Pfunction on the operated side between groups at the pre-operative, 1-week or 2 1/2 year post-operative follow-up (P>0.05). The sensory function......BACKGROUND: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function...

  10. Iloprost Instillation in Two Neonates with Pulmonary Hypertension

    International Nuclear Information System (INIS)

    Aktas, S.; Aksu, M.; Hirfanoglu, I. M.; Atalay, Y.; Turkyilmaz, C.; Unal, S.

    2017-01-01

    Pulmonary hypertension may coexist with certain diseases in neonates. Iloprost inhalation is one of the treatments which cause selective pulmonary vasodilatation. Inhalation is not an easy way of drug administration in mechanically ventilated infants; as some exhibit desaturations during inhalation. Moreover, inhalation of drug requires cessation of mechanical ventilation, if patient is on high frequency oscillatory ventilation. We presented two patients with pulmonary hypertension; term baby with congenital diaphragmatic hernia and preterm baby with respiratory distress syndrome; who had iloprost instillation during mechanical ventilation treatment. Iloprost instillation was well tolerated with no side effects in the term patient with diaphragmatic hernia; whereas severe blood pressure fluctuations were observed in the preterm infant. This report may courage administration of iloprost in term neonates with resistant pulmonary hypertension. (author)

  11. Effects of Mikania glomerata Spreng. and Mikania laevigata Schultz Bip. ex Baker (Asteraceae) extracts on pulmonary inflammation and oxidative stress caused by acute coal dust exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, T.P.; Silveira, P.C.; Rocha, L.G.; Rezin, G.T.; Rocha, J.; Citadini-Zanette, V.; Romao, P.T.; Dal-Pizzol, F.; Pinho, R.A.; Andrade, V.M.; Streck, E.L. [University Extremo Catarinense, Criciuma (Brazil)

    2008-12-15

    Several studies have reported biological effects of Mikania glomerata and Mikania laevigata, used in Brazilian folk medicine for respiratory diseases. Pneumoconiosis is characterized by pulmonary inflammation caused by coal dust exposure. In this work, we evaluated the effect of pretreatment with M. glomerata and M. laevigata extracts (MGE and MLE, respectively) (100 mg/kg, s.c.) on inflammatory and oxidative stress parameters in lung of rats subjected to a single coal dust intratracheal instillation. Rats were pretreated for 2 weeks with saline solution, MGE, or MLE. On day 15, the animals were anesthetized, and gross mineral coal dust or saline solutions were administered directly in the lung by intratracheal instillation. Fifteen days after coal dust instillation, the animals were killed. Bronchoalveolar lavage (BAL) was obtained; total cell count and lactate dehydrogenase (LDH) activity were determined. In the lung, myeloperoxidase activity, thiobarbituric acid-reactive substances (TBARS) level, and protein carbonyl and sulfhydryl contents were evaluated. In BAL of treated animals, we verified an increased total cell count and LDH activity. MGE and MLE prevented the increase in cell count, but only MLE prevented the increase in LDH. Myeloperoxidase and TBARS levels were not affected, protein carbonylation was increased, and the protein thiol levels were decreased by acute coal dust intratracheal administration. The findings also suggest that both extracts present an important protective effect on the oxidation of thiol groups. Moreover, pretreatment with MGE and MLE also diminished lung inflammatory infiltration induced by coal dust, as assessed by histopathologic analyses.

  12. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Saber, Anne T.; Williams, Andrew

    2015-01-01

    Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instil...

  13. Exposure of pregnant mice to carbon black by intratracheal instillation

    DEFF Research Database (Denmark)

    Jackson, Petra; Hougaard, Karin S.; Vogel, Ulla

    2011-01-01

    Exposure to nanomaterials (NM) during sensitive developmental stages may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced re......Exposure to nanomaterials (NM) during sensitive developmental stages may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM...... only in the high dose group. Analysis of newborn livers by DNA microarrays revealed that female offspring were more sensitive to maternal exposure than male offspring. Cellular signalling, inflammation, cell cycle and lipid metabolism were among the biological pathways affected in female offspring...

  14. [Creation of experimental emphysema by the intratracheal administration of papain].

    Science.gov (United States)

    Basmadzhieva, K; Kolev, K; Balabaeva, L

    1981-01-01

    The authors formed lung emphysema in white rats under experimental conditions by intratracheal application of various concentrations of papaine at different intervals. In the performed experiment the most suitable dose for formation of emphysema was two fold administration of 2 milligrams of papaine. The following indices were observed in the experimental and control animals: body weight, weight coefficient of the internal organs, indices of lipid and nucleinic metabolism in homogenates of lung as well as histomorphologic examination of lung.

  15. Comparison of the effect of lignocaine instilled through the endotracheal tube and intravenous lignocaine on the extubation response in patients undergoing craniotomy with skull pins: A randomized double blind clinical trial

    Directory of Open Access Journals (Sweden)

    Smitha Elizabeth George

    2013-01-01

    Full Text Available Background: A desirable combination of smooth extubation and an awake patient after neurosurgical procedures is difficult to achieve in patients with skull pins. Lignocaine instilled into endotracheal tube has been reported to suppress cough by a local mucosal anesthetizing effect. We aimed to evaluate if this effect will last till extubation, if given before pin removal. Materials and Methods: A total of 114 patients undergoing elective craniotomy were divided into three groups and were given 1 mg/kg of intravenous (IV, 2% lignocaine (Group 1, placebo (Group 2 and 1 mg/kg of 2% lignocaine sprayed down the endotracheal tube (Group 3 before skull pin removal. The effectiveness of each to blunt extubation response was compared. Plasma levels of lignocaine were measured 10 min after administration of the study drug and at extubation. Sedation scores were noted, immediately after extubation and 10 min later. Results: Two percent of lignocaine instilled through endotracheal route was not superior to the IV route or placebo in attenuating cough or hemodynamic response at extubation when given 20-30 min before extubation. The plasma levels of lignocaine (0.8 μg/ml were not high enough even at the end of 10 min to have a suppressive effect on cough if given IV or intratracheally (IT. Lignocaine did not delay awakening in these groups. Conclusion: IT lignocaine in the dose of 1 mg/kg does not prevent cough at extubation if given 20-30 min before extubation. If the action is by a local mucosal anesthetizing effect, it does not last for 20-30 min to cover the period from pin removal to extubation.

  16. Combined radiofrequency ablation and acetic acid-hypertonic saline solution instillation: an in vivo study of rabbit liver

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong-Min; Han, Joon-Koo; Kim, Se-Hyung; Choi, Byung-Ihn [Seoul National University, Seoul (Korea, Republic of); Kim, Young-Kon; Kim, Sang-Won [Chonbuk National University, Chonju (Korea, Republic of)

    2004-03-15

    We wanted to determine whether combined radiofrequency ablation (RFA) and acetic acid-hypertonic saline solution (AHS) instillation can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. We also wished to determine the optimal concentration of the solution in order to maximize its effect on extent of the RFA-induced coagulation. Forty thermal ablation zones were produced in 40 rabbits by using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound guidance. The rabbits were assigned to one of four groups: group A: RFA alone (n=10); group B: RFA with 50% AHS instillation (n=10); group C: RFA with 25% AHS instillation (n=10); group D: RFA with 15% AHS instillation (n=10). A range of acetic acid concentrations diluted in 36% NaCl to a total volume of 2 mL were instilled into the liver before RFA. The RF energy (30W) was applied for three minutes. After RFA, in each group, the maximum diameters to the thermal ablation zones in the gross specimens were compared. Technical success and the complication that arose were evaluated by CT and on the basis of autopsy findings. All procedures are technically successful. There were six procedure-related complications (6/40; 15%); two localized perihepatic hematomas and four chemical peritonitis. The incidence of chemical peritonitis was highest for group B with the 50% AHS solution instillation (30%). With instillation of 15% AHS solution, a marked decrease of tissue impedance (24.5 {+-} 15.6 {omega}) and an increase of current (250 mA) occurred as compared to RFA alone. With instillation of the solutions before RFA (group B, C and D). this produced a greater mean diameter of coagulation necrosis than the diameters for rabbits not instilled with the solution (group A) ({rho}<0.05). However, there was no significant difference between group B, C, and D. Combined AHS instillation and RFA can increase the dimension of coagulation necrosis in the liver with a single

  17. Ectopic Intratracheal Thyroid: A Rare Cause of Airway Obstruction

    Directory of Open Access Journals (Sweden)

    Waheed Rahman

    2018-01-01

    Full Text Available Ectopic intratracheal thyroid tissue (EITT is a rare abnormality with only limited cases reported so far. The presenting symptoms can be very similar to those of bronchial asthma. We discuss the case of a 29-year-old man with subglottic ectopic thyroid, with a history of thyroid surgery for goiter, which has been managed with laser-assisted endoscopic approach. We have also included presenting symptoms, pathophysiology, diagnosis, and management of EITT. We aim to include EITT in the differentials of airway obstruction, particularly in those patients who have goiter or previous thyroid surgeries.

  18. Effects of lung exposure to carbon nanotubes on female fertility and pregnancy. A study in mice

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Jackson, Petra; Kyjovska, Zdenka O.

    2013-01-01

    We studied the effects of preconceptional exposure to multiwalled carbon nanotubes (MWCNTs): mature, female C57BL/6J mice were intratracheally instilled with 67μg NM-400 MWCNT, and the following day co-housed with mature males, in breeding pairs. Time to delivery of the first litter, litter...

  19. Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

    DEFF Research Database (Denmark)

    Christophersen, Daniel V.; Jacobsen, Nicklas R.; Andersen, Maria H. G.

    2016-01-01

    or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only...

  20. Octreotide: a powerful non-narcotic analgesic for ocular instillation

    Directory of Open Access Journals (Sweden)

    Nicola Maratea

    2015-05-01

    Full Text Available The development of alternative substances for pain treatment is necessary for patients who cannot tolerate the side effects of opioids or cannot reach an adequate analgesia with these drugs. The technique using the endo-ocular instillation of drops, 2 ml of solution containing 0.05 mg of octreotide plus 1 ml of water for injectable preparations, thus obtaining a solution containing 0.025 mg / ml of octreotide, was instilled via a precision dropping that provided 0.00119 mg / drop of octreotide. Due to characteristics of pain, we administered the doses ranging from 1 to 3 drops per eye. The absence of side effects and the simplicity of execution have prompted to consider this method with extreme interest, in order to research the drugs and routes of administration which follow more the conditions of tolerability and selectivity of effects.

  1. Impact of serum as a dispersion agent for in vitro and in vivo toxicological assessments of TiO2 nanoparticles

    DEFF Research Database (Denmark)

    Vranic, Sandra; Gosens, Ilse; Jacobsen, Nicklas Raun

    2017-01-01

    the pro-inflammatory response. We also determined the acute pulmonary and hepatic toxicity in vivo 24 h after intratracheal instillation of TiO2 NPs in C57BL/6N mice. The use of serum resulted in an underestimation of the local acute inflammatory response in the lung, while a systemic response...

  2. Morphometric analysis of stab wounds by MSCT and MRI after the instillation of contrast medium.

    Science.gov (United States)

    Fais, Paolo; Cecchetto, Giovanni; Boscolo-Berto, Rafael; Toniolo, Matteo; Viel, Guido; Miotto, Diego; Montisci, Massimo; Tagliaro, Franco; Giraudo, Chiara

    2016-06-01

    To analyze the morphology and depth of stab wounds experimentally produced on human legs amputated for medical reasons using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) after the instillation of a single contrast medium solution (CMS). For morphological analysis, MSCT and MRI scans were performed before and after the instillation of CMS into the wound cavity. Depth measurements were performed on the sagittal view only after CMS instillation. Subsequently, each wound was dissected using the layer-by-layer technique and the depth was measured by a ruler. One-way between-groups pairwise analysis of variance (ANOVA) and Bland-Altman plot analysis were used for comparing radiological and anatomical measurements. Unenhanced MSCT images did not identify the wound channels, whereas unenhanced MRI evidenced the wound cavity in 50 % of cases. After the instillation of CMS, both MSCT and MRI depicted the wound channel in all the investigated stabbings, although the morphology of the cavity was irregular and did not resemble the shape of the blade. The radiological measurements of the wounds' depth, after the application of CMS, exhibited a high level of agreement (about 95 % at Bland-Altman plot analysis) with the anatomical measurements at dissection. A similar systematic underestimation, however, has been evidenced for MSCT (average 11.4 %; 95 % CI 7-17) and MRI (average 9.6 %; 95 % CI 6-13) data after the instillation of CMS with respect to wound dissection measurements. MSCT and MRI after the instillation of CMS can be used for depicting the morphometric features of stab wounds, although depth measurements are affected by a slight systematic underestimation compared to layer-by-layer dissection.

  3. Retrograde Instillation of Methylene Blue in the Difficult Diagnosis of BPF

    Directory of Open Access Journals (Sweden)

    F. Ravenna

    2012-01-01

    Full Text Available We report two cases in which we were able to diagnose bronchopleural fistula through retrograde methylene blue instillation during bronchoscopy. In the first case, methylene blue was injected through an abdominal drain, followed by air instillation and detected in the left bronchial tree, demonstrating the presence of a fistula in the lingula’s bronchus. In the second case, methylene blue was injected into a pleural drain, through a breach on a surgical suture and detected in the right bronchial tree, demonstrating the presence of a fistula in the right inferior bronchus. The retrograde instillation of methylene blue, through a drain in the abdomen or the thoracic wall, is a safe, cheap, and practical method that allows the bronchoscopist to identify the presence of a fistula and, more importantly, to identify the exact point on the bronchial tree where a fistula is located. This provides the possibility of sealing the fistula with a variety of devices. It is our opinion that this procedure should be considered a primary method of diagnosis when a bronchopleural fistula is suspected and a drain on the thoracic or abdominal wall is positioned such that effusions are able to drain.

  4. Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2016-09-01

    Full Text Available Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR. Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2, one of the major components of bee venom (BV, to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway.

  5. Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.

    Science.gov (United States)

    Wiersma, Lidewij C M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; van Run, Peter; Nieuwkoop, Nella J; Ladwig, Mechtild; Banneke, Stefanie; Schaefer, Hubert; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2015-03-01

    To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Induction of lung cancer in rats by intratracheal insufflation of carcinogenic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Pylev, L N

    1963-01-01

    One, 3, or 5 monthly intratracheal injections of 2 to 2.5 mg dimethylbenzanthracene (DMBA) in India ink-solvent or 5 or 7 monthly injections of 5 mg benzyprene (BaP) in India ink-solvent into rats produced tumors, starting at 5 months, mostly around accumulations of ink. Results showed 27.8% of 151 animals receiving DMBA and surviving to 5 months developed carcinomas, as compared to 7 of 12 animals receiving BaP.

  7. Analyzing the effects of instillation volume on intravesical delivery using biphasic solute transport in a deformable geometry.

    Science.gov (United States)

    Smith, Sean G; Griffith, Boyce E; Zaharoff, David A

    2018-04-05

    Ailments of the bladder are often treated via intravesical delivery-direct application of therapeutic into the bladder through a catheter. This technique is employed hundreds of thousands of times every year, but protocol development has largely been limited to empirical determination. Furthermore, the numerical analyses of intravesical delivery performed to date have been restricted to static geometries and have not accounted for bladder deformation. This study uses a finite element analysis approach with biphasic solute transport to investigate several parameters pertinent to intravesical delivery including solute concentration, solute transport properties and instillation volume. The volume of instillation was found to have a substantial impact on the exposure of solute to the deeper muscle layers of the bladder, which are typically more difficult to reach. Indeed, increasing the instillation volume from 50-100 ml raised the muscle solute exposure as a percentage of overall bladder exposure from 60-70% with higher levels achieved for larger instillation volumes. Similar increases were not seen for changes in solute concentration or solute transport properties. These results indicate the role that instillation volume may play in targeting particular layers of the bladder during an intravesical delivery.

  8. Micro-instillation of fluorescein with an inoculation loop for ocular surface staining in dry eye syndrome.

    Science.gov (United States)

    Courrier, Emilie; Renault, Didier; Kaspi, Mathilde; Marcon, Agathe; Lambert, Victor; Garcin, Thibaud; Chiambaretta, Frederic; Garhofer, Gerhard; Thuret, Gilles; Gain, Philippe

    2018-03-01

    To describe and validate the micro-instillation of fluorescein on the ocular surface by a disposable calibrated inoculation loop to improve corneal and conjunctival staining quality. Accuracy and precision of the volume of 0.5% sodium fluorescein collected by a single use 1 μl-calibrated inoculation loop were measured using a precision balance. Twenty patients (40 eyes) suffering from dry eye syndrome were enrolled in a prospective interventional nonrandomized study. Fluorescein was instilled with the loop, and slit-lamp images were taken within 30 seconds using cobalt blue light with and without a yellow barrier filter. For comparison, after a washout period, the same images were retaken after instillation of one drop of fluorescein from a single-dose unit. The main outcome measure was the staining quality assessed by three experts, blind to the instillation method. Patient discomfort (tolerance, by a questionnaire) was also compared. The mean volume collected by the loop was 1.18 ± 0.12 μl, compared with 33.70 ± 6.10 μl using the single-dose unit. The loop avoided excess dye responsible for unpleasant tearing, masking of lesions and rapid diffusion into the stroma. Micro-instillation greatly improved image quality without losing information. The yellow filter further improved image contrast. Tolerance was excellent. The 1 μl-calibrated inoculation loop is a safe, convenient, inexpensive, disposable, sterile, well-tolerated tool for reproducible micro-instillation of commercial fluorescein. By greatly improving staining quality, it will help standardize assessment of dry eye severity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Toxicokinetics of hexavalent chromium in the rat after intratracheal administration of chromates of different solubilities

    NARCIS (Netherlands)

    Bragt, P.C.; Dura, E.A. van

    1983-01-01

    The kinetics of chromium in the rat after a single intratracheal dose of sodium, zinc or lead 51Cr-chromate have been investigated. Sodium chromate and the less soluble zinc chromate were absorbed into the blood and this resulted in increased excretion of chromium into the urine. The insoluble lead

  10. Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital lifting

    Directory of Open Access Journals (Sweden)

    Ivana Cardoso Pereira

    2014-12-01

    Full Text Available Purpose: To quantify and compare the effects of instillation with 10% phenylephrine and digital lifting on the contralateral upper eyelid of patients with involutional bilateral blepharoptosis. Methods: The present prospective clinical study involved patients with involutional bilateral blepharoptosis who underwent two tests: 1 digital lifting of the more ptotic eyelid and observation of the effect on the contralateral eyelid and 2 instillation of two drops of 10% phenylephrine in the more ptotic eye and observation of the effect on the contralateral eyelid. Patients were filmed before and 5, 10, and 15 min after instillation, and the resulting images were analyzed to obtain eyelid measurements. The results were tested using a linear mixed-effects model. Results: A total of 27 patients, ranging from 52 to 82 years of age (mean age 68.51 ± 8.21 years, 24 (88.88% of whom were women, were included in the present study. In eyes that received instillation, the marginal distance reflex-1 (MDR1 values increased from baseline (1.21 ± 0.60 mm until 10 min after instillation, then remained statistically unchanged until 15 min after instillation (2.42 ± 0.90 mm. Significant differences were observed in the contralateral eye of the group that underwent digital lifting (1.51 ± 0.53 mm - 1.63 ± 0.56 mm and in the contralateral eye of the group that underwent 10% phenylephrine instillation (1.38 ± 0.54 mm - 1.63 ± 0.56 mm; p=0.02 and p<0.01, respectively. Conclusion: In all eyes, 10% phenylephrine elevated the upper eyelid, with improved eyelid height at 10 min after instillation. Significant differences were observed in the height of the contralateral eyelid when compared before and after each intervention in each group; however, this difference was very small and nearly undetectable by conventional clinical evaluation in the digital lifting group. However, the 10% phenylephrine eye-drop test resulted in substantial changes in MDR1 values in the

  11. Effects of particles on macrophage migration

    International Nuclear Information System (INIS)

    Mueller, H.L.; Robinson, B.; Muggenburg, B.A.; Guilmette, R.A.

    1988-01-01

    Random and directed migration of cells lavaged from the lungs of rats and dogs were studied in vitro using formyl-methionyl-leucyl-phenylalanine (FMLP) as a chemo attractant. Rats and dogs were intratracheally instilled with either saline (controls) or about 10 9 fluorescent polystyrene microspheres, and lungs were lavaged after 1 or 7 days. More rat cells than dog cells migrated at 1 day after both particle and saline instillations; at 7 days, only cells lavaged from rats after particle instillations showed enhanced migration abilities. FMLP caused a 1.5 to 2-fold enhancement compared to random migration in cell numbers counted on the lower sides of chemotactic membranes. Cells with low particle numbers were more likely to migrate than those with high numbers of ingested particles. (author)

  12. Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium

    Directory of Open Access Journals (Sweden)

    Noriaki Nagai

    2018-04-01

    Full Text Available Sericin is a major constituent of silk produced by silkworms. We previously found that the instillation of sericin enhanced the proliferation of corneal epithelial cells, and acted to promote corneal wound healing in both normal and diabetic model rats. However, the mechanisms by which sericin promotes the proliferation of corneal cells have not been established. In this study, we investigated the effects of sericin on Akt and ERK activation in a human corneal epithelial cell line (HCE-T cells and rat debrided corneal epithelium. Although Akt phosphorylation was not detected following the treatment of HCE-T cells with sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated with sericin was significantly increased, with the cell growth of sericin-treated HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells. On the other hand, both of an ERK inhibitor U0126 (non-specific specific inhibitor and SCH772984 (specific inhibitor attenuated the enhanced cell growth by sericin, and the growth level in the case of co-treatment with sericin and ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor alone. In an in vivo study using rat debrided corneal epithelium, the corneal wound healing rate was enhanced by the instillation of sericin, and this enhancement was also attenuated by the instillation of U0126. In addition, the corneal wound healing rate in rats co-instilled with sericin and U0126 was similar to that following the instillation of U0126 alone. In conclusion, we found that the instillation of sericin enhanced cell proliferation via the activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound healing in rat eyes. These findings provide significant information for designing further studies to develop potent corneal wound-healing drugs.

  13. Mini-open vacuum-assisted closure therapy with instillation for debilitated and septic patients with pleural empyema.

    Science.gov (United States)

    Sziklavari, Zsolt; Ried, Michael; Neu, Reiner; Schemm, Rudolf; Grosser, Christian; Szöke, Tamas; Hofmann, Hans-Stefan

    2015-08-01

    This prospective study is an evaluation of the mini-open vacuum-assisted closure with instillation (Mini-VAC-Instill) therapy for the treatment of complicated pleural empyema. We investigated septic patients in poor general physical condition (Karnofsky index ≤50%) with multimorbidity and/or immunosuppression who were treated by minimally invasive intrathoracic VAC-Instill therapy without the insertion of an open-window thoracostomy (OWT) between December 2012 and November 2014. All patients underwent mini-thoracotomy with position of a tissue retractor, surgical debridement and local decortication. Surgery was followed by intrathoracic vacuum therapy including periodic instillation using antiseptics. The VAC dressings were changed under general anaesthesia and the chest wall was closed during the same hospital stay. All patients received systemic antibiotic therapy. Fifteen patients (13 males, median age: 71 years) underwent intrathoracic Mini-VAC-Instill dressings for the management of pleural empyema without bronchopleural fistula. The median length of vacuum therapy was 9 days (5-25 days) and the median number of VAC changes per patient was 1 (1-5). In-hospital mortality was 6.7% (n = 1) and was not related to Mini-VAC-Instill therapy or intrathoracic infection. Control of intrathoracic infection and closure of the chest cavity was achieved in 85.7% of surviving patients (12 of 14). After the follow-up at an average of 13.2 months (range, 3-25 months), we observed recurrence once, 21 days after discharge. Two patients died in the late postoperative period (Day 43 and Day 100 after discharge) of fulminant urosepsis and carcinoma-related multiorgan failure, respectively. Analysis of the follow-up interviews in the outpatient clinic showed a good quality of life and a subjectively good long-term aesthetic result. Mini-VAC-Instill therapy is an upgrade of Mini-VAC, which guarantees the advantage of an open treatment, including flushing but without OWT. This

  14. Steroid instillation for idiopathic urethritis in children: an 8-year experience.

    Science.gov (United States)

    Jayakumar, Sivasankar; Ninan, George Kaithayil; Pringle, Kirsty

    2015-04-01

    Idiopathic urethritis (IU) in children is of unknown etiology and treatment options are limited. We aim to report our experience with steroid instillation in IU in children. Retrospective data collection of all male children diagnosed with IU over a period of 8 years. Patients with balanitis xerotica obliterans (BXO) and positive urine culture at presentation were excluded from the study. Data were collected on patient demographics, laboratory and radiological investigations, cystoscopy findings, management, and outcomes. A total of 16 male children were diagnosed with IU. The mean age was 11.6 (7-16) years. Presenting symptoms included dysuria in 10; frank hematuria in 7; loin pain in 5; and scrotal pain in 2 patients. Serum C-reactive protein and full blood count was tested in 13 patients and was within normal limits in all of them. Endoscopy findings included posterior urethritis in 12, anterior urethritis in 2, and urethral stricture with inflammation in 2 patients. Ten patients required more than one episode of steroid instillation. Mean follow-up was 19.4 (1-74) months. Complete resolution of symptoms and signs occurred in 15 (93.6%) patients and improvement of symptoms and signs noted with ongoing treatment in 1 (6.4%) patient. IU in children can be successfully managed with steroid instillation. In our series, 93.6% of children had complete resolution of symptoms. Georg Thieme Verlag KG Stuttgart · New York.

  15. Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

    Directory of Open Access Journals (Sweden)

    Eric Gomez

    2009-01-01

    Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

  16. Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia.

    Science.gov (United States)

    Caruso, Pedro; Denari, Silvia; Ruiz, Soraia A L; Demarzo, Sergio E; Deheinzelin, Daniel

    2009-01-01

    To compare the incidence of ventilator-associated pneumonia (VAP) with or without isotonic saline instillation before tracheal suctioning. As a secondary objective, we compared the incidence of endotracheal tube occlusion and atelectasis. Randomized clinical trial. The study was conducted in a medical surgical intensive care unit of an oncologic hospital. We selected consecutive patients needing mechanical ventilation for >72 hrs. Patients were allocated into two groups: a saline group that received instillation of 8 mL of saline before tracheal suctioning and a control group which did not. VAP was diagnosed based on clinical suspicion and confirmed by bronchoalveolar lavage quantitative culture. The incidence of atelectasis on daily chest radiography and endotracheal tube occlusions were recorded. The sample size was calculated to a power of 80% and a type I error probability of 5%. One hundred thirty patients were assigned to the saline group and 132 to the control group. The baseline demographic variables were similar between groups. The rate of clinically suspected VAP was similar in both groups. The incidence of microbiological proven VAP was significantly lower in the saline group (23.5% x 10.8%; p = 0.008) (incidence density/1.000 days of ventilation 21.22 x 9.62; p < 0.01). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p = 0.02, log-rank test). The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval, 18%-74%) and the number needed to treat was eight (95% confidence interval, 5-27). The incidence of atelectases and endotracheal tube occlusion were similar between groups. Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP.

  17. The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

    Science.gov (United States)

    Puntorieri, Valeria; Hiansen, Josh Qua; McCaig, Lynda A; Yao, Li-Juan; Veldhuizen, Ruud A W; Lewis, James F

    2013-11-20

    Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation. Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours). For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate. The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

  18. Airway exposure to multi-walled carbon nanotubes disrupts the female reproductive cycle without affecting pregnancy outcomes in mice

    DEFF Research Database (Denmark)

    Johansson, Hanna Katarina Lilith; Hansen, J. S.; Elfving, B.

    2017-01-01

    response and inflammation in experimental animals, which may affect female reproduction. This proof-of-principle study therefore aimed to investigate if lung exposure by intratracheal instillation of the MWCNT NM-400 would affect the estrous cycle and reproductive function in female mice.Results: Estrous...... of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation....

  19. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    Directory of Open Access Journals (Sweden)

    Barfod Kenneth K

    2010-09-01

    Full Text Available Abstract Background The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF, clearance of bacteria from the lung lumen and histological alterations of the lungs. Hazard identifications of the biopesticides were carried out using intratracheal (i.t. instillation, followed by an inhalation study. The two commercial biopesticides used were based on the Bt. subspecies kurstaki and israelensis, respectively. Groups of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU per mouse of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU counts. Results BALF cytology showed an acute inflammatory response dominated by neutrophils 24 hours after instillation of biopesticide. Four days after instillation, the neutrophil number was normalised and inflammation was dominated by lymphocytes and eosinophils, whereas 70 days after instillation, the inflammation was interstitially located with few inflammatory cells present in the lung lumen. Half of the instilled mice had remaining CFU recovered from BALF 70 days after exposure. To gain further knowledge with relevance for risk assessment, mice were exposed to aerosols of biopesticide one hour per day for 2 × 5 days. Each mouse received 1.9 × 104 CFU Bt israelensis or 2.3 × 103 CFU Bt kurstaki per exposure. Seventy days after end of the aerosol exposures, 3 out of 17 mice had interstitial lung inflammation. CFU could be recovered from 1 out of 10 mice 70 days after exposure to aerosolised Bt kurstaki. Plethysmography showed that inhalation of Bt aerosol did not induce airway irritation. Conclusions Repeated low dose aerosol

  20. Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice

    DEFF Research Database (Denmark)

    Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua

    2016-01-01

    , intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent...... within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180....... Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP...

  1. On the influence of the instillation time on the results of HAL (Hexvix) fluorescence detection of superficial bladder cancer

    Science.gov (United States)

    Jichlinski, Patrice; Aymon, Daniela; Wagnieres, Georges A.; Marti, Alexandre; Lange, Norbert; Guillou, Louis; Leisinger, Hans-Juerg; van den Bergh, Hubert

    2003-10-01

    Hexyl aminolevulinate (HAL) fluorescence cystoscopy is being investigated as a new diagnostic tool for the detection of flat urothelial malignancies in bladder cancers. However, the influence of the bladder instillation time on the performance of this detection modality has not been addressed up to now. We report our initial experience comparing different instillation schedules of HAL cystoscopy in the diagnosis of superficial bladder cancer. A total of 718 fluorescent positive (433) and fluorescence negative (285) biopsies have been taken in the bladder of 143 patients using the Storz D-light fluorescence imaging system (Karl Storz, Tuttlingen, Germany) which allows both white and blue light (380-450 nm) bladder wall inspection. Following hospitalisation, 50 ml of HAL (8mM) phosphate buffer solution was instilled into the bladder of patients during one hour (1 hour protocol involving 57 patients), or during two hours followed by a two hours resting time after removal of the solution (2+2 hours protocol involving 86 patients). Both instillation subgroups were homogeneous in terms of proportion of high risk disease, previous BCG treatment and/or recurrent disease. This study indicates that the instillation duration does not influence the results of HAL (Hexvix) fluorescence cystoscopy in our conditions. Compared to the standard use of ALA, HAL (Hexvix) fluorescence cystoscopy allows a significant reduction of the instillation time (to less than one hour) without prejudicing the efficacy of the method, what represents a real advantage in daily clinical practice.

  2. Intravesical Glycosaminoglycan Replacement with Chondroitin Sulphate (Gepan? instill) in Patients with Chronic Radiotherapy- or Chemotherapy-Associated Cystitis

    OpenAIRE

    Schwalenberg, Thilo; Berger, Frank Peter; Horn, Lars Christian; Thi, Phuc Ho; Stolzenburg, Jens?Uwe; Neuhaus, Jochen

    2015-01-01

    Background and Objective Intravesical instillation of glycosaminoglycans is a promising option for the treatment of chronic cystitis, as it supports the regeneration of the damaged urothelial layer. We investigated the efficacy of short-term intravesical chondroitin sulphate treatment (six courses of instillation) in patients with chronic radiotherapy- or chemotherapy-associated cystitis. Methods This prospective, observational study included patients with chronic radiotherapy- or chemotherap...

  3. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  4. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime

    2011-04-01

    Full Text Available Abstract Background There have been few reports on the role of Fc receptors (FcRs and immunoglobulin G (IgG in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. Methods In FcγRIIB deficient (KO and C57BL/6 (WT mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA. Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL. Results In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. Conclusion Antigen-specific IgG ameliorates

  5. Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway

    International Nuclear Information System (INIS)

    Weng, T.I.; Chen, W.J.; Liu, S.H.

    2005-01-01

    Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-α translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator β-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-α translocation was impaired in the bladder; LPS did not affect PKC-δ translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-α translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment

  6. A newly developed tool for intra-tracheal temperature and humidity assessment in laryngectomized individuals: the Airway Climate Explorer (ACE)

    NARCIS (Netherlands)

    Zuur, J.K.; Muller, S.H.; Jongh, F.H.C.; Horst, M.J. van der; Shehata, M.; Leeuwen, J. van; Sinaasappel, M.; Hilgers, F.J.M.

    2007-01-01

    The aim of this study is to develop a postlaryngectomy airway climate explorer (ACE) for assessment of intratracheal temperature and humidity and of influence of heat and moisture exchangers (HMEs). Engineering goals were within-device condensation prevention and fast response time characteristics.

  7. Mitomycin C instillation following ureterorenoscopic laser ablation of upper urinary tract carcinoma

    Directory of Open Access Journals (Sweden)

    Omar M Aboumarzouk

    2013-01-01

    Conclusions: Using a set standard protocol, MMC can safely be instilled into the UUT after TCC ablation with minimal complications or side effects, good preservation of renal function, and with a low recurrences rate comparable to the literature.

  8. Expression of cyclin D{sub 1} during endotoxin-induced aleveolar type II cell hyperplasia in rat lung and the detection of apoptotic cells during the remodeling process

    Energy Technology Data Exchange (ETDEWEB)

    Tesfaigzi, J.; Wood, M.B.; Johnson, N.F.

    1995-12-01

    Our studies have shown that endotoxin intratracheally instilled into the rat lung induces proliferation of alveolar type II cells. In that study, the alveolar type II cells. In that study, the alveolar type II cell hyperplasia occurred 2 d after instillation of endotoxin and persisted for a further 2 d. After hyperplasia, the lung remodeled and returned to a normal state within 24-48 h. Understanding the mechanisms involved in the remodeling process of this transient hyperplasia may be useful to identify molecular changes that are altered in neoplasia. The purpose of the present study was to corroborate induction of epithelial cell hyperplasia by endotoxin and to delineate mechanisms involved in tissue remodeling after endotoxin-induced alveolar type II cell hyperplasia. In conclusion, immonostaining with cyclin D1 and cytokeratin shows that endotoxin induced epithelial cell proliferation and resulted in hyperplasia in the lung which persisted through 4 d post-instillation.

  9. Time course of changes in tear meniscus radius and blink rate after instillation of artificial tears.

    Science.gov (United States)

    Bandlitz, Stefan; Purslow, Christine; Murphy, Paul J; Pult, Heiko

    2014-08-26

    Using a novel digital meniscometer (PDM), alterations in tear meniscus radius (TMR) were measured simultaneously with blink rate (BR) following the instillation of artificial tears. Central TMR and BR of 22 subjects (11 male and 11 female; mean age, 24.3 ± 2.6 SD years) were measured at baseline, and 0, 1, 5, 10, and 30 minutes after instillation of an artificial tear containing hydroxypropyl-guar and glycol (SYS) or saline (SAL). A dose of 35 μL was applied in one eye in a randomized order with a washout period between each drop. For SAL, compared to baseline TMR (0.33 ± 0.08 mm), TMR significantly increased with drop instillation (1.55 ± 0.69 mm) and at 1 minute (0.66 ± 0.36 mm; P tears. Difference in residence time reflects the different viscosity of each drop. An overload with a large drop may result in an initially increased BR. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  10. Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia.

    OpenAIRE

    Kemmerich, B; Small, G J; Pennington, J E

    1986-01-01

    The therapeutic activity of ciprofloxacin, enoxacin, and ofloxacin was evaluated in guinea pigs with acute and chronic experimental Pseudomonas aeruginosa pneumonia. Intratracheal instillations of P. aeruginosa resulted in fatal pneumonia in all untreated animals within 36 h. Among treatment groups (80 mg/kg [body weight] per day), cumulative survival rates were: 47%, ciprofloxacin; 55%, enoxacin; and 42%, ofloxacin. These rates were not significantly different. Intrapulmonary killing of P. a...

  11. Particles from wood smoke and road traffic differently affect the innate immune system of the lung.

    Science.gov (United States)

    Samuelsen, Mari; Cecilie Nygaard, Unni; Løvik, Martinus

    2009-09-01

    The effect of particles from road traffic and wood smoke on the innate immune response in the lung was studied in a lung challenge model with the intracellular bacterium Listeria monocytogenes. Female Balb/cA mice were instilled intratracheally with wood smoke particles, particles from road traffic collected during winter (studded tires used; St+), and during autumn (no studded tires; St-), or diesel exhaust particles (DEP). Simultaneously with, and 1 or 7 days after particle instillation, 10(5) bacteria were inoculated intratracheally. Bacterial numbers in the lungs and spleen 1 day after Listeria challenge were determined, as an indicator of cellular activation. In separate experiments, bronchoalveolar lavage (BAL) fluid was collected 4 h and 24 h after particle instillation. All particles tested reduced the numbers of bacteria in the lung 24 h after bacterial inoculation. When particles were given simultaneously with Listeria, the reduction was greatest for DEP, followed by St+ and St-, and least for wood smoke particles. Particle effects were no longer apparent after 7 days. Neutrophil numbers in BAL fluid were increased for all particle exposed groups. St+ and St- induced the highest levels of IL-1beta, MIP-2, MCP-1, and TNF-alpha, followed by DEP, which induced no TNF-alpha. In contrast, wood smoke particles only increased lactate dehydrogenase (LDH) activity, indicating a cytotoxic effect of these particles. In conclusion, all particles tested activated the innate immune system as determined with Listeria. However, differences in kinetics of anti-Listeria activity and levels of proinflammatory mediators point to cellular activation by different mechanisms.

  12. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M. [University of Extremo Catarinense, Criciuma, SC (Brazil)

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  13. Intravesical or intrarectal instillation of Maalox for the treatment of radiation cystitis or proctitis

    International Nuclear Information System (INIS)

    Kawagoe, Koh; Kawana, Takashi

    1989-01-01

    Intravesical or intrarectal instillation of Maalox, a well-known material for protection of mucous epithelia, was performed in 3 cases of radiation cystitis and one case of radiation proctitis, resulting in successful control of hemorrhage. Four cases of uterine cervical cancer with radiotherapy, including 2 cases of primary and 2 cases of postoperative radiotherapy, were managed by Maalox treatment with intervals of one to nine years between radiotherapy and Maalox instillation. One of the three patients with hemorrhagic cystitis, who had received internal iliac arterial embolization at the another hospital, was to be performed the operation of the urinary tract diversion. 50-100 ml of original or 1/2 diluted Maalox was instilled into urinary bladder or rectum with clump of catheter for 30 min. to 1 hr. after sufficient irrigation with 500 ml of 100 times diluted isodine. Blood transfusion for anemia was done in all cases, and antibiotics, or anticoagulant agents were systematically administered in some cases. Macrohematuria or melena ceased within 2 to 8 days after initiation of Maalox therapy in all cases. In one of the three cases of hemorrhagic cystitis, macroscopic hematuria, which reappeared one year later, was also successfully treated by Maalox therapy. In a case of radiation proctitis, though the melena disappeared in 5 days, diarrhea continued and the patient died of the primary disease two months later with the formation of rectovaginal fistula. No ultimate way of treatment of radiation hemorrhagic cystitis or proctitis has been established, though both of them were clinically important and serious side effects of radiotherapy. Therefore, intravesical or intrarectal instillation of Maalox could become one of the leading ways of treatment of intractable hemorrhagic cystitis, because the technique was simple and the effectiveness was valid without any notable side effects. (author)

  14. Distribution of endotracheally instilled surfactant protein SP-C in lung-lavaged rabbits.

    NARCIS (Netherlands)

    Bambang Oetomo, Sidarto; de Leij, Louis; Curstedt, T; ter Haar, J G; Schoots, Coenraad; Wildevuur, Charles; Okken, Albert

    In lung-lavaged surfactant-deficient rabbits (n = 6) requiring artificial ventilation, porcine surfactant was instilled endotracheally. This resulted in improvement of lung function so that the animals could be weaned off artificial ventilation. The animals were killed 4 1/2 h after surfactant

  15. Effect of combined nitrogen dioxide and carbon nanoparticle exposure on lung function during ovalbumin sensitization in Brown Norway rat.

    Directory of Open Access Journals (Sweden)

    Skander Layachi

    Full Text Available The interaction of particulate and gaseous pollutants in their effects on the severity of allergic inflammation and airway responsiveness are not well understood. We assessed the effect of exposure to NO(2 in the presence or absence of repetitive treatment with carbon nanoparticle (CNP during allergen sensitization and challenges in Brown-Norway (BN rat, in order to assess their interactions on lung function and airway responses (AR to allergen and methacholine (MCH, end-expiratory lung volume (EELV, bronchoalveolar lavage fluid (BALF cellular content, serum and BALF cytokine levels and histological changes. Animals were divided into the following groups (n = 6: Control; CNP (Degussa-FW2: 13 nm, 0.5 mg/kg instilled intratracheally ×3 at 7-day intervals; OVA: ovalbumin-sensitised; OVA+CNP: both sensitized and exposed to CNP. Rats were divided into equal groups exposed either to air or to NO(2, 10 ppm, 6 h/d, 5d/wk for 4 weeks. Exposure to NO(2, significantly enhanced lung inflammation and airway reactivity, with a significantly larger effect in animals sensitized to allergen, which was related to a higher expression of TH1 and TH2-type cytokines. Conversely, exposure to NO(2 in animals undergoing repeated tracheal instillation of CNP alone, increased BALF neutrophilia and enhanced the expression of TH1 cytokines: TNF-α and IFN-γ, but did not show an additive effect on airway reactivity in comparison to NO(2 alone. The exposure to NO(2 combined with CNP treatment and allergen sensitization however, unexpectedly resulted in a significant decrease in both airway reactivity to allergen and to methacholine, and a reduction in TH2-type cytokines compared to allergen sensitization alone. EELV was significantly reduced with sensitization, CNP treatment or both. These data suggest an immunomodulatory effect of repeated tracheal instillation of CNP on the proinflammatory effects of NO(2 exposure in sensitized BN rat. Furthermore, our findings suggest

  16. Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

    Science.gov (United States)

    Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

    2016-12-01

    Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

  17. Localization and (semi-)quantification of fluorescent beads of 2 sizes in chickens over time after simultaneous intratracheal and cloacal administration

    NARCIS (Netherlands)

    Berghof, T.V.L.; Lai, T.L.H.; Lammers, A.; Vries Reilingh, de G.; Nieuwland, M.G.B.; Aarnink, A.J.A.; Parmentier, H.K.

    2013-01-01

    Environmental particles enter the chicken via several routes. Entry via the respiratory and cloacal routes likely activates immune responses. We studied the localization of simultaneous intratracheally and cloacally applied beads of 2 sizes in the chicken body in time, and when possible,

  18. Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment.

    Science.gov (United States)

    Fukushima, Shoji; Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Sasaki, Toshiaki; Matsumoto, Michiharu

    2018-01-25

    This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m 3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

  19. Intratunical bupivacaine and methylprednisolone instillation for scrotal pain after testicular sperm retrieval procedures

    Institute of Scientific and Technical Information of China (English)

    GulK.Talu; TibetErdogru; TanselKaplancan; MustafaBahceci

    2003-01-01

    Aim:To investigate the effect of intratunical instillation of bupivacaine and methylprednisolone for scrotal pain,swelling and peritesticular fibrosis due to testicular sperm retrieval procedures.Methods:A total of 65 patients were randomly divided into two groups.In the instillation group(GI),34 patients were administered 2.5mL of 0.5% bupivacaine combined with 10 mg/mL methylprednisolone before closure of the tunica vaginalis.In the control group (GC),31 patients only received analgesics postoperatively by intramuscular route.The pain(by visual analogue scale,VAS)and duration of pain-free period after surgery between the two groups were evaluated at 2 and 4 h and at days 2 and 7 postoperatively.Results:The mean pain scores were significantly lower in the GI than in the GC group at 2 and 4 h after surgery(P<0.05 and P<0.01,respectively).The mean duration of pain free interval after the procedure was 47.8±16.9(12-76)h in GI,which was significantly longer than that in GC[(9.9±3.6;4-20)h].Besides,in the GI,29% of patients were completely free from pain and 67% had no scrotal swelling,but in the GC,all the patients required additional NSAID injection due to pain and only 3 % had no scrotal swelling.Conclusion:This study confirms that direct intratunical instillation of bupivacaine and methylprednisolone around the testis reduces the postoperative pain,scrotal swelling and peritesticular fibrosis.

  20. Histologic observations on the pathogenesis of lung cancer in hamsters following administration of polonium-210

    International Nuclear Information System (INIS)

    Lisco, H.; Kennedy, A.R.; Little, J.B.

    1974-01-01

    A serial sacrifice experiment was carried out to study the site of origin and the stages in development of lung cancer in hamsters induced by polonium-210 ( 210 Po). 1 or 2 animals were sacrificed weekly during and after a course of 7 intratracheal instillations of 0.1 μCi of 210 Po in saline. This exposure produced a transient radiation pneumonitis of moderate severity during, and for several weeks after, the instillation period. Subsequent pathological changes included hyperplasia of bronchiolar epithelium, and focal proliferation of epithelial cells in peribronchiolar and more remote alveoli, termed epithelialization of alveoli. Hyperplastic bronchiolar epithelium frequently showed numerous Clara cells which exhibited pleomorphism of cells and nuclei, multinucleated cells, and striking changes in staining characteristics of secretory granules. Epithelialization of alveoli showed steady progression from well-circumscribed small foci to larger confluent lesions which were composed of various cell types and resembled tumors. Malignant tumors occurred in many animals surviving more than 24 weeks after the last instillation of 210 Po

  1. Role of wound instillation with bupivacaine through surgical drains for postoperative analgesia in modified radical mastectomy

    Directory of Open Access Journals (Sweden)

    Nirmala Jonnavithula

    2015-01-01

    Full Text Available Background and Aims: Modified Radical Mastectomy (MRM is the commonly used surgical procedure for operable breast cancer, which involves extensive tissue dissection. Therefore, wound instillation with local anaesthetic may provide better postoperative analgesia than infiltration along the line of incision. We hypothesised that instillation of bupivacaine through chest and axillary drains into the wound may provide postoperative analgesia. Methods: In this prospective randomised controlled study 60 patients aged 45-60 years were divided into three groups. All patients were administered general anaesthesia. At the end of the surgical procedure, axillary and chest wall drains were placed before closure. Group C was the control with no instillation; Group S received 40 ml normal saline, 20 ml through each drain; and Group B received 40 ml of 0.25% bupivacaine and the drains were clamped for 10 min. After extubation, pain score for both static and dynamic pain was evaluated using visual analog scale and then 4 th hourly till 24 h. Rescue analgesia was injection tramadol, if the pain score exceeds 4. Statistical analysis was performed using SPSS version 13. Results : There was a significant difference in the cumulative analgesic requirement and the number of analgesic demands between the groups (P: 0.000. The mean duration of analgesia in the bupivacaine group was 14.6 h, 10.3 in the saline group and 4.3 h in the control group. Conclusion : Wound instillation with local anaesthetics is a simple and effective means of providing good analgesia without any major side-effects.

  2. Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA.

    Directory of Open Access Journals (Sweden)

    Sahu S

    1996-07-01

    Full Text Available An 82 year old man developed antibodies against coagulation factor VIII:C without any apparent cause. Bleeding from the soft tissue cavity could not be controlled by factor VIII:C concentrates, immunosuppression with steroids and intravenous immunoglobulin therapy in the standard dosages. However, a single injection of Epsilon Aminocaproic Acid (EACA instilled into the cavity under aseptic precautions achieved lasting hemostasis with resultant wound healing.

  3. Time-Dependent Subcellular Distribution and Effects of Carbon Nanotubes in Lungs of Mice

    DEFF Research Database (Denmark)

    Købler, Carsten; Poulsen, Sarah S.; Saber, Anne T.

    2015-01-01

    Background and Methods Pulmonary deposited carbon nanotubes (CNTs) are cleared very slowly from the lung, but there is limited information on how CNTs interact with the lung tissue over time. To address this, three different multiwalled CNTs were intratracheally instilled into female C57BL/6 mice...... of cellular interactions in lung tissue, with the longer and thicker CNTs resulting inmore severe effects in terms of eosinophil influx and incidence of eosinophilic crystalline pneumonia (ECP)....

  4. Prophylactic vesical instillations with 0.2% chondroitin sulfate may reduce symptoms of acute radiation cystitis in patients undergoing radiotherapy for gynecological malignancies

    NARCIS (Netherlands)

    Hazewinkel, M.H.; Stalpers, L.J.A.; Dijkgraaf, M.G.; Roovers, J.P.W.R.

    2011-01-01

    We studied the feasibility and efficacy of intravesical instillations with 40 ml chondroitin sulfate 0.2% solution to prevent or reduce acute radiation cystitis in women undergoing pelvic radiotherapy. In a comparative pilot study in 20 patients, half of the patients received instillations.

  5. Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

    2016-08-01

    Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

  6. Intravesical instillation of Formalin for hemorrhagic cystitis secondary to radiation for gynecologic malignancies

    International Nuclear Information System (INIS)

    Behnam, K.; Patil, U.B.; Mariano, E.

    1983-01-01

    Our experience with the use of Formalin instillation in intractable gross hematuria secondary to radiation cystitis in patients with gynecological malignancies is reported. This study indicates coagulative effect of low concentration of Formalin with minimal side effects as a method to control hemorrhage

  7. Intravesical instillation of Adriamycin plus irradiation in the prophylactic treatment of recurring bladder tumors

    International Nuclear Information System (INIS)

    Yoneda, Fumio; Kan, Masaharu; Tsujimura, Haruhiro; Nakajima, Mikio

    1989-01-01

    The prevention of the recurrence of bladder tumors was attempted in 45 patients by intravesical instillation of Adriamycin plus irradiation (20 Gy). 30 ml saline solution containing ADM 30mg was instilled into the bladder and then irradiation was performed every day for 10 days. Patients' ages ranged from 36 to 84 years with a mean of 66.5 years; the sex ratio was 3(M) : 1(F). The recurrence rate following therapy was 8.1% after 1 year, 29.4% after 2 years and 29.4% after 3 years. The recurrence rate was low in patients with low grade tumors, those with single tumors and those who received this combination therapy after surgery. Only one patient was obliged to interrupt the therapy due to a bladder irritation. (author)

  8. Elimination of radioactivity after intratracheal instillation of tritiated 3, 4-benzopyrene in hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Pylev, L N; Roe, F J.C.; Warwick, G P

    1969-01-01

    Injection and recovery experiments of tritiated 3,4-benzopyrene (BaP) injected alone or with particulate carriers into hamsters were performed. After 21 days, asbestos or carbon black carriers had significantly increased the retention of BaP in the lung. Elimination was rapid at first (2 weeks: and little influenced by carrier; slower rate of elimination was noted after that. Carriers increased recoverable macrophages but decreased the amount of radioactivity per macrophage. Radioactivity was similar in all groups for kidney, liver, blood, feces, and urine.

  9. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    OpenAIRE

    Almeida-Reis, Rafael; Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Lopes, Fernanda D. T. Q. S.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Leick, Edna A.; Oliva, Maria L. V.; Tibério, Iolanda F. L. C.

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.??C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respirator...

  10. Elastase-induced emphysema in guinea pigs

    International Nuclear Information System (INIS)

    Loscutoff, S.M.

    1979-01-01

    Pulmonary function changes measured in guinea pigs 4 to 5 wk following intratracheal instillation of crystalline porcine pancreatic elastase resembled comparable changes in humans with moderately severe pulmonary emphysema. Compared with saline-treated controls, elastase-treated animals had increased values for all divisions of lung volume, increased static compliance and prolonged time constants. Since humans with emphysema are especially sensitive to air pollutants, elastase-treated animals may be useful as sensitive animal models in inhalatio toxicology

  11. [Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor].

    Science.gov (United States)

    Chesnokova, N B; Beznos, O V; Lozinskaya, N A; Beyshenova, G A; Nesterova, T V

    2016-01-01

    Acute immunogenic uveitis was modeled in rabbits via the subcutaneous and intravitreal injections of normal horse serum. We studied the effect of instillations of 0.1% melatonin solution on the clinical course of uveitis and biochemical parameters of tear fluid and aqueous humor: antioxi-dant activity, protein concentration and α(2)-macroglobulin level. Melatonin instillations decreased clinical manifestations of uveitis. We found that the antioxidant activity in tears of the rabbits treated with melatonin was substantially higher and the α(2)-macroglobulin level lower than in untreated animals. Antioxidant activity in aqueous humor taken on day 10 of uveitis was also twice higher while protein and α(2)-macroglobulin levels were 1.5-2 times lower than in untreated animals. These data indicate that instillations of melatonin increase the local antioxidant activity and decrease the acuity of inflammation and permeability of hematoophthalmic barrier in uveitis.

  12. A pharmacoeconomic analysis of the use of single MMC instillation in low risk NMIBC in Italy

    Directory of Open Access Journals (Sweden)

    Renzo Colombo

    2013-03-01

    Full Text Available BACKGROUND: Bladder cancer accounts for 5-10% of all cancers in Europe and up to 85% patients presents a noninvasive tumor, whose treatment of choice is the transurethral bladder resection (TURB paired with adjuvant intravesical chemotherapy or immunotherapy. Despite several clinical trials showed that this treatment is safe and decreases recurrences by 17% to 44% this practice is limited for many reasons. The study objective is to analyze the economical advantages of the single immediate post operative Mitomycin C instillation in Non Muscle-invasive Bladder Cancer (NMIBC low-risk patients.METHODS: A cost-benefit analysis was performed evaluating the economical gain that would raised from a scenario with a single immediate post operative mitomycin C instillation in each low-risk NMIBC patient who underwent to TURB. Net present value and cost-benefit ratio were calculated and sensitivity analyses were performed. Base case analysis was performed considering tumor recurrence rate reduction of 11.7% and a TURB costs of 2,167.0 €, while sensitivity analyses were performed using a recurrence rate reduction of 19.2% and 15.0% and a TURB cost of 2,472.93 €. The discount rate was 2%.RESULTS: The single immediate post operative instillation of mitomycin C resulted to be cost-beneficial with a cost-benefit ratio that goes from 0.48 to 0.79 when compared to TURB alone raising a Net Present Value that goes from 660,284.39 € to 2,650,530.79 €.CONCLUSION: This study demonstrates that even assuming conservative parameters for recurrence rates reduction, a single immediate post operative mitomycin C instillation in low risk NMIBC patients would lower not only the recurrence rate but also the caring cost for bladder cancer.

  13. The effect of intravesical instillations with Hyaluronic Acid on sexual dysfunction in women with recurrent urinary tract infections (RUTI).

    Science.gov (United States)

    Nightingale, Gemma; Shehab, Qasem; Kandiah, Chandrakumaran; Rush, Lorraine; Rowe-Jones, Clare; Phillips, Christian H

    2018-02-01

    To determine whether sexual dysfunction in women with recurrent urinary tract infections (RUTI) improved following treatment with intravesical Hyaluronic Acid (HA) instillations. Ethical approval was obtained for a prospective study to be performed. Patients referred for bladder instillations to treat RUTI, and who were sexually active, were recruited to the study. A selection of validated questionnaires (ICIQ-UI, ICIQ-VS, FSDS-R, ICIQ-FLUTS, O'Leary/Sant and PGI-I) were completed at baseline, three, six and 12 months after initiation of treatment with bladder instillations. Treatment consisted of weekly bladder instillations with a preparation containing HA for four weeks then monthly for two further treatments. Results were populated in SPSS for statistical analysis and statistical significance was powered for 22 patients. Thirty women were included in the study. FSDS-R was used to determine sexual dysfunction and showed that 57% patients with RUTI had significant sexual distress. There was a significant improvement in FSDS-R at three, six and 12 months when compared to baseline (Friedman two-way analysis p sexual dysfunction, and an improvement in bladder symptoms following treatment with HA. To our knowledge, this is the first study to prove an improvement in sexual dysfunction following intravesical treatment with HA which is sustained for up to 12 months. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. CT-guided lung biopsy: incidence of pneumothorax after instillation of NaCl into the biopsy track

    International Nuclear Information System (INIS)

    Billich, Christian; Brenner, Gerhard; Schmidt, Stefan A.; Brambs, Hans-Juergen; Pauls, Sandra; Muche, Rainer; Krueger, Stefan

    2008-01-01

    This study was conducted to evaluate whether instillation of NaCl 0.9% solution into the biopsy track reduces the incidence of pneumothoraces after CT-guided lung biopsy. A total of 140 consecutive patients with pulmonary lesions were included in this prospective study. All patients were alternatingly assigned to one of two groups: group A in whom the puncture access was sealed by instillation of NaCl 0.9% solution during extraction of the guide needle (n 70) or group B for whom no sealing was performed (n = 70). CT-guided biopsy was performed with a 18-G coaxial system. Localization of lesion (pleural, peripheral, central), lesion size, needle-pleural angle, rate of pneumothorax and alveolar hemorrhage were evaluated. In group A, the incidence of pneumothorax was lower compared to group B (8%, 6/70 patients vs. 34%, 24/70 patients; P < 0.001). All pneumothoraces occurred directly post punctionem after extraction of the guide needle. One patient in group A and eight patients in group B developed large pneumothoraces requiring chest tube placement (P 0.01). The frequency of pneumothorax was independent of other variables. After CT-guided biopsy, instillation of NaCl 0.9% solution into the puncture access during extraction of the needle significantly reduces the incidence of pneumothorax. (orig.)

  15. CT-guided lung biopsy: incidence of pneumothorax after instillation of NaCl into the biopsy track

    Energy Technology Data Exchange (ETDEWEB)

    Billich, Christian; Brenner, Gerhard; Schmidt, Stefan A.; Brambs, Hans-Juergen; Pauls, Sandra [University of Ulm, Department of Diagnostic and Interventional Radiology, Ulm (Germany); Muche, Rainer [University of Ulm, Institute of Biometrics, Ulm (Germany); Krueger, Stefan [University of Ulm, Department of Internal Medicine, Ulm (Germany)

    2008-06-15

    This study was conducted to evaluate whether instillation of NaCl 0.9% solution into the biopsy track reduces the incidence of pneumothoraces after CT-guided lung biopsy. A total of 140 consecutive patients with pulmonary lesions were included in this prospective study. All patients were alternatingly assigned to one of two groups: group A in whom the puncture access was sealed by instillation of NaCl 0.9% solution during extraction of the guide needle (n = 70) or group B for whom no sealing was performed (n = 70). CT-guided biopsy was performed with a 18-G coaxial system. Localization of lesion (pleural, peripheral, central), lesion size, needle-pleural angle, rate of pneumothorax and alveolar hemorrhage were evaluated. In group A, the incidence of pneumothorax was lower compared to group B (8%, 6/70 patients vs. 34%, 24/70 patients; P < 0.001). All pneumothoraces occurred directly post punctionem after extraction of the guide needle. One patient in group A and eight patients in group B developed large pneumothoraces requiring chest tube placement (P = 0.01). The frequency of pneumothorax was independent of other variables. After CT-guided biopsy, instillation of NaCl 0.9% solution into the puncture access during extraction of the needle significantly reduces the incidence of pneumothorax. (orig.)

  16. Intratracheal transplantation of endothelial progenitor cells attenuates smoking-induced COPD in mice

    Directory of Open Access Journals (Sweden)

    Shi Z

    2017-03-01

    Full Text Available Zhihui Shi,1 Yan Chen,1 Jun Cao,2 Huihui Zeng,1 Yue Yang,1 Ping Chen,1 Hong Luo,1 Hong Peng,1 Shan Cai,1 Chaxiang Guan3 1Department of Internal Medicine, Division of Respiratory Disease, The Second Xiangya Hospital, Central-South University, 2Department of Internal Medicine, Division of Respiratory Disease, The People’s Hospital of Hunan Province, 3Department of Physiology, Xiangya Medical School, Central-South University, Changsha, Hunan, People’s Republic of China Background: Endothelial progenitor cells (EPCs might play a protective role in COPD. The aim of this study was to investigate whether intratracheal allogeneic transplantation of bone-marrow-derived EPCs would attenuate the development of smoking-induced COPD in mice.Methods: Isolated mononuclear cells from the bone marrow of C57BL/6J mice were cultured in endothelial cell growth medium-2 for 10 days, yielding EPCs. A murine model of COPD was established by passive 90-day exposure of cigarette smoke. On day 30, EPCs or phosphate-buffered saline alone was administered into the trachea. On day 90, EPCs or 30 µL phosphate-buffered saline alone was administered into the trachea, and on day 120, inflammatory cells, antioxidant activity, apoptosis, matrix metalloproteinase (MMP-2, and MMP-9 were measured.Results: After EPC treatment, the lung function of the mice had improved compared with the untreated mice. Mean linear intercept and destructive index were reduced in the EPCs-treated group compared with the untreated group. In addition, the EPCs-treated mice exhibited less antioxidant activity in bronchoalveolar lavage fluid compared with the untreated mice. Moreover, decreased activities of MMP-2, MMP-9, and TUNEL-positive cells in lung tissues were detected in EPCs-treated mice.Conclusion: Intratracheal transplantation of EPCs attenuated the development of pulmonary emphysema and lung function disorder probably by alleviating inflammatory infiltration, decelerating apoptosis

  17. Comparison of Outcomes for Normal Saline and an Antiseptic Solution for Negative-Pressure Wound Therapy with Instillation.

    Science.gov (United States)

    Kim, Paul J; Attinger, Christopher E; Oliver, Noah; Garwood, Caitlin; Evans, Karen K; Steinberg, John S; Lavery, Larry A

    2015-11-01

    Negative-pressure wound therapy with instillation is an adjunctive treatment that uses periodic instillation of a solution and negative pressure for a wide diversity of wounds. A variety of solutions have been reported, with topical antiseptics as the most frequently chosen option. The objective of this study was to compare the outcomes of normal saline versus an antiseptic solution for negative-pressure wound therapy with instillation for the adjunctive treatment of infected wounds. This was a prospective, randomized, effectiveness study comparing 0.9% normal saline versus 0.1% polyhexanide plus 0.1% betaine for the adjunctive treatment of infected wounds that required hospital admission and operative débridement. One hundred twenty-three patients were eligible, with 100 patients randomized for the intention-to-treat analysis and 83 patients for the per-protocol analysis. The surrogate outcomes measured were number of operative visits, length of hospital stay, time to final surgical procedure, proportion of closed or covered wounds, and proportion of wounds that remained closed or covered at the 30-day follow-up. There were no statistically significant differences in the demographic profiles in the two cohorts except for a larger proportion of male patients (p = 0.004). There was no statistically significant difference in the surrogate outcomes with the exception of the time to final surgical procedure favoring normal saline (p = 0.038). The authors' results suggest that 0.9% normal saline may be as effective as an antiseptic (0.1% polyhexanide plus 0.1% betaine) for negative-pressure wound therapy with instillation for the adjunctive inpatient management of infected wounds. Therapeutic, II.

  18. Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field.

    Science.gov (United States)

    Zanchi, Ana Claudia; Saiki, Mitiko; Saldiva, Paulo Hilário Nascimento; Barros, Helena Maria Tannhauser; Rhoden, Claudia Ramos

    2010-01-01

    Epidemiological studies have demonstrated the adverse effects of particulate matter (PM) inhalation on the respiratory and cardiovascular systems. It has been reported that air pollution may affect the central nervous system and decrease cognitive function. In rats, residual oil fly ash (ROFA) instillation causes decreased motor activity and increased lipid peroxidation in the striatum and the cerebellum. Our objective was to determine whether chronic instillation of particles induces changes in learning and memory in rats and whether oxidants in the hippocampus may contribute to these adverse effects. Forty-five-day-old male Wistar rats were exposed to ROFA by intranasal instillation and were treated with N-acetylcysteine (NAC) at 150 mg/kg i.p. for 30 days. Control groups were exposed to ROFA, NAC, or neither. On days 1, 8, and 30 of the protocol, rats were submitted to the open field test to evaluate habituation. After the last open field session, the rats were killed by decapitation. The hippocampus was used to determine lipid peroxidation (LP) by the thiobarbituric acid-reactive substances test. ROFA instillation induced an increase in LP in the hippocampus compared to all treatment groups (p = .012). NAC treatment blocked these changes. All of the treatment groups presented a decrease in the frequency of peripheral walking (p = .001), rearing (p = .001), and exploration (p = .001) over time. Our study demonstrates that exposure to particles for 30 days and/or NAC treatment do not modify habituation to an open field, a simple form of learning and memory in rats, and that oxidative damage induced by ROFA does not modulate these processes.

  19. Role of oxidative stress in thuringiensin-induced pulmonary toxicity

    International Nuclear Information System (INIS)

    Tsai, S.-F.; Yang Chi; Liu, B.-L.; Hwang, J.-S.; Ho, S.-P.

    2006-01-01

    To understand the effect of thuringiensin on the lungs tissues, male Sprague-Dawley rats were administrated with thuringiensin by intratracheal instillation at doses 0.8, 1.6 and 3.2 mg/kg of body weight, respectively. The rats were sacrificed 4 h after treatment, and lungs were isolated and examined. Subsequently, an effective dose of 1.6 mg/kg was selected for the time course study (4, 8, 12, and 24 h). Intratracheal instillation of thuringiensin resulted in lung damage, as evidenced by increase in lung weight and decrease in alkaline phosphatase (10-54%), an enzyme localized primarily in pulmonary alveolar type II epithelial cells. Furthermore, the administration of thuringiensin caused increases in lipid peroxidation (21-105%), the indices of lung injury. In addition, the superoxide dismutase (SOD) and glutathione (GSH) activities of lung tissue extracts were measured to evaluate the effect of thuringiensin on antioxidant defense system. The SOD activity and GSH content in lung showed significant decreases in a dose-related manner with 11-21% and 15-37%, respectively. Those were further supported by the release of proinflammatory cytokines, as indicated by increases in IL-1β (229-1017%) and TNF-α (234%) levels. Therefore, the results demonstrated that changes in the pulmonary oxidative-antioxidative status might play an important role in the thuringiensin-induced lung injury

  20. Recurrent pregnancy-related upper airway obstruction caused by intratracheal ectopic thyroid tissue

    DEFF Research Database (Denmark)

    Døssing, H; Jørgensen, K E; Oster-Jørgensen, E

    1999-01-01

    An unusual case of recurrent pregnancy-related thyroid growth stimulation is reported. A 27-year-old euthyroid woman had pulmonary symptoms, thought to be asthma during her first pregnancy, that improved postpartum. Bronchodilatators had no effect and symptoms recurred from gestational week 22...... during her second pregnancy. Her 58-mL multinodular goiter (by ultrasound) was not thought to be responsible for her upper airway symptoms. Therefore, fiber laryngoscopy and computed tomographic (CT) scan were performed and revealed a 20 x 15 x 10 mm intratracheal tumor. After tracheostomy...... developed normally. We believe that this case illustrates the recurrent effect of pregnancy-related thyroid tissue stimulation by a combination of increasing human chorionic gonadotropin (hCG) stimulation and iodine deficiency in a borderline iodine-deficient region. This is the first report on symptomatic...

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

    Directory of Open Access Journals (Sweden)

    Schaller Peter

    2006-03-01

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

  2. Synchrotron microradiography study on acute lung injury of mouse caused by PM2.5 aerosols

    International Nuclear Information System (INIS)

    Tong Yongpeng; Zhang Guilin; Li Yan; Tan Mingguan; Wang Wei; Chen Jianmin; Hwu Yeukuang; Hsu, Pei-Chebg; Je, Jung Ho; Margaritondo, Giorgio; Song Weiming; Jiang, Rongfang; Jiang Zhihai

    2006-01-01

    In order to investigate FeSO 4 , ZnSO 4 (the two of main metal compositions of Shanghai PM 2.5 (particle matter with those aerodynamical diameter 2.5 aerosol particles, FeSO 4 , ZnSO 4 and their mixtures were instilled intratracheally into mouse lungs for experiment. By 2 days after instillation, the live mice were checked in vivo by synchrotron refractive index microradiography. In addition after extracted and examined by dissection, the right lobes of lung were fixed by formalin, then imaged by synchrotron microradiography again. Corresponding parts of those lung tissues were embedded in paraffin for histopathologic study. The synchrotron X-ray microradiographs of live mouse lung showed different lung texture changes after instilled with different toxic solutions. Hemorrhage points in lung were observed more from those mice instilled by FeSO 4 contained toxin solutions groups. Bronchial epithelial hyperplasia can be observed in ZnSO 4 contained solution-instilled groups from histopathologic analysis. It was found that the acute lung injury of mice caused by solution of PM 2.5 + FeSO 4 + ZnSO 4 was more serious than other toxin solutions. Results suggested that FeSO 4 mainly induced hemorrhage and ZnSO 4 mainly induced inflammation and bronchiolar epithelial hyperplasia in the early toxicological effects of PM 2.5

  3. Hepatic microsomal phospholipids in rats exposed intratracheally to coal fly ash

    International Nuclear Information System (INIS)

    Srivastava, P.K.; Chauhan, S.S.; Misra, U.K.

    1986-01-01

    The effects of intratracheal administration of fly ash (50 mg/kg body weight, daily for 7 days) on hepatic microsomal phospholipid metabolism has been studied in rats using various phospholipid precursors, viz NaH 2 32 PO 4 , (methyl- 14 C)-choline, and (methyl- 14 C)-methionine. Fly ash administration significantly increased microsomal phosphatidylcholine (PC), and lysophosphatidylcholine (LPC). The incorporation of NaH 2 32 PO 4 into total liver phospholipids, PC and Phosphatidyl ethanolamine (PE) was significantly increased in fly ash-treated rats as compared to the control. Fly ash administration also increased the incorporation of (methyl- 14 C)-choline into microsomal PC. Incorporation of (methyl- 14 C)-methionine into microsomal PC was not affected. Fly ash administration decreased the per cent distribution of arachidonic acid in PC and PE and increased that of oleic acid in PC and of linoleic acid in PE. (orig.)

  4. Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice.

    Science.gov (United States)

    Hamzawy, Mohamed A; Abo-Youssef, Amira M; Salem, Heba F; Mohammed, Sameh A

    2017-11-01

    The current study aimed to develop gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) as drug carriers for temozolomide (TMZ) and investigate the possible therapeutic effects of intratracheal inhalation of nanoformulation of TMZ-loaded gold nanoparticles (TGNPs) and liposome-embedded TGNPs (LTGNPs) against urethane-induced lung cancer in BALB/c mice. Physicochemical characters and zeta potential studies for gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) were performed. The current study was conducted by inducing lung cancer chemically via repeated exposure to urethane in BALB/C mice. GNPs and LGNPs were exhibited in uniform spherical shape with adequate dispersion stability. GNPs and LGNPs showed no significant changes in comparison to control group with high safety profile, while TGNPs and LTGNPs succeed to improve all biochemical data and histological patterns. GNPs and LGNPs are promising drug carriers and succeeded in the delivery of small and efficient dose of temozolomide in treatment lung cancer. Antitumor activity was pronounced in animal-treated LTGNPs, these effects may be due to synergistic effects resulted from combination of temozolomide and gold nanoparticles and liposomes that may improve the drug distribution and penetration.

  5. Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

  6. Respiratory tract carcinogenesis induced by radionuclides in the Syrian hamister

    International Nuclear Information System (INIS)

    Smith, D.M.; Thomas, R.G.; Anderson, E.C.

    1979-01-01

    Syrian hamsters were exposed to lung irradiation by various modalities that differed in degree of localization and the fraction of lung exposed. The animals were given alpha emitters under several exposure conditions: intratracheal (IT) instillation of 210 Po and 239 PuO 2 -ZrO 2 microspheres; inhalation (INH) of 238 239 PuO 2 -ZrO 2 particles; and/or intravenous (IV) injection of 238 239 PuO 2 -ZrO 2 microspheres. Beta-emitting 147 Pm was also administered; the radionuclide was incorporated into 10 μm diameter ZrO 2 microspheres and deposited in the lungs via the jugular vein. These microspheres lodge quantitatively in the pulmonary capillary bed for the duration of the animal's life span. Total IV Pu microsphere lung burdens have ranged from 0.14 nCi to 484 nCi and the number of spheres from 1500 to 880 000. Pu burdens from inhalation have ranged from 8 nCi to 101 nCi, IT Po burdens from 25 to 122 nCi, and Pm-laden microsphere burdens from 427 to 15 750 nCi. Intratracheal instillation of 210 Po solution gave nearly uniform alpha irradiation of the entire lung, intravenous injection of large numbers of ZrO 2 microspheres laden with 147 Pm gave whole lung exposures to low LET radiation, and IV injection of Pu-microspheres provided a gradation of focal alpha exposures. The Po and Pm exposures were highly tumorigenic, whereas the Pu microspheres produced tumors only when a large fraction of the lung was exposed to large radiation doses. However, Pu-ZrO 2 administered via inhalation was very carcinogenic and resulted in tumor incidences of 50% in some experiments. The IT instillation of Fe 2 O 3 following IV or IT Pu-ZrO 2 microsphere administration dramatically enhanced lung tumor induction

  7. Prenatal Exposure to Carbon Black (Printex 90)

    DEFF Research Database (Denmark)

    Jackson, Petra; Vogel, Ulla; Wallin, Håkan

    2011-01-01

    Maternal pulmonary exposure to ultrafine particles during pregnancy may affect the health of the child. Developmental toxicity of carbon black (Printex 90) nanoparticles was evaluated in a mouse model. Time-mated mice were intratracheally instilled with Printex 90 dispersed in Millipore water on ...... on gestation days (GD) 7, 10, 15 and 18, with total doses of 11, 54 and 268 mu g Printex 90/animal. The female offspring prenatally exposed to 268 mu g Printex 90/animal displayed altered habituation pattern during the Open field test....

  8. Pulmonary toxicity screening studies in male rats with TiO2 particulates substantially encapsulated with pyrogenically deposited, amorphous silica

    Directory of Open Access Journals (Sweden)

    Webb TR

    2006-01-01

    Full Text Available Abstract The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO2 particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1 R-100 TiO2 particles (hydrophilic in nature; 2 quartz particles, 3 carbonyl iron particles. Phosphate-buffered saline (PBS instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 hrs, 1 week, 1 month and 3 months. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to Pigment A or R-100 TiO2 particles produced transient inflammatory and cell injury effects at 24 hours postexposure (pe, but these effects were not sustained when compared to quartz-related effects. Exposures to carbonyl iron particles or PBS resulted only in minor, short-term and reversible lung inflammation, likely related to the effects of the instillation procedure. Histopathological analyses of lung tissues revealed that pulmonary exposures to Pigment A TiO2 particles produced minor inflammation at 24 hours postexposure and these effects were not significantly different from exposures to R-100 or carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid

  9. Evaluation of alcaftadine 0.25% ophthalmic solution in acute allergic conjunctivitis at 15 minutes and 16 hours after instillation versus placebo and olopatadine 0.1%

    Directory of Open Access Journals (Sweden)

    Jack V Greiner

    2011-01-01

    Full Text Available Jack V Greiner1,2, Kimberly Edwards-Swanson3, Avner Ingerman41Schepens Eye Research Institute, Boston, MA; 2Department of Ophthalmology, Harvard Medical School, Boston, MA; 3Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ; 4Ora Inc, Andover, MA, USAPurpose: To evaluate the effectiveness of alcaftadine 0.05%, 0.1%, and 0.25% ophthalmic solutions in treating the signs and symptoms of allergic conjunctivitis when compared with olopatadine hydrochloride 0.1% and placebo using the conjunctival allergen challenge (CAC model.Methods: One hundred and seventy subjects were randomized and 164 subjects completed all visits. CAC was performed to determine and confirm subjects’ eligibility at visits 1 and 2, respectively. The CAC was repeated at visit 3 (day 0 ± 3, 16 hours after study medication instillation, and at visit 4 (day 14 ± 3, 15 minutes after instillation. Ocular itching and conjunctival redness were evaluated after an allergen challenge, along with several secondary endpoints.Results: Alcaftadine 0.25% and olopatadine 0.1% treatments exhibited significantly lower mean scores compared with placebo for ocular itching and conjunctival redness at visits 3 and 4. Most adverse events were self-limiting and mild in severity. No serious treatment-related adverse events occurred.Conclusion: Treatment with alcaftadine 0.25% ophthalmic solution resulted in mean differences of >1 unit (ocular itching and approximately >1 unit (conjunctival redness, which was significant (P < 0.001 compared with placebo treatment. All doses of alcaftadine were safe and well tolerated in the population studied.Keywords: alcaftadine, allergic conjunctivitis, conjunctival allergen challenge

  10. Synchrotron microradiography study on acute lung injury of mouse caused by PM{sub 2.5} aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Tong Yongpeng [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhang Guilin [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)]. E-mail: glzhang@sinap.ac.cn; Li Yan [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Tan Mingguan [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Wang Wei [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Chen Jianmin [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Hwu Yeukuang [Institute of Physics, Academia Sinica, Nankang, Taipei (China); Hsu, Pei-Chebg [Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan (China); Je, Jung Ho [Department of Material Science and Engineering, Pohang University of Science and Technology, Pohang (Korea, Republic of); Margaritondo, Giorgio [Faculte des sciences de base, CH-1015 Lausanne, Ecole Polytechnique Federale de Lausanne (EPFL) (Switzerland); Song Weiming [School of Public Health, Fudan University, Shanghai 200032 (China); Jiang, Rongfang [School of Public Health, Fudan University, Shanghai 200032 (China); Jiang Zhihai [School of Public Health, Fudan University, Shanghai 200032 (China)

    2006-05-15

    In order to investigate FeSO{sub 4}, ZnSO{sub 4} (the two of main metal compositions of Shanghai PM{sub 2.5} (particle matter with those aerodynamical diameter <2.5 {mu}m)) effects on acute lung injury, six solutions contained PM{sub 2.5} aerosol particles, FeSO{sub 4}, ZnSO{sub 4} and their mixtures were instilled intratracheally into mouse lungs for experiment. By 2 days after instillation, the live mice were checked in vivo by synchrotron refractive index microradiography. In addition after extracted and examined by dissection, the right lobes of lung were fixed by formalin, then imaged by synchrotron microradiography again. Corresponding parts of those lung tissues were embedded in paraffin for histopathologic study. The synchrotron X-ray microradiographs of live mouse lung showed different lung texture changes after instilled with different toxic solutions. Hemorrhage points in lung were observed more from those mice instilled by FeSO{sub 4} contained toxin solutions groups. Bronchial epithelial hyperplasia can be observed in ZnSO{sub 4} contained solution-instilled groups from histopathologic analysis. It was found that the acute lung injury of mice caused by solution of PM{sub 2.5} + FeSO{sub 4} + ZnSO{sub 4} was more serious than other toxin solutions. Results suggested that FeSO{sub 4} mainly induced hemorrhage and ZnSO{sub 4} mainly induced inflammation and bronchiolar epithelial hyperplasia in the early toxicological effects of PM{sub 2.5}.

  11. A comparative study of lung toxicity in rats induced by three types of nanomaterials

    Science.gov (United States)

    Lin, Zhiqing; Ma, Li; X, Zhu-ge; Zhang, Huashan; Lin, Bencheng

    2013-12-01

    The public is increasingly exposed to various engineered nanomaterials because of their mass production and wide application. Even when the biological effects of nanomaterials have been assessed, the underlying mechanisms of action in vivo are poorly understood. The present study was designed to seek a simple, effective, and oxidative stress-based biomarker system used for screening toxicity of nanomaterials. Nano-ferroso-ferric oxide (nano-Fe3O4), nano-silicon dioxide (nano-SiO2), and single-walled carbon nanotubes (SWCNTs) were dispersed in corn oil and characterized using transmission electron microscopy (TEM). Rats were exposed to the three nanomaterials by intratracheal instillation once every 2 days for 5 weeks. We investigated their lung oxidative and inflammatory damage by bronchoalveolar lavage fluid (BALF) detection and comparative proteomics by lung tissue. Two-dimensional electrophoresis (2-DE) of proteins isolated from the lung tissue, followed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, was performed. In the present study, we chose to detect lactate dehydrogenase, total antioxidant capacity, superoxide dismutase, and malondialdehyde as the biomarker system for screening the oxidative stress of nanomaterials and IL-6 as the inflammatory biomarker in BALF. Proteomics analysis revealed 17 differentially expressed proteins compared with the control group: nine were upregulated and eight were downregulated. Our results indicated that exposure by intratracheal instillation to any of the three typical nanomaterials may cause lung damage through oxidative damage and/or an inflammatory reaction.

  12. Intraperitoneal instillation of saline and local anesthesia for prevention of shoulder pain after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Donatsky, Anders Meller; Bjerrum, Flemming; Gögenür, Ismayil

    2013-01-01

    instillation (IPI) of saline and local anesthesia (LA) to minimize SP. METHODS: A search of the literature was conducted using PubMed and Excerpta Medica Database (EMBASE). Eligibility criteria were: randomized clinical trials (RCT) evaluating IPI of saline and/or LA to minimize incidence or severity of SP...

  13. Inflammatory and genotoxic effects of sanding dust generated from nanoparticle-containing paints and lacquers

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Koponen, Ismo Kalevi; Jensen, Keld Alstrup

    2012-01-01

    -containing and the conventional lacquer and the outdoor acrylic-based reference paint increased the level of DNA strand breaks in bronchoalveolar fluid cells. In conclusion, addition of nanoparticles to paint or lacquers did not increase the potential of sanding dust for causing inflammation, oxidative stress or DNA damage...... of boards painted with paints with and without nanoparticles were determined 24 h after intratracheal instillation of a single dose of 54 mu g in mice. Dusts from nanoparticle-containing paints and lacquers did not generate pulmonary inflammation or oxidative stress. Sanding dust from both the nanoparticle...

  14. An innovative approach to sampling complex industrial emissions for use in animal toxicity tests: application to iron casting operations.

    Science.gov (United States)

    Palmer, W G; Scholz, R C; Moorman, W J

    1983-03-01

    Sampling of complex mixtures of airborne contaminants for chronic animal toxicity tests often involves numerous sampling devices, requires extensive sampling time, and yields forms of collected materials unsuitable for administration to animals. A method is described which used a high volume, wet venturi scrubber for collection of respirable fractions of emissions from iron foundry casting operations. The construction and operation of the sampler are presented along with collection efficiency data and its application to the preparation of large quantities of samples to be administered to animals by intratracheal instillation.

  15. Low translocation of Bacillus thuringiensis israelensis to inner organs in mice after pulmonary exposure to commercial biopesticide

    DEFF Research Database (Denmark)

    Barfod, Kenneth Klingenberg; Ørum-Smidt, Lasse; Krogfelt, Karen A.

    2010-01-01

    Translocation of viable cells from a Bacillus thuringiensis israelensis-based biopesticide to inner organs in a mouse model was studied. Mice were exposed to the originally formulated product through the lungs and gastrointestinal tract by intratracheal instillation. Colony forming units (CFU) were...... grown from lungs, caecum, spleen and liver on Bacillus cereus-specific agar (BCSA) after 24 h and finally determined to be biopesticide strain B. t. israelensis by large plasmid profile. No CFU were found in spleen or liver of the control mice or in any aerosol background or material. We have shown...

  16. Identification of Gene Transcription Start Sites and Enhancers Responding to Pulmonary Carbon Nanotube Exposure in Vivo

    DEFF Research Database (Denmark)

    Bornholdt, Jette; Saber, Anne Thoustrup; Lilje, Bait

    2017-01-01

    Increased use of nanomaterials in industry, medicine, and consumer products has raised concerns over their toxicity. To ensure safe use of nanomaterials, understanding their biological effects at the molecular level is crucial. In particular, the regulatory mechanisms responsible for the cascade...... of genes activated by nanomaterial exposure are not well-characterized. To this end, we profiled the genome-wide usage of gene transcription start sites and linked active enhancer regions in lungs of C57BL/6 mice 24 h after intratracheal instillation of a single dose of the multiwalled carbon nanotube...

  17. Intratracheal administration of fullerene nanoparticles activates splenic CD11b+ cells

    International Nuclear Information System (INIS)

    Ding, Ning; Kunugita, Naoki; Ichinose, Takamichi; Song, Yuan; Yokoyama, Mitsuru; Arashidani, Keiichi; Yoshida, Yasuhiro

    2011-01-01

    Highlights: → Fullerene administration triggered splenic responses. → Splenic responses occurred at different time-points than in the lung tissue. → CD11b + cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-α. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-κB and NFAT in splenocytes at 6 days post-administration. Finally, CD11b + cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

  18. Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass.

    Science.gov (United States)

    Gebhard, Caroline Eva; Desjardins, Georges; Gebhard, Cathérine; Gavra, Paul; Denault, André Y

    2017-04-01

    To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Honglei Chen

    Full Text Available Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI. However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran intranasally.For the mouse model of direct ALI, lipopolysaccharide (LPS was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  20. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Science.gov (United States)

    Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

    2014-01-01

    Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  1. Proliferative and morphological changes in the pulmonary epithelium of the Syrian golden hamster during carcinogenesis initiated by 210Po alpha alpha-radiation

    International Nuclear Information System (INIS)

    Shami, S.G.; Thibodeau, L.A.; Kennedy, A.R.; Little, J.B.

    1982-01-01

    The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups

  2. Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Warner, R L

    1997-01-01

    model. This increase was reduced by 81% after treatment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) antibody and by 37% after treatment with anti-interleukin-1 (IL-1) antibody. The same interventions reduced whole-lung ICAM-1 protein by 85% and 25%, respectively. The studies were...... extended to assess the locale in lung of ICAM-I upregulation. Lung vascular ICAM-1 content, which was assessed by vascular fixation of [125I]anti-ICAM-1, rose 4-fold after airway instillation of LPS. This rise was also TNF-alpha-dependent. Under the same experimental conditions, fixation of [125I...... lavage fluids (BALFs) of animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in surface expression of ICAM-1. These data indicate, at the very least, a dual compartmentalized (vascular and airway) upregulation of ICAM-1 after...

  3. Efficacy and safety of 0.75% ropivacaine instillation into subinguinal wound in patients after bilateral microsurgical varicocelectomy: a bi-center, randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Cui WS

    2017-07-01

    Full Text Available Wan Shou Cui,1,* Yu Seob Shin,2,3,* Jae Hyung You,3 A Ram Doo,4 Kiran Kumar Soni,3 Jong Kwan Park3 1Andrology Center, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Urology, Armed Forces Capital Hospital, Seongnam, 3Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Medical Device Clinical Trial Center of Chonbuk National University Hospital, Jeonju, 4Department of Anesthesiology and Pain Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea *These authors contributed equally to this work Objective: To evaluate the efficacy and safety of 0.75% ropivacaine instillation into inguinal wound in patients who have undergone bilateral microsurgical varicocelectomy.Patients and methods: Eighty-five men who were screened for bilateral varicoceles from March 2015 to July 2016 were randomized for the treatment. All patients underwent inguinal varicocelectomy by general anesthesia. After ligation of the internal spermatic veins from the spermatic cord, additional delivery of testis through inguinal incision site was done to ligate external spermatic veins and gubernacular veins. Before repairing external oblique aponeurosis, 6 mL of 0.75% ropivacaine and 6 mL of normal saline were instilled under the fascia and around the funiculus (spermatic cord by a randomized and double-blind method. Visual analog scale (VAS pain score and Prince Henry Pain Score (PHPS were used for evaluating operative sites at 1, 2, 4, and 8 hours and 7 days after surgery. Safety and tolerability were evaluated throughout the course of this study by assessing adverse events.Results: A total of 55 men completed the study. Of these 55 men, 31 received instillation of ropivacaine on the left operative site, while 24 received instillation of ropivacaine on the right operative site. VAS pain scores and PHPS in

  4. Metabolism of nasally instilled benzo(a)pyrene and dihydrosafrole in dogs and monkeys

    International Nuclear Information System (INIS)

    Petridou-Fischer, J.; Whaley, S.; Dahl, A.

    1987-01-01

    Cytochrome P-450 monooxygenases are found in the nasal cavities of a variety of species and could play an important role in the metabolism of inhaled airborne xenobiotics. The object of this study was to examine the metabolism of 14 C-benzo(a)pyrene (BaP) and 3 H-dihydrosafrole (DHS) deposited at the ethmoid and maxillary turbinate regions in Beagle dogs and Cynomolgus monkeys. While the animals were anesthetized, either compound was instilled at 10 minute intervals for 2 hours through catheters positioned at each region. Cotton swab samples of mucus from the nasopharynx were collected at 30 minute intervals during instillation. Metabolites in mucus were identified using high pressure liquid chromatography. Results showed that both regions in both species were capable of metabolizing BaP and DHS. BaP metabolites identified in the mucus were dihydrodiols, quinones, phenols, and tetrols. DHS metabolites were 2-methoxy-4-propyl-phenol, 2-methoxy-4-(2-propenyl)benzene, and 3,4-methylenedioxy-1-(1-hydroxypropyl)benzene. Radioactivity was found in urine and feces of animals treated with either compound, and was detected in the blood of animals treated with DHS. No differences were noted for the nasal metabolism between the two species. This study indicated that not only the nasal tissues, but also the alimentary tract, may be exposed to metabolites of inhaled xenobiotics carried by the mucus

  5. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    Directory of Open Access Journals (Sweden)

    Ladefoged Ole

    2009-01-01

    Full Text Available Abstract Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-. We studied the effects instillation or inhalation Printex 90 of carbon black (CB and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60 and single walled carbon nanotubes (SWCNT as well as gold particles and quantum dots (QDs. Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.

  6. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

    International Nuclear Information System (INIS)

    Roedel, Erik Q.; Cafasso, Danielle E.; Lee, Karen W.M.; Pierce, Lisa M.

    2012-01-01

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24 h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W

  7. Spectral-domain optical coherence tomography study on dynamic changes of human tears after instillation of artificial tears.

    Science.gov (United States)

    Napoli, Pietro Emanuele; Satta, Giovanni Maria; Coronella, Franco; Fossarello, Maurizio

    2014-07-01

    To analyze in vivo the dynamic changes induced by different artificial tears (ATs) in the precorneal tear film (PCTF) and lower tear meniscus (LTM) by using spectral-domain (SD) anterior segment optical coherence tomography (OCT). We prospectively examined 42 normal human eyes by using SD-OCT imaging. On the day before OCT imaging, all enrolled subjects were evaluated for abnormalities of ocular surface. All tear film images were obtained before and after instillation of three different types of ATs (mucomimetic, lipid-based, and saline) in five serial scans: immediately (within 30 seconds), at the first, fifth, 10th, and 20th minute. Subjects received a drop of 35 μL in one randomly selected eye. All examinations were conducted in the same conditions of temperature, brightness, humidity, and time of day. Changes in the morphological pattern of both LTM and PCTF were associated with the type of artificial tear instilled on the ocular surface. Similarly, the radius of curvature (rc), the height (h), and the depth (d) showed dynamic variations depending on treatment. Although by the 20th minute, both h and d returned to baseline values in all groups, a significant difference in rc (compared with baseline) was detected for mucomimetic ATs (P = 0.04) and lipid ATs (P = 0.02). Spectral-domain OCT imaging has preliminarily proved to be a noninvasive tool to evaluate, in real time, the different changes induced by ATs instillation. An important stride in understanding the clinical response to various tear substitutes can be achieved by this objective and quantitative approach. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  8. Intravesical Glycosaminoglycan Replacement with Chondroitin Sulphate (Gepan(®) instill) in Patients with Chronic Radiotherapy- or Chemotherapy-Associated Cystitis.

    Science.gov (United States)

    Schwalenberg, Thilo; Berger, Frank Peter; Horn, Lars Christian; Thi, Phuc Ho; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

    2015-08-01

    Intravesical instillation of glycosaminoglycans is a promising option for the treatment of chronic cystitis, as it supports the regeneration of the damaged urothelial layer. We investigated the efficacy of short-term intravesical chondroitin sulphate treatment (six courses of instillation) in patients with chronic radiotherapy- or chemotherapy-associated cystitis. This prospective, observational study included patients with chronic radiotherapy- or chemotherapy-associated cystitis, who received six once-weekly intravesical instillations of 0.2% chondroitin sulphate 40 mL. Every week, patients recorded their symptoms and their benefits and tolerance of treatment, using a self-completed questionnaire. The study included 16 patients (mean age 68.5 years; 50% male). During the study, a reduction in all evaluated parameters was observed. After one dose of chondroitin sulphate, symptom improvement was observed in 38% of patients, and after the second dose, an additional 31% of patients showed improvement. At week 6, 80% of patients had either improved or were symptom free, and significant improvements in urinary urgency (p = 0.0082), pollakisuria (p = 0.0022), urge frequency (p = 0.0033) and lower abdominal pain (p = 0.0449) were observed. Haematuria, present in 9 of the 16 patients at baseline, was completely resolved in all cases after 6 weeks. The majority of patients (93%) evaluated the tolerance of chondroitin sulphate as 'good' or 'very good'. No treatment-related adverse events were reported. Intravesical administration of chondroitin sulphate was effective for the treatment of radiotherapy- or chemotherapy-associated cystitis. Even short-term treatment appears to be effective in reducing symptoms and improving the quality of life of patients.

  9. Management of the open abdomen using negative pressure wound therapy with instillation in severe abdominal sepsis: A review of 48 cases in Hospital Mexico, Costa Rica.

    Science.gov (United States)

    Sibaja, Pablo; Sanchez, Alfredo; Villegas, Guillermo; Apestegui, Alvaro; Mora, Esteban

    2017-01-01

    Despite the numerous advances in recent years, severe abdominal sepsis (with associated organ failure associated with infection) remains a serious, life-threatening condition with a high mortality rate. OA is a viable alternative to the previously used scheduled repeat laparotomy or continuous peritoneal lavage. The use of Negative Pressure Wound Therapy (NPWT) has been described as a successful method of management of the open abdomen. Adding instillation of saline solution to NPWT in a programmed and controlled manner, could offer the clinician an additional tool for the management of complex septic abdomen. To explore if the concept of active two-way therapy (Negative pressure wound therapy with instillation or NPWT-I) yields superior control of underlying, life-threatening abdominal infections and its effects on survival and morbidity in patients with severe abdominal sepsis when management with an open abdomen is required. A retrospective review of 48 patients with severe abdominal sepsis, who were managed with and open abdomen and NPWT-I was performed. NPWT-I was initiated utilizing the same parameters on all patients, this consisted of cycles of instillation of saline solution, which was removed through negative pressure after a short dwell period. We observed the effects on primary fascia closure rate, mortality, hospital and SICU length of stay and associated complications. Our patient group consisted of 20 (42%) males and 28 (58%) females. Average age was 48 years. Mortality in these patients was attributed to pulmonary embolism (n=1), acute renal failure (n=2) and cardiopulmonary arrest (n=1). Average total hospital stay was 24days, and stay in the SICU (n=26) averaged 7.5days. No acute complications related to the NPWT-I. All patients presenting with abdominal compartment syndrome resolved after initiation of the NPWT-I. A total of 46 patients (96%) patients achieved fascia closure after NPWT-I therapy after an average of 6days. Four patients (8%) died

  10. Evaluation of the conservative treatment of Trigger finger by local instillation of corticosteroids

    Directory of Open Access Journals (Sweden)

    Muris Pecar

    2011-12-01

    Full Text Available Introduction: Trigger Finger (tenosynovitis stenosans is a specific, named disease from a group of repetitive strain injury (RSI diseases, caused by inflammation which results in difficulties during muscle contraction and weakened and painful tendon movement. It is common in the outpatient physical medicine and rehabilitation practice. The aim of our study was to evaluate the success of conservative treatment of Trigger Finger by local instillation of corticosteroids.Methods: The study was designed as an observational and open analysis of the results of conservative treatment of 45 patients. We used precise instillation of steroid anti-inflammatory antirheumatic drugs in the area of patho-anatomic, microtraumatic injuries of tendon and its sheath. Patients were evaluated before and after the treatment with 0 to 5 evaluation score scale. The data were analyzed using X2 test.Results: Most of the patients had evaluation score of 2, 3 and 4, before the treatment. After the treatment 10 (29% patients had achieved score 4 and 35 (71% patients had achieved score 5. All of the patients with score 5 had excellent working ability with full working capacity. Other patients had well-preserved working ability, which improved to excellent in maximum of 7 days.Conclusions: Conservative treatment of Trigger finger shows good therapeutic effects and taking into account the benefits, convenience and generally lower cost of conservative treatment for the patient, should be considered as an effective alternative to surgical treatment.

  11. Comparative Proteomics and Pulmonary Toxicity of Instilled Single-Walled Carbon Nanotubes, Crocidolite Asbestos, and Ultrafine Carbon Black in Mice

    Science.gov (United States)

    Teeguarden, Justin G.; Webb-Robertson, Bobbie-Jo; Waters, Katrina M.; Murray, Ashley R.; Kisin, Elena R.; Varnum, Susan M.; Jacobs, Jon M.; Pounds, Joel G.; Zanger, Richard C.; Shvedova, Anna A.

    2011-01-01

    Reflecting their exceptional potential to advance a range of biomedical, aeronautic, and other industrial products, carbon nanotube (CNT) production and the potential for human exposure to aerosolized CNTs are increasing. CNTs have toxicologically significant structural and chemical similarities to asbestos (AB) and have repeatedly been shown to cause pulmonary inflammation, granuloma formation, and fibrosis after inhalation/instillation/aspiration exposure in rodents, a pattern of effects similar to those observed following exposure to AB. To determine the degree to which responses to single-walled CNTs (SWCNT) and AB are similar or different, the pulmonary response of C57BL/6 mice to repeated exposures to SWCNTs, crocidolite AB, and ultrafine carbon black (UFCB) were compared using high-throughput global high performance liquid chromatography fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR-MS) proteomics, histopathology, and bronchoalveolar lavage cytokine analyses. Mice were exposed to material suspensions (40 micrograms per mouse) twice a week for 3 weeks by pharyngeal aspiration. Histologically, the incidence and severity of inflammatory and fibrotic responses were greatest in mice treated with SWCNTs. SWCNT treatment affected the greatest changes in abundance of identified lung tissue proteins. The trend in number of proteins affected (SWCNT [376] > AB [231] > UFCB [184]) followed the potency of these materials in three biochemical assays of inflammation (cytokines). SWCNT treatment uniquely affected the abundance of 109 proteins, but these proteins largely represent cellular processes affected by AB treatment as well, further evidence of broad similarity in the tissue-level response to AB and SWCNTs. Two high-sensitivity markers of inflammation, one (S100a9) observed in humans exposed to AB, were found and may be promising biomarkers of human response to SWCNT exposure. PMID:21135415

  12. Protective effects of a bacterially expressed NIF-KGF fusion protein against bleomycin-induced acute lung injury in mice.

    Science.gov (United States)

    Li, Xinping; Li, Shengli; Zhang, Miaotao; Li, Xiukun; Zhang, Xiaoming; Zhang, Wenlong; Li, Chuanghong

    2010-08-01

    Current evidence suggests that the keratinocyte growth factor (KGF) and the polymorphonuclear leukocyte may play key roles in the development of lung fibrosis. Here we describe the construction, expression, purification, and identification of a novel NIF (neutrophil inhibitory factor)-KGF mutant fusion protein (NKM). The fusion gene was ligated via a flexible octapeptide hinge and expressed as an insoluble protein in Escherichia coli BL21 (DE3). The fusion protein retained the activities of KGF and NIF, as it inhibited both fibroblast proliferation and leukocyte adhesion. Next, the effects of NKM on bleomycin-induced lung fibrosis in mice were examined. The mice were divided into the following four groups: (i) saline group; (ii) bleomycin group (instilled with 5 mg/kg bleomycin intratracheally); (iii) bleomycin plus dexamethasone (Dex) group (Dex was given intraperitoneally (i.p.) at 1 mg/kg/day 2 days prior to bleomycin instillation and daily after bleomycin instillation until the end of the treatment); and (iv) bleomycin plus NKM group (NKM was given i.p. at 2 mg/kg/day using the same protocol as the Dex group). NKM significantly improved the survival rates of mice exposed to bleomycin. The marked morphological changes and increased hydroxyproline levels resulted from the instillation of bleomycin (on Day 17) in the lungs were significantly inhibited by NKM. These results revealed that NKM can attenuate bleomycin-induced lung fibrosis, suggesting that NKM could be used to prevent bleomycin-induced lung damage or other interstitial pulmonary fibrosis.

  13. Intratracheal administration of fullerene nanoparticles activates splenic CD11b{sup +} cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ning [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Kunugita, Naoki [Department of Environmental Health, National Institute of Public Health, 2-3-6, Minami, Wako 351-0197 (Japan); Ichinose, Takamichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Song, Yuan [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yokoyama, Mitsuru [Bio-information Research Center, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Arashidani, Keiichi [School of Health Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yoshida, Yasuhiro, E-mail: freude@med.uoeh-u.ac.jp [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan)

    2011-10-30

    Highlights: {yields} Fullerene administration triggered splenic responses. {yields} Splenic responses occurred at different time-points than in the lung tissue. {yields} CD11b{sup +} cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-{alpha}. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-{kappa}B and NFAT in splenocytes at 6 days post-administration. Finally, CD11b{sup +} cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

  14. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

    Science.gov (United States)

    Gugliotta, Giorgio; Calagna, Gloria; Adile, Giorgio; Polito, Salvatore; Saitta, Salvatore; Speciale, Patrizia; Palomba, Stefano; Perino, Antonino; Granese, Roberta; Adile, Biagio

    2015-10-01

    Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis. Copyright © 2015. Published by Elsevier B.V.

  15. Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows.

    Science.gov (United States)

    Wijma, R; Stangaferro, M L; Giordano, J O

    2016-06-01

    Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at -1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and

  16. Transcatheter instillation of urokinase into loculated pleural effusion: analysis of treatment effect

    International Nuclear Information System (INIS)

    Chung, Won Mo; Park, Chan Sup; Cho, Chul Ho; Suh, Chang Hae; Chung, Won Kyun

    1995-01-01

    To evaluate the indication for intracavitary Urokinase(UK) in the treatment of loculated pleural effusion. We analyzed CT and US in 31 patients who were treated with intracavitary UK in loculated pleural effusion. In each patient, a single chest catheter (10-12F) was insected under imaging guidance. When the amount of drainage was less than 100 ml/day, UK was instilled through the catheter until less than 50 ml/day was drained. On follow-up chest radiographs of more than 1 month, we classified the results of treatment into 3 groups: (1) completely effective (lung expansion, over 80%); (2) partially effective (20-80%); (3) ineffective (below 20%) group. Sonographic pattern of pleural fluid was classified into anechoic, linear septated, and honeycomb appearances and the thickness of parietal pleura was measured on CT. Sixteen patients were completely effective, nine were partially effective, and six were ineffective. All patients with completely or partially effective outcome had anechoic and linear septated appearance on US and had less than 4 mm of parietal pleural thickness on CT. Of six ineffective patients, US showed linear septated in one patient and honeycomb appearance in five patients and the thickness of parietal pleura on CT was 3 mm in one patient, 4 mm in two patients, 5 mm in one patient, and 6 mm in two patients. UK instillation through percutaneous catheter was an effective method in the treatment of loculated pleural effusion. However, we found near complete reaccumulation of pleural fluid when honeycomb appearance of pleural fluid on US or more than 5 mm parietal pleural thickness on CT was observed, which might suggest that we should consider the other kinds of treatment method in those patients

  17. In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

    Science.gov (United States)

    Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

    2017-02-01

    Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (pbladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

  18. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

    Directory of Open Access Journals (Sweden)

    Konrad Urbanek

    Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

  19. Induction of phosphatidylcholine biosynthesis via CDPcholine pathway in lung and liver of rats following intratracheal administration of DDT and endosulfan

    International Nuclear Information System (INIS)

    Narayan, S.; Dani, H.M.; Misra, U.K.

    1989-01-01

    The induction of phosphatidylcholine (PC) biosynthesis via the CDPcholine pathway in lung and liver of rats has been shown following the intratracheal administration of 1,1,1-trichloro-2m2-bis(p-chlorophenyl) ethane (DDT) (5 mg/100 g body weight) and endosulfan (1 mg/100 g body weight) for 3 days. Controls received only the vehicle solution (groundnut oil, 0.1 m1/100 g body weight). The treatment of DDT and endosulfan significantly increased the PC contents and the incorporation of radioactive [methyl-3H]choline into PC of lung and liver microsomes. The incorporation of radioactive [methyl-14C]methionine into microsomal PC of lung and liver was not affected significantly by treatment with either of the insecticides. 1,4,5,6,7-hexachloro-5-norbornene-2,3-dimethano cyclic sulfite (endosulfan) administration significantly increased the activity of choline kinase and phosphocholine cytidylyltransferase (both cytosolic and microsomal) of lung, whereas DDT increased the activity of only latter. In liver, both DDT and endosulfan administration significantly increased the activity of choline kinase and phosphocholine cytidylyltransferase (both cytosolic and microsomal). However, the activity of phosphocholinetransferase was not affected in both lung and liver microsomes of rats treated with these insecticides. The PC precursor pool sizes, choline and phosphorylcholine, of lung and liver tissues were not altered by DDT and endosulfan treatments. The present results suggest that the increased level of PC and incorporation of radioactive [methyl-3H]choline into microsomal PC could be the result of increased activity of choline kinase and phosphocholine cytidylyltransferase of lung and liver of rats following intratracheal administration of DDT and endosulfan

  20. Oxidative DNA damage in vitamin C-supplemented guinea pigs after intratracheal instillation of diesel exhaust particles

    DEFF Research Database (Denmark)

    Moller, P.; Daneshvar, B.; Loft, S.

    2003-01-01

    . The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model...... for the study of oxidative damage induced by particulate matter. (C) 2003 Elsevier Science (USA). All rights reserved....

  1. A Very Rare Cause of Subglottic Stenosis: Non-Malignant Intratracheal Thyroid Tissue

    Directory of Open Access Journals (Sweden)

    Ümit Aydogmus

    2014-08-01

    Full Text Available We present a case of subglottic stenosis associated with benign thyroid tissue involvement due to relapse of multinodular goiter despite surgery 14 years ago.The patient had undergone bilateral subtotal thyroidectomy 14 years ago and the pathology report had been multinodular thyroid tissue at the time. The patient recently presented to an emergency service due to sudden development of respiratory distress and was then directed to our center. Cervical tomography showed bilateral thyroid tissue that narrowed the tracheal diameter by 80% by invading the trachea from the left wall at the level of the thyroid gland. The patient required urgent tracheostomy due to serious respiratory trouble. The trachea was incised vertically about 2.5 cm below the cricoid cartilage. A 2 cm endotracheal lesion with margins that could not be distinguished from the left vocal cord was observed and biopsies were taken from both this lesion and the tissue surrounding the trachea. A Montgomery T-tube extending from the subglottic area to the distal section was placed. Pathology evaluation revealed histopathological findings that matched normal thyroid tissue. Although infrequent, tracheal invasion associated with a thyroid cancer is known to occur. We present a case with postoperative intratracheal relapse due to a benign cause and the emergency treatment.

  2. Comparative in Vivo Assessment of Some Adverse Bioeffects of Equidimensional Gold and Silver Nanoparticles and the Attenuation of Nanosilver’s Effects with a Complex of Innocuous Bioprotectors

    Directory of Open Access Journals (Sweden)

    Boris A. Katsnelson

    2013-01-01

    Full Text Available Stable suspensions of nanogold (NG and nanosilver (NS with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water three times a week, up to 20 injections. A group of rats was thus injected with NS after oral administration of a “bioprotective complex” (BPC comprised of pectin, multivitamins, some amino acids, calcium, selenium, and omega-3 PUFA. After the termination of the injections, many functional and biochemical indices and histopathological features of the spleen, kidneys and liver were evaluated for signs of toxicity, and accumulation of NG or NS in these organs was measured. From the same rats, we obtained cell suspensions of different tissues for performing the RAPD test. It was demonstrated that, although both nanometals were adversely bioactive in all respects considered in this study, NS was more noxious as compared with NG, and that the BPC tested by us attenuated both the toxicity and genotoxicity of NS.

  3. PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis.

    Science.gov (United States)

    Bondue, Benjamin; Sherer, Félicie; Van Simaeys, Gaetan; Doumont, Gilles; Egrise, Dominique; Yakoub, Yousof; Huaux, François; Parmentier, Marc; Rorive, Sandrine; Sauvage, Sébastien; Lacroix, Simon; Vosters, Olivier; De Vuyst, Paul; Goldman, Serge

    2015-01-01

    Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments. C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with (18)F-FDG- or (18)F-4-fluorobenzamido-N-ethylamino-maleimide ((18)F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively. In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice. (18)F-FDG- and (18)F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  4. Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

    International Nuclear Information System (INIS)

    Coccini, Teresa; Manzo, Luigi; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Roda, Elisa

    2011-01-01

    Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl 2 (400 μg/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil T M T700 Degussa) with average pore size of 20 nm and surface area of 240 m 2 /g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4x44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

  5. Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

    Science.gov (United States)

    Coccini, Teresa; Fabbri, Marco; Roda, Elisa; Grazia Sacco, Maria; Manzo, Luigi; Gribaldo, Laura

    2011-07-01

    Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl2 (400 μg/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil™ T700 Degussa) with average pore size of 20 nm and surface area of 240 m2/g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4×44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

  6. Importance of surface characteristics of QUARTZ DQ 12 for acute inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Albrecht, C.; Becher, A.; Scins, R.P.F.; Hoehr, D.; Unfried, K.; Knaapen, A.M.; Borm, P.J.A. [Institut fuer medizinische Forschung (IUF), Duesseldorf (Germany)

    2004-07-01

    Although quartz is known to induce inflammation in rat lungs, mechanisms are not yet fully understood. The importance of particle surface characteristics was investigated in vivo after intratracheal instillation of different preparations of quartz in rat lungs. Three days after instillation of 2 mg DQ12 quartz, or DQ12 coated with polyvinylpyridine-N-oxide (PVNO) or Aluminium lactate (AL), lungs of female Wistar rats were lavaged in situ to determine markers of inflammation. Control rats received saline or the coating substances alone. DQ12 induced a marked inflammatory response, as indicated by a significant increase in the number of neutrophils and macrophages, as well as in the levels of b-glucuronidase and myeloperoxidase. None of these inflammatory markers was increased for both coated quartz preparations, with the exception of neutrophil influx which was also increased after treatment with AL quartz. Our results indicate that surface characteristics are important in the onset of quartz-induced lung inflammation which could imply a different development of persistent inflammation. This will be investigated in later follow-up time points of the same animal study. (orig.)

  7. Instilling fear makes good business sense: unwarranted hysterectomies in Karnataka.

    Science.gov (United States)

    Xavier, Teena; Vasan, Akhila; S, Vijayakumar

    2017-01-01

    This paper uses data from two fact-finding exercises in two districts of Karnataka to trace how government and private doctors alike pushed women to undergo hysterectomies. The doctors provided grossly unscientific information to poor Dalit women to instil a fear of "cancer" in their minds to wilfully mislead them to undergo hysterectomies, following which many suffered complications and died. The paper examines a review, made by two separate panels of experts, of women's medical records from private hospitals to illustrate that a large proportion of the hysterectomies performed were medically unwarranted; that private doctors were using highly suspect diagnostic criteria, based on a single ultrasound scan, to perform the hysterectomies and had not sent even a single sample for histopathology; and that the medical records were incomplete, erroneous and, in several instances, manipulated. The paper describes how a combination of patriarchal bias, professional unscrupulousness and pro-private healthcare policies posed a serious threat to the survival and well-being of women in Karnataka.

  8. Expression of circadian gens in different rat tissues is sensitive marker of in vivo silver nanoparticles action

    Science.gov (United States)

    Minchenko, D. O.; Yavorovsky, O. P.; Zinchenko, T. O.; Komisarenko, S. V.; Minchenko, O. H.

    2012-09-01

    Circadian factors PER1, PER2, ARNTL and CLOCK are important molecular components of biological clock system and play a fundamental role in the metabolism at both the behavioral and molecular levels and potentially have great importance for understanding metabolic health and disease, because disturbance the circadian processes lead to developing of different pathology. The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronics, home products, and for water disinfection, but little is yet known about their toxicity. These nanoparticles induce blood-brain barrier destruction, astrocyte swelling, cause degeneration of neurons and impair neurodevelopment as well as embryonic development. We studied the expression of genes encoded the key molecular components of circadian clock system in different rat organs after intratracheally instilled silver nanoparticles which quite rapidly translocate from the lungs into the blood stream and accumulate in different tissues. We have shown that silver nanoparticles significantly affect the expression levels of PER1, PER2, ARNTL and CLOCK mRNA in different rat tissues in time-dependent and tissue-specific manner. High level of PER1, ARNTL and CLOCK mRNA expression was observed in the lung on the 1st 3rd and 14th day after treatment of rats with silver nanoparticles. At the same time, the expression level of PER1 mRNA in the brain and liver increases predominantly on the 1st and 14th day but decreases in the testis. Significant increase of the expression level of PER2 and ARNTL mRNA was detected only in the brain of treated by silver nanoparticles rats. Besides that, intratracheally instilled silver nanoparticles significantly reduced the expression levels of CLOCK mRNA in the brain, heart and kidney. No significant changes in the expression level of PER2 mRNA were found in the lung, liver, heart and testis, except kidney where this mRNA expression decreases on the 3rd and 14th

  9. Diabetic foot wounds: the value of negative pressure wound therapy with instillation.

    Science.gov (United States)

    Dalla Paola, Luca

    2013-12-01

    Chronic wounds such as diabetic foot wounds are a tremendous burden to the health care system and often require a multidisciplinary approach to prevent amputations. Advanced technologies such as negative pressure wound therapy (NPWT) and bioengineered tissues have been successfully used in the treatment of these types of complex wounds. However, the introduction of NPWT with instillation (NPWTi) has provided an alternative treatment for treating complex and difficult-to-heal wounds. This article provides an overview of NPWT and the new NPWTi system and describes preliminary experience using NPWTi on patients with complicated infected diabetic foot wounds after surgical debridement and in a multidisciplinary setting. © 2013 The Author. International Wound Journal © 2013 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  10. Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

    International Nuclear Information System (INIS)

    Ye, Bo; Zhang, Yu-Xia; Yang, Fei; Chen, Hong-Lei; Xia, Dong; Liu, Ming-Qiu; Lai, Bai-Tang

    2007-01-01

    The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression. First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays. NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group. (1) A single dose of 25 mg/kg body weight

  11. Long-term follow-up of lung biodistribution and effect of instilled SWCNTs using multiscale imaging techniques

    International Nuclear Information System (INIS)

    Al Faraj, Achraf; Bessaad, Amine; Cieslar, Katarzyna; Canet-Soulas, Emmanuelle; Cremillieux, Yannick; Lacroix, Ghislaine

    2010-01-01

    Due to their distinctive properties, single-walled carbon nanotubes (SWCNTs) are being more and more extensively used in nanotechnology, with prospects in nanomedicine. It would therefore appear essential to develop and apply appropriate imaging tools for detecting and evaluating their biological impacts with the prospect of medical applications or in the situation of accidental occupational exposure. It has been shown recently that raw SWCNTs with metallic impurities can be noninvasively detected in the lungs by hyperpolarized 3 helium (HP- 3 He) MRI. Moreover raw and purified SWCNTs had no acute biological effect. The purpose of the present longitudinal study was to investigate long-term follow-up by imaging, as well as chronic lung effects. In a 3-month follow-up study, multiscale imaging techniques combining noninvasive HP- 3 He and proton (H) MRI to ex vivo light (histopathological analysis) and transmission electron microscopy (TEM) were used to assess the biodistribution and biological effects of intrapulmonary instilled raw SWCNTs. Specific in vivo detection of carbon nanotubes with MRI relied on their intrinsic metal impurities. MRI also has the ability to evaluate tissue inflammation by the follow-up of local changes in signal intensity. MRI and ex vivo microscopy techniques showed that granulomatous and inflammatory reactions were produced in a time and dose dependent manner by instilled raw SWCNTs.

  12. [Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients].

    Science.gov (United States)

    Van Agt, S; Gobet, F; Sibert, L; Leroi, A-M; Grise, P

    2011-03-01

    We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  13. Combined field block and i.p. instillation of ropivacaine for pain management after laparoscopic sterilization

    DEFF Research Database (Denmark)

    Callesen, T; Hjort, D; Mogensen, T

    1999-01-01

    We have studied the effect of ropivacaine for combined port site and mesosalpinx infiltration, and peritoneal instillation on pain, nausea and vomiting after laparoscopic sterilization, in a double-blind, placebo-controlled study in 80 patients. The total dose of ropivacaine was 285 mg. All...... patients received intra- and postoperative NSAID in fixed doses. Abdominal and shoulder pain, nausea and vomiting were recorded during the first 8 h after operation and in a diary for 3 days. In the ropivacaine group, abdominal pain scores were lower during the first 4 h (P

  14. Colleges Urged to Instill "Charitable Impulse" in Students, Inspire Them to Reorient Public Policy as Well as Donate Their Time and Money.

    Science.gov (United States)

    McMillen, Liz

    1987-01-01

    The president of the Council on Foundations, James A. Joseph, urges educators to develop volunteers who can eliminate the causes of social problems. Colleges and universities are in a special position to instill a sense of social responsibility in students. (MLW)

  15. Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

    Science.gov (United States)

    Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

    2014-01-01

    We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

  16. Asian sand dust enhances murine lung inflammation caused by Klebsiella pneumoniae

    International Nuclear Information System (INIS)

    He, Miao; Ichinose, Takamichi; Yoshida, Seiichi; Yamamoto, Shoji; Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie; Nishikawa, Masataka; Mori, Ikuko; Sun, Guifan; Shibamoto, Takayuki

    2012-01-01

    Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were excluded by heat treatment at 360 °C for 30 min. ICR mice were instilled intratracheally with ASD at doses of 0.05 mg or 0.2 mg/mouse four times at 2-week intervals (total dose of 0.2 mg or 0.8 mg/mouse) and were administrated with ASD in the presence or absence of KP at the last intratracheal instillation. Pathologically, ASD caused exacerbation of pneumonia by KP as shown by increased inflammatory cells within the bronchiolar and the alveolar compartments. ASD enhanced the neutrophil number dose dependently as well as the expression of cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-α) and chemokines (KC, MCP-1, MIP-1α) related to KP in BALF. In an in vitro study using RAW264.7 cells, combined treatment of ASD and KP increased gene expression of IL-1β, IL-6, IFN-β, KC, MCP-1, and MIP-1α. The same treatment tended to increase the protein level of IL-1β, TNF-α and MCP-1 in a culture medium compared to each treatment alone. The combined treatment tended to increase the gene expression of Toll-like receptor 2 (TLR2), and NALP3, ASC and caspase-1 compared with KP alone. These results suggest that the exacerbation of pneumonia by ASD + KP was due to the enhanced production of pro-inflammatory mediators via activation of TLR2 and NALP3 inflammasome pathways in alveolar macrophages.

  17. Asian sand dust enhances murine lung inflammation caused by Klebsiella pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    He, Miao [Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001, Shenyang (China); Ichinose, Takamichi; Yoshida, Seiichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201, Oita (Japan); Yamamoto, Shoji; Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie [Pathophysiology Research Team, National Institute for Environmental Studies, 305-8506, Tsukuba, Ibaraki (Japan); Nishikawa, Masataka; Mori, Ikuko [Environmental Chemistry Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Ibaraki (Japan); Sun, Guifan [Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001, Shenyang (China); Shibamoto, Takayuki, E-mail: tshibamoto@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616 (United States)

    2012-01-15

    Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were excluded by heat treatment at 360 °C for 30 min. ICR mice were instilled intratracheally with ASD at doses of 0.05 mg or 0.2 mg/mouse four times at 2-week intervals (total dose of 0.2 mg or 0.8 mg/mouse) and were administrated with ASD in the presence or absence of KP at the last intratracheal instillation. Pathologically, ASD caused exacerbation of pneumonia by KP as shown by increased inflammatory cells within the bronchiolar and the alveolar compartments. ASD enhanced the neutrophil number dose dependently as well as the expression of cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-α) and chemokines (KC, MCP-1, MIP-1α) related to KP in BALF. In an in vitro study using RAW264.7 cells, combined treatment of ASD and KP increased gene expression of IL-1β, IL-6, IFN-β, KC, MCP-1, and MIP-1α. The same treatment tended to increase the protein level of IL-1β, TNF-α and MCP-1 in a culture medium compared to each treatment alone. The combined treatment tended to increase the gene expression of Toll-like receptor 2 (TLR2), and NALP3, ASC and caspase-1 compared with KP alone. These results suggest that the exacerbation of pneumonia by ASD + KP was due to the enhanced production of pro-inflammatory mediators via activation of TLR2 and NALP3 inflammasome pathways in alveolar macrophages.

  18. Fate of inhaled azodicarbonamide in rats

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

    1987-01-01

    Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [ 14 C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14 C-labeled compound present in excreta. [ 14 C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [ 14 C]ADA equivalents were not observed. The rate of buildup of [ 14 C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [ 14 C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine

  19. Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Coccini, Teresa; Manzo, Luigi [Toxicology Division, Salvatore Maugeri Foundation IRCCS, Pavia (Italy); Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura [European Commission, Joint Research Centre, IHCP- 21027 Ispra (Italy); Roda, Elisa [European Centre for Nanomedicine, University of Pavia, 27100 Pavia (Italy)

    2011-07-06

    Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl{sub 2} (400 {mu}g/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil{sup TM} T700 Degussa) with average pore size of 20 nm and surface area of 240 m{sup 2}/g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4x44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

  20. Modifying effects of pre-existing fibrosis in rats exposed to aerosols of 239PuO2. II

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Mauderly, J.L.; Gillett, N.A.; Hahn, F.F.

    1988-01-01

    We have initiated a study using rats to determine the modifying effects of pre-existing pulmonary fibrosis on the retention and biological effects of inhaled 239 PuO 2 . Pulmonary fibrosis was induced by intratracheal instillation of 8.5 IU/kg body weight of bleomycin at 45 to 49 days before inhalation exposure to an aerosol of 239 PuO 2 . The clearance of 239 Pu from the lungs of rats was decreased significantly (p 239 Pu, apparently by entrapping the particles in fibrotic areas of the lung. The life span of the rats with pulmonary fibrosis was decreased by up to 25% compared with control rats having similar initial lung burdens of 239 Pu. (author)

  1. Histochemical, light and electron microscopic study of polonium-210 induced peripheral tumours in hamster lungs -evidence implicating the Clara Cell as the cell of origin

    International Nuclear Information System (INIS)

    Kennedy, A.R.; McGandy, R.B.; Little, J.B.

    1977-01-01

    Peripheral lung tumors induced in Syrian golden hamsters by intratracheally administered polonium-210 ( 210 Po) are similar to the peripheral lung tumours induced in many species by a variety of carcinogens. In addition, they show many of the histopathological features observed in human bronchiolar-alveolar carcinomas. Serial sacrifice studies of hamsters exposed to multiple instillations of 210 Po have been carried our to identify the cell of origin of these tumors. By means of thin, plastic (glycol methacrylate) sections, electron microscopy, and histochemistry, it is concluded that the bronchiolar Clara cell is the probable cell of origin, and that this view is generally compatible with many of the reported cytological characteristics of the human tumor. (author)

  2. Late effects of inhaled 253Es(NO3)3 in the rat

    International Nuclear Information System (INIS)

    Ballou, J.E.; Smith, L.G.; Dagle, G.E.; Gies, R.A.

    1979-01-01

    The lungs of rats exposed to 253 Es(NO 3 ) 3 aerosols sustained the greatest cumulative radiation dose, approximately 6-fold higher than the skeletal dose. Malignant lung tumors (incidence 8.5, 27.6%) were observed after a mean cumulative lung dose of 26 and 400 rad, respectively. Higher lung doses were associated with severe life shortening that precluded the expression of delayed effects. Osteosarcomas of the skeleton (incidence 6.9%) were found after a mean cumulative skeletal dose of 68 rad. Earlier studies, which showed a high incidence of bone tumors and relatively fewer lung tumors after intratracheal instillation of 253 EsCl 3 , were not confirmed in this study with inhaled 253 Es(NO 3 ) 3

  3. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

    Science.gov (United States)

    Bhargava, Rhea; Janssen, William; Altmann, Christopher; Andrés-Hernando, Ana; Okamura, Kayo; Vandivier, R William; Ahuja, Nilesh; Faubel, Sarah

    2013-01-01

    Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.

  4. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Rhea Bhargava

    Full Text Available Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury, intraperitoneal (IP endotoxin administration (indirect lung injury and, for comparison, intratracheal (IT endotoxin administration (direct lung injury with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation.Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10, BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration], and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping, IP endotoxin (10 µg, or IT endotoxin (80 µg with and without intratracheal (IT IL-6 (25 ng or 200 ng treatment.Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin.IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of

  5. Técnica da instilação de colírios em pacientes portadores de glaucoma crônico Eye drop instillation technique in chronic glaucoma patients

    Directory of Open Access Journals (Sweden)

    Paulo Gelman Vaidergorn

    2003-12-01

    observed, and 61.6% repeatedly blinked right after instilling the drop. CONCLUSIONS: Most patients did not use the eye drops properly. That may result in some undesirable consequences, such as, a partial wastage of the bottle's content, a possible increase in systemic toxicity, the risk of contamination of the bottletip, and, mainly, a decrease in the full hypotensive effect of the drugs. Therefore, the patients have to be carefully taught the correct way to use eye drops.

  6. Pulmonary toxicity and kinetic study of Cy5.5-conjugated superparamagnetic iron oxide nanoparticles by optical imaging

    International Nuclear Information System (INIS)

    Cho, Wan-Seob; Cho, Minjung; Kim, Seoung Ryul; Choi, Mina; Lee, Jeong Yeon; Han, Beom Seok; Park, Sue Nie; Yu, Mi Kyung; Jon, Sangyong; Jeong, Jayoung

    2009-01-01

    Recent advances in the development of nanotechnology and devices now make it possible to accurately deliver drugs or genes to the lung. Magnetic nanoparticles can be used as contrast agents, thermal therapy for cancer, and be made to concentrate to target sites through an external magnetic field. However, these advantages may also become problematic when taking into account safety and toxicological factors. This study demonstrated the pulmonary toxicity and kinetic profile of anti-biofouling polymer coated, Cy5.5-conjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) by optical imaging. Negatively charged, 36 nm-sized, Cy5.5-conjugated TCL-SPION was prepared for optical imaging probe. Cy5.5-conjugated TCL-SPION was intratracheally instilled into the lung by a non-surgical method. Cy5.5-conjugated TCL-SPION slightly induced pulmonary inflammation. The instilled nanoparticles were distributed mainly in the lung and excreted in the urine via glomerular filtration. Urinary excretion was peaked at 3 h after instillation. No toxicity was found under the concentration of 1.8 mg/kg and the half-lives of nanoparticles in the lung and urine were estimated to be about 14.4 ± 0.54 h and 24.7 ± 1.02 h, respectively. Although further studies are required, our results showed that Cy5.5-conjugated TCL-SPION can be a good candidate for use in pulmonary delivery vehicles and diagnostic probes.

  7. Modulation of epithelial sodium channel (ENaC expression in mouse lung infected with Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Radzioch Danuta

    2005-01-01

    Full Text Available Abstract Background The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC and the catalytic subunit of Na+-K+-ATPase. Methods Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c and susceptible (DBA/2, C57BL/6 and A/J mouse strains. The mRNA expression of ENaC and Na+-K+-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. Results The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p 1Na+-K+-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. Conclusions These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs.

  8. Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

    Science.gov (United States)

    CHOI, Gil Soon; OAK, Chulho; CHUN, Bong-Kwon; WILSON, Donald; JANG, Tae Won; KIM, Hee-Kyoo; JUNG, Mannhong; TUTKUN, Engin; PARK, Eun-Kee

    2014-01-01

    Titanium dioxide (TiO2) is increasingly widely used in industrial, commercial and home products. TiO2 aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO2. One ml of 10, 50 and 250 µg of P25 TiO2 was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO2 exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO2 exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO2 and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO2 showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO2 exposure. P25 TiO2 induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO2 induces lung inflammation in rabbits which is associated with eosinophilic inflammation. PMID:24705802

  9. Lung inflammation and genotoxicity in mice lungs after pulmonary exposure to candle light combustion particles

    DEFF Research Database (Denmark)

    Skovmand, Astrid; Damiao Gouveia, Ana Cecilia; Koponen, Ismo Kalevi

    2017-01-01

    Candle burning produces a large amount of particles that contribute substantially to the exposure to indoor particulate matter. The exposures to various types of combustion particles, such as diesel exhaust particles, have been associated with increased risk of lung cancer by mechanisms that invo......Candle burning produces a large amount of particles that contribute substantially to the exposure to indoor particulate matter. The exposures to various types of combustion particles, such as diesel exhaust particles, have been associated with increased risk of lung cancer by mechanisms...... that involve oxidative stress, inflammation and genotoxicity. The aim of this study was to compare pulmonary effects of candle light combustion particles (CP) with two benchmark diesel exhaust particles (A-DEP and SRM2975). Intratracheal (i.t.) instillation of CP (5mg/kg bodyweight) in C57BL/6n mice produced......-DEP or SRM2975. The i.t. instillation of CP did not generate oxidative damage to DNA in lung tissue, measured as DNA strand breaks and human 8-oxoguanine glycosylase-sensitive sites by the comet assay. The lack of genotoxic response was confirmed in lung epithelial (A549) cells, although the exposure to CP...

  10. [Experimental study of an intratracheal stent made of shape memory alloy].

    Science.gov (United States)

    Yoshimura, M; Tsugawa, C; Tsubota, N

    1994-11-01

    To develop a new prosthesis for treating tracheal stenosis and tracheobronchomalacia, we examined the usefulness of an intratracheal stent made of shape memory alloy (SMA), a titanium-nickel alloy composed of 50% of each metal. At its recovery temperature (37 degrees C), the SMA stent was designed to recall the memorized shape of a coil with a diameter of 5 or 6 mm and a length of 10 mm. For the present experiment, it was transformed to a smaller coil 3 mm in diameter at a low temperature (-50 degrees C) and then loaded into the prosthesis introducer tube. An experimental model of potentially fatal tracheomalacia was made surgically by cutting and fracturing the tracheal cartilages of rabbits and tracheal collapse was confirmed by rigid bronchoscope. The introducer tube with the SMA stent was inserted and then the prosthesis was advanced into the collapsed segment of the trachea using the stent pusher. The SMA stent warmed bo body temperature and recovered its memorized shape after 1-2 min. In 3 out of 8 rabbits, follow-up bronchoscopy performed at 6, 8, and 10 months after implantation revealed satisfactory patency of the SMA stent and the trachea. After follow-up, 3 animals were sacrificed for histological observation, which showed little proliferation of granulation tissue and no dislocation of the SMA stent from the malacic portion. The remaining 5 rabbits have been followed for 18-24 months and are doing well. We conclude that the SMA stent maintains good tracheal patency, causes little reaction in the tracheal wall, and is easy to handle. Thus, it shows the potential for clinical application.

  11. Intraperitoneal instillation of ropivacaine plus dexmedetomidine for pain relief after laparoscopic hysterectomy: A comparison with ropivacaine alone

    Directory of Open Access Journals (Sweden)

    Sunil Chiruvella

    2016-01-01

    Full Text Available Background and Aims: Intraperitoneal (IP instillation of local anesthetics has been shown to minimize postoperative pain after laparoscopic surgeries. We compared the antinociceptive effects of IP dexmedetomidine combined with ropivacaine with that of IP ropivacaine alone in the patients undergoing laparoscopic hysterectomy. Materials and Methods: At the end of laparoscopic hysterectomy, in a double-blind, randomized manner, one of the following injections was given intraperitoneally. The patients were allocated into the following two groups: The patients in ropivacaine group (R group (N = 30 were given 30 mL of 0.2% ropivacaine plus 2 mL of normal saline; the patients in ropivacaine plus dexmedetomidine group (RD group (N = 30 were given 30 mL of 0.2% ropivacaine combined with 1 μg/kg dexmedetomidine (diluted in 2 mL normal saline through trocars. All the patients were given diclofenac sodium when they had pain [visual analogue scale (VAS 3]. Results: VAS score at different time intervals, overall VAS in 24 h was significantly lower (1.86 ± 0.46 vs 4.7 ± 0.94, time to first request of analgesia (min was longest (126 ± 24 vs 59 ± 13 and total analgesic consumption (mg was lowest (95 ± 15 vs 175 ± 75 in RD group than in R group. Conclusion: The antinociceptive effects of the intraperitoneal instillation of ropivacaine in combination with dexmedetomidine is superior to ropivacaine alone.

  12. Study of consistency properties of instillation liniment-gel for therapy of pyoinflammatory diseases of maxillofacial region

    Directory of Open Access Journals (Sweden)

    A. V. Kurinnoy

    2012-12-01

    Full Text Available Using rotary viscometer «Reotest 2» researches of consistency properties of instillation gel-liniment for antimicrobial therapy of pyoinfl ammatory diseases of maxillufacial area are conducted. It is defi ned, that consistency properties of gel-liniment for antimicrobial therapy of pyoinflammatory diseases of maxillufacial area are within the limits of rheological optimum of consistency of ointments, and value «mechanical stability» (1,33 characterizes the system as exceptionally thixotropic, providing recoverability of the system after loading and allows to forecast stability of consistency properties of gel-liniment at the prolonged storage.

  13. The deposition, distribution and retention of inhaled 239PuO2 in the lungs of rats with pulmonary emphysema

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Damon, E.G.; Diel, J.H.; Hahn, F.F.

    1981-01-01

    Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled 239 PuO 2 in rats. (author)

  14. Deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in the lungs of rats with pulmonary emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D L; Damon, E G; Diel, J H; Hahn, F F [Lovelace Foundation for Medical Education and Research, Albuquerque, NM (USA). Inhalation Toxicology Research Inst.

    1981-02-01

    Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in rats.

  15. Combined effects of inhaled plutonium oxide and benzo[a]pyrene on lung carcinogenesis in rats

    International Nuclear Information System (INIS)

    Metivier, H.; Masse, R.; Wahrendorf, J.; Lafuma, J.

    1986-01-01

    This study describes the effect of two intratracheal instillations (5 mg each) of benzo[a]pyrene (BP) on lung carcinogenesis in rats that had previously inhaled three levels of 239 PuO 2 . The BP does not modify survival in the high-level 239 PuO 2 -exposed rats, but markedly reduces survival in the two other groups. Median survival time with BP alone is shorter (666 days) than for the control group (838 days). Tumor incidence was increased by BP exposure, and the tumors were usually fatal, whereas tumors observed after 239 PuO 2 inhalation alone were usually not fatal. Statistical analysis of these data poses a problem because of the need to compare incidental and fatal tumors. 22 refs., 5 figs., 7 tabs

  16. Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2

    DEFF Research Database (Denmark)

    Mikkelsen, Lone; Sheykhzade, Majid; Jensen, Keld A

    2011-01-01

    of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO2-induced alterations in nitric oxide (NO...... were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO2 (pTiO2, 12 nm), or rutile nano TiO2 (nTiO2, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression...

  17. Rapport du congrès EUROCALL 2000 et du symposium InSTIL 2000 (Dundee, Ecosse

    Directory of Open Access Journals (Sweden)

    Pierre Machu

    2000-12-01

    Full Text Available Le congrès annuel de EUROCALL (2000 (European Association for Computer Assisted Language Learning s'est déroulé du 31 août au 2 septembre 2000 à l'Université d'Abertay-Dundee et avait pour thème : Innovations dans l'apprentissage des langues au troisième millénaire - Réseaux pour la formation continue, interdisciplinarité et réponse intelligente de la machine (voir le site EUROCALL 2000 (2000. Environ 230 délégués provenant de 30 pays se sont rassemblés à Dundee. Les séances plénières et les communications (présentation de recherches ou démonstrations s'articulaient par conséquent autour de sous-thèmes tels que recherche en acquisition d'une langue seconde et ALAO, exploitation ou conception de matériaux pour la toile, communication médiatisée par ordinateur, centres de langues et apprentissage des langues de spécialité, traitement du language naturel et technologie de la parole. La technologie de la parole était également au coeur des préoccupations et travaux des 80 participants au symposium d'InSTIL 2000 (2000 (Intégration des technologies de la parole dans l'apprentissage des langues qui s'est déroulé durant les deux jours précédant le congrès EUROCALL 2000. InSTIL 2000 était organisé par le groupe d'intérêts spéciaux (GIS InSTIL (2000, (Integrating Speech Technology in Language Learning issu des trois associations CALICO (2000 (Computer Assisted Language Instruction Consortium, EUROCALL (2000 et ISCA (2000 (International Speech Communication Association.

  18. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis

    OpenAIRE

    Giorgio Gugliotta; Gloria Calagna; Giorgio Adile; Salvatore Polito; Salvatore Saitta; Patrizia Speciale; Stefano Palomba; Antonino Perino; Roberta Granese; Biagio Adile

    2015-01-01

    Objective: Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. Materials and methods: This was a retrospective...

  19. The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain

    DEFF Research Database (Denmark)

    Aasvang, Eske K; Hansen, Jeanette B; Malmstrøm, Jørgen

    2008-01-01

    , preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 microg ultrapurified capsaicin (ALGRX......BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro...... 4975) after open mesh groin hernia repair in 41 adult male patients. The primary end-point was average daily visual analog scale (VAS) pain scores during the first week after surgery assessed as area under the curve (AUC). Pain was recorded twice daily in a pain diary for 4 wk. Physical examination...

  20. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.

    2015-01-01

    by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 m...

  1. In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors.

    Science.gov (United States)

    Minigalieva, Ilzira A; Katsnelson, Boris A; Panov, Vladimir G; Privalova, Larisa I; Varaksin, Anatoly N; Gurvich, Vladimir B; Sutunkova, Marina P; Shur, Vladimir Ya; Shishkina, Ekaterina V; Valamina, Irene E; Zubarev, Ilya V; Makeyev, Oleg H; Meshtcheryakova, Ekaterina Y; Klinova, Svetlana V

    2017-04-01

    Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.t.) (for performing a broncho-alveolar lavage in 24h to estimate the cytological and biochemical indices of the response of the lower airways), while in the other, Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks (for estimating the accumulation of corresponding metals in the blood and their excretion with urine and feces and for assessing subchronic intoxication by a large number of functional and morphological indices). Mathematical description of the results from both experiments with the help of the Response Surface Methodology has shown that, as well as in the case of any other binary toxic combinations previously investigated by us, the response of the organism to a simultaneous exposure to any two of the Me-NPs under study is characterized by complex interactions between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which effect it is estimated for as well as on the levels of the effect and dose. With any third Me-NP species acting in the background, the type of combined toxicity displayed by the other two may change significantly (as in the earlier described case of a triple combination of soluble metal salts). It is shown that various harmful effects produced by CuO-NP+ZnO-NP+PbO-NP combination may be substantially attenuated by giving rats per os a complex of innocuous bioactive substances theoretically expected to provide a protective integral and/or metal-specific effect during one month before i.t. instillation or during the entire period of i.p. injections

  2. Non-Invasive Detection of Lung Inflammation by Near-Infrared Fluorescence Imaging Using Bimodal Liposomes.

    Science.gov (United States)

    Desu, Hari R; Wood, George C; Thoma, Laura A

    2016-01-01

    Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome results in respiratory obstruction and severe lung inflammation. Critical characteristics of ALI are alveolar edema, infiltration of leukocytes (neutrophils and monocytes), release of pro-inflammatory cytokines and chemokines into broncho-alveolar lavage fluid, and activation of integrin receptors. The purpose of the study was to demonstrate non-invasive detection of lung inflammation using integrin receptor targeted fluorescence liposomes. An inflammation similar to that observed in ALI was elicited in rodents by intra-tracheal instillation of interleukin-1beta (IL-1beta). Cyclic arginine glycine-(D)-aspartic acid-peptide (cRGD-peptide) grafted fluorescence liposomes were administered to ALI induced male Sprague-Dawley rats for targeting lung integrin receptors. Near-infrared fluorescence imaging (NIRFI) was applied for visualization and quantitation of lung inflammation. NIRFI signals were correlated with inflammatory cellular and biochemical markers of lungs. A positive correlation was observed between NIRF signals and lung inflammation markers. Compared to control group, an intense NIRF signal was observed in ALI induced rats in the window 6-24 h post-IL-1beta instillation. Interaction of integrin receptors with targeted liposomes was assumed to contribute to intense NIRF signal. RT-PCR studies showed an elevated lung expression of alphavbeta5 integrin receptors, 12 h post-IL-1beta instillation. In vitro studies demonstrated integrin receptor specificity of targeted liposomes. These targeted liposomes showed binding to alphavbeta5 integrin receptors expressed on alveolar cells. Non-invasive detection of lung inflammation was demonstrated using a combination of integrin receptor targeting and NIRFI.

  3. Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

    Science.gov (United States)

    Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

    2018-01-01

    There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, pMimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug

  4. Focal seizures after instillation of cyclomydril to a neonate with congenital CMV infection.

    Science.gov (United States)

    Hu, L; Dow, K

    2014-01-01

    We present the case of a term neonate who underwent a diagnostic eye examination on day one for possible genetic disorders. Five minutes after Cyclomydril (0.2% clyclopentolate and 1% phenylephrine) eye drops were instilled, a focal seizure lasting for approximately one hour occurred. The electroencephalograph (EEG) was normal but the magnetic resonance imaging (MRI) revealed calcifications in the bilateral periventricular regions. Urine CMV-DNA and maternal serum CMV-IgM were both positive. Auditory brainstem testing suggested severe sensoneural hearing loss. The baby was treated for congenital CMV infection and did not have further seizures. In this case the congenital CMV infection may have been the predisposing factor to central nervous system (CNS) toxicity induced by cyclopentolate. The exact mechanism is unknown but severe neurological impairment may be considered a contraindication for cyclopentolate eye drops in the neonate. To our knowledge, this is the first report of seizures occurring within the first week of life secondary to cyclomydril eye drops in a term neonate.

  5. Effects of transuranics on pulmonary lymph nodes of rodents

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1976-01-01

    Pulmonary lymph nodes have been suggested as the ''critical'' tissue for insoluble, inhaled transuranic compounds owing to the high concentration of transuranics in these lymph nodes. About 800 rats were given from 0.2 to 3600 nCi of 238 PuO 2 or 239 PuO 2 by inhalation, intratracheal instillation, intrapleural injection, or intraperitoneal injection. From about 1 to 10 percent of deposited plutonium was translocated to pulmonary lymph nodes, the amount depending on the time after deposition and the route of administration; 238 PuO 2 was cleared from pulmonary lymph nodes faster than 239 PuO 2 owing to the greater in vivo solubility of 238 PuO 2 . No primary tumors of pulmonary lymph nodes were observed, indicating that this tissue was not the critical tissue for carcinogenic induction

  6. Pulmonary exposure to carbonaceous nanomaterials and sperm quality

    DEFF Research Database (Denmark)

    Skovmand, Astrid; Lauvas, Anna Jacobsen; Christensen, Preben

    2018-01-01

    Background: Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung...... inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model.Methods: Effects on sperm quality after pulmonary inflammation induced by carbonaceous...... nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 mu g/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks...

  7. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja

    2015-01-01

    has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18,54 or 162 mu...... levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater...... response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk...

  8. Pulmonary exposure to particles from diesel exhaust, urban dust or single-walled carbon nanotubes and oxidatively damaged DNA and vascular function in apoE(-/-)mice

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Jantzen, Kim; Sheykhzade, Majid

    2012-01-01

    Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells and acell......Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells...... and acellullarly, whereas the exposure to urban dust did not generate ROS. ApoE(-/-) mice, which were exposed twice to 0.5 mg/kg of the particles by intratracheal instillation, had unaltered acetylcholine-elicited vasorelaxation in aorta segments. There was unaltered pulmonary expression level of Vcam-1, Icam-1...

  9. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression...... in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta......-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO-/- mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO-/- AMs...

  10. Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Løhr, Mille; Roursgaard, Martin

    2014-01-01

    BackgroundThe liver has a crucial role in metabolic homeostasis as well as being the principal detoxification centre of the body, removing xenobiotics and waste products which could potentially include some nanomaterials (NM). With the ever increasing public and occupational exposure associated...... with accumulative production of nanomaterials, there is an urgent need to consider the possibility of detrimental health consequences of engineered NM exposure. It has been shown that exposure via inhalation, intratracheal instillation or ingestion can result in NM translocation to the liver. Traditional in vitro...... or ex vivo hepatic nanotoxicology models are often limiting and/or troublesome (i.e. reduced metabolism enzymes, lacking important cell populations, unstable with very high variability, etc.).MethodsIn order to rectify these issues and for the very first time we have utilised a 3D human liver...

  11. Time-dependent subcellular distribution and effects of carbon nanotubes in lungs of mice.

    Directory of Open Access Journals (Sweden)

    Carsten Købler

    Full Text Available Pulmonary deposited carbon nanotubes (CNTs are cleared very slowly from the lung, but there is limited information on how CNTs interact with the lung tissue over time. To address this, three different multiwalled CNTs were intratracheally instilled into female C57BL/6 mice: one short (850 nm and tangled, and two longer (4 μm and 5.7 μm and thicker. We assessed the cellular interaction with these CNTs using transmission electron microscopy (TEM 1, 3 and 28 days after instillation.TEM analysis revealed that the three CNTs followed the same overall progression pattern over time. Initially, CNTs were taken up either by a diffusion mechanism or via endocytosis. Then CNTs were agglomerated in vesicles in macrophages. Lastly, at 28 days post-exposure, evidence suggesting CNT escape from vesicle enclosures were found. The longer and thicker CNTs more often perturbed and escaped vesicular enclosures in macrophages compared to the smaller CNTs. Bronchoalveolar lavage (BAL showed that the CNT exposure induced both an eosinophil influx and also eosinophilic crystalline pneumonia.Two very different types of multiwalled CNTs had very similar pattern of cellular interactions in lung tissue, with the longer and thicker CNTs resulting in more severe effects in terms of eosinophil influx and incidence of eosinophilic crystalline pneumonia (ECP.

  12. Rare Case of Intratracheal Metastasis Detected on 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan in a Case of Thyroglobulin Elevated Negative Iodine Scan Syndrome.

    Science.gov (United States)

    Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Oommen, Karuna Elza; Jayakumar, R

    2018-04-01

    A 64-year-old woman underwent completion thyroidectomy with upper tracheal ring resection and right-sided neck dissection for papillary carcinoma of the thyroid infiltrating the trachea and was given I radioiodine treatment. Three years later, she presented with hemoptysis. On evaluation, she had increased serum thyroglobulin and negative iodine scan (TENIS). F-FDG PET/CT scan did not identify any site of disease. One year later, Ga-PSMA scan done revealed a moderate focal tracer-avid intratracheal soft tissue; biopsy revealed it to be metastatic papillary carcinoma of the thyroid. This case kindles the possibility of using Ga-PSMA PET/CT to reveal occult disease in cases of TENIS.

  13. Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice

    Science.gov (United States)

    Trivedi, Ruchit; Redente, Elizabeth F.; Thakur, Ashish; Riches, David W. H.; Kompella, Uday B.

    2012-12-01

    Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation. Poly(lactide-co-glycolide) nanoparticles containing pirfenidone (NPs) were prepared and characterized. Biodistribution of NPs and solution was assessed using LC-MS after intratracheal administration in C57Bl/6 mice at 3 and 24 h and 1 week post-administration. Efficacy was tested in C57Bl/6 mice in a bleomycin-induced pulmonary fibrosis model. Mice received 10 μg pirfenidone intratracheally in solution or NPs, once a week, for 3 weeks after bleomycin administration. Drug effects were monitored on day 28. Lung hydroxyproline content, total number of cells, and numbers of macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage (BAL) were assessed. Numbers of macrophages, lymphocytes, and neutrophils were assessed in the lung as well. NPs sustained significantly higher levels of pirfenidone in the lungs and BAL at 24 h and 1 week, compared to the solution group. Pirfenidone solution and NPs significantly reduced hydroxyproline levels by 57 and 81%, respectively, compared to bleomycin alone. At the end of 4 weeks, BAL cellularity was reduced by 25.4% and 56% with solution and NP treatment, respectively. The numbers of lymphocytes and neutrophils in the BAL were also reduced by 58.9 and 82.4% for solution and 74.5% and 89.7% for NPs, respectively. The number of inflammatory macrophages in the lung was reduced by 62.8% and the number of neutrophils was reduced by 59.1% in the NP group and by 37.7% and 44.5%, respectively, in the solution group, compared to bleomycin alone. In conclusion, nanoparticles sustain lung pirfenidone delivery and enhance its anti-fibrotic efficacy.

  14. Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

    Science.gov (United States)

    Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

    2004-08-01

    .5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure

  15. Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and enphysema in rats

    International Nuclear Information System (INIS)

    Kirschvink, Nathalie; Vincke, Gregoire; Fievez, Laurence; Onclinx, Cecile; Wirth, Delphine; Belleflamme, Michele; Louis, Renaud; Cataldo, Didier; Peck, Michael J.; Gustin, Pascal

    2005-01-01

    This study describes induction of pulmonary inflammation, production of matrix metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups: one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n = 30) and one Cd-exposed group undergoing cadmium (CdCl 2 0.1%) inhalation (n = 30). The animals of the placebo- and Cd-exposed groups were divided in five subgroups (n = 6). Subgroups underwent either a single exposure of 1 h or repeated exposures three times weekly for 1 h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2 weeks without exposure (5W + 2) or 5 weeks followed by 4 weeks without exposure (5W + 4). Each animal underwent determination of enhanced pause (Penh) as index of airflow limitation prior to the first exposure as well as before sacrifice. The animals were sacrificed the day after their last exposure. The left lung was fixed for histomorphometric analysis (determination of median interwall distance (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined by gelatine zymography. Twelve rats previously instilled with pancreatic elastase were used as positive emphysema controls and underwent the same investigations. Cd-exposure induced a significant increase of BALF macrophages, neutrophils and MMP-9 up to 5W + 4, whereas MMP-2 gelatinolytic activity returned to baseline levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a single exposure and after 3W. MMP gelatinolytic activity was significantly correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats, MIWD was positively and significantly correlated with MMP gelatinolytic activity, suggesting that increased MMP-2 and MMP-9 production favours the development

  16. Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

    Science.gov (United States)

    Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

    2012-01-01

    Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a

  17. Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.

    Science.gov (United States)

    Lulli, Matteo; Witort, Ewa; Papucci, Laura; Torre, Eugenio; Schipani, Christian; Bergamini, Christian; Dal Monte, Massimo; Capaccioli, Sergio

    2012-12-17

    To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

  18. [Study and development of a new automatic suction system (SS) of intratracheal sputum in order to improve QOL of many patients with tracheostomy mechanical ventilation (TMV) and their family members by this new autonomic SS].

    Science.gov (United States)

    Hokezu, Youichi; Yamamoto, Makoto; Tokunaga, Syuichi; Niikura, Makoto; Nagamatsu, Keiji; Kira, Jun-ichi; Fukunaga, Toshihide; Shima, Kouji; Kikuchi, Seiji; Kimura, Itaru; Kondo, Kiyohiko; Mori, Teruhiko; Goto, Katumasa; Takigami, Shigeru; Shioya, Keiichi; Uehara, Minako

    2009-11-01

    In Japan, many patients equipped with TMV are under medical treatment at home after 1990. These patients can't put out sputa in trachea, so that these patient's family members must suck these patient's intratracheal sputa all days. Mr Yamamoto and Mr Tokunaga, main researchers of this study, began the study on the automatic SS of itratracheal sputa from 1999. In first stage, They developed the intermittent SS in detaining the suction tube within tracheal cannula, monitering the intratracheal pressure, but this system takes the ventilation away from the patient. Hypoventilation caused by this SS may cause the serious accident in patient. Therefore, we remodel the SS from intermittent SS to rollerpomp-type SS continuing to suck the itratracheal sputa with low volume from 2004, and thereafter we made up the SS of piston pomp type-SS finally at 2007. We developed the tracheal cannula with double suction holes of inner and lower hole in the lower part of its cannula together with the suction machine. We think that the practical use of this automatic SS will bring these patients with TMV and their family members great benefits. We desire that the practical use of this SS will be realized as soon as possible.

  19. Pharmacokinetic/Pharmacodynamic Profiles of Tiamulin in an Experimental Intratracheal Infection Model of Mycoplasma gallisepticum.

    Science.gov (United States)

    Xiao, Xia; Sun, Jian; Yang, Tao; Fang, Xi; Cheng, Jie; Xiong, Yan Q; Liu, Ya-Hong

    2016-01-01

    Mycoplasma gallisepticum is the most important pathogen in poultry among four pathogenic Mycoplasma species. Tiamulin is a pleuromutilin antibiotic that shows a great activity against M. gallisepticum and has been approved for use in veterinary medicine particularly for poultry. However, the pharmacokinetic/pharmacodynamics (PK/PD) profiles of tiamulin against M. gallisepticum are not well understood. Therefore, in the current studies, we investigated the in vivo PK/PD profiles of tiamulin using a well-established experimental intratracheal infection model of M. gallisepticum. The efficacy of tiamulin against M. gallisepticum was studied in 8-day-old chickens after intramuscular (i.m.) administration at 10 doses between 0-80 mg/kg. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the PK parameters of tiamulin following i.m. administration at doses of 5, 40, and 80 mg/kg in Mycoplasma gallisepticum-infected neutropenic chickens. Real-time PCR (RT-PCR) was used for quantitative detection of M. gallisepticum. The MIC of tiamulin against M. gallisepticum strain S6 was 0.03 μg/mL. The PK/PD index, AUC24h/MIC, correlated well with the in vivo antibacterial efficacy. The in vivo data suggest that animal dosage regimens should supply AUC24h/MIC of tiamulin of 382.68 h for 2 log10 ccu equivalents M. gallisepticum reduction. To attain that goal, the administered dose is expected to be 45 mg/kg b.w. for treatment of M. gallisepticum infection with an MIC90 of 0.03 μg/mL.

  20. Pharmacokinetic/Pharmacodynamic Profiles of Tiamulin in an Experimental Intratracheal Infection Model of Mycoplasma gallisepticum

    Directory of Open Access Journals (Sweden)

    Xia Xiao

    2016-09-01

    Full Text Available Mycoplasma gallisepticum is the most important pathogen in poultry among four pathogenic Mycoplasma species. Tiamulin is a pleuromutilin antibiotic that shows a great activity against M. gallisepticum and has been approved for use in veterinary medicine particularly for poultry. However, the Pharmacokinetic/Pharmacodynamics (PK/PD profiles of tiamulin against M. gallisepticum are not well understood. Therefore, in the current studies, we investigated the in vivo PK/PD profiles of tiamulin using a well-established experimental intratracheal infection model of M. gallisepticum. The efficacy of tiamulin against M. gallisepticum was studied in 8-day-old chickens after intramuscular (i.m. administration at 10 doses between 0-80 mg/kg. Liquid chromatography-tandem mass spectrometry (LC-MS/MS was used to evaluate the PK parameters of tiamulin following i.m. administration at doses of 5, 40 and 80 mg/kg in Mycoplasma gallisepticum infected neutropenic chickens. Real time PCR (RT-PCR was used for quantitative detection of M. gallisepticum. The MIC of tiamulin against M. gallisepticum strain S6 was 0.03 μg/mL. The PK/PD index, AUC24h/MIC, correlated well with the in vivo antibacterial efficacy. The in vivo data suggest that animal dosage regimens should supply AUC24h/MIC of tiamulin of 382.68 h for 2 log10 ccu equivalents M. gallisepticum reduction. To attain that goal, the administered dose is expected to be 45 mg/kg b.w. for treatment of M. gallisepticum infection with an MIC90 of 0.03 μg/mL.

  1. Intratracheal infection as an efficient route for testing vaccines against Chlamydia abortus in sheep.

    Science.gov (United States)

    Álvarez, D; Salinas, J; Buendía, A J; Ortega, N; del Río, L; Sánchez, J; Navarro, J A; Gallego, M C; Murcia-Belmonte, A; Cuello, F; Caro, M R

    2015-09-01

    Pregnant ewes have been widely used to test vaccines against Chlamydia abortus. However, this model entails many disadvantages such as high economic costs and long periods of pregnancy. The murine model is very useful for specific studies but cannot replace the natural host for the later stages of vaccine evaluation. Therefore, a non-pregnant model of the natural host might be useful for a vaccine trial to select the best vaccine candidates prior to use of the pregnant model. With this aim, two routes of infection were assessed in young non-pregnant sheep, namely, intranasal (IN) and intratracheal (IT). In addition, groups of non-vaccinated sheep and sheep immunised with an inactivated vaccine were established to investigate the suitability of the model for testing vaccines. After the experimental infection, isolation of the microorganism in several organs, with pathological and immunohistochemical analyses, antibody production assessment and investigation by PCR of the presence of chlamydia in the vagina or rectum were carried out. Experimental IT inoculation of C. abortus induced pneumonia in sheep during the first few days post-infection, confirming the suitability of the IT route for testing vaccines in the natural host. The course of infection and the resulting pathological signs were less severe in vaccinated sheep compared with non-vaccinated animals, demonstrating the success of vaccination. IN infection did not produce evident lesions or demonstrate the presence of chlamydial antigen in the lungs and cannot be considered an appropriate model for testing vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille

    2015-01-01

    Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were...

  3. Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

    Science.gov (United States)

    Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

    2015-05-01

    Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

    Science.gov (United States)

    Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien

    2013-09-01

    To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

  5. Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation

    Directory of Open Access Journals (Sweden)

    Abid Aamir D

    2013-01-01

    Full Text Available Abstract The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS. The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.

  6. Preliminary studies on gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats

    International Nuclear Information System (INIS)

    Liu Chunjie; Wang Dewen; Zhang Zhaoshan; Gao Yabing; Xiong Chengqi; Long Jianyin; Wang Huixin; Peng Ruiyun; Cui Xuemei

    2001-01-01

    Objective: To observed the efficiency of gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats. Methods: TGFβ1 sense and antisense gene expression vectors and adenovirus transfer vector were introduced into rat bronchus by way of intratracheal instillation. Results: At day 1.5 after TGFβ1 sense and antisense gene transfer, PCR amplification using neo gene-specific primer from lung tissue DNA was all positive. After day 5.5, 67% (2/3) of lung tissue DNA was positive. RNA dot blot hybridization indicated that TGFβ1 mRNA content of lung tissue transfected with pMAMneo-antiTGFβ1 gene decreased. Detection of lung hydroxyproline (Hyp) content after day 35 of gene transfer showed that even in lung of rats received pMAMneo-AntiTGFβ1 lipid complexes it raised remarkably (P 9 pfu/ml were instilled into bronchus at 0.5 ml per rat. After day 2 day 6, the lung tissues of all six rats (three per each group )expressed the transfected luciferase gene by luminometer. Conclusion: Cationic lipid-mediated TGFβ1 antisense gene therapy was a simple and easy method. It can slow down the course of pathogenesis of lung fibrosis. Replication-deficient recombinant adenovirus-mediated gene therapy of lung diseases is a good and efficient method

  7. Repeating and non-repeating fast radio bursts from binary neutron star mergers

    Science.gov (United States)

    Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

    2018-04-01

    Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

  8. Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis.

    Science.gov (United States)

    Habibi, Mehri; Asadi Karam, Mohammad Reza; Bouzari, Saeid

    2016-06-01

    Urinary tract infections (UTIs) are among the most common infections in human. Innate immunity recognizes pathogen-associated molecular patterns (PAMPs) by Toll-like receptors (TLRs) to activate responses against pathogens. Recently, we demonstrated that MrpH.FimH fusion protein consisting of MrpH from Proteus mirabilis and FimH from Uropathogenic Escherichia coli (UPEC) results in the higher immunogenicity and protection, as compared with FimH and MrpH alone. In this study, we evaluated the innate immunity and adjuvant properties induced by fusion MrpH.FimH through in vitro and in vivo methods. FimH and MrpH.FimH were able to induce significantly higher IL-8 and IL-6 responses than untreated or MrpH alone in cell lines tested. The neutrophil count was significantly higher in the fusion group than other groups. After 6 h, IL-8 and IL-6 production reached a peak, with a significant decline at 24 h post-instillation in both bladder and kidney tissues. Mice instilled with the fusion and challenged with UPEC or P. mirabilis showed a significant decrease in the number of bacteria in bladder and kidney compared to control mice. The results of these studies demonstrate that the use of recombinant fusion protein encoding TLR-4 ligand represents an effective vaccination strategy that does not require the use of a commercial adjuvant. Furthermore, MrpH.FimH was presented as a promising vaccine candidate against UTIs caused by UPEC and P. mirabilis. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  9. Effects of inhaled insoluble 239PuO2 on immune responses following lung immunization

    International Nuclear Information System (INIS)

    Bice, D.E.; Harris, D.L.; Brooks, A.L.; Mewhinney, J.A.

    1978-01-01

    To determine if inhaled 239 PuO 2 suppresses immunity in lung-associated lymph nodes, Chinese hamsters were exposed to a polydisperse aerosol of 239 PuO 2 produced at 1150 0 C. The mean lung burden of these animals was estimated to be 10 nCi at 8 days after exposure. At 128, 256 and 400 days after exposure, sham exposed controls and experimental animals were immunized by intratracheal instillation of 1 x 10 8 sheep red blood cells (SRBC). Six days later, they were sacrificed and the number of antibody forming cells (AFC) in lung-associated lymph nodes, spleen and cervical lymph nodes was evaluated. Results of these studies indicated that the number of AFC in lung-associated lymph modes was significantly lower in animals exposed to 239 PuO 2 . Only a few AFC were found in spleen and cervical lymph nodes after intratracheal immunization and the number in exposed animals was not significantly different than in the controls. These data indicate that even though the 239 PuO 2 exposure had suppressed immune responses in lung-associated lymph nodes, their filtering capacity was unaffected and antigen did not translocate to the spleen. We conclude that, at the sacrifice intervals evaluated, the immune function of lung-associated lymph nodes was suppressed and that distant lymphoid tissue (e.g., spleen and cervical lymph nodes) did not replace the immune function of the lung-associated lymph nodes

  10. Elastase-coupled beads as a tool for characterizing localized alveolar tissue destruction associated with the onset of emphysema

    Science.gov (United States)

    Craig, J. M.; Scott, A. L.

    2013-01-01

    Intratracheal elastase challenge of laboratory animals has long been established as a model for observing the physiological and morphological changes that result from alveolar destruction, the hallmark of emphysema. However, instillation of elastase suspended in buffer results in widespread inflammation and variable emphysematous lesions, which has made the identification of specific cellular and molecular events associated with the onset of emphysema difficult to define. Here we establish a bead-based elastase delivery system that induces localized tissue destruction, a key event in the initiation of emphysema. Elastase was coupled to bisacrylamide beads, which were shown to retain enzymatic activity prior to intratracheal administration in mice. C57BL/6 mice were given a single dose of 40,000 beads, which became distributed throughout the small airways and parenchyma of the lung. Elastase-coupled beads resulted in a quantifiable loss of alveolar tissue immediately surrounding the beads, an effect that was not observed with beads that lacked protein altogether or with beads containing elastase inactivated by an irreversible inhibitor. Furthermore, beads bound with active elastase elicited local recruitment of mononuclear cells, including macrophages, and polymorphonuclear neutrophils to the site of bead deposition, a feature consistent with the cellular infiltration observed following conventional solubilized elastase challenges. This work identifies a novel bead-based enzyme delivery system that also extends the elastase model of emphysema to permit the characterization of mechanisms that drive alveolar surface area loss following elastin degradation in focal emphysematous lesions. PMID:23558388

  11. Characterization of particle-induced Clara cell hyperplasia in rat lungs; Charakterisierung der Partikel-induzierten Clarazell-Hyperplasie in der Rattenlunge

    Energy Technology Data Exchange (ETDEWEB)

    Albrecht, C.; Adolf, B.; Weishaupt, C.; Hoehr, D.; Zeittraeger, I.; Borm, P.J.A. [Heinrich-Heine Univ., Duesseldorf (Germany). Medizinisches Inst. fuer Umwelthygiene; Friemann, J. [Unfallkrankenhaus Berlin (Germany). Inst. fuer Pathologie

    2001-10-01

    The aim of this study was to examine Clara cells after particle exposure by in situ hybridization as well as to characterize cell proliferation and function in xenobiotic metabolism. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz (DQ12), Titanium dioxide, or saline solution containing 0.5% Tween 80. After 126-129 weeks, all particle-exposed animals developed Clara cell hyperplasia i.e. up to 0.48% of the total lung area which was significantly increased compared to Titanium dioxide and control animals. Our data also showed proliferation and hyperplasia of bronchiolar Clara cells by coal dusts independent of their quartz content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithelium. After the migration they keep their function in the xenobiotic metabolism as shown by expansion of CYP2E1 active Clara cells. The minor development of Clara cell hyperplasia in Titanium dioxide treated rats indicates that this is not a general particle effect, and possibly due to its lower toxicity to epithelial cells. (orig.) [German] Ziel dieser Studie war die Untersuchung der Clarazellen nach Partikelexposition mittels in situ Hybridisierung sowie die Charakterisierung hinsichtlich Zellproliferation und Funktion im xenobiotischen Stoffwechsel. Weibliche Wistar-Ratten wurden intratracheal mit Kohlenstaeuben unterschiedlichen Quarzgehaltes, Quarz DQ12, Titandioxide oder physiologischer Kochsalzloesung mit einem Gehalt von 0,5% Tween 80 instilliert. Die 126-129 Wochen nach der intratrachealen Instillation mit schwerloeslichen Partikeln obduzierten Tiere wiesen alle eine Clarazellhyperplasie in bis zu 0,48% des gesamten Lungengewebes auf, die gegenueber den Titandioxid-behandelten und den Kontrolltieren statistisch signifikant war. Die Clarazellproliferation und

  12. Treatment of infected bulla with alcohol sclerosis combined with percutaneous catheter drainage: a preliminary report

    International Nuclear Information System (INIS)

    Han, Young Min; Lee, Jeong Min; Kim, Chong Soo; Chung, Gyung Ho; Rhee, Yang Keen; Lee, Yong Chul; Sohn, Myung Hee; Choi, Ki Chul

    1995-01-01

    To evaluate effectiveness of alcohol sclerosis combined with percutaneous catheter drainage (PCD) for treatment of infected bulla. Infected bulla in four consecutive patients were treated. In all patients, percutaneous catheter drainage of the bulla was performed. Instillation of sterile alcohol (99% ethanol) was carried out into the cavity of the bulla. Alcohol was left in the cavity for approximately 30 minutes in each session. Alcohol instillation was repeated according to the size of bulla. Patients were subsequently followed up with serial chest radiographs and CT scans. All patients showed significant improvement both clinically and radiologically. Disappearance of the bulla and reexpansion of surrounding lung parenchyma was observed in two patients and partial resolution (80% reduction in size) was seen in another two patients. Complications included mild chest pain during instillation of alcohol in all patients and delayed radiating shoulder pain in one patient. We provisionally conclude that intracavitary alcohol instillation combined with PCD is effective in the treatment of the infected bulla

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

    Directory of Open Access Journals (Sweden)

    Grassian Vicki H

    2011-09-01

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

  14. Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

    Science.gov (United States)

    Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

    2013-08-01

    To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

  15. Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun

    2013-01-01

    We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected...... at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar...... lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. Results Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma...

  16. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    International Nuclear Information System (INIS)

    Bagchi, Manjari

    2017-01-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  17. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    Energy Technology Data Exchange (ETDEWEB)

    Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  18. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-12-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  19. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

  20. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  1. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  2. The leucine-rich repeat structure.

    Science.gov (United States)

    Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

    2008-08-01

    The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

  3. IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema.

    Science.gov (United States)

    Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W; Cua, Daniel J; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko

    2016-11-01

    We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23 -/- ) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23 -/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23 -/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

  4. Tocopherol Supplementation Reduces NO Production and Pulmonary Inflammatory Response to Bleomycin

    Science.gov (United States)

    Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S.; Gow, Andrew J.

    2013-01-01

    Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated. PMID:23669183

  5. An experimental study on carcinogenesis related to localized fibrosis in the lung

    International Nuclear Information System (INIS)

    Ohwada, Hidemi; Hayashi, Yutaka; Seki, Masatoshi.

    1980-01-01

    The present series of experiments was carried out in order to see what role pre-existing localized fibrosis plays in carcinogenesis of the lung. Hemorrhagic infarction was produced in the lung of 180 male Wistar rats by injecting 0.05 ml of hexachlorotetrafluorobutane into the tail vein. This resulted in localized fibrosis in the lung 3 months later. One hundred and fifteen rats were alive 3 months after administration of the chemical. Of these animals, 30 were given no further treatment (control). The remaining 85 rats were given intratracheal instillation of 0.2 μCi of polonium-210 once a week, a total of 15 times. It was subsequently found that lung carcinoma was induced in close proximity to the localized pulmonary fibrosis in 3 of 26 rats (11.5%) during the period from completion of the 15 weekly administrations of polonium-210 until the end of this experiment (21 months after the 1st instillation of polonium-210). Polonium-210 was found to be deposited in the fibrous thickening of the alveolus around the subpleural fibrotic lesion, bronchial epithelium, and peribronchial lymph apparati at the initial period of administration of polonium-210, but during the period of pulmonary carcinogenesis, it was deposited in the localized fibrotic lesion in the lung and in a few cancer cells. This suggests that polonium-210 deposited in the pulmonary fibrotic lesion remains there over a long period of time, indicating a reduced clearance ability at this site. (author)

  6. Sensitivity of MRI in detecting alveolar infiltrates. Experimental studies

    International Nuclear Information System (INIS)

    Biederer, J.; Busse, I.; Grimm, J.; Reuter, M.; Heller, M.; Muhle, C.; Freitag, S.

    2002-01-01

    Purpose: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T 1 - and T 2 -weighted MRI sequences. Material and Methods: 10 porcine lung explants were intubated, transferred into the cavity of a MRI-compatible chest phantom and inflated by continuous evacuation of the artificial pleural space. All lungs were examined with MRI at 1.5 T before and after intra-tracheal instillation of either 100 or 200 ml gelatine-stabilised liquid to simulate alveolar infiltrates. MR-examination comprised gradient echo (2D- and 3D-GRE) and fast spin echo sequences (T 2 -TSE and T 2 -HASTE). The signal intensity of lung parenchyma was evaluated at representative cross sections using a standardised scheme. Control studies were acquired with helical CT. Results: The instilled liquid caused patchy confluent alveolar infiltrates resembling the findings in patients with pneumonia or ARDS. CT revealed typical ground-glass opacities. Before the application of the liquid, only T 2 -HASTE and T 2 -TSE displayed lung parenchyma signals with a signal/noise ratio of 3.62 and 1.39, respectively. After application of the liquid, both T 2 -weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30% at 100 ml (p 2 -weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to detect pneumonia in patients. (orig.) [de

  7. Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang, E-mail: yangsun@nju.edu.cn; Wu, Xuefeng, E-mail: wuxf@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

    2016-07-15

    Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

  8. The influence of high iron diet on rat lung manganese absorption

    International Nuclear Information System (INIS)

    Thompson, Khristy; Molina, Ramon; Donaghey, Thomas; Brain, Joseph D.; Wessling-Resnick, Marianne

    2006-01-01

    Individuals chronically exposed to manganese are at high risk for neurotoxic effects of this metal. A primary route of exposure is through respiration, although little is known about pulmonary uptake of metals or factors that modify this process. High dietary iron levels inversely affect intestinal uptake of manganese, and a major goal of this study was to determine if dietary iron loading could increase lung non-heme iron levels and alter manganese absorption. Rats were fed a high iron (1% carbonyl iron) or control diet for 4 weeks. Lung non-heme iron levels increased ∼2-fold in rats fed the high iron diet. To determine if iron-loading affected manganese uptake, 54 Mn was administered by intratracheal (it) instillation or intravenous (iv) injection for pharmacokinetic studies. 54 Mn absorption from the lungs to the blood was lower in it-instilled rats fed the 1% carbonyl iron diet. Pharmacokinetics of iv-injected 54 Mn revealed that the isotope was cleared more rapidly from the blood of iron-loaded rats. In situ analysis of divalent metal transporter-1 (DMT1) expression in lung detected mRNA in airway epithelium and bronchus-associated lymphatic tissue (BALT). Staining of the latter was significantly reduced in rats fed the high iron diet. In situ analysis of transferrin receptor (TfR) mRNA showed staining in BALT alone. These data demonstrate that manganese absorption from the lungs to the blood can be modified by iron status and the route of administration

  9. Species differences in biliary excretion of benzo[a]pyrene

    International Nuclear Information System (INIS)

    Weyand, E.H.; Bevan, D.R.

    1986-01-01

    Biliary excretion of benzo[a]pyrene (B[a]P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. [ 3 H]-B[a]P, in amounts of approximately 150 ng or 350 μg, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of [ 3 H]-B[a]P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B[a]P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B[a]P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B[a]P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose

  10. Tumor necrosis factor-alpha release from rat pulmonary leukocytes exposed to ultrafine cobalt: in vivo and in vitro studies

    International Nuclear Information System (INIS)

    Zhang Qunwei; Kusaka, Yukinori; Sato, Kazuhiro; Wang Deweng; Donaldson, Kenneth

    1999-01-01

    Ultrafine cobalt (Uf-Co), one of the new category of ultrafine particles, is generated in some industrial situations and it also exists in environmental particles. The aim of this study was to investigate the ability of rat pulmonary leukocytes to release tumor necrosis factor alpha (TNF-alpha) after exposure to Uf-Co in vivo and in vitro. Rats were intratracheally instilled with 1 mg of Uf-Co, and then wet lung weight and bronchoalveolar lavage fluid (BASF) profile were analysed 1, 3, 7, 15, and 30 days later. The effects of Uf-Co on indices that can be presumed to reflect epithelial injury and permeability (lactate dehydrogenase (LDH) and total protein (TP)) were increased throughout the 30 day post-exposure period. Furthermore, at 3 days after exposure, leukocytes were collected by bronchoalveolar lavage (BAL). After 3, 6, 12, 24, 48, and 72 hours of incubation, TNF-alpha in supernatants were determined by ELISA method. The results showed that TNF-alpha secretion by activated leukocytes from rats instilled with Uf-Co was significantly higher than that of the controls. BAL leucocytes from the lung of exposed rats revealed time-and dose-related increases in TNF-alpha release. In conclusion, our results reveal, for the first time to our knowledge, that exposure to Uf-Co can stimulate leukocytes to secrete TNF-alpha. These data suggest that the TNF-alpha release from pulmonary leukocytes probably plays a role in the pathogenesis of 'cobalt lung'. (author)

  11. Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

    International Nuclear Information System (INIS)

    Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang; Wu, Xuefeng; Xu, Qiang

    2016-01-01

    Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

  12. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Science.gov (United States)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-02-01

    The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  13. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    International Nuclear Information System (INIS)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-01-01

    The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis

  14. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  15. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  16. DYNAMICS OF HEAT SHOCK PROTEIN-70 SYNTHESIS IN LUNGS DEPENDS ON THE STAGE OF EXPERIMENTAL RESPIRATORY DISTRESS SYNDROME

    Directory of Open Access Journals (Sweden)

    E. V. Prutkina

    2013-01-01

    Full Text Available Abstract. Acute respiratory distress syndrome (ARDS was reproduced in a rat model, by means of intratracheal instillation of granulocyte lysates (a method protected by Russian patent. Expression of HSP-70 in lung cells was determined by immunohistochemical technique at each ARDS stage. A significant increase of HSP-70 expression by all cell types was revealed during exudative stage, being more intensive in alveolocytes type 1, and less expressed in endothelium. During proliferative stage of the disorder, a decreased HSP-70 expression was noted in all cell populations. At these terms, it proved to be high in neutrophils and alveveolocytes type 1, whereas lower expression was registered in endothelium. At fibrotic stage, HSP-70 synthesis remained at high levels in neutrophils, macrophages, fibroblasts and alveolocytes type 1. Endothelium and alveolocytes type 2 exhibited a recurrent increase at fibrotic stage of ARDS, however it did not reach the values typical to the initial stage of the syndrome.

  17. Transcriptional profiling identifies physicochemical properties of nanomaterials that are determinants of the in vivo pulmonary response

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Saber, Anne Thoustrup; Decan, Nathalie

    2015-01-01

    meta-analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO2NP gene expression response. Embedding of TiO2NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary...... inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (P ≤ 0.05; fold change ≥ 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO2NPs clustered mainly by postexposure timepoint followed by particle type. A pathway-based...... in paint matrices. Adult C57BL/6 mice were exposed via single intratracheal instillations to free forms of TiO2NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO2NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO2NPs were characterized...

  18. Facilitating Effects of Nanoparticles/Materials on Sensitive Immune-Related Lung Disorders

    International Nuclear Information System (INIS)

    Inoue, K.I.; Takano, H.

    2011-01-01

    Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully examined. In this paper, we provide insights into the immunotoxicity of nanoparticles/materials as an aggravating factor in hyper susceptible subjects, especially those with immune-related respiratory disorders using our in vivo experimental model. We first exhibit the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS) in vivo as a disease model in innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Secondly, we introduce the effects of nanoparticles/materials on allergic asthma in vivo as a disease model in adaptive immunity, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

  19. Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice*

    Science.gov (United States)

    Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L.; Jerome, Jacob A.; Madsen, Daniel H.; Christofidou-Solomidou, Melpo; Speicher, David W.; Bachovchin, William W.; Feghali-Bostwick, Carol; Puré, Ellen

    2016-01-01

    Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2–4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. PMID:26663085

  20. Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Farinas, E.M.

    1986-01-01

    Glycosaminoglycans (GAG) have previously been demonstrated to be synthesized in greater than normal amounts following a single intratracheal insufflation of bleomycin in hamsters. This suggests that GAG may play a role in the propagation of pulmonary fibrotic reactions. To further test this hypothesis, GAG synthesis was studied in a new hamster model of interstitial lung injury, induced by the cardiac drug, aminodarone. Animals received a single intratracheal instillation of 1.25 mg aminodarone. At 4, 9, and 21 days post-insufflation, the animals were sacrificed, their lungs removed, and 1 mm fragments placed in explant culture for 6 hours at 37 0 C in the presence of 35 S-sulfate. The labeled GAG were isolated and measured for 35 S incorporation. The author then isolated the hexosamine portions of the respective GAGs, Heparan Sulfate (HEP S), Chondroitin-6-Sulfate (Ch-6-S) and Chondroitin-4-Sulfate and Dermatan Sulfate (CH-4-S and DS) using the enzyme ABC and paper chromatography. They also studied the GAG content and distribution in hamster lung fibroblasts incorporated with 35 S for 48 hours and subjected to either 0, 0.01 mg, 0.1 mg, or 1 mg of aminodarone. GAG synthesis is increased at an early stage following the induction of lung injury by aminodarone and remains elevated for a 3 week period. The change in GAG distribution boards elevated CH-4-S and DS may be characteristic of interstitial diseases in general. The GAGs that are synthesized by fibroblasts may be responsible for the increased CH-4-S and DS synthesis

  1. Rapid and selective removal of preservative from ophthalmic formulations during eyedrops instillation.

    Science.gov (United States)

    Hsu, Kuan-Hui; Chauhan, Anuj

    2015-11-01

    About 70% of eyedrops contain benzalkonium chloride (BAK) as a preservative to prevent the growth of microorganisms. While preservatives are mandated to maintain sterility, many patients exhibit irritation and toxicity to such compounds. We propose to mitigate the ocular toxicity in the ocular formulations without compromising sterility by designing a device that can be incorporated into an eyedrops bottle to selectively remove the preservatives during the process of drop instillation. Here, we specifically focus on macroporous poly(2-hydroxyethyl methacrylate) (pHEMA) gel due to its excellent biocompatibility and high partition coefficient for BAK. In addition to specific selectivity for BAK, the device also requires high hydraulic permeability to allow drop dispensing without excessive pressure drop. The pHEMA monolith can remove nearly 100% of contained BAK from a 25 ml, 0.012% BAK solution with negligible uptake of the hydrophilic drugs such as timolol and dorzolamide. The filter, however, had to be pre-equilibrated with hydrophobic drugs to reach a high separation of BAK without reducing the concentration of the active drug. The average hydraulic permeability of the filter was 0.025 Darcy, which is about 5-fold lower than the ideal value. Incorporation of a pHEMA macroporous gel into an eyedrops bottle can virtually eliminate the exposure of the eyes to the preservatives without compromising the sterility. Our novel design can eliminate the preservative induced toxicity from eyedrops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases such as glaucoma and dry eyes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.

    Science.gov (United States)

    Osaki, Takashi; Ozaki, Mineo; Takamura, Norito; Ogata, Kenji; Tokunaga, Jin; Setoguchi, Nao; Arimori, Kazuhiko

    2014-05-01

    Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin-binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Negative Pressure Wound Therapy With Instillation (NPWTi) Better Reduces Post-debridement Bioburden in Chronically Infected Lower Extremity Wounds Than NPWT Alone.

    Science.gov (United States)

    Goss, S G; Schwartz, J A; Facchin, F; Avdagic, E; Gendics, C; Lantis, J C

    2012-12-01

    An overabundance of bacteria in the chronic wound plays a significant role in the decreased ability for primary closure. One means of decreasing the bioburden in a wound is to operatively debride the wound for wound bed optimization prior to application of other therapy, such as Negative Pressure Wound Therapy (NPWT). We undertook a prospective pilot study to assess the efficacy of wound bed preparation for a standard algorithm (sharp surgical debridement followed by NPWT) versus one employing sharp surgical debridement followed by Negative Pressure Wound Therapy with Instillation (NPWTi). Thirteen patients, corresponding to 16 chronic lower leg and foot wounds were taken to the operating room for debridement. The patients were sequentially enrolled in 2 treatment groups: the first receiving treatment with operative debridement followed by 1 week of NPWT with the instillation of quarter strength bleach solution; the other receiving a standard algorithm consisting of operative debridement and 1 week of NPWT. Quantitative cultures were taken pre-operatively after sterile preparation and draping of the wound site (POD # 0, pre-op), post-operatively once debridement was completed (POD # 0, post-op), and on post-operative day 7 after operative debridement (POD # 7, post-op). After operative debridement (post-operative day 0) there was a mean of 3 (±1) types of bacteria per wound. The mean CFU/gram tissue culture was statistically greater - 3.7 × 10(6) (±4 × 10(6)) in the NPWTi group, while in the standard group (NPWT) the mean was 1.8 × 10(6) (±2.36 × 10(6)) CFU/gram tissue culture (p = 0.016); at the end of therapy there was no statistical difference between the two groups (p = 0.44). Wounds treated with NPWTi had a mean of 2.6 × 10(5) (±3 × 10(5)) CFU/gram of tissue culture while wounds treated with NPWT had a mean of 2.79 × 10(6) (±3.18 × 10(6)) CFU/gram of tissue culture (p = 0.43). The mean absolute reduction in bacteria for the

  4. In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

    2012-12-01

    Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.

  5. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... coordinators estimate the effect on coordination fees? Does the supposed benefit that mobile repeater stations... allow the licensing and operation of vehicular repeater systems and other mobile repeaters by public... email: [email protected] or phone: 202-418- 0530 or TTY: 202-418-0432. For detailed instructions for...

  6. Tevatron serial data repeater system

    International Nuclear Information System (INIS)

    Ducar, R.J.

    1981-01-01

    A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

  7. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  8. Film repeats in radiology department

    International Nuclear Information System (INIS)

    Suwan, A. Z.; Al-Shakharah, A. I

    1997-01-01

    During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

  9. Repeat migration and disappointment.

    Science.gov (United States)

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  10. Quantum repeated games revisited

    International Nuclear Information System (INIS)

    Frąckiewicz, Piotr

    2012-01-01

    We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable. (paper)

  11. Investigations into the formal pathogenesis of quartz-dust-induced tumours of the lungs in rats. Pt. 1. Pneumocyte proliferation and changes in the lung tissue; Untersuchungen zur formalen Pathogenese quarzstaubinduzierter Lungen-Tumoren bei der Ratte. T. 1. Pneumozytenproliferation und Lungenumbau

    Energy Technology Data Exchange (ETDEWEB)

    Friemann, J. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany); Kubitza, R. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany); Weishaupt, C. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany); Varnai, M. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany); Pott, F. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany); Musinski, G. [Medizinisches Inst. fuer Umwelthygiene, Univ. Duesseldorf (Germany)

    1995-12-31

    In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of {alpha} quartz. In our retrospective study we evaluated lung specimens of 153 Wistar rats from larger experiments, which had been exposed to quartz by inhalation (10 mg/m{sup 3}, 56 weeks, 5 days/week, 7 h/day: n=27) or intratracheal instillations (5 mg: n=38; 20 mg: n=10; 50 mg: n=28; 15x3 mg: n=25). Animals were sacrificed 1-32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The agryophil (AgNOR) method for the demonstration of nuclear organizer region (NOR) was used as second marker of type II cell proliferation. Morphomtrical measurements were carried out for quantitative analysis of silicosis and quartz dust induced bronchiolo-alveolar hyperplasia of the lung. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate as well as an multifocal adenomatous hyperplasia (bronchiolo-alveolar hyperplasia). As nitrogenesis increases carcinogenesis both of them might be prerequisites for enhanced tumor development. (orig.) [Deutsch] Bei Ratten entstehen nach inhalativer Quarzstaubbelastung ueberwiegend aus Typ II-Pneumozyten aufgebaute periphere Lungentumoren. In unserer retrospektiven Untersuchung werteten wir Lungenpraeparate von 153 Wistar Ratten aus, denen zuvor Quarz inhalativ (10 mg/m{sup 3}, 56 Wochen, 5 Tage pro Woche, 7 Std./Tag: n=27) oder i.tr. (5 mg: n=38; 20 mg: n=10; 50 mg: n=28; 15x3 mg: n=25) verabreicht worden war. Die Toetung der Tiere erfolgte 1-32 Monate nach Expositionsbeginn. Die Bestimmung der Proliferationsrate der Typ II-Pneumozyten wurde mittels statischer DNA-Zytophotometrie nach Silberfaerbung Nucleolus

  12. The management of non-invasive bladder tumours with Doxorubicin intravesical instillation after transurethral resection.

    Science.gov (United States)

    Al-Gallab, Musa I; Naddaf, Louai A; Kanan, Mohamad R

    2009-04-01

    Evaluation of the intravesical instillation of doxorubicin for its effect on disease recurrence for patients with non-invasive bladder tumour. The study was performed at Al Assad University Hospital in Lattakia, Syria and included patients with non-invasive bladder tumours who were managed with transurethral resection and induction and maintenance therapy with intravesical doxorubicin. They were followed up by cystoscopy every 3 months for 2 years and every 6 months thereafter with special emphasis on recurrence rates. The study included 85 patients with non-invasive bladder tumours: 23 with non-invasive papillary carcinoma (Stage Ta), 62 with tumour invading subepithelial connective tissue (Stage T1). Twelve patients had well differentiated tumours (Grade 1), 48 had moderately differentiated (Grade 2), 25 had poorly differentiated (Grade 3) tumours. The total recurrence rate was 23%. The rates of recurrence were 56% in Grade 3 and 0% in Grade 1. The recurrence rate was 41% in patients with large tumours versus 17% in those with small tumours; 44% in those with multiple tumours compared to 18% in those with solitary tumours; 30% of Stage Ta tumours recurred and 21% of Stage T1 tumours. In short term follow-up, our rate of recurrence was 23%. Adjuvant intravesical doxorubicin was shown to reduce the recurrence of superficial bladder cancer. Tumour grade, size and number were shown to be prognostic factors for recurrence.

  13. Macau, world capital for gambling: A longitudinal study of a youth program designed to instill positive values

    Directory of Open Access Journals (Sweden)

    Andrew Leung Luk

    2013-11-01

    Full Text Available Macau, world capital for gambling: A longitudinal study of a youth program designed to instil positive valuesABSTRACTThis study investigated the effectiveness of a positive youth development program for Chinese Secondary 3 students in two schools, who had been followed up since their entry to Secondary 1. A mixed research method was carried out using a pre- and post-test pre-experimental design and a focus group for the participants. The subjective outcome evaluations included participants’ perceptions of the program, program instructors, benefits of the program and overall satisfaction, and were positive. The longitudinal data from the objective outcome evaluation showed some notable improvements, and the overall effect of the program was also found to be positive for newcomers in the junior secondary years. The focus group interviews revealed mostly positive feedback in terms of the students’ general impressions of the program, with the majority of participants perceiving benefits to themselves from the program. The findings offer positive evidence of the effectiveness of the program. KEYWORDS: adolescents, positive youth development, objective outcome evaluation, subjective outcome evaluation

  14. Repeatability of visual acuity measurement.

    Science.gov (United States)

    Raasch, T W; Bailey, I L; Bullimore, M A

    1998-05-01

    This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

  15. The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain: A double-blind, randomized, placebo-controlled study

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Hansen, J.B.; Malmstrom, J.

    2008-01-01

    and laboratory tests were done before and I wk after surgery, together with recordings of adverse events up to 28 days. Adverse events were recorded. Data were also analyzed using a mixed-effects analysis with NONMEM. RESULTS: VAS AUC was significantly lower during the first 3 days postoperatively (P ....05), but not for the whole I or 4 wk postoperatively. Mixed-effects analysis with NONMEM revealed that pain scores were significantly lower (P adverse events were observed, although a mild transient increase in liver enzymes was seen......, preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 mu g ultrapurified capsaicin (ALGRX...

  16. Fostering repeat donations in Ghana.

    Science.gov (United States)

    Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

    2010-01-01

    Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

  17. Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

    Science.gov (United States)

    Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

    2017-07-01

    Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  18. Rapid clearance of xanthines from airway and pulmonary tissues

    International Nuclear Information System (INIS)

    Kroell, F.K.; Karlsson, J.A.; Nilsson, E.; Ryrfeldt, A.; Persson, C.G.

    1990-01-01

    The airway and pulmonary fate of two antiasthma xanthines was examined in a guinea pig perfused lung preparation where the airway mechanics and airway microvascular perfusion are maintained at near normal values. 14C-theophylline or 14C-enprofylline was infused for 10, 30, and 300 s into the pulmonary artery of the guinea pig isolated lung. The radioactivity increased rapidly (within 10 s) in tracheobronchial as well as in lung tissue, confirming that the large airway microcirculation was well supplied also by the perfusion. The effluent concentrations of total 3H and 14C radioactivity at the onset, during, and after intrapulmonary infusion of 14C-labeled xanthines and 3H-sucrose were closely associated, suggesting that the xanthines, like sucrose, largely distributed in extracellular fluid and were not taken up by the tissues. No metabolites of enprofylline or theophylline could be detected in the lung tissue or lung effluent, suggesting that xanthines are not biotransformed by the guinea pig lung. After intratracheal instillation of 14C-theophylline, the peak radioactivity in the lung effluent appeared in the second 15-s fraction after instillation, and after 10 and 60 min, 68.1 +/- 4.7% and 86.9 +/- 8.4%, respectively, of the given dose had appeared in the lung effluent. The present data suggest a mainly extracellular distribution and a rapid clearance of xanthines from the lung and airway tissues. The rapid disappearance of topical theophylline may explain the lack of success of inhalation therapy with this drug

  19. Repeated DNA sequences in fungi

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, S K

    1974-11-01

    Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10 to 20 percent repeated DNA sequences. There are approximately 100 to 110 copies of repeated DNA sequences of approximately 4 x 10/sup 7/ daltons piece size of each. Repeated DNA sequence homoduplexes showed on average 5/sup 0/C difference of T/sub e/50 (temperature at which 50 percent duplexes dissociate) values from the corresponding homoduplexes of unfractionated whole DNA. It is suggested that a part of repetitive sequences in fungi constitutes mitochondrial DNA and a part of it constitutes nuclear DNA. (auth)

  20. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  1. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

    Science.gov (United States)

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-06-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  2. Gel instillation sonohysterography (GIS) and saline contrast sonohysterography (SCSH): comparison of two diagnostic techniques.

    Science.gov (United States)

    Bij de Vaate, A J M; Brölmann, H A M; van der Slikke, J W; Emanuel, M H; Huirne, J A F

    2010-04-01

    To compare gel instillation sonohysterography (GIS) with saline contrast sonohysterography (SCSH) as diagnostic methods for the evaluation of the uterine cavity. A prospective cohort study was performed at the Department of Obstetrics and Gynecology of the VU University Medical Center, Amsterdam, between September 2007 and April 2008. We included 65 women suspected of having an intrauterine abnormality with an indication for SCSH/GIS. First SCSH and subsequently GIS were performed in all women. Distension of the uterine cavity, image quality, visualization of intrauterine abnormalities and pain experienced on a visual analog scale (VAS score) were recorded for both procedures. The mean distension with GIS was 9.0 mm and with SCSH it was 8.5 mm (P = 0.15). The mean image quality, on a scale from 0 to 5, for SCSH was 4.0 and for GIS it was 3.6 (P = 0.01). No difference was found for the visualization of intrauterine abnormalities, and the VAS scores for pain experienced on SCSH and GIS were 1.5 and 1.6, respectively (P = 0.62). The image quality of SCSH is slightly better than that of GIS. This difference is likely to be attributable to the presence of air bubbles in the gel. The small difference in uterine cavity distension in favor of GIS and comparable stable distension during at least 4 min make GIS a suitable alternative for SCSH if air bubbles can be prevented. Copyright 2009 ISUOG. Published by John Wiley & Sons, Ltd.

  3. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  4. Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Loft, Steffen; Jacobsen, Nicklas Raun

    2010-01-01

    Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric...

  5. Reject/repeat analysis and the effect prior film viewing has on a department's reject/repeat rate

    International Nuclear Information System (INIS)

    Clark, P.A.; Hogg, P.

    2003-01-01

    Purpose: Achieving cost-effectiveness within the NHS is an old initiative but one that has again been highlighted by recent government policies (The New NHS-Modern and Dependable, Stationary Office, London, 1997). It has been reiterated that it is the responsibility of individual Trusts to devise means to provide such a service. Reject/repeat analyses have long been the primary tool used to assess the cost-effectiveness of radiography departments (Quality Assurance in Diagnostic Radiology, WHO, Geneva, 1982). This research paper examines an in-house initiative (viewing patients' previous films) commonly employed in other Health Trusts in order to reduce departmental repeat/reject rates. Method: Three hundred orthopaedic patients with hip, knee and ankle prostheses were included in a reject/repeat analysis. The aim was to investigate whether or not viewing patient's previous relevant radiographs would be advantageous to the practicing radiographer. This was done through an audit cycle consisting of two audit periods each lasting for 3 months. The primary audit period recorded the baseline repeat/reject rate, with the secondary audit period recording the repeat/reject rate under an experimental condition of viewing the relevant radiographs. Results: The baseline audit revealed repeat rates of 33% in orthopaedic patients with hip, knee and ankle prostheses. The availability of prior film viewing to the radiographer reduced this repeat rate to 10.6%. Conclusion: Prior film viewing dramatically reduced the department's repeat/reject rate by 22.4%. This provides scope for significant patient dose reductions as well as reducing departmental film expenses. This is an underestimated initiative and should be used appropriately in routine clinical practice

  6. Repeating Marx

    DEFF Research Database (Denmark)

    Fuchs, Christian; Monticelli, Lara

    2018-01-01

    This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

  7. Intratracheal injection of adenovirus containing the human MNSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis

    International Nuclear Information System (INIS)

    Epperly, Michael W.; Bray, Jenifer A.; Krager, Stephen; Berry, Luann M.; Gooding, William; Engelhardt, John F.; Zwacka, Ralf; Travis, Elizabeth L.; Greenberger, Joel S.

    1999-01-01

    Purpose: A dose and volume limiting factor in radiation treatment of thoracic cancer is the development of fibrosis in normal lung. The goal of the present study was to determine whether expression prior to irradiation of a transgene for human manganese superoxide dismutase (MnSOD) or human copper/zinc superoxide dismutase (Cu/ZnSOD) protects against irradiation-induced lung damage in mice. Methods and Materials: Athymic Nude (Nu/J) mice were intratracheally injected with 10 9 plaque-forming units (PFU) of a replication-incompetent mutant adenovirus construct containing the gene for either human MnSOD, human copper/zinc superoxide dismutase (Cu/ZnSOD) or LacZ. Four days later the mice were irradiated to the pulmonary cavity to doses of 850, 900, or 950 cGy. To demonstrate adenoviral infection, nested reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out with primers specific for either human MnSOD or Cu/ZnSOD transgene on freshly explanted lung, trachea, or alveolar type II cells, and immunohistochemistry was used to measure LacZ expression. RNA was extracted on day 0, 1, 4, or 7 after 850 cGy of irradiation from lungs of mice that had previously received adenovirus or had no treatment. Slot blot analysis was performed to quantitate RNA expression for IL-1, tumor necrosis factor (TNF)-α, TGF-β, MnSOD, or Cu/ZnSOD. Lung tissue was explanted and tested for biochemical activity of MnSOD or Cu/ZnSOD after adenovirus injection. Other mice were sacrificed 132 days after irradiation, lungs excised, frozen in OCT, (polyvinyl alcohol, polyethylene glycol mixture) sectioned, H and E stained, and evaluated for percent of the lung demonstrating organizing alveolitis. Results: Mice injected intratracheally with adenovirus containing the gene for human MnSOD had significantly reduced chronic lung irradiation damage following 950 cGy, compared to control mice or mice injected with adenovirus containing the gene for human Cu/ZnSOD or LacZ. Immunohistochemistry

  8. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  9. Dissolution and clearance of titanium tritide particles in the lungs of F344/Crl rats

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yung-Sung; Snipes, M.B.; Wang, Yansheng

    1995-12-01

    Metal tritides are compounds in which the radioactive isotope tritium, following adsorption onto the metal, forms a stable chemical compound with the metal. When particles of tritiated metals become airborne, they can be inhaled by workers. Because the particles may be retained in the lung for extended periods, the resulting dose will be greater than doses following exposure to tritium gas or tritium oxide (HTO). Particles of triated metals may be dispersed into the air during routine handling, disruption of contaminated metals, or as a result of spontaneous radioactive decay processes. Unlike metal hydrides and deuterides, tritides are radioactive, and the decay of the tritium atoms affects the metal. Because helium is a product of the decay, helium bubbles form within the metal tritide matrix. The pressure from these bubbles leads to respirable particles breaking off from the tritide surface. Our results show that a substantial amount of titanium tritide remains in the rat lung 10 d after intratracheal instillation, confirming results previously obtain in an in vitro dissolution study.

  10. Modifying effects of pre-existing fibrosis in rats exposed to aerosols of {sup 239}PuO{sub 2}. II

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D L; Mauderly, J L; Gillett, N A; Hahn, F F

    1988-12-01

    We have initiated a study using rats to determine the modifying effects of pre-existing pulmonary fibrosis on the retention and biological effects of inhaled {sup 239}PuO{sub 2}. Pulmonary fibrosis was induced by intratracheal instillation of 8.5 IU/kg body weight of bleomycin at 45 to 49 days before inhalation exposure to an aerosol of {sup 239}PuO{sub 2}. The clearance of {sup 239}Pu from the lungs of rats was decreased significantly (p < 0.01) in rats with pre-existing pulmonary fibrosis compared with controls. Respiratory function, lung morphometric measurements and histological evaluations were all consistent with the presence of mild pulmonary fibrosis in the rats treated with bleomycin. Pre-existing pulmonary fibrosis resulted in an increased retention of the initial lung burdens of {sup 239}Pu, apparently by entrapping the particles in fibrotic areas of the lung. The life span of the rats with pulmonary fibrosis was decreased by up to 25% compared with control rats having similar initial lung burdens of {sup 239}Pu. (author)

  11. The Pharmacokinetics and Biodistribution of a 64 kDa PolyPEG Star Polymer After Subcutaneous and Pulmonary Administration to Rats.

    Science.gov (United States)

    Khor, Song Yang; Hu, Jinming; McLeod, Victoria M; Quinn, John F; Porter, Christopher J H; Whittaker, Michael R; Kaminskas, Lisa M; Davis, Thomas P

    2016-01-01

    PolyPEG star polymers have potential utility as cost-effective polymeric drug delivery vehicles, and as such, it is important to develop an understanding of their biopharmaceutical behavior. Moreover, although a number of studies have evaluated the utility of PolyPEG stars in vitro, investigation of these novel materials in vivo has been limited. Herein, we evaluated the pharmacokinetics of a 64 kDa tritiated PEG-based star polymer after subcutaneous and pulmonary administration in rats. After subcutaneous administration, the star polymer showed near complete bioavailability (∼80%) and a similar organ biodistribution profile to the polymer after intravenous administration. After intratracheal instillation to the lungs, the star polymer showed limited bioavailability (∼3%), and most of the administered radiolabel was recovered in lung tissue and feces after 6 d. The data reported here suggest that star polymers display similar pharmaceutical behavior to PEGylated dendrimers after subcutaneous and inhaled delivery and may therefore be used as similar, but more cost-effective drug delivery vehicles. Copyright © 2016. Published by Elsevier Inc.

  12. The Protective Effects of the Supercritical-Carbon Dioxide Fluid Extract of Chrysanthemum indicum against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Modulating Toll-Like Receptor 4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiao-Li Wu

    2014-01-01

    Full Text Available The supercritical-carbon dioxide fluid extract of Chrysanthemum indicum Linné. (CFE has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI induced by lipopolysaccharide (LPS in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1β, and IL-6, inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx. Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.

  13. Assessment of respiratory carcinogenicity associated with exposure to metallic nickel: a review.

    Science.gov (United States)

    Sivulka, Donna J

    2005-11-01

    Human studies prior to 1990 have shown an association between respiratory cancer and exposure to some nickel compounds, but not to metallic nickel. Numerous reviews have examined the nature of the association between nickel compounds and respiratory cancer, but little has been published on metallic nickel. This paper reviews the animal and human cancer-related data on metallic nickel to determine whether the conclusions regarding metallic nickel reached a decade ago still apply. Based upon past and current human studies, metallic nickel appears to show little evidence of carcinogenicity when present at the same or higher concentrations than those seen in current workplace environments. By comparison, animal studies currently available have shown mixed results. A number of studies have shown evidence of carcinogenicity in animals exposed to nickel powders via injection, but other studies have shown no or inconsistent results in animals exposed via inhalation or intratracheal instillation. Further studies in animals via inhalation and humans would be helpful in elucidating the respiratory carcinogenic potential of metallic nickel.

  14. Facilitating Effects of Nanoparticles/Materials on Sensitive Immune-Related Lung Disorders

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Inoue

    2011-01-01

    Full Text Available Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully examined. In this paper, we provide insights into the immunotoxicity of nanoparticles/materials as an aggravating factor in hypersusceptible subjects, especially those with immune-related respiratory disorders using our in vivo experimental model. We first exhibit the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS in vivo as a disease model in innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Secondly, we introduce the effects of nanoparticles/materials on allergic asthma in vivo as a disease model in adaptive immunity, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

  15. simple sequence repeats (EST-SSR)

    African Journals Online (AJOL)

    Yomi

    2012-01-19

    Jan 19, 2012 ... 212 primer pairs selected, based on repeat patterns of n≥8 for di-, tri-, tetra- and penta-nucleotide repeat ... Cluster analysis revealed a high genetic similarity among the sugarcane (Saccharum spp.) breeding lines which could reduce the genetic gain in ..... The multiple allele characteristic of SSR com-.

  16. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  17. Repeated Prescribed Burning in Aspen

    Science.gov (United States)

    Donald A. Perala

    1974-01-01

    Infrequent burning weather, low flammability of the aspen-hardwood association, and prolific sprouting and seeding of shrubs and hardwoods made repeated dormant season burning a poor tool to convert good site aspen to conifers. Repeat fall burns for wildlife habitat maintenance is workable if species composition changes are not important.

  18. The Pentapeptide Repeat Proteins

    OpenAIRE

    Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S,T,A,V][D,N][L,F]-[S,T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Myc...

  19. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K.

    1989-01-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance

  20. In Vivo Protective Effects of Nootkatone against Particles-Induced Lung Injury Caused by Diesel Exhaust Is Mediated via the NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2018-02-01

    Full Text Available Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t. instilled with either DEP (30 µg/mouse or saline (control. Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.

  1. In Vivo Protective Effects of Nootkatone against Particles-Induced Lung Injury Caused by Diesel Exhaust Is Mediated via the NF-κB Pathway.

    Science.gov (United States)

    Nemmar, Abderrahim; Al-Salam, Suhail; Beegam, Sumaya; Yuvaraju, Priya; Hamadi, Naserddine; Ali, Badreldin H

    2018-02-26

    Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.

  2. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-09-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43/sup 0/C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with /sup 60/Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author).

  3. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    International Nuclear Information System (INIS)

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-01-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43 0 C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with 60 Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author)

  4. In situ detection of tandem DNA repeat length

    Energy Technology Data Exchange (ETDEWEB)

    Yaar, R.; Szafranski, P.; Cantor, C.R.; Smith, C.L. [Boston Univ., MA (United States)

    1996-11-01

    A simple method for scoring short tandem DNA repeats is presented. An oligonucleotide target, containing tandem repeats embedded in a unique sequence, was hybridized to a set of complementary probes, containing tandem repeats of known lengths. Single-stranded loop structures formed on duplexes containing a mismatched (different) number of tandem repeats. No loop structure formed on duplexes containing a matched (identical) number of tandem repeats. The matched and mismatched loop structures were enzymatically distinguished and differentially labeled by treatment with S1 nuclease and the Klenow fragment of DNA polymerase. 7 refs., 4 figs.

  5. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  6. Intermittent negative pressure wound therapy with instillation for the treatment of persistent periprosthetic hip infections: a report of two cases

    Directory of Open Access Journals (Sweden)

    Söylemez MS

    2016-02-01

    Full Text Available Mehmet Salih Söylemez,1 Korhan Özkan,2 Bülent Kılıç,3 Samet Erinç41Department of Orthopaedics and Traumatology, Bingöl State Hospital, Bingöl, 2Department of Orthopaedics and Traumatology, Faculty of Medicine, Medeniyet University, Istanbul, 3Department of Orthopaedics and Traumatology, Orthopaedic Surgery Clinic, Istanbul Gelişim University, Tekirdağ, 4Department of Orthopaedics and Traumatology, Istanbul Medeniyet University, Göztepe Training and Research Hospital, Istanbul, TurkeyAbstract: Intermittent negative pressure wound therapy with instillation (NPWTi is starting to be used successfully to treat early periprosthetic infections of endoprostheses. However, few articles have reported the outcome of treatment with intermittent NPWTi for late persistent periprosthetic infections of the hip. In this study, we report two cases who underwent several rounds of radical wound debridement for the treatment of a late persistent periprosthetic infection of the hip. Intermittent NPWTi was used in both cases. Patients were treated successfully and there was no recurrence after 3 and 1 years of follow-up, respectively.Keywords: negative pressure, vacuum-assisted, periprosthetic infection, hip

  7. Digital repeat analysis; setup and operation.

    Science.gov (United States)

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  8. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao

    2003-01-01

    terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also...... recognizes both main families of repeat sequences in S. solfataricus. The recombinant protein, expressed in Escherichia coli, showed the same binding properties to the SRSR repeat as the native one. The SSO454 protein exhibits a tripartite internal repeat structure which yields a good sequence match...... with a helix-turn-helix DNA-binding motif. Although this putative motif is shared by other archaeal proteins, orthologs of SSO454 were only detected in species within the Sulfolobus genus and in the closely related Acidianus genus. We infer that the genus-specific protein induces an opening of the structure...

  9. Coexistence of 3G repeaters with LTE base stations.

    Science.gov (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  10. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  11. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan; Manolescu, Ioana; Afanasiev, Loredana; Feng, Jieling; Gou, G.; Hadjieleftheriou, Marios; Harizopoulos, Stavros; Kalnis, Panos; Karanasos, Konstantinos; Laurent, Dominique; Lupu, M.; Onose, N.; Ré , C.; Sans, Virginie; Senellart, Pierre; Wu, T.; Shasha, Dennis E.

    2010-01-01

    SIGMOD 2008 was the first database conference that offered to test submitters' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  12. FRB 121102: A Starquake-induced Repeater?

    Science.gov (United States)

    Wang, Weiyang; Luo, Rui; Yue, Han; Chen, Xuelei; Lee, Kejia; Xu, Renxin

    2018-01-01

    Since its initial discovery, the fast radio burst (FRB) FRB 121102 has been found to be repeating with millisecond-duration pulses. Very recently, 14 new bursts were detected by the Green Bank Telescope during its continuous monitoring observations. In this paper, we show that the burst energy distribution has a power-law form which is very similar to the Gutenberg–Richter law of earthquakes. In addition, the distribution of burst waiting time can be described as a Poissonian or Gaussian distribution, which is consistent with earthquakes, while the aftershock sequence exhibits some local correlations. These findings suggest that the repeating FRB pulses may originate from the starquakes of a pulsar. Noting that the soft gamma-ray repeaters (SGRs) also exhibit such distributions, the FRB could be powered by some starquake mechanisms associated with the SGRs, including the crustal activity of a magnetar or solidification-induced stress of a newborn strangeon star. These conjectures could be tested with more repeating samples.

  13. Novel expressed sequence tag- simple sequence repeats (EST ...

    African Journals Online (AJOL)

    Using different bioinformatic criteria, the SUCEST database was used to mine for simple sequence repeat (SSR) markers. Among 42,189 clusters, 1,425 expressed sequence tag- simple sequence repeats (EST-SSRs) were identified in silico. Trinucleotide repeats were the most abundant SSRs detected. Of 212 primer pairs ...

  14. Role of memory errors in quantum repeaters

    International Nuclear Information System (INIS)

    Hartmann, L.; Kraus, B.; Briegel, H.-J.; Duer, W.

    2007-01-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication

  15. Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer.

    Science.gov (United States)

    Chao, Cecilia; Stapleton, Fiona; Badarudin, Ezailina; Golebiowski, Blanka

    2015-02-01

    To determine the repeatability of ocular surface threshold measurements using the Cochet-Bonnet esthesiometer on the same day and 3 months apart. Two separate studies were conducted to determine the repeatability of ocular surface threshold measurements made on the same day (n = 20 subjects) and 3 months apart (n = 29 subjects). The Cochet-Bonnet esthesiometer was used to measure corneal and inferior conjunctival thresholds using the ascending method of limits. The pressure exerted by the Cochet-Bonnet esthesiometer was determined using an analytical balance, for both the 0.08- and 0.12-mm-diameter filaments. This calibration was then used to convert filament length measurements to pressure. Repeatability was determined using a Bland and Altman analysis. The pressure exerted at each filament length differed between the two filament diameters. The measured pressure also differed from values provided by the manufacturer. Repeatability of threshold measurements at the central cornea was shown to be good, with better repeatability for same-day measurements (coefficient of repeatability [CoR] = ±0.23 g/mm²) than for those 3 months apart (CoR = ±0.52 g/mm²). Threshold measurements at the inferior conjunctiva, in contrast, were poorly repeatable (CoR = ±12.78 g/mm²). Cochet-Bonnet esthesiometry is repeatable when performed on the central cornea on the same day and 3 months apart, but this instrument is not recommended for conjunctival threshold measurements.

  16. Safety of Repeated Yttrium-90 Radioembolization

    International Nuclear Information System (INIS)

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-01-01

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver’s cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51–71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction

  17. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  18. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Via, Laura E. [Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Kumar, Mia R.; Cornish, Joseph P. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD (United States); Johnson, Joshua C. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Pickel, James [Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD (United States); Hensley, Lisa E. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States)

    2015-11-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

  19. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

    International Nuclear Information System (INIS)

    Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

    2015-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

  20. Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study.

    Science.gov (United States)

    Autenrieth, Michael E; Seidl, Christof; Bruchertseifer, Frank; Horn, Thomas; Kurtz, Florian; Feuerecker, Benedikt; D'Alessandria, Calogero; Pfob, Christian; Nekolla, Stephan; Apostolidis, Christos; Mirzadeh, Saed; Gschwend, Jürgen E; Schwaiger, Markus; Scheidhauer, Klemens; Morgenstern, Alfred

    2018-07-01

    Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure. A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213 Bi coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213 Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter. The study proved that intravesical instillation of the 213 Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment. Intravesical instillation of 213 Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213 Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.

  1. Distribution of cyclosporine A in ocular tissues after topical administration of cyclosporine A cationic emulsions to pigmented rabbits.

    Science.gov (United States)

    Daull, Philippe; Lallemand, Frédéric; Philips, Betty; Lambert, Grégory; Buggage, Ronald; Garrigue, Jean-Sébastien

    2013-03-01

    The aim of this study was to compare the ocular and systemic distribution of cyclosporine A (CsA) in rabbits after the instillation of preservative-free CsA cationic and anionic emulsions. For the single-dose pharmacokinetic (PK) study, rabbits were instilled with 50 μL of the test material. For the multiple-dose PK study, rabbits were instilled twice daily with Restasis or once daily with NOVA22007 for 10 days. At each time point, the cornea, conjunctiva, and whole blood were harvested for CsA quantification. Ocular and systemic distribution were determined after 4 times daily instillations with 50 μL of 3H-CsA cationic and anionic emulsions for 7 days. Restasis was used as a reference in all studies. Single-dose PK data demonstrated that NOVA22007 0.1% and 0.05% delivered higher CsA concentrations to the cornea than Restasis [concentration maximum (C max): 2692, 1372, and 748 ng/g, respectively] and have a better exposition (area under the curve). Conjunctival Cmax values were 1914, 696, and 849 ng/g and area under the curve values were 3984, 2796, and 2515 ng/g · h, for either dose of the cationic emulsions and Restasis, respectively. The multiple-dose PK and the 3H-CsA distribution data demonstrated that the systemic distribution after repeated instillations was low and comparable for all emulsions. These data demonstrate that the CsA cationic emulsions were more effective than Restasis at delivering CsA to target tissues, thus confirming the potential advantage of cationic emulsions over anionic emulsions as vehicle for ocular drug delivery for the treatment of ocular surface diseases.

  2. Dental Fear in Children with Repeated Tooth Injuries.

    Science.gov (United States)

    Negovetić Vranić, Dubravka; Ivančić Jokić, Nataša; Bakarčić, Danko; Carek, Andreja; Rotim, Željko; Verzak, Željko

    2016-06-01

    Tooth injuries are serious clinical conditions. Some children experience dental trauma only once, while others are more prone to repeated tooth injuries. Repeated dental trauma occurs in 19.4% to 30% of patients. Pain and dental trauma are the most common reasons for fear and anxiety. The main objective of this study was to investigate how dental trauma, as well as repeated dental trauma affects the occurrence and development of dental fear in children. The study was conducted on a random sample of 147 subjects (88 boys and 59 girls) aged 5-8 and 9-12 years. Subjects in both age groups were divided into subroups without dental trauma, with one dental trauma and with repeated dental trauma. The validated Children’s Fear Survey Schedule – Dental Subscale was used on fear assessment. Results showed that only 12.2% of children without trauma, 33.3% with one trauma and 51.7% with repeated trauma were not afraid of injection. Older children had a significantly lower fear of injections, touch of an unknown person, choking, going to the hospital and people in white uniforms. Dentist was not the cause of fear in 65.5% of patients with repeated trauma. With each repeated injury of teeth, the degree of their fear of dental treatment was lower.

  3. Erroneous Memories Arising from Repeated Attempts to Remember

    Science.gov (United States)

    Henkel, Linda A.

    2004-01-01

    The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

  4. Identification, variation and transcription of pneumococcal repeat sequences

    Science.gov (United States)

    2011-01-01

    Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

  5. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.; Maity, A.; Mammen, E.; Yu, K.

    2009-01-01

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements

  6. Quantum key distribution with two-segment quantum repeaters

    Energy Technology Data Exchange (ETDEWEB)

    Kampermann, Hermann; Abruzzo, Silvestre; Bruss, Dagmar [Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf (Germany)

    2014-07-01

    Quantum repeaters represent one possible way to achieve long-distance quantum key distribution. One way of improving the repeater rate and decreasing the memory coherence time is the usage of multiplexing. Motivated by the experimental fact that long-range connections are practically demanding, we extend the analysis of the quantum repeater multiplexing protocol to the case of short-range connections. We derive formulas for the repeater rate and we show that short-range connections lead to most of the benefits of a full-range multiplexing protocol. A less demanding QKD-protocol without quantum memories was recently introduced by Lo et al. We generalize this measurement-device-independent quantum key Distribution protocol to the scenario where the repeater Station contains also heralded quantum memories. We assume either single-photon sources or weak coherent pulse sources plus decay states. We show that it is possible to significantly outperform the original proposal, even in presence of decoherence of the quantum memory. We give formulas in terms of device imperfections i.e., the quantum bit error rate and the repeater rate.

  7. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  8. R-loops: targets for nuclease cleavage and repeat instability.

    Science.gov (United States)

    Freudenreich, Catherine H

    2018-01-11

    R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

  9. Repeat profile analysis in an x-ray department

    International Nuclear Information System (INIS)

    Bassey, C.E.; Ojo, O.O.; Akpabio, I.

    1991-01-01

    The repeat profile of an x-ray department in a developing country was analysed monthly between July 1989 and June 1990. Results showed an average repeat rate of 3.7% for the period of study. The main causes of film repetition were: equipment fault, 33.9%; radiographer's fault, 27.4%; film fault, 19.3%; processing fault, 10.8% and patient's fault, 8.6%. The average repeat rate in the first 6 months of study reduced by 50% in the last 6 months. This was due to the effectiveness of implementation of corrective actions. The overall repeat rate was found to correlate well with both the equipment fault and radiographer's fault with correlation coefficients, r, of 0.94 and 0.91, respectively. It is expected that a further reduction in the repeat rate will be obtained after the introduction of quality assurance programmes. (author)

  10. The effect of pupil size on stimulation of the melanopsin containing retinal ganglion cells, as evaluated by monochromatic pupillometry

    DEFF Research Database (Denmark)

    Nissen, Claus Jeppe; Sander, Birgit; Lund-Andersen, Henrik

    2012-01-01

    or contracted, the entire sequence of red and blue light exposure repeated. After at least 3¿days, when the effect of the eye drop had subsided, the entire experiment was repeated, this time employing the other substance. Results: Prior dilatation of the left pupil augmented the post light contraction to blue...... (660¿nm) and in a following session, blue (470¿nm) light. The consensual pupillary diameter in the right eye was continuously measured before, during, and after light exposure. Subsequently, Tropicamide 1% or Pilocarpine 2% was instilled into the left eye and when the pupil was either maximally dilated...

  11. Studies of single-walled carbon nanotubes-induced hepatotoxicity by NMR-based metabonomics of rat blood plasma and liver extracts

    Science.gov (United States)

    Lin, Bencheng; Zhang, Huashan; Lin, Zhiqing; Fang, Yanjun; Tian, Lei; Yang, Honglian; Yan, Jun; Liu, Huanliang; Zhang, Wei; Xi, Zhuge

    2013-05-01

    The toxicological effects of single-walled carbon nanotubes (SWCNTs) were investigated after intratracheal instillation in male Wistar rats over a 15-day period using metabonomic analysis of 1H (nuclear magnetic resonance) NMR spectra of blood plasma and liver tissue extracts. Concurrent liver histopathology examinations and plasma clinical chemistry analyses were also performed. Significant changes were observed in clinical chemistry features, including alkaline phosphatase, total protein, and total cholesterol, and in liver pathology, suggesting that SWCNTs clearly have hepatotoxicity in the rat. 1H NMR spectra and pattern recognition analyses from nanomaterial-treated rats showed remarkable differences in the excretion of lactate, trimethylamine oxide, bilineurin, phosphocholine, amylaceum, and glycogen. Indications of amino acid metabolism impairment were supported by increased lactate concentrations and decreased alanine concentrations in plasma. The rise in plasma and liver tissue extract concentrations of choline and phosphocholine, together with decreased lipids and lipoproteins, after SWCNTs treatment indicated a disruption of membrane fluidity caused by lipid peroxidation. Energy, amino acid, and fat metabolism appeared to be affected by SWCNTs exposure. Clinical chemistry and metabonomic approaches clearly indicated liver injury, which might have been associated with an indirect mechanism involving nanomaterial-induced oxidative stress.

  12. Metabolic fate and evaluation of injury in rats and dogs following exposure to the hydrolysis products of uranium hexafluoride: implications for a bioassay program related to potential releases of uranium hexafluoride, July 1979-October 1981

    International Nuclear Information System (INIS)

    Morrow, P.E.; Leach, L.J.; Smith, F.A.

    1982-12-01

    This final report summarizes the experimental studies undertaken in rats and dogs in order to help provide adequate biological bases for quantifying and evaluating uranium hexafluoride (UF 6 ) exposures. Animals were administered the hydrolysis products of UF 6 by inhalation exposures, intratracheal instillations and intravenous injections. Attention was given to dose-effect relationships appropriate to the kidney, the unique site of subacute toxicity; to the rates of uranium excretion; and to uranium retention in renal tissue. These criteria were examined in both naive and multiply-exposed animals. The findings of these studies partly substantiate the ICRP excretion model for hexavalent uranium; generally provide a lower renal injury threshold concentration than implicit in the MPC for natural uranium; indicate distinctions in response (for example, uranium excretion) are based on exposure history; compare and evaluate various biochemical indices of renal injury; raise uncertainties about prevailing views of reversible renal injury, renal tolerance and possible hydrogen fluoride synergism with uranium effects; and reveal species differences in several areas, for example, renal retention of uranium. While these studies present some complicating features to extant bioassay practice, they nevertheless supply data supportive of the bioassay concept

  13. Multi-walled carbon nanotube-induced genotoxic, inflammatory and pro-fibrotic responses in mice: Investigating the mechanisms of pulmonary carcinogenesis

    DEFF Research Database (Denmark)

    Rahman, Luna; Jacobsen, Nicklas Raun; Aziz, Syed Abdul

    2017-01-01

    The International Agency for Research on Cancer has classified one type of multi-walled carbon nanotubes (MWCNTs) as possibly carcinogenic to humans. However, the underlying mechanisms of MWCNT- induced carcinogenicity are not known. In this study, the genotoxic, mutagenic, inflammatory, and fibr......The International Agency for Research on Cancer has classified one type of multi-walled carbon nanotubes (MWCNTs) as possibly carcinogenic to humans. However, the underlying mechanisms of MWCNT- induced carcinogenicity are not known. In this study, the genotoxic, mutagenic, inflammatory......, and fibrotic potential of MWCNTs were investigated. Muta™Mouse adult females were exposed to 36±6 or 109±18μg/mouse of Mitsui-7, or 26±2 or 78±5μg/mouse of NM-401, once a week for four consecutive weeks via intratracheal instillations, alongside vehicle-treated controls. Samples were collected 90days following...... extents. However, there was no evidence of DNA damage as measured by the comet assay following Mitsui-7 exposure, or increases in lacZ mutant frequency, for either MWCNTs. Increased p53 expression was observed in the fibrotic foci induced by both MWCNTs. Gene expression analysis revealed perturbations...

  14. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

    Directory of Open Access Journals (Sweden)

    Ken-Ichiro Inoue

    2011-01-01

    Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

  15. [Application of continuous intra-arterial blood gas monitoring system "Paratrend 7" for pulmonary lavage of a patient with alveolar proteinosis].

    Science.gov (United States)

    Harigae, M; Hirose, Y; Gamo, M; Hirose, M; Fujiwara, C; Matsuo, K

    1999-03-01

    We applied a continuous intra-arterial blood gas monitoring system (Paratrend 7) to a patient with pulmonary alveolar proteinosis during pulmonary lavage. Lavage was performed under general anesthesia with one lung ventilation. We inserted the sensor of Patatrend 7 through a 20 G catheter into the radial artery, and monitored pH, PaCO2 and PaO2 continuously throughout the procedure. SpO2 and EtCO2 were also monitored. Saline 1000-1500 ml was instilled and drained repeatedly by volume limited methods. PaO2 values by Paratrend 7 increased during instillation and decreased during drainage of the irrigating fluid. In contrast, PaCO2 value by Paratrend 7 decreased slightly during instillation and increased during drainage. The change of SpO2 was almost the same as that by Paratrend 7, but the response time of pulse oxymetry was a little quicker than Paratrend 7. During the lavage procedure, respiratory and circulatory condition changed very rapidly, and it is necessary to monitor blood gas change intensively. Paratrend 7 is useful as a perioperative monitoring system, but pulse oxymetry might be sufficient during pulmonary lavage considering its cost.

  16. Animal models of asthma: utility and limitations

    Directory of Open Access Journals (Sweden)

    Aun MV

    2017-11-01

    Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

  17. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  18. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Monego, Simeone dal [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Larsson, Emanuel [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); University of Trieste, Trieste (Italy); Linköping University, SE-581 83 Linkoeping (Sweden); Mohammadi, Sara [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); Krenkel, Martin [University of Göttingen, Göttingen (Germany); Garrovo, Chiara; Biffi, Stefania [IRCCS Burlo Garofolo, Trieste (Italy); Lorenzon, Andrea [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Markus, Andrea [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Napp, Joanna [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Salditt, Tim [University of Göttingen, Göttingen (Germany); Accardo, Agostino [University of Trieste, Trieste (Italy); Alves, Frauke [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Tromba, Giuliana [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy)

    2015-01-01

    This study presents an approach to increase the sensitivity of lung computed tomography (CT) imaging by utilizing in-line phase contrast CT in combination with single-distance phase-retrieval algorithms and a dedicated image-processing regime. As demonstrated here, functional CT imaging can be achieved for the assessment of both structural alterations in asthmatic mouse lung tissue and the accumulation pattern of instilled barium-sulfate-labelled macrophages in comparison with healthy controls. Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.

  19. Tyrosine Mutation in AAV9 Capsid Improves Gene Transfer to the Mouse Lung.

    Science.gov (United States)

    Martini, Sabrina V; Silva, Adriana L; Ferreira, Debora; Rabelo, Rafael; Ornellas, Felipe M; Gomes, Karina; Rocco, Patricia R M; Petrs-Silva, Hilda; Morales, Marcelo M

    2016-01-01

    Adeno-associated virus (AAV) vectors are being increasingly used as the vector of choice for in vivo gene delivery and gene therapy for many pulmonary diseases. Recently, it was shown that phosphorylation of surface-exposed tyrosine residues from AAV capsid targets the viral particles for ubiquitination and proteasome-mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo in different organs. In this study, we evaluated the pulmonary transgene expression efficacy of AAV9 vectors containing point mutations in surface-exposed capsid tyrosine residues. Eighteen C57BL/6 mice were randomly assigned into three groups: (1) a control group (CTRL) animals underwent intratracheal (i.t.) instillation of saline, (2) the wild-type AAV9 group (WT-AAV9, 1010 vg), and (3) the tyrosine-mutant Y731F AAV9 group (M-AAV9, 1010 vg), which received (i.t.) self-complementary AAV9 vectors containing the DNA sequence of enhanced green fluorescence protein (eGFP). Four weeks after instillation, lung mechanics, morphometry, tissue cellularity, gene expression, inflammatory cytokines, and growth factor expression were analyzed. No significant differences were observed in lung mechanics and morphometry among the experimental groups. However, the number of polymorphonuclear cells was higher in the WT-AAV9 group than in the CTRL and M-AAV9 groups, suggesting that the administration of tyrosine-mutant AAV9 vectors was better tolerated. Tyrosine-mutant AAV9 vectors significantly improved transgene delivery to the lung (30%) compared with their wild-type counterparts, without eliciting an inflammatory response. Our results provide the impetus for further studies to exploit the use of AAV9 vectors as a tool for pulmonary gene therapy. © 2016 The Author(s) Published by S. Karger AG, Basel.

  20. Development of analog watch with minute repeater

    Science.gov (United States)

    Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

    A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

  1. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    Directory of Open Access Journals (Sweden)

    Aisling Frizzell

    2014-03-01

    Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

  2. Isolation of human simple repeat loci by hybridization selection.

    Science.gov (United States)

    Armour, J A; Neumann, R; Gobert, S; Jeffreys, A J

    1994-04-01

    We have isolated short tandem repeat arrays from the human genome, using a rapid method involving filter hybridization to enrich for tri- or tetranucleotide tandem repeats. About 30% of clones from the enriched library cross-hybridize with probes containing trimeric or tetrameric tandem arrays, facilitating the rapid isolation of large numbers of clones. In an initial analysis of 54 clones, 46 different tandem arrays were identified. Analysis of these tandem repeat loci by PCR showed that 24 were polymorphic in length; substantially higher levels of polymorphism were displayed by the tetrameric repeat loci isolated than by the trimeric repeats. Primary mapping of these loci by linkage analysis showed that they derive from 17 chromosomes, including the X chromosome. We anticipate the use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species.

  3. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  4. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    Science.gov (United States)

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. The effect of repeated testing vs repeated practice on skills learning in undergraduate dental education.

    Science.gov (United States)

    Sennhenn-Kirchner, S; Goerlich, Y; Kirchner, B; Notbohm, M; Schiekirka, S; Simmenroth, A; Raupach, T

    2018-02-01

    Recent studies in undergraduate medical education have demonstrated the advantage of repeated testing over repeated practice with regard to knowledge and skills retention. The aim of this study was to investigate whether this "testing effect" also applies to skills retention in undergraduate dental education. In this prospective, randomised controlled trial, fourth-year dental students at Göttingen University Medical Centre participated in a training session on surgical suturing in winter term 2014/2015. Following this, they were either assigned to two sessions of additional skills training (group A) or two sessions of skills assessment with feedback (group B). These sessions were spaced over a period of 4 weeks. Skills retention was assessed in a summative objective structured clinical examination (OSCE) at the end of term, that is 6 months after the initial teaching session. A total of 32 students completed the study. With regard to suturing, OSCE performance was significantly better in group B than group A (81.9±13.1% vs 63.0±15.4%; P=0.001; Cohen's d=1.33). There was no significant OSCE performance difference in the two groups with regard to other learning objectives that were addressed in the end-of-term examination. Thus, the group difference was specific to suturing skills. This is the first study to demonstrate that in dental education, repeated testing produces more favourable skills retention than repeated practice. Test-enhanced learning might be a viable concept for skills retention in undergraduate dentistry education. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    OpenAIRE

    Aisling Frizzell; Jennifer H.G. Nguyen; Mark I.R. Petalcorin; Katherine D. Turner; Simon J. Boulton; Catherine H. Freudenreich; Robert S. Lahue

    2014-01-01

    SUMMARY Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG·CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vi...

  7. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten

    2013-01-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective ...... of paternal germ-line repeat sequence instability of the expanded SCA2 locus.European Journal of Human Genetics advance online publication, 10 October 2012; doi:10.1038/ejhg.2012.231....

  8. Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

    Directory of Open Access Journals (Sweden)

    Ahmed Abdulkadhim Hamad

    2017-08-01

    Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

  9. Analysis of CR1 Repeats in the Zebra Finch Genome

    Directory of Open Access Journals (Sweden)

    George E. Liu

    2013-06-01

    Full Text Available Most bird species have smaller genomes and fewer repeats than mammals. Chicken Repeat 1 (CR1 repeat is one of the most abundant families of repeats, ranging from ~133,000 to ~187,000 copies accounting for ~50 to ~80% of the interspersed repeats in the zebra finch and chicken genomes, respectively. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to multiple CR1 subfamilies in the chicken. In this study, we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the zebra finch genome. We identified and validated 34 CR1 subfamilies and further analyzed the correlation between these subfamilies. We also discovered 4 novel lineage-specific CR1 subfamilies in the zebra finch when compared to the chicken genome. We built various evolutionary trees of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.

  10. Measurement of repeat effects in Chicago’s criminal social network

    Directory of Open Access Journals (Sweden)

    Paul Kump

    2016-07-01

    Full Text Available The “near-repeat” effect is a well-known criminological phenomenon in which the occurrence of a crime incident gives rise to a temporary elevation of crime risk within close physical proximity to an initial incident. Adopting a social network perspective, we instead define a near repeat in terms of geodesic distance within a criminal social network, rather than spatial distance. Specifically, we report a statistical analysis of repeat effects in arrest data for Chicago during the years 2003–2012. We divide the arrest data into two sets (violent crimes and other crimes and, for each set, we compare the distributions of time intervals between repeat incidents to theoretical distributions in which repeat incidents occur only by chance. We first consider the case of the same arrestee participating in repeat incidents (“exact repeats” and then extend the analysis to evaluate repeat risks of those arrestees near one another in the social network. We observe repeat effects that diminish as a function of geodesic distance and time interval, and we estimate typical time scales for repeat crimes in Chicago.

  11. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Directory of Open Access Journals (Sweden)

    Shanshan Huang

    2015-10-01

    Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

  12. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Science.gov (United States)

    Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

  13. A repeating fast radio burst.

    Science.gov (United States)

    Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  14. RTEL1 inhibits trinucleotide repeat expansions and fragility.

    Science.gov (United States)

    Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

    2014-03-13

    Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Contraceptive Use among Women Seeking Repeat Abortion in ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Compared with women seeking their first abortion, significantly more repeat abortion clients had ever used contraceptives ... findings, the level of repeat abortions in Europe, .... and contraceptive history, and post-abortion ..... working women.

  16. Environmental stress induces trinucleotide repeat mutagenesis in human cells.

    Science.gov (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

    2015-03-24

    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

  17. Oxidative stress adaptation with acute, chronic, and repeated stress.

    Science.gov (United States)

    Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

    2013-02-01

    Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. The Effect of Negative Pressure Wound Therapy With Antiseptic Instillation on Biofilm Formation in a Porcine Model of Infected Spinal Instrumentation.

    Science.gov (United States)

    Singh, Devinder P; Gowda, Arvind U; Chopra, Karan; Tholen, Michael; Chang, Sarah; Mavrophilipos, Vasilios; Semsarzadeh, Nina; Rasko, Yvonne; Holton Iii, Luther

    2017-06-01

    This study evaluates the effect of negative pressure wound therapy with antiseptic instillation (NPWTi) in the clearance of infection and biofilm formation in an in vivo model of infected spinal implants compared to traditional treatment modalities. Five pigs underwent titanium rod implantation of their spinous processes followed by injection of 1 x 106 CFUs/100μL of methicillin-resistant Staphylococcus aureus through the fascia at each site. At 1 week postoperatively, an experimental arm of 3 pigs received NPWTi, and a control arm of 2 pigs received wet-to-dry dressings. The persistence of local infection in the experimental group was compared to the control group using tissue cultures. Biofilm development on spinal implants was evaluated using scanning electron microscopy. Mean bacterial count showed a statistical difference between the experimental and the control groups (P < .05). Scanning electron microscopy revealed the presence of uniform biofilm formation across the surface of control group instrumentation, whereas the experimental group showed interrupted areas between biofilm formations. The authors concluded that NPWTi is associated with decreased bacterial load and biofilm formation compared to wet-to-dry dressings in an in vivo porcine model of infected spinal instrumentation.

  19. TEACHERS AND EDUCATION OF CHARACTER INSTILLATION (Research Result at Private Elementary School of Muhammadiyah in Medan

    Directory of Open Access Journals (Sweden)

    Amini

    2018-04-01

    Full Text Available Teachers are the most important element in the development of character education in elementary school, because it becomes the main foundation for a child. Therefore character education made a continuous process to produce a future human figure rooted in the cultural values of the Indonesian nation. Character education in the current context is very relevant to students to tackle the ongoing moral crisis in our country, including free association, crime against friends, teenage theft, cheating, drug abuse and drugs, pornography, brawls, and others. This is based on the results of research on SDS Muhammadiyah about teacher and character education education. The research methodology was conducted with qualitative descriptive analysis. Data obtained based on interviews, observation, and study documentation with the object of research. The result of the research shows that character education education in SDS Muhammadiyah 29 Medan City is contained in all subjects and outside subjects that are instilled early on by all teachers. Cultivation of character education conducted in all subjects through 3 content, ie general content (PAI, PKn, IPS, IPA, Bahasa Indonesia, Mathematics, Arts and Culture, special content (Kemuhammadiyahan, and Local Content (Malay Arabic / Arabic, English, Computer. Character education model performed outside the subjects through 4 things, namely: religious habituation (religious, discipline exercises, fun activities, and sports activities. Commonalities include (the implementation of Zuhr prayers bertamaaah, dhuha congregation, tadarus Al-Qur'an and memorizing the verses of Al-Qur'an, and culture shake. Discipline includes (the existence of rules and school rules and liaison books every day. Kewiraaan include (Flag ceremony and Hizbul wathan. Exercise includes (physical fitness exercise.

  20. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-01-01

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  1. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  2. Repeat Assessed Values Model for Housing Price Index

    Directory of Open Access Journals (Sweden)

    Carini Manuela

    2017-12-01

    Full Text Available This study proposes an innovative methodology, named Repeat Appraised Price Model (RAV, useful for determining the price index numbers for real estate markets and the corresponding index numbers of hedonic prices of main real estate characteristics in the case of a lack of data. The methodological approach proposed in this paper aims to appraise the time series of price index numbers. It integrates the principles of the method of repeat sales with the peculiarities of the Hedonic Price Method, overcoming the problem of an almost total absence of repeat sales for the same property in a given time range; on the other hand, the technique aims to overcome the limitation of the repeat sales technique concerning the inability to take into account the characteristics of individual properties.

  3. Repeatability and reproducibility of decisions by latent fingerprint examiners.

    Directory of Open Access Journals (Sweden)

    Bradford T Ulery

    Full Text Available The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as "difficult" than for "easy" or "moderate" comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4; 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization. Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases.

  4. Reproducibility and Reliability of Repeated Quantitative Fluorescence Angiography

    DEFF Research Database (Denmark)

    Nerup, Nikolaj; Knudsen, Kristine Bach Korsholm; Ambrus, Rikard

    2017-01-01

    INTRODUCTION: When using fluorescence angiography (FA) in perioperative perfusion assessment, repeated measures with re-injections of fluorescent dye (ICG) may be required. However, repeated injections may cause saturation of dye in the tissue, exceeding the limit of fluorescence intensity...... that the camera can detect. As the emission of fluorescence is dependent of the excitatory light intensity, reduction of this may solve the problem. The aim of the present study was to investigate the reproducibility and reliability of repeated quantitative FA during a reduction of excitatory light....

  5. Clinical oversight and the avoidance of repeat induced abortion.

    Science.gov (United States)

    Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

    2018-06-03

    To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, Pabortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

  6. Methods for analysing cardiovascular studies with repeated measures

    NARCIS (Netherlands)

    Cleophas, T. J.; Zwinderman, A. H.; van Ouwerkerk, B. M.

    2009-01-01

    Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects. Objective. To review methods adequate for the analysis of cardiovascular studies

  7. TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats

    Directory of Open Access Journals (Sweden)

    Valentine Mosbach

    2018-02-01

    Full Text Available Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington’s disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the absence of RAD50 on both sides of the break, whereas it was reduced in a sae2Δ mutant on the side of the break containing the longest repeat tract, suggesting that secondary structures at double-strand break ends must be removed by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break, single-strand annealing occurred between both sides of the repeat tract, leading to repeat contraction.

  8. In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

    Directory of Open Access Journals (Sweden)

    Hane James K

    2010-11-01

    Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

  9. The effectiveness of ayurvedic oil-based nasal instillation (Nasya) medicines in the treatment of facial paralysis (Ardita): a systematic review.

    Science.gov (United States)

    Vivera, Manuel Joseph; Gomersall, Judith Streak

    2016-04-01

    Ardita (facial paralysis) is a medical condition that disfigures or distorts the facial appearance of the sufferer causing facial asymmetry and malfunction. Ardita patients may benefit from considering alternative treatments such as Ayurveda, including Taila Nasya (nasal instillation of medicated oil). To synthesize the best available evidence on the effectiveness of different Nasya oils in the treatment of Ardita. Studies conducted on adult sufferers (18-70 years) of Ardita (chronic or acute) in any setting were considered. Studies including participants who were pregnant or suffered allergic rhinitis, fever, intracranial tumor/hemorrhage and bilateral facial palsy were excluded. Standalone treatment of Nasya (at all dosages and frequencies) compared to Nasya in combination with other Ayurvedic treatments was considered. Comparisons between different interventions including Taila Nasya alone, Taila Nasya in combination with other Ayurvedic interventions and Ayurvedic interventions that did not include Taila Nasya were also considered. Changes in Ardita symptoms, including facial distortion, speech disorders and facial pain, were measured. All quantitative study designs (experimental, quasi-experimental and observational) were considered. Relevant studies were identified following a comprehensive literature search. References provided within these key studies identified additional resources. Indian universities were also contacted for results of Ardita studies undertaken in their institutions.A three-step search strategy aimed to find studies of published and unpublished studies was undertaken. Studies published in the English language were considered for inclusion, irrespective of publication date/year. Following an initial limited search of MEDLINE and CINAHL, the text words contained in the title and abstract, and of the index terms used to describe each articles were analyzed. From the identified keywords and index terms, searches were undertaken across all

  10. Open-lung protective ventilation with pressure control ventilation, high-frequency oscillation, and intratracheal pulmonary ventilation results in similar gas exchange, hemodynamics, and lung mechanics.

    Science.gov (United States)

    Sedeek, Khaled A; Takeuchi, Muneyuki; Suchodolski, Klaudiusz; Vargas, Sara O; Shimaoka, Motomu; Schnitzer, Jay J; Kacmarek, Robert M

    2003-11-01

    Pressure control ventilation (PCV), high-frequency oscillation (HFO), and intratracheal pulmonary ventilation (ITPV) may all be used to provide lung protective ventilation in acute respiratory distress syndrome, but the specific approach that is optimal remains controversial. Saline lavage was used to produce acute respiratory distress syndrome in 21 sheep randomly assigned to receive PCV, HFO, or ITPV as follows: positive end-expiratory pressure (PCV and ITPV) and mean airway pressure (HFO) were set in a pressure-decreasing manner after lung recruitment that achieved a ratio of Pao2/Fio2 > 400 mmHg. Respiratory rates were 30 breaths/min, 120 breaths/min, and 8 Hz, respectively, for PCV, ITPV, and HFO. Eucapnia was targeted with peak carinal pressure of no more than 35 cm H2O. Animals were then ventilated for 4 h. There were no differences among groups in gas exchange, lung mechanics, or hemodynamics. Tidal volume (PCV, 8.9 +/- 2.1 ml/kg; ITPV, 2.7 +/- 0.8 ml/kg; HFO, approximately 2.0 ml/kg) and peak carinal pressure (PCV, 30.6 +/- 2.6 cm H2O; ITPV, 22.3 +/- 4.8 cm H2O; HFO, approximately 24.3 cm H2O) were higher in PCV. Pilot histologic data showed greater interstitial hemorrhage and alveolar septal expansion in PCV than in HFO or ITPV. These data indicate that HFO, ITPV, and PCV when applied with an open-lung protective ventilatory strategy results in the same gas exchange, lung mechanics, and hemodynamic response, but pilot data indicate that lung injury may be greater with PCV.

  11. simple sequence repeat (SSR)

    African Journals Online (AJOL)

    In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 linkage groups of adzuki bean were evaluated for transferability to mungbean and related Vigna spp. 41 markers amplified characteristic bands in at least one Vigna species. The transferability percentage across the genotypes ranged ...

  12. Simple sequence repeat marker development and genetic mapping ...

    Indian Academy of Sciences (India)

    polymorphic SSR (simple sequence repeats) markers from libraries enriched for GA, CAA and AAT repeats, as well as 6 ... ers for quinoa was the development of a genetic linkage map ...... Weber J. L. 1990 Informativeness of human (dC-dA)n.

  13. Repeatability study of replicate crash tests: A signal analysis approach.

    Science.gov (United States)

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

    2017-10-03

    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

  14. Repeating pneumatic pellet injector in JAERI

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Satoshi; Hasegawa, Kouichi; Suzuki, Sadaaki; Miura, Yukitoshi (Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment); Oda, Yasushi; Onozuka, Masanori; Tsujimura, Seiichi.

    1992-09-01

    A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author).

  15. Repeating pneumatic pellet injector in JAERI

    International Nuclear Information System (INIS)

    Kasai, Satoshi; Hasegawa, Kouichi; Suzuki, Sadaaki; Miura, Yukitoshi; Oda, Yasushi; Onozuka, Masanori; Tsujimura, Seiichi.

    1992-09-01

    A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author)

  16. ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

    Science.gov (United States)

    Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

    2006-06-16

    The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

  17. [Bladder pain syndrome--an urological-gynecological problem].

    Science.gov (United States)

    Zabkowski, Tomasz; Bortnowski, Leszek; Zieliński, Henryk

    2011-03-01

    Bladder Pain Syndrome remains a great challenge for urologists, both in diagnostics and treatment. Etiopathogenesis of the disease is unknown. It is reported that the reason for Bladder Pain Syndrome is the urothelium dysfunction resulting in the destruction of the protective glycosaminoglycan layer/barrier protecting the urothelium from bacteria adhesion and penetration of toxic substances/by bacteria. It is considered to be a syndrome of dysuria and diuresis. Urine analysis usually is normal. It is diagnosed after exclusion of other causes leading to painful symptoms. It is estimated that 90% of the cases of the disease concern women. Treatment with glycocorticosteroids, antihistaminic drugs and antiallergic drugs was not successful. The attempts to find the right method of treatment led to the introduction of hyaluronic acid, which alleviated Bladder Pain Syndrome and its symptoms. Hyaluronic acid reacting with glycosaminoglycans on the bladder decreases penetrability of irritant substances. The patients were treated with 4-8 weekly instillations--40 mg of hyaluronic acid in 50 ml NaCl solution for 1-2 months. After the last instillation, therapy is repeated for the next 6-8 months with one instillation monthly. This method is for patients a chance for getting rid of painful symptoms from the bladder

  18. Derecruitment Test and Surfactant Therapy in Patients with Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Alexey A. Smetkin

    2012-01-01

    Full Text Available Introduction. A recruitment maneuver (RM may improve gas exchange in acute lung injury (ALI. The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI. Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group, n=6 or vehicle only (conventional therapy group, n=7 was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI. Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO2 following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs. Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

  19. Electromyographic analysis of repeated bouts of eccentric exercise.

    Science.gov (United States)

    McHugh, M P; Connolly, D A; Eston, R G; Gartman, E J; Gleim, G W

    2001-03-01

    The repeated bout effect refers to the protective effect provided by a single bout of eccentric exercise against muscle damage from a similar subsequent bout. The aim of this study was to determine if the repeated bout was associated with an increase in motor unit activation relative to force production, an increased recruitment of slow-twitch motor units or increased motor unit synchronization. Surface electromyographic (EMG) signals were recorded from the hamstring muscles during two bouts of submaximal isokinetic (2.6 rad x s(-1)) eccentric (11 men, 9 women) or concentric (6 men, 4 women) contractions separated by 2 weeks. The EMG per unit torque and median frequency were analysed. The initial bout of eccentric exercise resulted in strength loss, pain and muscle tenderness, while the repeated eccentric bout resulted in a slight increase in strength, no pain and no muscle tenderness (bout x time effects, P exercise. The EMG per unit torque and median frequency were not different between the initial and repeated bouts of eccentric exercise. The EMG per unit torque and median frequency increased during both bouts of eccentric exercise (P < 0.01) but did not change during either concentric bout. In conclusion, there was no evidence that the repeated bout effect was due to a neural adaptation.

  20. 40 CFR 1065.305 - Verifications for accuracy, repeatability, and noise.

    Science.gov (United States)

    2010-07-01

    ..., repeatability, and noise. 1065.305 Section 1065.305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Verifications for accuracy, repeatability, and noise. (a) This section describes how to determine the accuracy, repeatability, and noise of an instrument. Table 1 of § 1065.205 specifies recommended values for individual...

  1. Two tandemly repeated telomere-associated sequences in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Chen, C M; Wang, C T; Wang, C J; Ho, C H; Kao, Y Y; Chen, C C

    1997-12-01

    Two tandemly repeated telomere-associated sequences, NP3R and NP4R, have been isolated from Nicotiana plumbaginifolia. The length of a repeating unit for NP3R and NP4R is 165 and 180 nucleotides respectively. The abundance of NP3R, NP4R and telomeric repeats is, respectively, 8.4 x 10(4), 6 x 10(3) and 1.5 x 10(6) copies per haploid genome of N. plumbaginifolia. Fluorescence in situ hybridization revealed that NP3R is located at the ends and/or in interstitial regions of all 10 chromosomes and NP4R on the terminal regions of three chromosomes in the haploid genome of N. plumbaginifolia. Sequence homology search revealed that not only are NP3R and NP4R homologous to HRS60 and GRS, respectively, two tandem repeats isolated from N. tabacum, but that NP3R and NP4R are also related to each other, suggesting that they originated from a common ancestral sequence. The role of these repeated sequences in chromosome healing is discussed based on the observation that two to three copies of a telomere-similar sequence were present in each repeating unit of NP3R and NP4R.

  2. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

    Full Text Available Abstract Background Proline-rich tyrosine kinase 2 (Pyk2 is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1 myeloperoxidase content in lung tissues, 2 vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3 the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and

  3. 47 CFR 80.469 - Maritime mobile repeater stations in Alaska.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime mobile repeater stations in Alaska. 80... RADIO SERVICES STATIONS IN THE MARITIME SERVICES Public Coast Stations Use of Telephony § 80.469 Maritime mobile repeater stations in Alaska. (a) Maritime mobile repeater stations are authorized to extend...

  4. RNA FISH for detecting expanded repeats in human diseases.

    Science.gov (United States)

    Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

    2016-04-01

    RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. StaRProtein, A Web Server for Prediction of the Stability of Repeat Proteins

    Science.gov (United States)

    Xu, Yongtao; Zhou, Xu; Huang, Meilan

    2015-01-01

    Repeat proteins have become increasingly important due to their capability to bind to almost any proteins and the potential as alternative therapy to monoclonal antibodies. In the past decade repeat proteins have been designed to mediate specific protein-protein interactions. The tetratricopeptide and ankyrin repeat proteins are two classes of helical repeat proteins that form different binding pockets to accommodate various partners. It is important to understand the factors that define folding and stability of repeat proteins in order to prioritize the most stable designed repeat proteins to further explore their potential binding affinities. Here we developed distance-dependant statistical potentials using two classes of alpha-helical repeat proteins, tetratricopeptide and ankyrin repeat proteins respectively, and evaluated their efficiency in predicting the stability of repeat proteins. We demonstrated that the repeat-specific statistical potentials based on these two classes of repeat proteins showed paramount accuracy compared with non-specific statistical potentials in: 1) discriminate correct vs. incorrect models 2) rank the stability of designed repeat proteins. In particular, the statistical scores correlate closely with the equilibrium unfolding free energies of repeat proteins and therefore would serve as a novel tool in quickly prioritizing the designed repeat proteins with high stability. StaRProtein web server was developed for predicting the stability of repeat proteins. PMID:25807112

  6. Differential Regulation of Strand-Specific Transcripts from Arabidopsis Centromeric Satellite Repeats.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available Centromeres interact with the spindle apparatus to enable chromosome disjunction and typically contain thousands of tandemly arranged satellite repeats interspersed with retrotransposons. While their role has been obscure, centromeric repeats are epigenetically modified and centromere specification has a strong epigenetic component. In the yeast Schizosaccharomyces pombe, long heterochromatic repeats are transcribed and contribute to centromere function via RNA interference (RNAi. In the higher plant Arabidopsis thaliana, as in mammalian cells, centromeric satellite repeats are short (180 base pairs, are found in thousands of tandem copies, and are methylated. We have found transcripts from both strands of canonical, bulk Arabidopsis repeats. At least one subfamily of 180-base pair repeats is transcribed from only one strand and regulated by RNAi and histone modification. A second subfamily of repeats is also silenced, but silencing is lost on both strands in mutants in the CpG DNA methyltransferase MET1, the histone deacetylase HDA6/SIL1, or the chromatin remodeling ATPase DDM1. This regulation is due to transcription from Athila2 retrotransposons, which integrate in both orientations relative to the repeats, and differs between strains of Arabidopsis. Silencing lost in met1 or hda6 is reestablished in backcrosses to wild-type, but silencing lost in RNAi mutants and ddm1 is not. Twenty-four-nucleotide small interfering RNAs from centromeric repeats are retained in met1 and hda6, but not in ddm1, and may have a role in this epigenetic inheritance. Histone H3 lysine-9 dimethylation is associated with both classes of repeats. We propose roles for transcribed repeats in the epigenetic inheritance and evolution of centromeres.

  7. Telomerase Repeated Amplification Protocol (TRAP).

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al. , 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC - counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al. , 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

  8. Structure of thrombospondin type 3 repeats in bacterial outer membrane protein A reveals its intra-repeat disulfide bond-dependent calcium-binding capability

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Shuyan; Sun, Cancan; Tan, Kemin; Ye, Sheng; Zhang, Rongguang

    2017-09-01

    Eukaryotic thrombospondin type 3 repeat (TT3R) is an efficient calcium ion (Ca2+) binding motif only found in mammalian thrombospondin family. TT3R has also been found in prokaryotic cellulase Cel5G, which was thought to forfeit the Ca2+-binding capability due to the formation of intra-repeat disulfide bonds, instead of the inter-repeat ones possessed by eukaryotic TT3Rs. In this study, we have identified an enormous number of prokaryotic TT3R-containing proteins belonging to several different protein families, including outer membrane protein A (OmpA), an important structural protein connecting the outer membrane and the periplasmic peptidoglycan layer in gram-negative bacteria. Here, we report the crystal structure of the periplasmic region of OmpA from Capnocytophaga gingivalis, which contains a linker region comprising five consecutive TT3Rs. The structure of OmpA-TT3R exhibits a well-ordered architecture organized around two tightly-coordinated Ca2+ and confirms the presence of abnormal intra-repeat disulfide bonds. Further mutagenesis studies showed that the Ca2+-binding capability of OmpA-TT3R is indeed dependent on the proper formation of intra-repeat disulfide bonds, which help to fix a conserved glycine residue at its proper position for Ca2+ coordination. Additionally, despite lacking inter repeat disulfide bonds, the interfaces between adjacent OmpA-TT3Rs are enhanced by both hydrophobic and conserved aromatic-proline interactions.

  9. Discrepancy variation of dinucleotide microsatellite repeats in eukaryotic genomes

    Directory of Open Access Journals (Sweden)

    HUAN GAO

    2009-01-01

    Full Text Available To address whether there are differences of variation among repeat motif types and among taxonomic groups, we present here an analysis of variation and correlation of dinucleotide microsatellite repeats in eukaryotic genomes. Ten taxonomic groups were compared, those being primates, mammalia (excluding primates and rodentia, rodentia, birds, fish, amphibians and reptiles, insects, molluscs, plants and fungi, respectively. The data used in the analysis is from the literature published in the Journal of Molecular Ecology Notes. Analysis of variation reveals that there are no significant differences between AC and AG repeat motif types. Moreover, the number of alleles correlates positively with the copy number in both AG and AC repeats. Similar conclusions can be obtained from each taxonomic group. These results strongly suggest that the increase of SSR variation is almost linear with the increase of the copy number of each repeat motif. As well, the results suggest that the variability of SSR in the genomes of low-ranking species seem to be more than that of high-ranking species, excluding primates and fungi.

  10. REPEATABILITY OF FRUIT QUALITY TRAITS OF CACTUS PEAR

    Directory of Open Access Journals (Sweden)

    VALTÂNIA XAVIER NUNES

    2017-12-01

    Full Text Available ABSTRACT Repeatability analysis has been used to study traits in several crops, assisting in the definition of the minimum number needed to evaluate genotypes more efficiently and with less time and resource consumption. So far, however, no repeatability studies on cactus pear have been found in the literature. The objective of this study was to determine the coefficient of repeatability for cactus pear fruits traits and the minimum number of evaluations (fruit that can provide acceptable accuracy for the prediction of the true value. The experiment was conducted at the Federal Institute of Bahia/Campus Guanambi, with 150 fruits collected from three municipalities in the state of Bahia. The coefficients of repeatability were estimated by the methods of analysis of variance, principal components based on the covariance (PCCV and correlation (PCC matrices, and structural analysis based on the correlation matrix (SA. The analysis of variance showed that, except for fruit diameter, the effect of the production site (municipality was significant for all traits evaluated. The PCCV method was proven the most suitable for studying the repeatability of quality traits of cactus pear fruits. Seven fruits were required to determine, with 90% confidence, the traits length, diameter, fruit firmness, skin thickness, number of seeds, fruit mass, bark mass, pulp mass, pH, titratable acidity, soluble solids, SS/AT ratio, and pulp yield.

  11. Cytologic status changes of the conjunctiva and tears qualitative composition in patients with «dry eye» syndrome after instillation of modern topical fluoroquinolones

    Directory of Open Access Journals (Sweden)

    N. G. Zavgorodnyaya

    2014-06-01

    Full Text Available Aim. Use of the antibiotics for eye was approved as a rational method for reducing the risk of postoperative endophthalmitis. The aim of our investigation was to study the influence of the modern topical fluoroquinolones on the qualitative composition of tears and cytological status of the conjunctiva in patients with cataract and «dry eye» syndrome. Methods and results. 102 patients (109 eyes aged 36–87 years was examined. Qualitative composition of tear fluid was studied with method of native tears crystallography and conjunctiva cytological study using impression cytoscopy method. In 72.3% of cases the tears crystallography showed signs of pathology. Cytological examination of conjunctiva showed dystrophy in 86,8% of cases. In 11% of the patients typical cross-shaped crystals were detected. Conclusion. Correlation dependence analysis showed statistically significant positive relationship (Spearman’s correlation r=0.53 between the presence of cross-shaped crystals in crystallography and severe dystrophy of conjunctiva epithelium. Instillation of modern topical fluoroquinolones worsen the cytological status of conjunctiva epithelium.

  12. Improvement of Repeated-Sprint Ability and Horizontal-Jumping Performance in Elite Young Basketball Players With Low-Volume Repeated-Maximal-Power Training.

    Science.gov (United States)

    Gonzalo-Skok, Oliver; Tous-Fajardo, Julio; Arjol-Serrano, José Luis; Suarez-Arrones, Luis; Casajús, José Antonio; Mendez-Villanueva, Alberto

    2016-05-01

    To examine the effects of a low-volume repeated-power-ability (RPA) training program on repeated-sprint and change-of- direction (COD) ability and functional jumping performance. Twenty-two male elite young basketball players (age 16.2 ± 1.2 y, height 190.0 ± 10.0 cm, body mass 82.9 ± 10.1 kg) were randomly assigned either to an RPA-training group (n = 11) or a control group (n = 11). RPA training consisted of leg-press exercise, twice a week for 6 wk, of 1 or 2 blocks of 5 sets × 5 repetitions with 20 s of passive recovery between sets and 3 min between blocks with the load that maximized power output. Before and after training, performance was assessed by a repeated-sprint-ability (RSA) test, a repeated-COD-ability test, a hop for distance, and a drop jump followed by tests of a double unilateral hop with the right and left legs. Within-group and between-groups differences showed substantial improvements in slowest (RSAs) and mean time (RSAm) on RSA; best, slowest and mean time on repeated-COD ability; and unilateral right and left hop in the RPA group in comparison with control. While best time on RSA showed no improvement in any group, there was a large relationship (r = .68, 90% CI .43;.84) between the relative decrement in RSAm and RSAs, suggesting better sprint maintenance with RPA training. The relative improvements in best and mean repeated-COD ability were very largely correlated (r = .89, 90% CI .77;.94). Six weeks of lowvolume (4-14 min/wk) RPA training improved several physical-fitness tests in basketball players.

  13. The absolute number of repeat operations for complex intra ...

    African Journals Online (AJOL)

    abdominal sepsis, questions about futility of treatment frequently arise. This study focuses specifically on patients who required two or more repeat laparotomies and describes the spectrum of disease necessitating multiple repeat laparotomies ...

  14. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  15. Comparing Transcervical Intrauterine Lidocaine Instillation with Rectal Diclofenac for Pain Relief During Outpatient Hysteroscopy: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Sussan S. Mohammadi

    2015-05-01

    Full Text Available Objectives: There are a number of potential advantages to performing hysteroscopy in an outpatient setting. However, the ideal approach, using local uterine anesthesia or rectal non-steroidal anti-inflammatory drugs, has not been determined. Our objective was to compare the efficacy of intrauterine lidocaine instillation with rectal diclofenac for pain relief during diagnostic hysteroscopy. Methods: We conducted a double-blind randomized controlled trial on 70 nulliparous women with primary infertility undergoing diagnostic hysteroscopy. Subjects were assigned into one of two groups to receive either 100mg of rectal diclofenac or 5mL of 2% intrauterine lidocaine. The intensity of pain was measured by a numeric rating scale 0–10. Pain scoring was performed during insertion of the hysteroscope, during visualization of the intrauterine cavity, and during extrusion of the hysteroscope. Results: There were no statistically significant differences between the groups with regard to the mean pain score during intrauterine visualization (p=0.500. The mean pain score was significantly lower during insertion and extrusion of the hysteroscope in the diclofenac group (p=0.001 and p=0.030, respectively. Nine patients in the lidocaine group and five patients in diclofenac group needed supplementary intravenous propofol injection for sedation (p=0.060. Conclusions: Rectal diclofenac appears to be more effective than intrauterine lidocaine in reducing pain during insertion and extrusion of hysteroscope, but there are no significant statistical and clinical differences between the two methods with regard to the mean pain score during intrauterine inspection.

  16. A study on the repeatability of ultrasonic testing data

    International Nuclear Information System (INIS)

    Yoshimura, Seiichi; Fukumoto, Hiroshi

    1980-01-01

    Reliability improvement of ultrasonic testing data is strongly desired in ultrasonic testing working of nuclear power plants. This paper deals with the problems of the testing by the manual and the remote control apparatus, and with the factors which influence the repeatability of ultrasonic testing data. Following results are found in it. (1) In the testing by the manual, working time and posture influence the repeatability of testing data. (2) Glycerin in suitable for the couplant in the respect of the repeatability of testing data. In the case of using machine oil, the pressure to the probe necessitates to be over 0.2 kg/cm 2 . (3) In the testing by the remote control apparatus, working time, working environment and defect position does not influence the repeatability of testing data. (author)

  17. The Effects of Repeated Experience on Children's Suggestibility.

    Science.gov (United States)

    Powell, Martine B.; Roberts, Kim P.; Ceci, Stephen J.; Hembrooke, Helene

    1999-01-01

    Examined effect of suggestive questions on 3- to 5-year-olds' and 6- to 8-year-olds' recall of the final occurrence of repeated event. Found that relative to reports of children experiencing single occurrence, reports about fixed items of repeated events were less contaminated by false suggestions. Children's age and delay of interview were…

  18. Non-radioactive detection of trinucleotide repeat size variability.

    Science.gov (United States)

    Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

    2014-03-06

    Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitative data. The method relies on the amplification of a very low number of DNA molecules, through sucessive dilution of a stock genomic DNA solution. Radioactive Southern blot hybridization is sensitive enough to detect SP-PCR products derived from single template molecules, separated by agarose gel electrophoresis and transferred onto DNA membranes. We describe a variation of the detection method that uses digoxigenin-labelled locked nucleic acid probes. This protocol keeps the sensitivity of the original method, while eliminating the health risks associated with the manipulation of radiolabelled probes, and the burden associated with their regulation, manipulation and waste disposal.

  19. Repeated Causal Decision Making

    Science.gov (United States)

    Hagmayer, York; Meder, Bjorn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

  20. Intra-examiner repeatability and agreement in accommodative response measurements.

    Science.gov (United States)

    Antona, B; Sanchez, I; Barrio, A; Barra, F; Gonzalez, E

    2009-11-01

    Clinical measurement of the accommodative response (AR) identifies the focusing plane of a subject with respect to the accommodative target. To establish whether a significant change in AR has occurred, it is important to determine the repeatability of this measurement. This study had two aims: First, to determine the intraexaminer repeatability of AR measurements using four clinical methods: Nott retinoscopy, monocular estimate method (MEM) retinoscopy, binocular crossed cylinder test (BCC) and near autorefractometry. Second, to study the level of agreement between AR measurements obtained with the different methods. The AR of the right eye at one accommodative demand of 2.50 D (40 cm) was measured on two separate occasions in 61 visually normal subjects of mean age 19.7 years (range 18-32 years). The intraexaminer repeatability of the tests, and agreement between them, were estimated by the Bland-Altman method. We determined mean differences (MD) and the 95% limits of agreement [coefficient of repeatability (COR) and coefficient of agreement (COA)]. Nott retinoscopy and BCC offered the best repeatability, showing the lowest MD and narrowest 95% interval of agreement (Nott: -0.10 +/- 0.66 D, BCC: -0.05 +/- 0.75 D). The 95% limits of agreement for the four techniques were similar (COA = +/- 0.92 to +/-1.00 D) yet clinically significant, according to the expected values of the AR. The two dynamic retinoscopy techniques (Nott and MEM) had a better agreement (COA = +/-0.64 D) although this COA must be interpreted in the context of the low MEM repeatability (COR = +/-0.98 D). The best method of assessing AR was Nott retinoscopy. The BCC technique was also repeatable, and both are recommended as suitable methods for clinical use. Despite better agreement between MEM and Nott, agreement among the remaining methods was poor such that their interchangeable use in clinical practice is not recommended.

  1. Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

    Science.gov (United States)

    Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

    2009-02-01

    Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  3. Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Chilakapati, Shanmuga Reddy; Serasanambati, Mamatha; Manikonda, Pavan Kumar; Chilakapati, Damodar Reddy; Watson, Ronald Ross

    2014-08-01

    Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized by excessive collagen deposition, with no effective treatments. We investigated the efficacy of natural products with high anti-inflammatory activity, such as passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal instillation of bleomycin to induce PF. Daily PFPE treatment significantly reduced loss of body mass and mortality rate in mice compared with those treated with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid on both days 7 and 21, PFPE administration significantly attenuated these phenomena compared with bleomycin group. On day 7, the decreased superoxide dismutase and myeloperoxidase activities observed in the bleomycin group were significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline deposition in the bleomycin group was also suppressed by PFPE administration. PFPE treatment significantly attenuated extensive inflammatory cell infiltration and accumulation of collagen in lung tissue sections of bleomycin-induced mice on days 7 and 21, respectively. Our results indicate that administration of PFPE decreased bleomycin-induced PF because of anti-inflammatory and antioxidant activities.

  4. Lipid-derived free radical production in superantigen-induced interstitial pneumonia

    Science.gov (United States)

    Miyakawa, Hisako; Mason, Ronald P.; Jiang, JinJie; Kadiiska, Maria B.

    2009-01-01

    We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. PMID:19376221

  5. Influence of preexisting pulmonary emphysema on susceptibility of rats to inhaled diesel exhaust

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Griffith, W.C.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K.

    1990-01-01

    The susceptibilities of normal rats and rats with preexisting pulmonary emphysema to chronically inhaled diesel exhaust were compared. Rats were exposed 7 h/day, 5 days/wk for 24 months to diesel exhaust at 3.5 mg soot/m3, or to clean air as controls. Emphysema was induced in one-half of the rats by intratracheal instillation of elastase 6 wk before exhaust exposure. Measurements included lung burdens of diesel soot, respiratory function, bronchoalveolar lavage, clearance of radiolabeled particles, pulmonary immune responses, lung collagen, excised lung weight and volume, histopathology, and mean linear intercept of terminal air spaces. Parameters indicated by analysis of variance to exhibit significant interactions between the influences of emphysema and exhaust were examined to determine if the effects were more than additive (indicating increased susceptibility). Although 14 of 63 parameters demonstrated emphysema-exhaust interactions, none indicated increased susceptibility. Less soot accumulated in lungs of emphysematous rats than in those of nonemphysematous rats, and the reduced accumulation had a sparing effect in the emphysematous rats. The results did not support the hypothesis that emphysematous lungs are more susceptible than are normal lungs to chronic exposure to high levels of diesel exhaust. The superimposition of effects of emphysema and exhaust, however, might still warrant special concern for heavy exposures of emphysematous subjects

  6. Sustained Pulmonary Delivery of a Water-Soluble Antibiotic Without Encapsulating Carriers.

    Science.gov (United States)

    Ong, Winston; Nowak, Pawel; Cu, Yen; Schopf, Lisa; Bourassa, James; Enlow, Elizabeth; Moskowitz, Samuel M; Chen, Hongming

    2016-03-01

    Traditional polymeric nanoparticle formulations for prolonged local action during inhalation therapy are highly susceptible to muco-ciliary clearance. In addition, polymeric carriers are typically administered in high doses due to finite drug loading. For toxicological reasons, these carriers and their degradation byproducts are undesirable for inhalation therapy, particularly for chronic use, due to potential lung accumulation. We synthesized a novel, insoluble prodrug (MRPD) of a time-dependent β-lactam, meropenem, and formulated MRPD into mucus-penetrating crystals (MRPD-MPCs). After characterizing their mucus mobility (in vitro) and stability, we evaluated the lung pharmacokinetics of intratracheally-instilled MRPD-MPCs and a meropenem solution in guinea pigs. Meropenem levels rapidly declined in the lungs of guinea pigs receiving meropenem solution compared to those given MRPD-MPCs. At 9 h after dosing, drug levels in the lungs of animals that received meropenem solution dropped to 12 ng/mL, whereas those that received MRPD-MPCs maintained an average drug level of ≥1,065 ng/mL over a 12-h period. This work demonstrated that the combination of prodrug chemistry and mucus-penetrating platform created nanoparticles that produced sustained levels of meropenem in guinea pig lungs. This strategy represents a novel approach for sustained local drug delivery to the lung without using encapsulating matrices.

  7. Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

    Science.gov (United States)

    Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

    2014-01-01

    The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

  8. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  9. Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia.

    Directory of Open Access Journals (Sweden)

    Florry E van den Boogaard

    Full Text Available Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia. Anticoagulant strategies could benefit patients with pneumonia, but systemic administration of anticoagulant agents may lead to suboptimal local levels and may cause systemic hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human tissue factor pathway inhibitor (rh-TFPI in a well-established rat model of Streptococcus (S. pneumoniae pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S. pneumonia causing pneumonia, rats were subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42 hours. Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and systemic TFPI activity and systemic coagulation were not affected. Histopathology revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems feasible and safe; local anticoagulant treatment with rh-TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae pneumonia.

  10. Repeatability of cervical joint flexion and extension within and between days

    DEFF Research Database (Denmark)

    Wang, Xu; Lindstroem, René; Plocharski, Maciej

    2018-01-01

    OBJECTIVE: The purpose of this study was to investigate within- and between-day repeatability of free and unrestricted healthy cervical flexion and extension motion when assessing dynamic cervical spine motion. METHODS: Fluoroscopy videos of 2 repeated cervical flexion and 2 repeated extension...

  11. Analysis of genetic polymorphism of nine short tandem repeat loci in ...

    African Journals Online (AJOL)

    Yomi

    2012-03-15

    Mar 15, 2012 ... Key words: short tandem repeat, repeat motif, genetic polymorphism, Han population, forensic genetics. INTRODUCTION. Short tandem repeat (STR) is widely .... Data analysis. The exact test of Hardy-Weinberg equilibrium was conducted with. Arlequin version 3.5 software (Computational and Molecular.

  12. Repeated checking causes memory distrust

    NARCIS (Netherlands)

    van den Hout, M.; Kindt, M.

    2003-01-01

    This paper attempts to explain why in obsessive-compulsive disorder (OCD) checkers distrust in memory persists despite extensive checking. It is argued that: (1) repeated checking increases familiarity with the issues checked; (2) increased familiarity promotes conceptual processing which inhibits

  13. A family of DNA repeats in Aspergillus nidulans has assimilated degenerated retrotransposons

    DEFF Research Database (Denmark)

    Nielsen, M.L.; Hermansen, T.D.; Aleksenko, Alexei Y.

    2001-01-01

    In the course of a chromosomal walk towards the centromere of chromosome IV of Aspergillus nidulans, several cross- hybridizing genomic cosmid clones were isolated. Restriction mapping of two such clones revealed that their restriction patterns were similar in a region of at least 15 kb, indicati......) phenomenon, first described in Neurospora crassa, may have operated in A. nidulans. The data indicate that this family of repeats has assimilated mobile elements that subsequently degenerated but then underwent further duplications as a part of the host repeats....... the presence of a large repeat. The nature of the repeat was further investigated by sequencing and Southern analysis. The study revealed a family of long dispersed repeats with a high degree of sequence similarity. The number and location of the repeats vary between wild isolates. Two copies of the repeat...

  14. Repeated radiation injuries by fission products

    International Nuclear Information System (INIS)

    Vasilenko, I.Ya.

    1986-01-01

    Attention is given to repeated radiation injuries during internal irradiation of theoretical and practical interest, particularly in case of the intake into organism of young products of nuclear fission (PNF). The results of experiments with dogs with repeated radioactive iodine injury the isotopes of which (131-135sub(I)) constitute a considerable part of PNF activity are discussed. The blood reaction and protein metabolism state have been studied. Observations for dogs have been continued for about 4 years. The doses for thyroid, gastrointestinal tract and liver subjected to the most intensive irradiation consituted in the first series of experiments after the first intake about 3;0.3;0.05 Gy, after the second - 5;0.5;0.08 Gy and in the second series of experiments - 3;0.3;0.05 Gy and 0.6;0.06;0.01 Gy, respectively. Hematologic factors,thyroid function, changes in exchange and immunologic reactivity have been studied. The dogs have been under observation for 5 years. It is shown in case of repeated intake of Isup(131) PNF into animals organism in quantity which does not cause during the acute period a clinically outlined sickness, substantial differences in the organism reaction as compared with the first intake of radionuclides have not been found. The presence of residual radiation injuries did not cause charging action during the acute period during PNF and repeated intake which in the author's opinion testifies to perfection of compensator mechanisms in case of intake of such quantities of radioactive products. At the remote periods blastomogenic action manifested which is estimated as a result of general biological action of radionuclides administered to the organism. The necessity in subsequent investigations for obtaining the data on organism reactivity, clinic and pathogenesis with the aim of prophylaxis and treatment of such injuries is indicated

  15. Design and analysis of communication protocols for quantum repeater networks

    International Nuclear Information System (INIS)

    Jones, Cody; Kim, Danny; Rakher, Matthew T; Ladd, Thaddeus D; Kwiat, Paul G

    2016-01-01

    We analyze how the performance of a quantum-repeater network depends on the protocol employed to distribute entanglement, and we find that the choice of repeater-to-repeater link protocol has a profound impact on entanglement-distribution rate as a function of hardware parameters. We develop numerical simulations of quantum networks using different protocols, where the repeater hardware is modeled in terms of key performance parameters, such as photon generation rate and collection efficiency. These parameters are motivated by recent experimental demonstrations in quantum dots, trapped ions, and nitrogen-vacancy centers in diamond. We find that a quantum-dot repeater with the newest protocol (‘MidpointSource’) delivers the highest entanglement-distribution rate for typical cases where there is low probability of establishing entanglement per transmission, and in some cases the rate is orders of magnitude higher than other schemes. Our simulation tools can be used to evaluate communication protocols as part of designing a large-scale quantum network. (paper)

  16. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  17. Vital signs: Repeat births among teens - United States, 2007-2010.

    Science.gov (United States)

    2013-04-05

    Teen childbearing has potential negative health, economic, and social consequences for mother and child. Repeat teen childbearing further constrains the mother's education and employment possibilities. Rates of preterm and low birth weight are higher in teens with a repeat birth, compared with first births. To assess patterns of repeat childbearing and postpartum contraceptive use among teens, CDC analyzed natality data from the National Vital Statistics System (NVSS) and the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2007-2010. Based on 2010 NVSS data from all 50 states and the District of Columbia, of more than 367,000 births to teens aged 15-19 years, 18.3% were repeat births. The percentage of teen births that represented repeat births decreased by 6.2% between 2007 and 2010. Disparities in repeat teen births exist by race/ethnicity, with the highest percentages found among American Indian/Alaska Natives (21.6%), Hispanics (20.9%), and non-Hispanic blacks (20.4%) and lowest among non-Hispanic whites (14.8%). Wide geographic disparities in the percentage of teen births that were repeat births also exist, ranging from 22% in Texas to 10% in New Hampshire. PRAMS data from 16 reporting areas (15 states and New York City) indicate that 91.2% of teen mothers used a contraceptive method 2-6 months after giving birth, but only 22.4% of teen mothers used the most effective methods. Teens with a previous live birth were significantly more likely to use the most effective methods postpartum compared with those with no prior live birth (29.6% versus 20.9%, respectively). Non-Hispanic white and Hispanic teens were significantly more likely to use the most effective methods than non-Hispanic black teens (24.6% and 27.9% versus 14.3%, respectively). The percentage of teens reporting postpartum use of the most effective methods varied greatly geographically across the PRAMS reporting areas, ranging from 50.3% in Colorado to 7.2% in New York State. Although the

  18. t2prhd: a tool to study the patterns of repeat evolution

    Directory of Open Access Journals (Sweden)

    Pénzes Zsolt

    2008-01-01

    Full Text Available Abstract Background The models developed to characterize the evolution of multigene families (such as the birth-and-death and the concerted models have also been applied on the level of sequence repeats inside a gene/protein. Phylogenetic reconstruction is the method of choice to study the evolution of gene families and also sequence repeats in the light of these models. The characterization of the gene family evolution in view of the evolutionary models is done by the evaluation of the clustering of the sequences with the originating loci in mind. As the locus represents positional information, it is straightforward that in the case of the repeats the exact position in the sequence should be used, as the simple numbering according to repeat order can be misleading. Results We have developed a novel rapid visual approach to study repeat evolution, that takes into account the exact repeat position in a sequence. The "pairwise repeat homology diagram" visualizes sequence repeats detected by a profile HMM in a pair of sequences and highlights their homology relations inferred by a phylogenetic tree. The method is implemented in a Perl script (t2prhd available for downloading at http://t2prhd.sourceforge.net and is also accessible as an online tool at http://t2prhd.brc.hu. The power of the method is demonstrated on the EGF-like and fibronectin-III-like (Fn-III domain repeats of three selected mammalian Tenascin sequences. Conclusion Although pairwise repeat homology diagrams do not carry all the information provided by the phylogenetic tree, they allow a rapid and intuitive assessment of repeat evolution. We believe, that t2prhd is a helpful tool with which to study the pattern of repeat evolution. This method can be particularly useful in cases of large datasets (such as large gene families, as the command line interface makes it possible to automate the generation of pairwise repeat homology diagrams with the aid of scripts.

  19. Learning With Repeated-Game Strategies

    Directory of Open Access Journals (Sweden)

    Christos A. Ioannou

    2014-07-01

    Full Text Available We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2x2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we fi□nd that the strategy with the most occurrences is the Grim-Trigger. In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the Win-Stay, Lose-Shift and Grim-Trigger strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  20. Gene conversion homogenizes the CMT1A paralogous repeats

    Directory of Open Access Journals (Sweden)

    Hurles Matthew E

    2001-12-01

    Full Text Available Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect gene conversion between pairs of non-coding sequences is presented. It is shown that the 24 kb Charcot-Marie-Tooth type 1A paralogous repeats (CMT1A-REPs exhibit the imprint of gene conversion processes whilst control orthologous sequences do not. In addition, Monte Carlo simulations of the evolutionary divergence of the CMT1A-REPs, incorporating two alternative models for gene conversion, generate repeats that are statistically indistinguishable from the observed repeats. Bounds are placed on the rate of these conversion processes, with central values of 1.3 × 10-4 and 5.1 × 10-5 per generation for the alternative models. Conclusions This evidence presented here suggests that gene conversion may have played an important role in the evolution of the CMT1A-REP paralogous repeats. The rates of these processes are such that it is probable that homogenized CMT1A-REPs are polymorphic within modern populations. Gene conversion processes are similarly likely to play an important role in the evolution of other segmental duplications and may influence the rate of non-allelic homologous recombination between them.

  1. The impact of repeat-testing of common chemistry analytes at critical concentrations.

    Science.gov (United States)

    Onyenekwu, Chinelo P; Hudson, Careen L; Zemlin, Annalise E; Erasmus, Rajiv T

    2014-12-01

    Early notification of critical values by the clinical laboratory to the treating physician is a requirement for accreditation and is essential for effective patient management. Many laboratories automatically repeat a critical value before reporting it to prevent possible misdiagnosis. Given today's advanced instrumentation and quality assurance practices, we questioned the validity of this approach. We performed an audit of repeat-testing in our laboratory to assess for significant differences between initial and repeated test results, estimate the delay caused by repeat-testing and to quantify the cost of repeating these assays. A retrospective audit of repeat-tests for sodium, potassium, calcium and magnesium in the first quarter of 2013 at Tygerberg Academic Laboratory was conducted. Data on the initial and repeat-test values and the time that they were performed was extracted from our laboratory information system. The Clinical Laboratory Improvement Amendment criteria for allowable error were employed to assess for significant difference between results. A total of 2308 repeated tests were studied. There was no significant difference in 2291 (99.3%) of the samples. The average delay ranged from 35 min for magnesium to 42 min for sodium and calcium. At least 2.9% of laboratory running costs for the analytes was spent on repeating them. The practice of repeating a critical test result appears unnecessary as it yields similar results, delays notification to the treating clinician and increases laboratory running costs.

  2. Flanking Variation Influences Rates of Stutter in Simple Repeats

    Directory of Open Access Journals (Sweden)

    August E. Woerner

    2017-11-01

    Full Text Available It has been posited that the longest uninterrupted stretch (LUS of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL. While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.

  3. A COMPARISON OF PAIRS FIGURE SKATERS IN REPEATED JUMPS

    Directory of Open Access Journals (Sweden)

    William A. Sands

    2012-03-01

    Full Text Available Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare

  4. Characteristics of intergenerational contractions of the CTG repeat in myotonic dystropy

    Energy Technology Data Exchange (ETDEWEB)

    Ashizawa, T.; Anvret, M.; Grandell, U.; Baiget, M.; Cobo, A.M.; Barcelo, J.M.; Korneluk, R.G.; Dallapiccola, B.; Novelli, G.; Fenwick, R.G. Jr. (and others)

    1994-03-01

    In myotonic dystropy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evidence of anticipation. However, there have also been cases with an intergenerational contraction of the repeat. The authors have examined 1,489 DM parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of th 95 pairs, clinical data allowed an analysis of their anticipation status. It is surprising that anticipation occurred in 27 (48%) of these 56 pairs, while none clearly showed a later onset of DM in the asymptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmission and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P<.001). The parental repeat size correlated with the size of intergenerational contraction (r[sup 2] = .50, P [much lt].001), and the slope of linear regression was steeper in paternal ([minus].62) than in maternal ([minus].30) transmissions (P [much lt].001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contractions (6.4%) and the size of DM sib population (1.54 DM offspring per DM parent, in 968 DM parents). The authors conclude that (1) intergenerational contraction of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, and (2) the paternal origin of the repeat and the presence of the repeat contraction in a sibling increase the probability of the CTG repeat contraction. 43 refs., 1 fig., 4 tabs.

  5. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  6. Towards accurate de novo assembly for genomes with repeats

    NARCIS (Netherlands)

    Bucur, Doina

    2017-01-01

    De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

  7. Repeat cesarean delivery: what indications are recorded in the medical chart?

    Science.gov (United States)

    Lydon-Rochelle, Mona T; Gardella, Carolyn; Cárdenas, Vicky; Easterling, Thomas R

    2006-03-01

    National surveillance estimates reported a troubling 63 percent decline in the rate of vaginal birth after cesarean delivery (VBAC) from 1996 (28.3%) to 2003 (10.6%), with subsequent rising rates of repeat cesarean delivery. The study objective was to examine patterns of documented indications for repeat cesarean delivery in women with and without labor. We conducted a population-based validation study of 19 nonfederal short-stay hospitals in Washington state. Of the 4,541 women who had live births in 2000, 11 percent (n = 493) had repeat cesarean without labor and 3 percent (n = 138) had repeat cesarean with labor. Incidence of medical conditions and pregnancy complications, patterns of documented indications for repeat cesarean delivery, and perioperative complications in relation to repeat cesarean delivery with and without labor were calculated. Of the 493 women who underwent a repeat cesarean delivery without labor, "elective"(36%) and "maternal request"(18%) were the most common indications. Indications for maternal medical conditions (3.0%) were uncommon. Among the 138 women with repeat cesarean delivery with labor, 60.1 percent had failure to progress, 24.6 percent a non-reassuring fetal heart rate, 8.0 percent cephalopelvic disproportion, and 7.2 percent maternal request during labor. Fetal indications were less common (5.8%). Breech, failed vacuum, abruptio placentae, maternal complications, and failed forceps were all indicated less than 5.0 percent. Women's perioperative complications did not vary significantly between women without and with labor. Regardless of a woman's labor status, nearly 10 percent of women with repeat cesarean delivery had no documented indication as to why a cesarean delivery was performed. "Elective" and "maternal request" were common indications among women undergoing repeat cesarean delivery without labor, and nearly 10 percent of women had undocumented indications for repeat cesarean delivery in their medical record

  8. Cough reflex sensitivity is increased in the guinea pig model of allergic rhinitis.

    Science.gov (United States)

    Brozmanova, M; Plevkova, J; Tatar, M; Kollarik, M

    2008-12-01

    Increased cough reflex sensitivity is found in patients with allergic rhinitis and may contribute to cough caused by rhinitis. We have reported that cough to citric acid is enhanced in the guinea pig model of allergic rhinitis. Here we address the hypothesis that the cough reflex sensitivity is increased in this model. The data from our previous studies were analyzed for the cough reflex sensitivity. The allergic inflammation in the nose was induced by repeated intranasal instillations of ovalbumin in the ovalbumin-sensitized guinea pigs. Cough was induced by inhalation of doubling concentrations of citric acid (0.05-1.6 M). Cough threshold was defined as the lowest concentration of citric acid causing two coughs (C2, expressed as geometric mean [95% confidence interval]). We found that the cough threshold was reduced in animals with allergic rhinitis. C2 was 0.5 M [0.36-0.71 M] and 0.15 M [0.1-0.23 M] prior and after repeated intranasal instillations of ovalbumin, respectively, Preflex sensitivity. C2 was reduced in animals with allergic rhinitis treated orally with vehicle (0.57 M [0.28-1.1] vs. 0.09 M [0.04-0.2 M], Preflex sensitivity is increased in the guinea pig model of allergic rhinitis. Our results suggest that guinea pig is a suitable model for mechanistic studies of increased cough reflex sensitivity in rhinitis.

  9. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.; Sanbonmatsu, Ryoko; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Suzuki, Yoshiyuki; Chakraborty, Ranajit; Gojobori, Takashi; Imanishi, Tadashi

    2016-01-01

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat

  10. Characteristics of persons with repeat syphilis - Idaho, 2011-2015.

    Science.gov (United States)

    Kassem, Ahmed M; Bartschi, Jared; Carter, Kris K

    2018-03-14

    During 2011-2015 in Idaho, 14 (7%) of 193 persons with early syphilis had repeat syphilis. Persons with repeat infections were more likely to have had secondary or early latent syphilis (P = 0.037) and be infected with HIV (P < 0.001) compared with those having one infection.

  11. Relationship between quantum repeating devices and quantum seals

    International Nuclear Information System (INIS)

    He Guangping

    2009-01-01

    It is revealed that quantum repeating devices and quantum seals have a very close relationship, thus the theory in one field can be applied to the other. Consequently, it is shown that the fidelity bounds and optimality of quantum repeating devices for decoding quantum information can be violated when they are used for decoding classical information from quantum states and the security bounds for protocols sealing quantum data exist.

  12. A study on radiographic repeat rate data of several hospitals in Jeddah

    International Nuclear Information System (INIS)

    Al-Malki, M.A.; Abulfaraj, W.H.; Bhuiyan, S.I.; Kinsara, A.A.

    2003-01-01

    Radiographic repeat rate data in diagnostic radiology in King Fahad Hospital (KFH), King Abdulaziz Hospital (KAH), and Maternity and Children Hospital (MCH) in Jeddah, Saudi Arabia, have been studied. The study provided valuable information to suggest preventive measures to reduce repeats. The variables included in the study are exposure techniques, examination types, total number of films used, number of films repeated, the film sizes, gender, the age groups of the patients, and reason for repetition. The total number of examinations in all three hospitals is 6001 using 8887 films on 5412 patients. The average repeat rate was 7.93%, where the individual hospital repeat rates were 9.57% in the MCH, 7.84% in KAH and 7.44% in KFH. The repeat rate for children and infants was found to be undesirable. The quality assurance (QA) programme can effectively reduce the unnecessary exposure and can identify the cause of the exposure. The overexposure, underexposure and position fault were the foremost contributors for repeats and constitute 32.91%, 28.94% and 22.98% of the total respectively. The QA study identified that human error and equipment malfunction are the major contributors to these causes of repeats. The highest repetition rate was for pelvis, 13.64%, followed by skull, 11.59%, and abdomen, 10.41%. It is estimated that the total area of wasted film in all three hospitals is 74.3 m 2 . As per the average repeat rate, the cost of repeat films in the entire kingdom per year has been projected to be about US$1.82 million (SR 6.83 million) in the government hospitals only. Based on the findings of this study a set of recommendations have been prescribed for the radiology department to reduce the repeat rate and to improve the safety culture. (author)

  13. A study on radiographic repeat rate data of several hospitals in Jeddah

    Energy Technology Data Exchange (ETDEWEB)

    Al-Malki, M.A.; Abulfaraj, W.H.; Bhuiyan, S.I.; Kinsara, A.A

    2003-07-01

    Radiographic repeat rate data in diagnostic radiology in King Fahad Hospital (KFH), King Abdulaziz Hospital (KAH), and Maternity and Children Hospital (MCH) in Jeddah, Saudi Arabia, have been studied. The study provided valuable information to suggest preventive measures to reduce repeats. The variables included in the study are exposure techniques, examination types, total number of films used, number of films repeated, the film sizes, gender, the age groups of the patients, and reason for repetition. The total number of examinations in all three hospitals is 6001 using 8887 films on 5412 patients. The average repeat rate was 7.93%, where the individual hospital repeat rates were 9.57% in the MCH, 7.84% in KAH and 7.44% in KFH. The repeat rate for children and infants was found to be undesirable. The quality assurance (QA) programme can effectively reduce the unnecessary exposure and can identify the cause of the exposure. The overexposure, underexposure and position fault were the foremost contributors for repeats and constitute 32.91%, 28.94% and 22.98% of the total respectively. The QA study identified that human error and equipment malfunction are the major contributors to these causes of repeats. The highest repetition rate was for pelvis, 13.64%, followed by skull, 11.59%, and abdomen, 10.41%. It is estimated that the total area of wasted film in all three hospitals is 74.3 m{sup 2}. As per the average repeat rate, the cost of repeat films in the entire kingdom per year has been projected to be about US$1.82 million (SR 6.83 million) in the government hospitals only. Based on the findings of this study a set of recommendations have been prescribed for the radiology department to reduce the repeat rate and to improve the safety culture. (author)

  14. Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Karen Kelley

    2012-01-01

    Full Text Available The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs such as fragile X syndrome (FXS. After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5′-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR-activated long-term depression (LTD, leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.

  15. Kinematic repeatability of a multi-segment foot model for dance.

    Science.gov (United States)

    Carter, Sarah L; Sato, Nahoko; Hopper, Luke S

    2018-03-01

    The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux. Intra and inter-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability for the first metatarsophalangeal joint in the sagittal plane. Intra-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability during flex-point-flex across all inter-segmental angles except for the tibia-hindfoot and hindfoot-midfoot frontal planes. Inter-assessor repeatability ranged from poor to excellent (0.5 > ICC ≥ 0.75) for the 3D segment rotations. The most repeatable measure was the tibia-foot dorsiflexion/plantar flexion articulation whereas the least repeatable measure was the hindfoot-midfoot adduction/abduction articulation. The variation found in the inter-assessor results is likely due to inconsistencies in marker placement. This 3D dance specific multi-segment foot model provides insight into which kinematic measures can be reliably used to ascertain in vivo technical errors and/or biomechanical abnormalities in a dancer's foot motion.

  16. Automated detection of repeated structures in building facades

    Directory of Open Access Journals (Sweden)

    M. Previtali

    2013-10-01

    Full Text Available Automatic identification of high-level repeated structures in 3D point clouds of building façades is crucial for applications like digitalization and building modelling. Indeed, in many architectural styles building façades are governed by arrangements of objects into repeated patterns. In particular, façades are generally designed as the repetition of some few basic objects organized into interlaced and\\or concatenated grid structures. Starting from this key observation, this paper presents an algorithm for Repeated Structure Detection (RSD in 3D point clouds of building façades. The presented methodology consists of three main phases. First, in the point cloud segmentation stage (i the building façade is decomposed into planar patches which are classified by means of some weak prior knowledge of urban buildings formulated in a classification tree. Secondly (ii, in the element clustering phase detected patches are grouped together by means of a similarity function and pairwise transformations between patches are computed. Eventually (iii, in the structure regularity estimation step the parameters of repeated grid patterns are calculated by using a Least- Squares optimization. Workability of the presented approach is tested using some real data from urban scenes.

  17. Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

    Science.gov (United States)

    Kippert, Fred; Gerloff, Dietlind L

    2009-09-24

    HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

  18. Perfectionism and negative affect after repeated failure: Anxiety, depression, and anger

    OpenAIRE

    Stoeber, Joachim; Schneider, Natalia; Hussain, Rimi; Matthews, Kelly

    2014-01-01

    Perfectionists have shown increased negative affect after failure compared to nonperfectionists. However, little is known about how perfectionists react to repeated failure. This study investigated the effects of two forms of perfectionism--self-oriented perfectionism and socially prescribed perfectionism--on 100 university students’ reactions to repeated failure (versus repeated success) examining three negative emotions: anxiety, depression, and anger. Results showed that socially prescribe...

  19. Coordination in continuously repeated games

    NARCIS (Netherlands)

    Weeren, A.J.T.M.; Schumacher, J.M.; Engwerda, J.C.

    1995-01-01

    In this paper we propose a model to describe the effectiveness of coordination in a continuously repeated two-player game. We study how the choice of a decision rule by a coordinator affects the strategic behavior of the players, resulting in more or less cooperation. Our model requires the analysis

  20. Repeat-aware modeling and correction of short read errors.

    Science.gov (United States)

    Yang, Xiao; Aluru, Srinivas; Dorman, Karin S

    2011-02-15

    High-throughput short read sequencing is revolutionizing genomics and systems biology research by enabling cost-effective deep coverage sequencing of genomes and transcriptomes. Error detection and correction are crucial to many short read sequencing applications including de novo genome sequencing, genome resequencing, and digital gene expression analysis. Short read error detection is typically carried out by counting the observed frequencies of kmers in reads and validating those with frequencies exceeding a threshold. In case of genomes with high repeat content, an erroneous kmer may be frequently observed if it has few nucleotide differences with valid kmers with multiple occurrences in the genome. Error detection and correction were mostly applied to genomes with low repeat content and this remains a challenging problem for genomes with high repeat content. We develop a statistical model and a computational method for error detection and correction in the presence of genomic repeats. We propose a method to infer genomic frequencies of kmers from their observed frequencies by analyzing the misread relationships among observed kmers. We also propose a method to estimate the threshold useful for validating kmers whose estimated genomic frequency exceeds the threshold. We demonstrate that superior error detection is achieved using these methods. Furthermore, we break away from the common assumption of uniformly distributed errors within a read, and provide a framework to model position-dependent error occurrence frequencies common to many short read platforms. Lastly, we achieve better error correction in genomes with high repeat content. The software is implemented in C++ and is freely available under GNU GPL3 license and Boost Software V1.0 license at "http://aluru-sun.ece.iastate.edu/doku.php?id = redeem". We introduce a statistical framework to model sequencing errors in next-generation reads, which led to promising results in detecting and correcting errors

  1. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  2. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  3. The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury.

    Science.gov (United States)

    Rathinasabapathy, Anandharajan; Horowitz, Alana; Horton, Kelsey; Kumar, Ashok; Gladson, Santhi; Unger, Thomas; Martinez, Diana; Bedse, Gaurav; West, James; Raizada, Mohan K; Steckelings, Ulrike M; Sumners, Colin; Katovich, Michael J; Shenoy, Vinayak

    2018-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT 2 ) receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21), a selective AT 2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol, BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition), and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT 2 receptor by C21 attenuates

  4. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Williams, Andrew, E-mail: Andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Købler, Carsten, E-mail: carko@nanotech.dtu.dk [Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark); Atluri, Rambabu, E-mail: rba@nrcwe.dk [Nanologica AB, SE-114 28 Stockholm (Sweden); Pozzebon, Maria E., E-mail: mariaelena.pozzebon@yahoo.it [Veneto Nanotech SCpA, ECSIN — European Centre for the Sustainable Impact of Nanotechnology, I-45100 Rovigo (Italy); Mucelli, Stefano P., E-mail: stefano.pozzimucelli@venetonanotech.it [Veneto Nanotech SCpA, ECSIN — European Centre for the Sustainable Impact of Nanotechnology, I-45100 Rovigo (Italy); Simion, Monica, E-mail: moni304ro@gmail.com [Laboratory of Nanobiotechnology, National Institute for Research and Development in Microtechnologies, 077190 Bucharest (Romania); Rickerby, David, E-mail: david.rickerby@jrc.ec.europa.eu [European Commission Joint Research Centre Institute for Environment and Sustainability, I-21027 Ispra, VA (Italy); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Jackson, Petra, E-mail: pja@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Kyjovska, Zdenka O., E-mail: zky@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); and others

    2015-04-01

    Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT{sub Small}, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT{sub Large}, 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer–Emmett–Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT{sub Small} or CNT{sub Large} were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT{sub Large} elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT{sub Small}. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT{sub Large}, which may eventually lead to the different responses observed at day 28. - Highlights: • We evaluate the toxicogenomic response in mice following MWCNT instillation. • Two MWCNTs of different properties were examined and thoroughly characterized. • MWCNT exposure leads to increased pulmonary

  5. MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

    International Nuclear Information System (INIS)

    Poulsen, Sarah S.; Saber, Anne T.; Williams, Andrew; Andersen, Ole; Købler, Carsten; Atluri, Rambabu; Pozzebon, Maria E.; Mucelli, Stefano P.; Simion, Monica; Rickerby, David; Mortensen, Alicja; Jackson, Petra; Kyjovska, Zdenka O.

    2015-01-01

    Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT Small , 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT Large , 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer–Emmett–Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT Small or CNT Large were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT Large elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT Small . The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT Large , which may eventually lead to the different responses observed at day 28. - Highlights: • We evaluate the toxicogenomic response in mice following MWCNT instillation. • Two MWCNTs of different properties were examined and thoroughly characterized. • MWCNT exposure leads to increased pulmonary inflammation and acute phase

  6. The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Anandharajan Rathinasabapathy

    2018-03-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT2 receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21, a selective AT2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip either immediately (prevention protocol, BCP or after 3 days (treatment protocol, BCT of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition, and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT2 receptor by C21 attenuates

  7. Pulmonary exposure to carbonaceous nanomaterials and sperm quality.

    Science.gov (United States)

    Skovmand, Astrid; Jacobsen Lauvås, Anna; Christensen, Preben; Vogel, Ulla; Sørig Hougaard, Karin; Goericke-Pesch, Sandra

    2018-01-31

    Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung capillaries, enter the systemic circulation and ultimately reach the testes. Both the inflammatory response and the particles may induce oxidative stress which can directly affect spermatogenesis. Furthermore, spermatogenesis may be indirectly affected by changes in the hormonal milieu as systemic inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model. Effects on sperm quality after pulmonary inflammation induced by carbonaceous nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 μg/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks. Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA. Neutrophil numbers in the bronchoalveolar fluid showed sustained inflammatory response in the nanoparticle-exposed groups one week after the last instillation. No significant changes in epididymal sperm parameters, daily sperm production or plasma testosterone levels

  8. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  9. Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

    Science.gov (United States)

    Miller, J D; Sun, M; Gilyan, A; Roy, J; Rand, T G

    2010-01-05

    Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (por =1.5-fold or cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can

  10. Quantification of lung fibrosis and emphysema in mice using automated micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Ellen De Langhe

    Full Text Available BACKGROUND: In vivo high-resolution micro-computed tomography allows for longitudinal image-based measurements in animal models of lung disease. The combination of repetitive high resolution imaging with fully automated quantitative image analysis in mouse models of lung fibrosis lung benefits preclinical research. This study aimed to develop and validate such an automated micro-computed tomography analysis algorithm for quantification of aerated lung volume in mice; an indicator of pulmonary fibrosis and emphysema severity. METHODOLOGY: Mice received an intratracheal instillation of bleomycin (n = 8, elastase (0.25 U elastase n = 9, 0.5 U elastase n = 8 or saline control (n = 6 for fibrosis, n = 5 for emphysema. A subset of mice was scanned without intervention, to evaluate potential radiation-induced toxicity (n = 4. Some bleomycin-instilled mice were treated with imatinib for proof of concept (n = 8. Mice were scanned weekly, until four weeks after induction, when they underwent pulmonary function testing, lung histology and collagen quantification. Aerated lung volumes were calculated with our automated algorithm. PRINCIPAL FINDINGS: Our automated image-based aerated lung volume quantification method is reproducible with low intra-subject variability. Bleomycin-treated mice had significantly lower scan-derived aerated lung volumes, compared to controls. Aerated lung volume correlated with the histopathological fibrosis score and total lung collagen content. Inversely, a dose-dependent increase in lung volume was observed in elastase-treated mice. Serial scanning of individual mice is feasible and visualized dynamic disease progression. No radiation-induced toxicity was observed. Three-dimensional images provided critical topographical information. CONCLUSIONS: We report on a high resolution in vivo micro-computed tomography image analysis algorithm that runs fully automated and allows quantification of aerated lung volume in mice. This

  11. Does Dry Eye Affect Repeatability of Corneal Topography Measurements?

    Directory of Open Access Journals (Sweden)

    Aysun Şanal Doğan

    2018-04-01

    Full Text Available Objectives: The purpose of this study was to assess the repeatability of corneal topography measurements in dry eye patients and healthy controls. Materials and Methods: Participants underwent consecutive corneal topography measurements (Sirius; Costruzione Strumenti Oftalmici, Florence, Italy. Two images with acquisition quality higher than 90% were accepted. The following parameters were evaluated: minimum and central corneal thickness, aqueous depth, apex curvature, anterior chamber volume, horizontal anterior chamber diameter, iridocorneal angle, cornea volume, and average simulated keratometry. Repeatability was assessed by calculating intra-class correlation coefficient. Results: Thirty-three patients with dry eye syndrome and 40 healthy controls were enrolled to the study. The groups were similar in terms of age (39 [18-65] vs. 30.5 [18-65] years, p=0.198 and gender (M/F: 4/29 vs. 8/32, p=0.366. Intra-class correlation coefficients among all topography parameters within both groups showed excellent repeatability (>0.90. Conclusion: The anterior segment measurements provided by the Sirius corneal topography system were highly repeatable for dry eye patients and are sufficiently reliable for clinical practice and research.

  12. Does Dry Eye Affect Repeatability of Corneal Topography Measurements?

    Science.gov (United States)

    Doğan, Aysun Şanal; Gürdal, Canan; Köylü, Mehmet Talay

    2018-04-01

    The purpose of this study was to assess the repeatability of corneal topography measurements in dry eye patients and healthy controls. Participants underwent consecutive corneal topography measurements (Sirius; Costruzione Strumenti Oftalmici, Florence, Italy). Two images with acquisition quality higher than 90% were accepted. The following parameters were evaluated: minimum and central corneal thickness, aqueous depth, apex curvature, anterior chamber volume, horizontal anterior chamber diameter, iridocorneal angle, cornea volume, and average simulated keratometry. Repeatability was assessed by calculating intra-class correlation coefficient. Thirty-three patients with dry eye syndrome and 40 healthy controls were enrolled to the study. The groups were similar in terms of age (39 [18-65] vs. 30.5 [18-65] years, p=0.198) and gender (M/F: 4/29 vs. 8/32, p=0.366). Intra-class correlation coefficients among all topography parameters within both groups showed excellent repeatability (>0.90). The anterior segment measurements provided by the Sirius corneal topography system were highly repeatable for dry eye patients and are sufficiently reliable for clinical practice and research.

  13. Device-independent secret-key-rate analysis for quantum repeaters

    Science.gov (United States)

    Holz, Timo; Kampermann, Hermann; Bruß, Dagmar

    2018-01-01

    The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.

  14. Repfinder: Finding approximately repeated scene elements for image editing

    KAUST Repository

    Cheng, Ming-Ming

    2010-07-26

    Repeated elements are ubiquitous and abundant in both manmade and natural scenes. Editing such images while preserving the repetitions and their relations is nontrivial due to overlap, missing parts, deformation across instances, illumination variation, etc. Manually enforcing such relations is laborious and error-prone. We propose a novel framework where user scribbles are used to guide detection and extraction of such repeated elements. Our detection process, which is based on a novel boundary band method, robustly extracts the repetitions along with their deformations. The algorithm only considers the shape of the elements, and ignores similarity based on color, texture, etc. We then use topological sorting to establish a partial depth ordering of overlapping repeated instances. Missing parts on occluded instances are completed using information from other instances. The extracted repeated instances can then be seamlessly edited and manipulated for a variety of high level tasks that are otherwise difficult to perform. We demonstrate the versatility of our framework on a large set of inputs of varying complexity, showing applications to image rearrangement, edit transfer, deformation propagation, and instance replacement. © 2010 ACM.

  15. 30 CFR 250.522 - When do I have to repeat casing diagnostic testing?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When do I have to repeat casing diagnostic... Operations Casing Pressure Management § 250.522 When do I have to repeat casing diagnostic testing? Casing diagnostic testing must be repeated according to the following table: When * * * you must repeat diagnostic...

  16. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    International Nuclear Information System (INIS)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-01-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [ 3 H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

  17. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  18. Repeated nicotine exposure enhances reward-related learning in the rat.

    Science.gov (United States)

    Olausson, Peter; Jentsch, J David; Taylor, Jane R

    2003-07-01

    Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

  19. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.

  20. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...