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Sample records for intratracheal instillation studies

  1. 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.

  2. 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. PMID:26989787

  3. 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.

  4. Comparative study of the toxic effects of gallium arsenide, indium arsenide and arsenic trioxide following intratracheal instillations to the lung of Syrian golden hamsters.

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    Tanaka, A; Hirata, M; Omura, M; Zhao, M; Makita, Y; Yamazaki, K; Inoue, N; Gotoh, K

    2000-01-01

    Toxic effects of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were studied in male Syrian golden hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) particles were instilled intratracheally twice a week a total of 16 times, while InAs (7.7 mg/kg) was instilled a total of 14 times. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the instillation period, the cumulative body weight gain of the InAs-, but not the GaAs- or As2O3-treated hamsters was suppressed significantly, when compared with the control group. Slight to severe inflammatory responses were observed in the lung for all treatment groups. The most severe inflammatory change, characterized by an accumulation of neutrophils and macrophages, exudation, thickness of the pleura and fibrotic proliferation was found in the InAs-treated hamsters. Extensive alveolar or bronchiolar cell hyperplasia with or without keratinizing squamous cell metaplasia was observed in almost all the InAs-treated hamsters. Furthermore, squamous cell metaplasia or squamous cell hyperplasia developed in some of the InAs-treated hamsters, but not in the GaAs- or As2O3-treated hamsters. Slight to mild lesions were found in the convoluted tubules of the kidney in both the GaAs and InAs groups. From the present study, the toxic potency of these particles was provisionally estimated to be in the following order: InAs > GaAs > As2O3, at the dosage level used in this study. Furthermore, there was evidence that InAs particles could induce pulmonary, renal or systemic toxicity, and as such, InAs particles may produce pulmonary precancerous change when instilled intratracheally into hamsters.

  5. Pulmonary toxicity of printer toner following inhalation and intratracheal instillation.

    Science.gov (United States)

    Morimoto, Yasuo; Oyabu, Takako; Horie, Masanori; Kambara, Tatsunori; Izumi, Hiroto; Kuroda, Etsushi; Creutzenberg, Otto; Bellmann, Bernd; Pohlmann, Gerhard; Schuchardt, Sven; Hansen, Tanja; Ernst, Heinrich

    2013-10-01

    The pulmonary effects of a finished toner were evaluated in intratracheal instillation and inhalation studies, using toners with external additives (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups and persistent neutrophil infiltration in the high-dose groups. There were increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76 µm). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13 weeks, and the rats were sacrificed at 6 days and 91 days after the end of the exposure period. The low and medium concentrations did not induce neutrophil infiltration in the lung of statistical significance, but the high concentration did, and, in addition, upon histopathological examination not only showed findings of inflammation but also of fibrosis in the lung. Taken together, the results of our studies suggest that toners with external additives lead to pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload. The changes observed in the pulmonary responses in this inhalation study indicate that the high concentration (16 mg/m(3)) is an LOAEL and that the medium concentration (4 mg/m(3)) is an NOAEL.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Background The fate of gold nanoparticles, 2, 40 and 100 nm, administered intratracheally to adult female mice was examined. The nanoparticles were traced by autometallography (AMG) at both ultrastructural and light microscopic levels. Also, the gold content was quantified by inductively coupled...... 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...

  7. Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study.

    Science.gov (United States)

    Kuiper, Jan Willem; Groeneveld, A B Johan; Haitsma, Jack J; Smeding, Lonneke; Begieneman, Mark P V; Jothy, Serge; Vaschetto, Rosanna; Plötz, Frans B

    2014-07-29

    Intratracheal aspiration and sepsis are leading causes of acute lung injury that frequently necessitate mechanical ventilation (MV), which may aggravate lung injury thereby potentially increasing the risk of acute kidney injury (AKI). We compared the effects of ventilation strategies and underlying conditions on the development of AKI. Spraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause more lung injury after acid instillation than in sepsis. Rats were ventilated for 4 hrs and kidney function and plasma mediator levels were measured. Kidney injury was assessed by microscopy; apoptosis was quantified by TUNEL staining. During sepsis, but not after acid instillation, MV with HVT caused more renal apoptosis than MV with LVT. Increased plasma active plasminogen activator inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased apoptosis after HVT ventilation during sepsis was associated with a 40% decrease in creatinine clearance. AKI is more likely to develop after MV induced lung injury during an indirect (as in sepsis) than after a direct (as after intra-tracheal instillation) insult to the lungs, since it induces kidney apoptosis during sepsis but not after acid instillation, opposite to the lung injury it caused. Our findings thus suggest using protective ventilatory strategies in human sepsis, even in the absence of overt lung injury, to protect the kidney.

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

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    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2015-11-01

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) 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 CeO2 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 CeO2 nanoparticles (2, 10 mg/m3, 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 CeO2 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 CeO2 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 CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

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

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    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.

  10. 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.

  11. 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

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    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.

  12. 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.

  13. 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

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

    Science.gov (United States)

    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

    2015-06-01

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO2) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO2 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 TiO2 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 TiO2 may not lead to chronic, irreversible legions in the lung, and that TiO2 nanoparticles may not have a high potential for lung disorder.

  15. Changes in bronchoalveolar lavage cells after intratracheal instillation of dimethyl selenide in mice.

    Science.gov (United States)

    Cherdwongcharoensuk, Duangrudee; Upatham, Suchart; Oliveira, José Carlos; Sousa Pereira, António; AGuas, Artur P

    2004-01-01

    CD-1 mice were exposed to a single intratracheal instillation of either 0.025 or 0.075 mg Se/kg wt of dimethyl selenide (DMSe). They were studied over 4 weeks to define the cellular inflammatory response of the airways to DMSe. Bronchoalveolar (BAL) lavage was used to collect the DMSe-induced inflammatory exudates. The DMSe instillation resulted in phlogistic responses that had the neutrophil as the main leukocyte; they were present in BAL samples, mostly at days 1 and 7. Macrophages were also increased during DMSe-induced inflammation. The lower DMSe dose resulted in an inflammatory reaction lasting for 2 weeks. Mice treated with the higher DMSe dose still showed elevated numbers of neutrophils and macrophages 4 weeks after instillation. DMSe did not change the number of lymphocytes harvested from the airways. An early increase in total protein of BAL, and late enhancement in lactate dehydrogenase was observed in mice treated with the high DMSe dose. We conclude that inhalation of DMSe triggers a moderate and dose-dependent inflammatory reaction in the mouse airways, and that this phlogistic reaction is likely to participate in the damage of respiratory epithelia that occurs upon DMSe inhalation.

  16. 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.)

  17. Toxicity of Carbon Nanotubes in the Lungs of Mice 7 and 90 Days After Intratracheal Instillation

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    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2002-01-01

    Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  18. 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.

  19. Cardiopulmonary responses of intratracheally instilled tire particles and constituent metal components

    Science.gov (United States)

    Gottipolu, R.R.; Landa, E.R.; Schladweiler, M.C.; McGee, J.K.; Ledbetter, A.D.; Richards, J.H.; Wallenborn, G.J.; Kodavanti, U.P.

    2008-01-01

    Tire and brake wear particles contain transition metals, and contribute to near-road PM. We hypothesized that acute cardiopulmonary injury from respirable tire particles (TP) will depend on the amount of soluble metals. Respirable fractions of two types of TP (TP1 and TP2) were analyzed for water and acid-leachable metals using ICP-AES. Both TP types contained a variety of transition metals, including zinc (Zn), copper (Cu), aluminum, and iron. Zn and Cu were detected at high levels in water-soluble fractions (TP2 > TP1). Male Wistar Kyoto rats (12-14 wk) were intratracheally instilled, in the first study, with saline, TP1 or TP2 (5 mg/kg), and in the second study, with soluble Zn, Cu (0.5 ??mol/kg), or both. Pulmonary toxicity and cardiac mitochondrial enzymes were analyzed 1 d, 1 wk, or 4 wk later for TP and 4 or 24 h later for metals. Increases in lavage fluid markers of inflammation and injury were observed at d 1 (TP2 > TP1), but these changes reversed by wk 1. No effects on cardiac enzymes were noted with either TP. Exposure of rats to soluble Zn and Cu caused marked pulmonary inflammation and injury but temporal differences were apparent (Cu effects peaked at 4 h and Zn at 24 h). Instillation of Zn, Cu, and Zn+ Cu decreased the activity of cardiac aconitase, isocitrate dehydrogenase, succinate dehydrogenase, cytochrome-c-oxidase and superoxide dismutase suggesting mitochondrial oxidative stress. The observed acute pulmonary toxicity of TP could be due to the presence of water soluble Zn and Cu. At high concentrations these metals may induce cardiac oxidative stress. Copyright ?? Informa Healthcare USA, Inc.

  20. 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.

  1. Pulmonary responses to printer toner particles in mice after intratracheal instillation.

    Science.gov (United States)

    Bai, Ru; Zhang, Lili; Liu, Ying; Meng, Li; Wang, Liming; Wu, Yan; Li, Wei; Ge, Cuicui; Le Guyader, Laurent; Chen, Chunying

    2010-12-15

    The release of ultrafine particles from office equipment is currently receiving great concerns due to its potential threat to human health when inhaled. Printer toner is one of the largest consumables in daily office work, and the particles released from printers and photocopiers may pose damage to respiratory system. In this study, we found the particles can be released into the surrounding environment during the printing process and the concentrations of PM(2.5) and PM(10) particles increased obviously. To evaluate the time-course pulmonary responses caused by toner particles, the toner suspension was instilled into the lungs of the male mice through intratracheally instillation every other day for four times and the pulmonary responses of the lung were monitored at days 9, 28, 56 and 84. Indeed, mice treated with toner particles displayed a slower body weight growth rate during the recovery phase. The total cell number in bronchoalveolar lavage fluids (BALF) of toner-exposed groups was much higher than the saline-treated groups. The total protein, lactate dehydrogenase and acid phosphatase in BALF exhibited significant changes (ptoner-exposed groups also exhibited significant changes (ptoner particles can adhere to the alveolar septal walls, then enter into the alveoli and cause pulmonary lesion. During the experimental period, particles phagocytosed by alveolar macrophages (AMs) led to an increase of both AMs number and apoptosis. The pulmonary stress still remained over time even with a clearance period for 12 weeks. These results indicate that exposure to toner particles can inhibit the normal growth of the mice and induce significant inflammatory responses and lesion in the lung tissues. The health and safety effects from working indoors in offices with fumes and particles released from photocopiers and printers need to be paid more attention. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. [Clinical efficacy of porcine pulmonary surfactant combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome].

    Science.gov (United States)

    Tan, Xiu-Zhen; Wu, Shi-Guang; Zhang, Jian-Hua; Li, Xiao-Fen; Gao, Ping-Ming; Wang, Yu

    2016-12-01

    To study the clinical efficacy of porcine pulmonary surfactant (PS) combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome (MAS). Seventy neonates with MAS were enrolled for a prospective study. The neonates were randomly assigned to PS alone treatment group and PS+budesonide treatment group (n=35 each). The PS alone treatment group was given PS (100 mg/kg) by intratracheal instillation. The treatment group was given budesonide suspension (0.25 mg/kg) combined with PS (100 mg/kg). The rate of repeated use of PS in the PS+ budesonide group was significantly lower than that in the PS alone group 12 hours after treatment (p<0.05). The improvement of PaO 2 /FiO 2 , TcSaO 2 , PaO 2 , and PaCO 2 in the PS+ budesonide group was significantly greater than that in the PS alone group 6, 12, and 24 hours after treatment (p<0.05). The chest X-ray examination showed that the pulmonary inflammation absorption in the PS+ budesonide group was significantly better than that in the PS alone group 48 hours after treatment (p<0.05). The incidence of complications in the PS+budesonide group was significantly lower than that in the PS alone group (p<0.05), and the average hospitalization duration was significantly shorter than that in the PS alone group (p<0.01). PS combined with budesonide suspension intratracheal instillation for the treatment of neonatal MAS is effective and superior to PS alone treatment.

  4. 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...

  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. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.

    Science.gov (United States)

    Armstead, Andrea L; Minarchick, Valerie C; Porter, Dale W; Nurkiewicz, Timothy R; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.

  7. Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

    Science.gov (United States)

    Armstead, Andrea L.; Minarchick, Valerie C.; Porter, Dale W.; Nurkiewicz, Timothy R.; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs. PMID:25738830

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. 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

  11. 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.

  12. 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)

  13. Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3.

    Science.gov (United States)

    Kreyling, Wolfgang G; Holzwarth, Uwe; Haberl, Nadine; Kozempel, Ján; Wenk, Alexander; Hirn, Stephanie; Schleh, Carsten; Schäffler, Martin; Lipka, Jens; Semmler-Behnke, Manuela; Gibson, Neil

    2017-05-01

    The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48 V-radiolabeled [ 48 V]TiO 2 nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [ 48 V]TiO 2 -nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [ 48 V]TiO 2 -nanoparticle doses in the range of 40-240 μg·kg -1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [ 48 V]TiO 2 -nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48 V-ions not bound to TiO 2 -nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1 h and were retained mainly in the carcass (4%); 0.3% after 28 d. Highest organ fractions of [ 48 V]TiO 2 -nanoparticles present in liver and kidneys remained constant (0.03%). [ 48 V]TiO 2 -nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [ 48 V]TiO 2 -nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [ 48 V]TiO 2 -nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO 2 -particles (including nanoparticles) and accumulation in

  14. Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 2: intratracheal instillation and intravenous injection.

    Science.gov (United States)

    Guichard, Yves; Maire, Marie-Aline; Sébillaud, Sylvie; Fontana, Caroline; Langlais, Cristina; Micillino, Jean-Claude; Darne, Christian; Roszak, Joanna; Stępnik, Maciej; Fessard, Valérie; Binet, Stéphane; Gaté, Laurent

    2015-03-01

    Synthetic amorphous silica nanomaterials (SAS) are extensively used in food and tire industries. In many industrial processes, SAS may become aerosolized and lead to occupational exposure of workers through inhalation in particular. However, little is known about the in vivo genotoxicity of these particulate materials. To gain insight into the toxicological properties of four SAS (NM-200, NM-201, NM-202, and NM-203), rats are treated with three consecutive intratracheal instillations of 3, 6, or 12 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection (cumulative doses of 9, 18, and 36 mg/kg). Deoxyribonucleic acid (DNA) damage was assessed using erythrocyte micronucleus test and the standard and Fpg-modified comet assays on cells from bronchoalveolar lavage fluid (BALF), lung, blood, spleen, liver, bone marrow, and kidney. Although all of the SAS caused increased dose-dependent changes in lung inflammation as demonstrated by BALF neutrophilia, they did not induce any significant DNA damage. As the amount of SAS reaching the blood stream and subsequently the internal organs is probably to be low following intratracheal instillation, an additional experiment was performed with NM-203. Rats received three consecutive intravenous injections of 5, 10, or 20 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection. Despite the hepatotoxicity, thrombocytopenia, and even animal death induced by this nanomaterial, no significant increase in DNA damage or micronucleus frequency was observed in SAS-exposed animals. It was concluded that under experimental conditions, SAS induced obvious toxic effects but did cause any genotoxicity following intratracheal instillation and intravenous injection. © 2014 Wiley Periodicals, Inc.

  15. Intratracheal Instillation of High Dose Adenoviral Vectors Is Sufficient to Induce Lung Injury and Fibrosis in Mice

    Science.gov (United States)

    Zhou, Qiyuan; Chen, Tianji; Bozkanat, Melike; Ibe, Joyce Christina F.; Christman, John W.; Raj, J. Usha; Zhou, Guofei

    2014-01-01

    Rationale Replication deficient adenoviruses (Ad) vectors are common tools in gene therapy. Since Ad vectors are known to activate innate and adaptive immunity, we investigated whether intratracheal administration of Ad vectors alone is sufficient to induce lung injury and pulmonary fibrosis. Methods We instilled Ad viruses ranging from 107 to 1.625×109 ifu/mouse as well as the same volume of PBS and bleomycin. 14 and 21 days after administration, we collected bronchoalveolar lavage fluid (BALF) and mouse lung tissues. We measured the protein concentration, total and differential cell counts, and TGF-β1 production, performed Trichrome staining and Sircol assay, determined gene and protein levels of profibrotic cytokines, MMPs, and Wnt signaling proteins, and conducted TUNEL staining and co-immunofluorescence for GFP and α-SMA staining. Results Instillation of high dose Ad vectors (1.625×109 ifu/mouse) into mouse lungs induced high levels of protein content, inflammatory cells, and TGF-β1 in BALF, comparable to those in bleomycin-instilled lungs. The collagen content and mRNA levels of Col1a1, Col1a2, PCNA, and α-SMA were also increased in the lungs. Instillation of both bleomycin and Ad vectors increased expression levels of TNFα and IL-1β but not IL-10. Instillation of bleomycin but not Ad increased the expression of IL-1α, IL-13 and IL-16. Treatment with bleomycin or Ad vectors increased expression levels of integrin α1, α5, and αv, MMP9, whereas treatment with bleomycin but not Ad vectors induced MMP2 expression levels. Both bleomycin and Ad vectors induced mRNA levels of Wnt2, 2b, 5b, and Lrp6. Intratracheal instillation of Ad viruses also induced DNA damages and Ad viral infection-mediated fibrosis is not limited to the infection sites. Conclusions Our results suggest that administration of Ad vectors induces an inflammatory response, lung injury, and pulmonary fibrosis in a dose dependent manner. PMID:25551570

  16. Pulmonary toxicity of simulated lunar and Martian dusts in mice: II. Biomarkers of acute responses after intratracheal instillation

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.; Latch, Judith N.; Hamilton, Raymond F Jr; Holian, Andrij

    2002-01-01

    Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of

  17. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2004-01-01

    Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  18. 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 health effects of diesel exhaust particles (DEP) are thought to involve oxidative damage. We have investigated the effect of intratracheal DEP instillation to guinea pigs in three groups of 12 animals each given 0, 0.7, or 2.1 mg. Five days later guinea pigs exposed to DEP had increased levels...... of oxidized amino acids (gamma-glutamyl semialdehyde), DNA strand breaks, and 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the lung. Bulky DNA ad- ducts were not significantly elevated in the lung. The antioxidant enzyme activity of glutathione reductase was increased in the lung of DEP-exposed guinea pigs....... 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...

  19. 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

    of oxidized amino acids (gamma-glutamyl semialdehyde), DNA strand breaks, and 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the lung. Bulky DNA ad- ducts were not significantly elevated in the lung. The antioxidant enzyme activity of glutathione reductase was increased in the lung of DEP-exposed guinea pigs......, whereas glutathione peroxidase and superoxide dismutase enzyme activities were unaltered. There was no difference in DNA strand breaks in lymphocytes or urinary excretion of 8-oxodG at the two doses tested. Protein oxidations in plasma and in erythrocytes were not altered by DEP exposure......The health effects of diesel exhaust particles (DEP) are thought to involve oxidative damage. We have investigated the effect of intratracheal DEP instillation to guinea pigs in three groups of 12 animals each given 0, 0.7, or 2.1 mg. Five days later guinea pigs exposed to DEP had increased levels...

  20. 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...

  1. 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.

  2. 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

    compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 micrograms, respectively...

  3. Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis.

    Science.gov (United States)

    Nemmar, Abderrahim; Hoylaerts, Marc F; Hoet, Peter H M; Vermylen, Jozef; Nemery, Benoit

    2003-01-01

    Particulate air pollution is associated with cardiorespiratory effects and ultrafine particles (UFPs, diameter particles on bronchoalveolar lavage (BAL) indices and on peripheral thrombosis in hamster. The latter was assessed by measuring the extent of photochemically induced thrombosis in a femoral vein via transillumination. Unmodified and negative UFPs did not modify thrombosis and BAL indices. Positive UFPs increased thrombosis at 500 microg per animal (+ 341 +/- 96%) and at 50 microg per animal (+ 533 +/- 122%), but not at 5 microg per animal. Neutrophils, lactate dehydrogenase, and histamine were increased in BAL at all these doses but protein concentration was increased only at 500 microg per animal. Positive 400-nm particles (500 microg per animal) did not affect thrombosis, although they led to a neutrophil influx and an increase in BAL proteins and histamine. Using the Platelet Function Analyser (PFA-100), the platelets of hamsters were activated by the in vitro addition of positive UFPs and 400-nm particles to blood. We conclude that intratracheally administered positive ultrafine and 400-nm particles induce pulmonary inflammation within 1 h. Positive UFPs, but not the 400-nm particles enhance thrombosis. Hence, particle-induced lung inflammation and thrombogenesis can be partially uncoupled. Copyright 2003 Elsevier Science (USA)

  4. Rat strain differences in levels and effects of chronic inflammation due to intratracheal instillation of quartz on lung tumorigenesis induced by DHPN.

    Science.gov (United States)

    Nakano, Yuko; Yokohira, Masanao; Hashimoto, Nozomi; Yamakawa, Keiko; Kishi, Sosuke; Ninomiya, Fumiko; Kanie, Shohei; Saoo, Kousuke; Imaida, Katsumi

    2014-10-01

    Chronic inflammatory effects of single intratracheal instillation (i.t.) of quartz on rat lung tumorigenesis were examined using 4 different animal models. At first, in order to determine an appropriate dose of quartz i.t. to promote lung tumorigenesis, F344 male rats were administrated single 0, 0.5, 1, 2 or 4 mg quartz/rat after initiation by N-bis(2-hydroxypropyl) nitrosamine (DHPN). Further studies were performed to examine strain differences of the effects of chronic inflammation caused by quartz i.t. in 3 strains of rat, i.e. F344, Wistar-Hannover and SD. Each was instilled with 2mg quartz/rat after DHPN administration and sacrificed in week 24. In addition, strain differences in generation of inflammation were determined at days 1 and 28. Finally, for determination of long-term effects period, F344 and Wistar-Hannover rats were similarly treated, but the experiment was terminated at week 52. In F344 rats, the tumor areas in DHPN treated groups showed a tendency to increase along with the dose of quartz. F344 rats demonstrated the highest and Wistar-Hannover rats the lowest sensitivity to quartz in acute and chronic phases in the 3 strains. In 52 week, in F344 rats, the multiplicity of tumors and the serum concentration of IL-6 in the group treated with DHPN and quartz were significantly increased. The present experiments indicated that chronic inflammation due to quartz instillation exerted promoting effects on lung carcinogenesis in F344, SD and Wistar-Hannover rats. The strain differences in tumor promotion appeared to correlate with inflammatory reactions to quartz and increase of IL-6. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. In vitro the differences of inflammatory and oxidative reactions due to sulfur mustard induced acute pulmonary injury underlying intraperitoneal injection and intratracheal instillation in rats.

    Science.gov (United States)

    Yu, Dan; Bei, Yuan-Yuan; Li, Yuan; Han, Wei; Zhong, Yu-Xu; Liu, Fei; Zhao, Yu-Ling; Zhu, Xiao-Ji; Zhao, Jian

    2017-06-01

    This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD 50 =8mg/kg) and SM (0.98 LD 50 =2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD 50 doses. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 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

    mediators in plasma of exposed ApoE-/- mice was assessed in aorta rings isolated from naive C57BL/6 mice. Pulmonary exposure to CB and/or LPS resulted in pulmonary inflammation with a robust influx of neutrophils. The CB exposure did not promote plaque progression in aorta or BCA. Incubation with 0......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......-and systemic toxicity. We aimed to investigate if pulmonary inflammation would accelerate nanoparticle-induced atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. ApoE-/- mice were exposed to vehicle, 8.53 or 25.6 mu g nanosized carbon black (CB) alone or spiked with LPS (0.2 mu g...

  9. 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

    or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose...... expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results...... indicate that WSPM and CB exert the strongest effect in terms of oxidative stress-induced response, inflammation, and genotoxicity in the organ closest to the port of entry....

  10. 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.

  11. Biological availability of lead in a paint aerosol. 2. Absorption, distribution and excretion of intratracheally instilled lead paint particles in the rat.

    Science.gov (United States)

    Eaton, D L; Kalman, D; Garvey, D; Morgan, M; Omenn, G S

    1984-09-01

    Four groups of rats received by intratracheal instillation (1) a lead chromate paint particulate suspension, (2) lead tetraoxide suspension, (3) lead acetate solution, or (4) saline. Lead-dosed animals received an equivalent dose of 1 mg lead/kg body weight. Distribution of lead was monitored through assays of urine, feces, and tissues (lung, bone, muscle kidney, liver) obtained at post-mortem 5 weeks after exposure. Delta-aminolevulinic acid dehydratase (ALA-D) activity was measured to determine the effect of lead on heme biosynthesis. The vast majority of the dosed lead in the paint matrix remained in the lung. In contrast, in the lead acetate-dosed animals, little remained in the lung, but significant elevations were found in bone and kidney. Blood ADA-D was significantly depressed in the lead acetate-treated animals, but was not significantly different from control animals in the animals dosed with lead paint or lead tetraoxide. These findings suggest that lead chromate in an alkyd resin paint matrix is poorly absorbed from the lung compared with lead acetate and lead tetraoxide.

  12. 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 pr...

  13. 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

    instilled with 162μg CBNPs alongside vehicle controls. Lung tissues were examined 3h, and 1, 2, 3, 4, 5, 14, and 42days (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 3h post-exposure, and in lung tissues 2-5d 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...

  14. 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

  15. 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.

  16. Intrapulmonary perfluorooctyl bromide instillation in fetal rabbits.

    Science.gov (United States)

    Muensterer, Oliver J; Klis, Verena J; Till, Holger; Bergmann, Florian; Metzger, Roman; Simbruner, Georg

    2005-07-01

    Instilling perfluorooctyl bromide (PFOB) into the fetal lung may lead to alveolar distension. The aim of the study was to evaluate the safety of PFOB instillation into fetal lungs and to determine the radiographic distribution and tissue concentration of PFOB in New Zealand white rabbits. Sibling fetuses of pregnant (day 27) New Zealand white rabbits were randomized to intratracheal instillation of 1 mL PFOB with tracheal ligation, instillation without ligation, and unmanipulated controls. The maternal animals were killed directly after instillation, at 3 or 6 hours (n = 10 each). For each study cohort, we determined fetal lung/body weight (FLBW) ratios, the radiographic distribution of PFOB, as well as pulmonary PFOB and water content by tissue distillation. PFOB concentrations in maternal and fetal tissues were assessed by gas chromatography. The relative amount of fetal lung PFOB recovered by fractional distillation was highest in ligated (25%) and lower in unligated lungs (9%). Extrapulmonary PFOB was found in the fetal brain (2.0 +/- 0.7 ppm), but not in any other fetal or maternal tissues. Mean FLBW ratios were highest in ligated fetuses, followed by unligated fetuses and controls. PFOB partially displaced fetal lung water. PFOB was visible in the lungs of all treated fetuses. Fetal survival between manipulated and unmanipulated fetuses did not differ. After prenatal intrapulmonary instillation, some PFOB remains in the lung, even if the trachea is not ligated, and may exert distending pressure on the alveoli.

  17. Protective effect of heme oxygenase-1 on lung injury induced by erythrocyte instillation in rats.

    Science.gov (United States)

    Pang, Qing-Feng; Zhou, Qiao-Mei; Zeng, Si; Dou, Li-Dong; Ji, Yong; Zeng, Yin-Ming

    2008-09-05

    Intratracheal instillation of blood induces self-repaired acute lung injury. However, the mechanism of repair has been unclear. Heme-oxygenase (HO)-1, which catalyzes heme breakdown, acts as an inducible defense against oxidative stress and plays an important role in inflammation. The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells. Forty healthy, male Sprague-Dawley rats were randomly divided into five groups: normal group, saline group, erythrocyte group, erythrocyte+zinc-protoporphyrin (ZnPP, HO-1 inhibitor) group and saline+ZnPP group. At 2 days after intratracheal instillation of red cells, lung tissues and lavage samples were isolated for biochemical determinations and histological measurements. Histological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes. HO-1 was over-expressed in the erythrocyte group and in the erythrocyte + ZnPP group. Compared with the erythrocyte + ZnPP group, the levels of total protein, lactate dehydrogenase and tumor necrosis factor-alpha in the lavage were lower (P < 0.01), while the level of interleukin-10 was higher in the erythrocyte group (P < 0.01). HO-1 protects against erythrocyte-induced inflammatory injury in lung.

  18. Olfactory toxicity in rats following manganese chloride nasal instillation: A pilot study.

    Science.gov (United States)

    Foster, Melanie L; Rao, Deepa B; Francher, Taylor; Traver, Samantha; Dorman, David C

    2018-01-01

    Following inhalation, manganese travels along the olfactory nerve from the olfactory epithelium (OE) to the olfactory bulb (OB). Occupational exposure to inhaled manganese is associated with changes in olfactory function. This pilot study evaluated two related hypotheses: (a) intranasal manganese administration increases OE and OB manganese concentrations; and (b) intranasal manganese exposure impairs performance of previously trained rats on a go-no-go olfactory discrimination (OD) task. Male Fischer 344 rats were trained to either lever press ("go") in response to a positive conditioned stimulus (CS+: vanillin) or to do nothing ("no go") when a negative conditioned stimulus (CS-: amyl acetate) was present. Following odor training, rats were randomly assigned to either a manganese (200mM MnCl 2 ) or 0.9% saline treatment group (n=4-5 rats/group). Administration of either saline or manganese was performed on isoflurane-anesthetized rats as 40μL bilateral intranasal instillations. Rats were retested 48h later using the vanillin/amyl acetate OD task, then euthanized, followed by collection of the OE and OB. Manganese concentrations in tissue samples were analyzed by ICP-MS. An additional cohort of rats (n=3-4/group) was instilled similarly with saline or manganese and nasal and OB pathology assessed 48h later. Manganese-exposed rats had increased manganese levels in both the OE and OB and decreased performance in the OD task when compared with control animals. Histopathological evaluation of the caudal nasal cavity showed moderate, acute to subacute suppurative inflammation of the olfactory epithelium and submucosa of the ethmoid turbinates and mild suppurative exudate in the nasal sinuses in animals given manganese. No histologic changes were evident in the OB. The nasal instillation and OD procedures developed in this study are useful methods to assess manganese - induced olfactory deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

  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

    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...

  20. 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

  1. The value of perioperative mitomycin C instillation in improving subsequent bacillus calmette-guerin instillation efficacy in intermediate and high-risk patients with non-muscle invasıve bladder cancer: a prospective randomized study

    Directory of Open Access Journals (Sweden)

    Ömer Gülpinar

    2012-08-01

    Full Text Available PURPOSE: We evaluated the efficacy of perioperative mitomycin C (MMC instillation to improve subsequent bacillus Calmette-Guérin (BCG instillation efficacy in intermediate and high risk patients with non-muscle invasive bladder cancer (NMIBC. MATERIALS AND METHODS: From November 2004 to May 2006, 51 patients with intermediate or high risk NMIBC were enrolled in this prospective randomized trial. In group A, patients were treated with perioperative MMC (40 mg MMC in 40 mL saline was administered within 6 hours of surgery followed by delayed (at least 15 days from surgery BCG instillations (once a week for 6 weeks, 5 x 108 colony-forming units in 50 mL saline. Patients in group B were treated with delayed BCG instillations alone. The primary end points were recurrence-free interval and recurrence rate. RESULTS: There were 25 and 26 patients in groups A and B, respectively. Median follow-up was 41.3 months (range 8 to 64 in group A and 40.9 months (range 6 to 68 in group B. Recurrence rate was 36% (9 of 25 and 19.3% (5 of 26 in group A and B, respectively (p = 0.052. Median time to the first recurrence was 8 months in group A and 7 months in group B (p = 0.12. CONCLUSIONS: The present study showed no statistically significant difference in terms of recurrence rate and median time to first recurrence between intermediate or high-risk patients with NMIBC who were treated with early single dose instillation of MMC plus delayed BCG and those who were treated with only BCG.

  2. The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat.

    Science.gov (United States)

    Lasfargues, G; Lardot, C; Delos, M; Lauwerys, R; Lison, D

    1995-05-01

    Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous experimental studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture compared to Co or WC alone. The present study was undertaken to compare in the same animal model the delayed lung response after intratracheal administration of Co or WC-Co particles (cobalt particle 6.3 wt%). The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used a reference materials producing an acute toxic insult and a progressive fibrogenic response, respectively. Cellular (total and differential counts) and biochemical parameters (LDH, N-acetyl-beta-D-glucosaminidase, total protein, albumin, fibronectin, and hyaluronic acid) were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate that the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) or tungsten carbide alone (1, 5, 10 mg/ 100 g body wt) were very modest, if any. Following repeated intratracheal instillations (four administrations at 1-month interval), increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4 x 1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4 x 0.06 mg/100 g body wt) or WC (4 x 1 mg/100 g body wt). The mechanism of the fibrotic

  3. Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles.

    Science.gov (United States)

    Bai, Ru; Zhang, Lili; Liu, Ying; Li, Bai; Wang, Liming; Wang, Peng; Autrup, Herman; Beer, Christiane; Chen, Chunying

    2014-04-07

    Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (ptechniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. 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....

  5. 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

  6. 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

  7. 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

    , 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.......05), but not for the whole I or 4 wk postoperatively. Mixed-effects analysis with NONMEM revealed that pain scores were significantly lower (P observed, although a mild transient increase in liver enzymes was seen...

  8. Instillation of Hyaluronic Acid via Electromotive Drug Administration Can Improve the Efficacy of Treatment in Patients With Interstitial Cystitis/Painful Bladder Syndrome: A Randomized Prospective Study

    OpenAIRE

    Gülpınar, Ömer; Haliloğlu, Ahmet Hakan; Gökce, Mehmet İlker; Arıkan, Nihat

    2014-01-01

    Purpose In the treatment of interstitial cystitis, intravesical hyaluronic acid application may be suggested as a treatment option. In this randomized prospective study, the authors aimed to identify whether instilling the hyaluronic acid with electromotive drug administration (EMDA) would increase the tissue uptake and improve the efficacy. Materials and Methods The data of 31 patients who had been diagnosed with bladder pain syndrome/interstitial cystitis (BPS/IC) between 2004 and 2005 were...

  9. 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.

  10. Enhanced bioavailability of opiates after intratracheal administration

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-01

    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.

  11. 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.

  12. 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.

  13. Instillation of Hyaluronic Acid via Electromotive Drug Administration Can Improve the Efficacy of Treatment in Patients With Interstitial Cystitis/Painful Bladder Syndrome: A Randomized Prospective Study.

    Science.gov (United States)

    Gülpınar, Omer; Haliloğlu, Ahmet Hakan; Gökce, Mehmet İlker; Arıkan, Nihat

    2014-05-01

    In the treatment of interstitial cystitis, intravesical hyaluronic acid application may be suggested as a treatment option. In this randomized prospective study, the authors aimed to identify whether instilling the hyaluronic acid with electromotive drug administration (EMDA) would increase the tissue uptake and improve the efficacy. The data of 31 patients who had been diagnosed with bladder pain syndrome/interstitial cystitis (BPS/IC) between 2004 and 2005 were examined. The patients were randomized to two groups: patients in group A received hyaluronic acid directly with a catheter and patients in group B received hyaluronic acid with EMDA. The patients were followed for 24 months and the two groups were compared at certain time intervals. The primary end points of the study were visual analogue scale (VAS) score, global response assessment, and micturition frequency in 24 hours. There were 6 males and 25 females. The two groups were similar in baseline parameters. The decrease in VAS score and the micturition frequency in 24 hours were significantly lower with EMDA at months 6 and 12. The difference between the two groups was not significant at months 1 and 24. Also, treatment with EMDA, positive KCl test, and pretreatment voiding frequency >17 were associated with higher response rates. Hyaluronic acid installation is an effective glycosaminoglycan substitution therapy in patients with BPS/IC. Instillation of hyaluronic acid via EMDA can improve the efficacy of the treatment; however, lack of long-term efficacy is the major problem with this glycosaminoglycan substitution therapy.

  14. 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.

  15. Transoral intratracheal inoculation method for use with neonatal rats.

    Science.gov (United States)

    Martínez-Burnes, J; López, A; Lemke, K; Dobbin, G

    2001-04-01

    Studying the effects of toxic and infective compounds on the respiratory system requires a reliable method for delivering inoculum into the distal region of the lung. Although transoral intratracheal inoculation methods have been well documented for adult rats, to the authors' knowledge, a reliable method has not been validated for neonatal rats. The purpose of the study reported here was to develop a simple method for transoral inoculation in rat neonates. Seven-day-old Fischer 344 rats were anesthetized with halothane, and a spinal needle was inserted in the tracheal lumen, by use of illumination and a modified otoscope. Meconium was injected into the lungs as a marker, and the neonates were kept under close observation. After euthanasia at 24 h, lungs were removed and fixed in formalin, and the microscopic distribution of the inoculum was assessed in the left, right cranial, middle, median, and caudal lung lobes. Microscopic examination of lungs indicated that intratracheal inoculation was achieved in 100% of neonatal lungs and the inoculum was consistently distributed in the alveoli of all pulmonary lobes. Important complications or mortality were not observed in the neonates. Intratracheal inoculation of neonatal rats is possible by use of a modified otoscope for transoral illumination. This technique is simple and reproducible and ensures, without complications, widespread distribution of inoculum in the lungs of neonatal rats.

  16. 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.

  17. Comparison of efficacy of intraperitoneal instillation of bupivacaine ...

    African Journals Online (AJOL)

    Comparison of efficacy of intraperitoneal instillation of bupivacaine alone with bupivacaine – fentanyl and bupivacaine –tramadol combination for alleviation of post-operative pain following laparoscopic cholecystectomy: a randomized prospective study.

  18. Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin

    Directory of Open Access Journals (Sweden)

    Matsunaga Hirofumi

    2011-10-01

    Full Text Available Abstract Background Cluster of differentiation 69 (CD69, an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT and CD69-deficient (CD69-/- mice. Methods The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi. Lung inflammation in the acute phase (7 dpi was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1 in the lungs of BLM-treated mice. Results CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1 loss of body weight, (2 wet/dry ratio of lung, (3 cytokine levels in BALF, (4 histological evidence of lung injury, (5 lung collagen deposition, and (6 TGF-β1 mRNA expression in the lung. Conclusion The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

  19. Macau, World Capital for Gambling: A Longitudinal Study of a Youth Program Designed to Instill Positive Values

    Science.gov (United States)

    Luk, Andrew L.; Chan, W. U.; Hu, Sydney X. X.

    2013-01-01

    This 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. PMID:24350227

  20. Instillation of coarse ash particulate matter and lipopolysaccharide produces a systemic inflammatory response in mice

    Energy Technology Data Exchange (ETDEWEB)

    Finnerty, K.; Choi, J.E.; Lau, A.; Davis-Gorman, G.; Diven, C.; Seaver, N.; Linak, W.P.; Witten, M.; McDonagh, P.F. [Arizona Health Science Center, Tucson, AZ (United States)

    2007-07-01

    Coronary ischemic events increase significantly following a 'bad air' day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM > 2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 {mu} g), PM+ LPS10 (PM+ 10 {mu} g LPS), or PM+ LPS100 (PM+ 100 {mu} g LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-{alpha} and IL-6 both increased significantly with PM+ LPS100 treatment. Regarding plasma, TNF-{alpha} significantly increased in both PM+ LPS10 and PM+ LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM+ LPS100 group. The results of the follow-up study indicate that the responses to PM+ LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM > 2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.

  1. Intraocular penetration of sequentially instilled topical moxifloxacin, gatifloxacin, and levofloxacin

    Directory of Open Access Journals (Sweden)

    Koji Sugioka

    2009-10-01

    Full Text Available Koji Sugioka1, Masahiko Fukuda1, Shohei Komoto1, Motoki Itahashi1, Masakazu Yamada2, Yoshikazu Shimomura11Department of Ophthalmology, Kinki University School of Medicine, Osaka-Sayama City, Osaka, Japan; 2Division for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, JapanPurpose: The objective of the study was to compare the intraocular penetration levels of the newer fluoroquinolones, moxifloxacin, gatifloxacin, and levofloxacin in the rabbit’s cornea, aqueous humor, and conjunctiva after topical instillation.Methods: 0.5% moxifloxacin, 0.3% gatifloxacin, and 0.5% levofloxacin were instilled in random sequence in both eyes of nine New Zealand White rabbits at two-minute intervals. Instillation was repeated every 15 minutes for a total of three drops of each fluoroquinolone per eye. Three additional animals had only moxifloxacin instilled bilaterally using the same schedule. Sixty minutes after the final instillation, the rabbits were sacrificed for determination of corneal, aqueous humor, and conjunctival fluoroquinolone concentrations using highperformance liquid chromatography.Results: Moxifloxacin achieved significantly higher concentrations than levofloxacin and gatifloxacin in the cornea (P = 0.0102 and P = 0.0006, respectively, aqueous humor (P = 0.0015 and P < 0.0001, respectively, and conjunctiva (P = 0.0191 and P = 0.0236, respectively. Conclusions: 0.5% moxifloxacin eyedrops provided superior intraocular penetration in rabbits’ eyes compared with the two other fluoroquinolones, 0.5% levofloxacin and 0.3% gatifloxacin.Keywords: fluoroquinolone, gatifloxacin, levofloxacin, moxifloxacin, penetration, rabbit

  2. 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...

  3. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension

    NARCIS (Netherlands)

    J.N. van den Anker (John); A. de Jaegere (Anne)

    1998-01-01

    textabstractDoes endotracheal instilled prostacyclin (epoprostenol) improve oxygenation in preterm infants with persistent pulmonary hypertension? Four preterm infants were studied. Prostacyclin (50 ng x kg(-1)) was injected as an endotracheal bolus. In two patients the

  4. 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

  5. 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.

  6. Successful treatment of intratracheal cuterebrosis in two cats.

    Science.gov (United States)

    Dvorak, L D; Bay, J D; Crouch, D T; Corwin, R M

    2000-01-01

    Two cases of feline intratracheal myiasis due to Cuterebra spp. larvae are reported. Both cats presented with inspiratory dyspnea and a nonproductive cough. One larva was successfully removed during thoracotomy, and the other was removed during bronchoscopy using forceps passed through a bronchoscope operating channel. Clinical signs were alleviated following removal of the larvae.

  7. Alleviating effects of artificial tear instillation on S-1-induced ocular toxicity in dogs.

    Science.gov (United States)

    Kanie, Shohei; Fujieda, Mitsuhiro; Hitotsumachi, Tomoaki; Suzuki, Satoshi; Morita, Fumio; Hakoi, Kazuo; Yasui, Hirofumi

    2017-01-01

    S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and resectable gastric cancer. However, the extensive use of S-1 in clinical practice results in watery eyes, a serious clinical problem, which worsens patients' quality of life. Although repeated instillation of artificial tears is recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not been established. In the present study, we evaluated the alleviating effects of repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1 for up to 21 days. Five drops of artificial tears were instilled to the left eye, eight times daily, within 6 hr after S-1 administration. The mean cornea staining score tended to be low in the left eye with repeated artificial tear instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was more than 2-fold lower than that of the right eye. The incidence of dogs indicating normal tear drainage increased and stenosed tear drainage decreased by repeated artificial tear instillation. In conclusion, we demonstrated that artificial tear instillation can alleviate corneal surface damage induced by S-1 in dogs.

  8. 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

  9. Review of toxicity studies of carbon nanotubes.

    Science.gov (United States)

    Kobayashi, Norihiro; Izumi, Hiroto; Morimoto, Yasuo

    2017-09-28

    We reviewed studies on pulmonary, reproductive, and developmental toxicity caused by carbon nanotubes (CNTs). In paricular, we analyzed how CNT exposure affects the several processes of pulmonary toxicity, including inflammation, injury, fibrosis, and pulmonary tumors. In pulmonary toxicity, there are various processes, including inflammation, injury, fibrosis, respiratory tumor in the lungs, and biopersistence of CNTs and genotoxicity as tumor-related factors, to develop the respiratory tumor. We evaluated the evidence for the carcinogenicity of CNTs in each process. In the fields of reproductive and developmental toxicity, studies of CNTs have been conducted mainly with mice. We summarized the findings of reproductive and developmental toxicity studies of CNTs. In animal studies, exposure to CNTs induced sustained inflammation, fibrosis, lung cancer following long-term inhalation, and gene damage in the lung. CNTs also showed high biopersistence in animal studies. Fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offsprings after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported in mice-administered multi-walled carbon nanotubes (MWCNTs). Single-walled carbon nanotubes (SWCNTs) appeared to be embryolethal and teratogenic in mice when given by intravenous injection; moreover, the tubes induced death and growth retardation in chicken embryos. CNTs are considered to have carcinogenicity and can cause lung tumors. However, the carcinogenicity of CNTs may attenuate if the fiber length is shorter. The available data provide initial information on the potential reproductive and developmental toxicity of CNTs.

  10. 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.

  11. Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.

    Directory of Open Access Journals (Sweden)

    Mark A Miller

    Full Text Available Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane vs. parenteral (ketamine/xylazine anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

  12. On- and post-treatment symptom relief by repeated instillations of heparin and alkalized lidocaine in interstitial cystitis.

    Science.gov (United States)

    Nomiya, Akira; Naruse, Takashi; Niimi, Aya; Nishimatsu, Hiroaki; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

    2013-11-01

    To examine outcomes of intravesical instillations of heparin and alkalized lidocaine in patients with interstitial cystitis. Patients with interstitial cystitis refractory to conventional therapies were given a solution of 20 000 U heparin, 5 mL 4% lidocaine and 25 mL 7% sodium bicarbonate, intravesically, weekly for 12 weeks consecutively. The treatment was regarded as "effective", when patients rated "slightly improved" or "better" on a seven-graded scale of global response assessment. Other assessment measures included O'Leary and Sant's symptom index and problem index, visual analog scale for pain, and frequency volume chart variables. A total of 32 patients were enrolled in the study. The average age was 63.3 years. All participants had received hydrodistension 2.2 times on average, and fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria. The therapy was effective in 60.0% of the patients at the fourth instillation, in 76.7% at the last instillation, and 90.0%, 46.7% and 16.7% at 1, 2 and 6 months after the last instillation, respectively. Most of other assessment measures improved significantly at the fourth instillation and further beyond until the end of therapy. On termination of therapy, the efficacy gradually diminished, yet mostly maintained statistical significance by 2 months post-instillation. No severe adverse events occurred. A 12-week course of weekly intravesical instillations of heparin combined with alkalized lidocaine is safe and effective in relieving symptoms in interstitial cystitis patients. The effect of the treatment is maintained for 6 months. Further studies are required to optimize the number of instillations and maintenance intervals in order to maximize the therapeutic potential of simple or combined instillations in the management of interstitial cystitis. © 2013 The Japanese Urological Association.

  13. Instilling Service Learning to Undergraduate Business Students: A Case Study Approach to Understanding Business-Related Concepts with the Use of Kiva

    Science.gov (United States)

    Grotrian-Ryan, Sheri; Ryan, Kyle; Jackson, Alan

    2016-01-01

    Higher education continues to place an emphasis on service-learning, specifically within business and management sciences (Kenworthy-U'Ren & Peterson, 2005). A local academic business organization at a small institution chose to embark on a service-learning endeavor. The purpose of this study was for business majors, active in Phi Beta Lambda…

  14. 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.

  15. Which is best method for instillation of topical therapy to the upper urinary tract? An in vivo porcine study to evaluate three delivery methods

    Directory of Open Access Journals (Sweden)

    Zhenbang Liu

    Full Text Available ABSTRACT Purpose: To compare the staining intensity of the upper urinary tract (UUT urothelium among three UUT delivery methods in an in vivo porcine model. Materials and methods: A fluorescent dye solution (indigo carmine was delivered to the UUT via three different methods: antegrade perfusion, vesico-ureteral reflux via in-dwelling ureteric stent and retrograde perfusion via a 5F open-ended ureteral catheter. Twelve renal units were tested with 4 in each method. After a 2-hour delivery time, the renal-ureter units were harvested en bloc. Time from harvesting to analysis was also standardised to be 2 hours in each arm. Three urothelium samples of the same weight and size were taken from each of the 6 pre-defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and distal ureter and the amount of fluorescence was measured with a spectrometer. Results: The mean fluorescence detected at all 6 predefined points of the UUT urothelium was the highest for the retrograde method. This was statistically significant with p-value less than <0.05 at all 6 points. Conclusions: Retrograde infusion of UUT by an open ended ureteral catheter resulted in highest mean fluorescence detected at all 6 pre-defined points of the UUT urothelium compared to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents indicating retrograde method ideal for topical therapy throughout the UUT urothelium. More clinical studies are needed to demonstrate if retrograde method could lead to better clinical outcomes compared to the other two methods.

  16. Which is best method for instillation of topical therapy to the upper urinary tract? An in vivo porcine study to evaluate three delivery methods

    Science.gov (United States)

    Liu, Zhenbang; Ng, Junxiang; Yuwono, Arianto; Lu, Yadong; Tan, Yung Khan

    2017-01-01

    ABSTRACT Purpose: To compare the staining intensity of the upper urinary tract (UUT) urothelium among three UUT delivery methods in an in vivo porcine model. Materials and methods: A fluorescent dye solution (indigo carmine) was delivered to the UUT via three different methods: antegrade perfusion, vesico-ureteral reflux via in-dwelling ureteric stent and retrograde perfusion via a 5F open-ended ureteral catheter. Twelve renal units were tested with 4 in each method. After a 2-hour delivery time, the renal-ureter units were harvested en bloc. Time from harvesting to analysis was also standardised to be 2 hours in each arm. Three urothelium samples of the same weight and size were taken from each of the 6 pre-defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and distal ureter) and the amount of fluorescence was measured with a spectrometer. Results: The mean fluorescence detected at all 6 predefined points of the UUT urothelium was the highest for the retrograde method. This was statistically significant with p-value less than <0.05 at all 6 points. Conclusions: Retrograde infusion of UUT by an open ended ureteral catheter resulted in highest mean fluorescence detected at all 6 pre-defined points of the UUT urothelium compared to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents indicating retrograde method ideal for topical therapy throughout the UUT urothelium. More clinical studies are needed to demonstrate if retrograde method could lead to better clinical outcomes compared to the other two methods. PMID:29039888

  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. Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis.

    Science.gov (United States)

    Galvão, Andre M; Wanderley, Marcela S O; Silva, Roberto A; Filho, Carlos A M; Melo-Junior, Mário R; Silva, Luciano A; Streck, Emílio L; Dornelas de Andrade, Armele F; Souza Maia, Maria B; Barbosa de Castro, Celia M M

    2014-10-01

    Recent studies showed that both sepsis and antibiotic therapy are associated with cell death and linked to reactive oxygen species generation. This study investigated the effects of intratracheal administration of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in the treatment of sepsis-induced lung injury. Ninety-six male Wistar rats subjected to sepsis were treated with ceftriaxone plus NAC with or without vitamins C and E and compared to appropriate controls. As an index of oxidative damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide anion were measured, as well as superoxide dismutase and catalase. Histopathological alterations and mortality rate were also analyzed. Twenty-four hours after sepsis induction, markers of oxidative stress increased in all lungs examined. Ceftriaxone plus intratracheal combination of NAC, vitamins C and E decreased lung injury in infected animals by reducing superoxide anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and restored the redox status (7.5 times). This therapy also reduced the imbalance of antioxidant enzymes activities and attenuated the alveolar architectural disorganization, inflammatory cell infiltration and pulmonary oedema. Survival increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus antioxidants. Ceftriaxone plus intratracheal co-administration of antioxidants provides better protection, by decreasing pulmonary oxidative stress, limiting histophatological alterations and improving survival. Antioxidants should be explored as a co-adjuvant in the treatment of severe lung injury. © 2014 Asian Pacific Society of Respirology.

  19. 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

  20. Safety and Feasibility of Intravesical Instillation of Botulinum Toxin-A in Hydrogel-based Slow-release Delivery System in Patients With Interstitial Cystitis-Bladder Pain Syndrome: A Pilot Study.

    Science.gov (United States)

    Rappaport, Yishai H; Zisman, Amnon; Jeshurun-Gutshtat, Michal; Gerassi, Tami; Hakim, Gil; Vinshtok, Yuri; Stav, Kobi

    2018-01-04

    To assess the feasibility and the safety of a mixture instillation of TC-3 gel, a novel reverse-thermal gelation hydrogel, and botulinum toxin-A (BTX-A) for the treatment of interstitial cystitis-bladder pain syndrome (IC/BPS). TC-3 gel-BTX-A mix is instilled into the bladder as liquid, solidifies because of body heat, and gradually dissolves to release BTX-A for several hours. A single intravesical instillation of 200 U BTX-A premixed with 40 mL TC-3 gel was delivered to the bladder. Adverse events and preliminary efficacy outcome measures were assessed: bladder diary, visual analog scale (VAS) for pain, and Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) at baseline and at 2, 6, and 12 weeks. A total of 15 severely symptomatic patients with IC/BPS (ICSI and ICPI score ranges 12-19 and 12-16, respectively; median VAS = 7) were enrolled (male and female = 4 and 11, ages 24-76). In terms of safety, no increase in VAS score was noted at instillation. All adverse events were transient and mild, the most common being temporary mild constipation (n = 4, 26%). The mean VAS at baseline vs week 12 was 6.6 ± 2.7 vs 5.3 ± 2.8 (P = .044). The mean ICSI and ICPI scores were reduced at week 12 compared with baseline (15.4 ± 2.4 vs 12.9 ± 4.3, P = .004, and 14.8 ± 1.4 vs 11.9 ± 4.0, P = .004, respectively). The mean number of voids per night at baseline decreased for 6 weeks (3.3 ± 2.1 vs 1.8 ± 0.9, P = .046) and then returned to baseline level at week 12. Intravesical instillation of a TC-3 gel-BTX-A mixture is safe and tolerable. Preliminary results suggest temporary efficacy lasting for a few weeks. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. 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.

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

    Science.gov (United States)

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

    2010-06-01

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

  3. 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

  4. Prophylactic yttrium 90 instillation in the case of bladder carcinomas Jewett 0

    International Nuclear Information System (INIS)

    Donn, F.; Becker, H.; Kaufmann, J.; Montz, H.R.

    1982-01-01

    We performed in a prospective pilot study the treatment of bladder cancer Jewett 0 by 90-Yttrium-instillation. The chief aim is to prevent recurrent tumour formation. Our technique delivers an average dose of ca. 3000 rad to the surface of the bladder. The complication rate was moderate. The results were encouraging because the recurrent tumour formation was distinctly reduced. (orig.) [de

  5. 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.

  6. [Our experience with 1 mg BCG vaccine instillation in T1 stage cancer of the bladder].

    Science.gov (United States)

    Rivera, P; Orio, M; Hinostroza, J; Venegas, P; Pastor, P; Gorena, M; Lagos, M; Pinochet, R

    1999-10-01

    We studied 67 patients with bladder cancer in stage T1, with terminated BCG treatment and in pursuit. No stage Ta neither carcinoma in situ was included. The protocol was: beginning of treatment upon retiring vesical catheter, instilation of 1 mg of liofilized BCG vaccine (16 x 10(6) bacilles) in 40-50 ml of intravesical saline solution. A weekly instilation during the first month. An instilation each 15 days during the second and third month and one monthly until complete 12 months of treatment. Also was carried out an study of T lymphocites and cytokines. The average followup of the 67 patients treated was 51.3 months. 17 patients relapses (25.4%). A 33% were grade 3 and 27% grade 2. Like complications there was a case of inguinal TBC adenititis, 2 TBC prostatitis, 2 TBC cistitis and 5 cases of slight disuric syndrome. The study of subpopulations of lymphocites in peripheral blood demonstrated a significant increase of CD3 and CD4/CD8 ratio. The interleukin 2 measurement in serum also increased significantly after the BCG instilations. Our protocol gets similar results to the higher doses, but with minimal complications diminishing the relapses of the tumors in stage T1. A monthly maintenance dose would help to maintain immunity.

  7. 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.

  8. Gentamicin bladder instillations decrease symptomatic urinary tract infections in neurogenic bladder patients on intermittent catheterization.

    Science.gov (United States)

    Cox, Lindsey; He, Chang; Bevins, Jack; Clemens, J Quentin; Stoffel, John T; Cameron, Anne P

    2017-09-01

    This study aimed to determine if gentamicin bladder instillations reduce the rate of symptomatic urinary tract infection (UTI) in neurogenic bladder (NGB) patients on intermittent self-catheterization (ISC) who have recurrent UTIs. Secondary aims were to examine the effects of intravesical gentamicin on the organism resistance patterns. We retrospectively reviewed our prospective NGB database. Inclusion criteria were NGB patients performing ISC exclusively for bladder drainage with clinical data available for six months before and six months after initiating prophylactic intravesical gentamicin instillations. Symptomatic UTIs were defined as symptoms consistent with UTI plus the need for antibiotic treatment. Twenty-two patients met inclusion criteria; etiology of NGB was 63.6% spinal cord injury, 13.6% multiple sclerosis. Median time since injury/diagnosis was 14 years and 6/22 (27.3%) had undergone urological reconstruction. Patients had fewer symptomatic UTI's (median 4 vs. 1 episodes; pbladder instillations decrease symptomatic UTI episodes and reduce oral antibiotics in patients with NGB on ISC who were suffering from recurrent UTIs. Antibiotic resistance decreased while on gentamicin instillations.

  9. Extracellular matrix alterations after blood instillation in tunica albuginea of rats.

    Science.gov (United States)

    Cohen, David J; Oliveira, André V; Theodoro, Théresè R; Petri, Giuliana; Melo, Carina M; Cavalheiro, Renan P; Nader, Helena B; Mader, Ana M; Pinhal, Maria A S; Glina, Sidney

    2017-12-15

    The cause of Peyronie's disease (PD) is still not completely understood. The objective of this study, therefore, was to analyze the histological and biochemical alterations that occur after the instillation of blood in the tunica albuginea (TA) of rats with an emphasis on the remodeling process of ECM. Thirty male Wistar rats were divided into 4 groups: two control groups with instillation of distilled water in TA followed by penectomy after 15 days or 45 days, respectively and two experimental groups with instillation of blood in TA followed by penectomy after 15 days or 45 days, respectively. Histological, immunofluorescent and immunohistochemical analyses were performed. The higher presence of fibrotic tissue in rats injected with blood demonstrated alterations in TA similar to inflammation found in PD. The increased expression of TGF-β, MMP9, HPSE, and biglycan associated with the decreased expression of syndecan-1 and aggrecan in the experimental groups suggested an enhancement in the remodeling of ECM. The results contribute to show that blood instillation on TA appears to trigger alterations in the ECM similar to the ones found in inflammatory diseases such as PD.

  10. 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.

  11. 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.)

  12. Intratracheally administered pathogen-associated molecular patterns affect antibody responses of poultry.

    Science.gov (United States)

    Ploegaert, T C W; De Vries Reilingh, G; Nieuwland, M G B; Lammers, A; Savelkoul, H F J; Parmentier, H K

    2007-08-01

    Various potential immune-modulating microbially derived pathogen-associated molecular patterns (PAMP), or so called homotopes, are present in high concentrations in the environment of food animals. In previous studies, intravenously administered PAMP had variable effects on specific primary and secondary immune responses of poultry to systemically administered antigens. In the present study, we evaluated the effects of intratracheal (i.t.) challenge with the PAMP lipopolysaccharide, lipoteichoic acid (LTA), and Zymosan-A (containing 1,3 beta-glucan) on primary and secondary (total) antibody (Ab) responses and (isotype) IgM, IgG, and IgA responses to systemically administered human serum albumin (HuSA), and Ab titers to infectious bursal disease (Gumboro virus) and infectious bronchitis vaccines in layer hens at 9 and 22 wk of age. Birds were challenged via the trachea with PAMP for 5 consecutive days prior to primary and secondary immunization with HuSA. Intratracheally administered LTA and, to a minor extent, lipopolysaccharide significantly enhanced secondary total and IgG Ab responses to HuSA. 1,3 beta-Glucan did not significantly affect Ab responses to HuSA. All birds challenged with PAMP showed a decreased BW. Higher total Ab titers to infectious bursal disease and infectious bronchitis were found in birds challenged with LTA. The present results indicate that i.t. administered PAMP affect the humoral immune responsiveness of poultry, which may lead to an enhanced status of immune reactivity. Furthermore, our results suggest that the hygienic status of the environment influences BW (gain). The consequences of immune modulation by airborne PAMP or hygienic conditions in chicken husbandry for vaccine delivery and immune responsiveness of poultry are discussed.

  13. 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.

  14. 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.......05), but not for the whole 1 or 4 wk postoperatively. Mixed-effects analysis with NONMEM revealed that pain scores were significantly lower (P observed, although a mild transient increase in liver enzymes was seen...

  15. Nonvalue of Neomycin Instillation after Intermittent Urinary Catheterization

    Science.gov (United States)

    Haldorson, Alice M.; Keys, Thomas F.; Maker, Myron D.; Opitz, Joachim L.

    1978-01-01

    This study evaluated weekly urine cultures of patients with neurogenic bladder disease who underwent intermittent urinary catheterization for bladder retraining. One group of 53 patients in 1974 received regular instillations of 0.1% neomycin after each catheterization. A similar group of 55 patients in 1975 did not receive neomycin and constituted a control group. Distribution of age, sex, diagnosis, and duration of bladder retraining was comparable in both groups. Quantitative bacterial colony counts of 104 to 105 or greater per ml of urine were considered significant. There was no difference in the incidence of bacteriuria between the neomycin-treated group and the control group (53 versus 49%, respectively), and most patients in each group had colony counts >105/ml. Escherichia coli was seen less frequently in neomycin-treated patients (43.4 versus 62.5%), but a greater percentage of infections due to Pseudomonas aeruginosa, group D streptococci, and yeasts was noted in the neomycin-treated group than in the control group (41.5 versus 22.5%). PMID:360984

  16. [Negative Pressure Wound Therapy with Instillation in the Treatment of Critical Wounds].

    Science.gov (United States)

    Gathen, M; Petri, M; Krettek, C; Omar, M

    2016-04-01

    In recent decades, negative pressure wound therapy (NPWT) has become the gold standard in the treatment of infected wounds. Negative pressure wound therapy with instillation (NPWTi) is a new development, that combines conventional NPWT with instillation of fluids. The purpose of this study was to review the results of current literature on the clinical use of NPWTi in acute and chronic wounds. A literature search was performed using Pubmed and the Cochrane Library, including articles in English and German. The data suggest that NPWTi is a promising therapeutic option in the treatment of wounds, and applicable in various fields. NPWTi appears to be a useful adjunct in the treatment of critical wounds. However, data from prospective randomised trials to support the validity of the results are sparse. Georg Thieme Verlag KG Stuttgart · New York.

  17. 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.

  18. 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

  19. Lavage drain extension for local anaesthetic instillation into ...

    African Journals Online (AJOL)

    Thirty-one patients who had undergone abdominoplasty procedures were selected for instillation of a local anaesthetic preparation, ropivacaine (Naropin, AstraZeneca) into the wound site on day 1 and 2 after surgery, followed by early mobilisation. Efficacy of the system, patient comfort and mobilisation were documented.

  20. The effect of normal saline instillation on cardiorespiratory ...

    African Journals Online (AJOL)

    The effect of normal saline instillation on cardiorespiratory parameters in intubated cardiothoracic patients. ... S Schmollgruber, JC Bruce, JC Rachidi, PJ Becker ... Even though the patient population was at high risk of haemodynamic disturbance and hypoxia during this manoeuvre, there was no meaningful clinical effect; ...

  1. 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.

  2. 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

  3. 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

  4. Intratracheal catheter suction removes the same volume of meconium with less impact on desaturation compared with meconium aspirator in meconium aspiration syndrome.

    Science.gov (United States)

    Akazawa, Yohei; Ishida, Takefumi; Baba, Atsushi; Hiroma, Takehiko; Nakamura, Tomohiko

    2010-08-01

    To evaluate the impact of suction technique on the rate of meconium removal, oxygenation, and hemodynamics in an animal experimental model of meconium aspiration syndrome (MAS). MAS was induced in ventilated rabbits using 3.5 ml/kg of 20% human meconium. Tracheal suction with either catheter suction (CS) or meconium aspirator (MA) was performed after meconium instillation. Percentage of meconium collection rate, PaO(2) trends for 2h after tracheal suction, and acute-phase SpO(2) trends were compared between CS and the other three groups, the tube was withdrawn while meconium was aspirated with an MA, then the trachea was reintubated 5, 10 or 15s after suctioning of meconium. Percentage of meconium collection rate and PaO(2) showed no significant differences between groups. The MA group taking 15s for reintubation after meconium suctioning, showed a significantly lower acute-phase SpO(2) than the CS group (Por=90% was also longer in the MA group taking 15s for reintubation than in the CS group (Pmeconium with less impact on desaturation compared with meconium aspiration in an animal model of MAS. Intratracheal CS may be benefit to remove meconium in non-vigorous infants with meconium-stained amniotic fluid at birth. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Analysis of Japanese Patients Treated with or without Long-Term Epirubicin Plus Ara-C Intravesical Instillation Therapy for Low-Grade Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Tomonori Kato

    2015-01-01

    Full Text Available The high incidence of tumor recurrence following transurethral resection (TUR represents a major problem encountered in the management of bladder cancer. This study examined the efficacy of intravesical chemotherapy in superficial bladder cancer. We retrospectively analyzed 90 Japanese cases with low-grade superficial transitional cell carcinoma (stage T1, grades 1 and 2 who were rendered tumor-free by TURBT (TUR of bladder tumor and who thereafter were treated with or without intravesical chemotherapy. Among them, instillation was terminated in 2 patients due to adverse effects (severe but reversible chemical cystitis. Remaining 88 patients were divided into 2 groups according to therapy: the TURBT-only group (n=46, defined as patients treated with TURBT alone, and the Instillation group (n=42, defined as patients treated with weekly intravesical instillation therapies using epirubicin plus Ara-C. Recurrence-free rate was significantly higher in the Instillation group than in the TURBT-only group (p=0.02, HR = 0.457. The 5-year recurrence-free rate was 58.5% for the Instillation group and 38.6% for the TURBT-only group. Our instillation schedule represents the most intensive regimen among previously reported therapies and resulted in a 54.3% decrease in incidence of tumor recurrence. We believe that the results of this study could provide useful information on management of bladder cancer.

  6. Metallic intratracheal stent application on relapsing polychondritis with severe tracheobronchial malacia

    International Nuclear Information System (INIS)

    Ao Guokun; Zhao Weiguo; Guo Qinyun; Huang Qin

    2007-01-01

    Objective: To evaluate the therapeutic and adverse effects of metallic intratracheal stent placement in relapsing polychondritis with severe tracheobronchial malaeia. Methods: Five tracheal stents had been implanted in three patients with tracheobronchial malaeia. One patient was implanted with two tubular stents in trachea and one 'Y' shaped stent for bilateral bronchi. Another patient used a tubular stent in total tracheal segment. The last patient used a tubular stent in the upper segment of trachea. Results: All the stents were implanted successfully with obvious improvement of dyspnea after the treatment. Conclusions: Metallic intratracheal stent placement can really relieve symptoms and improve the life quality in patients with tracheobronchial malacia caused by relapsing polychondritis. (authors)

  7. Developing cell therapy techniques for respiratory disease: intratracheal delivery of genetically engineered stem cells in a murine model of airway injury

    Science.gov (United States)

    Leblond, Anne-Laure; Naud, Patrice; Forest, Virginie; Gourden, Clothilde; Sagan, Christine; Romefort, Bénédicte; Mathieu, Eva; Delorme, Bruno; Collin, Christine; Pagès, Jean-Christophe; Sensebé, Luc; Pitard, Bruno; Lemarchand, Patricia

    2009-01-01

    Over the past decade, interest has increased in the use of exogenous stem cells to optimize lung repair and serve as carriers of a therapeutic gene for genetic airway disease such as cystic fibrosis. We investigated the survival and the engraftment of exogenous stem cells after intratracheal injection, in a murine model of acute epithelial airway injury already used in gene therapy experiments on cystic fibrosis. Embryonic stem cells and mesenchymal stem cells were intratracheally injected 24hr after 2% polidocanol administration, when epithelial airway injury was maximal. Stem cells were transfected with reporter genes immediately prior to administration. Reporter gene expression was analyzed in trachea-lungs and bronchoalveolar lavages using non-fluorescent, quantitative and sensitive methods. ELISA quantitative results showed that 0.4 to 5.5% stem cells survived in the injured airway. Importantly, no stem cells survived in healthy airway or in the epithelial lining fluid. Using X-Gal staining, transduced mesenchymal stem cells were detected in injured trachea and bronchi lumen. When the epithelium was spontaneously regenerated, the in vivo amount of engrafted mesenchymal stem cells from cell line decreased dramatically. No stem cells from primary culture were located within lungs at 7 days. This study demonstrated the feasibility of the intratracheal cell delivery for airway diseases with acute epithelial injury. PMID:19606934

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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)

  14. 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.

  15. 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.

  16. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder.

    Science.gov (United States)

    Elzein, Fatehi; Albogami, Nada; Saad, Mustafa; El Tayeb, Nazik; Alghamdi, Abdullah; Elyamany, Ghaleb

    2016-01-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) remains a first-line treatment for superficial transitional cell carcinoma of the bladder. Although its use is relatively safe, severe complications such as granulomatous hepatitis, osteomyelitis, pneumonitis, and sepsis occur in few patients. Complications of intravesical instillation of BCG can be local or systemic, with early or late presentation. Here, we report an 88-year-old man who developed fever, rigors, and episodes of syncope following fourth intravesical BCG instillation for the treatment of superficial transitional cell carcinoma of the bladder. Pancytopenia, disseminated intravascular coagulation, ground glass appearance on computerized tomography of the chest scan in addition to multiple bone marrow granulomas, suggested the diagnosis of disseminated BCG infection. All these features recovered on antituberculosis treatment. Our case study highlights the importance of early recognition and prompt treatment of patients with disseminated BCG infection following intravesical instillation. Although isolation of mycobacterium is desirable to make the diagnosis, it is not unusual to have negative smears and cultures and this should not be used to dismiss the possibility of BCG infection.

  17. 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

  18. 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

    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...

  19. 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

  20. 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.

  1. 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

  2. Comparison of Three Different Administration Positions for Intratracheal Beractant in Preterm Newborns with Respiratory Distress Syndrome.

    Science.gov (United States)

    Karadag, Ahmet; Ozdemir, Ramazan; Degirmencioglu, Halil; Uras, Nurdan; Dilmen, Ugur; Bilgili, Gokmen; Erdeve, Omer; Cakir, Ufuk; Atasay, Begum

    2016-04-01

    The aim of this study was to compare the efficacy and adverse effects of various intratracheal beractant administration positions in preterm newborns with respiratory distress syndrome. This study was performed on preterm newborns with respiratory distress syndrome. The inclusion criteria were being between 26 weeks and 32 weeks of gestational age, having a birth weight between 600 g and 1500 g, having received clinical and radiological confirmation for the diagnosis of respiratory distress syndrome (RDS) within 3 hours of life, having been born in one of the centers where the study was carried out, and having fractions of inspired oxygen (FiO2) ≥ 0.40 to maintain oxygen saturation by pulse oximeter at 88-96%. Beractant was administered in four positions to Group I newborns, in two positions to Group II, and in neutral position to Group III. Groups I and II consisted of 42 preterm infants in each whereas Group III included 41 preterm infants. No significant differences were detected among the groups with regards to maternal and neonatal risk factors. Groups were also similar in terms of the following complications: patent ductus arteriosus (PDA), pneumothorax, intraventricular hemorrhage (IVH), chronic lung disease (CLD), retinopathy of prematurity (ROP), necrotising enterocolitis (NEC), death within the first 3 days of life, death within the first 28 days of life, and rehospitalization within 1 month after discharge. Neither any statistically significant differences among the parameters related with surfactant administration, nor any significant statistical differences among the FiO2 levels and the saturation levels before and after the first surfactant administration among the groups were determined. In terms of efficacy and side effects, no important difference was observed between the recommended four position beractant application, the two position administration, and the neutral position. Copyright © 2016. Published by Elsevier B.V.

  3. Studies on the biological behaviour of uranium-plutonium mixed oxide aerosols: Inhalation experiments with rats and in vitro studies with alveolar macrophages

    International Nuclear Information System (INIS)

    Mueller, H.L.; Drosselmeyer, E.; Hotz, G.; Seidel, A.; Thiele, H.; Pickering, S.; Ray, I.C.

    1987-02-01

    The retention of spherical and of irregularly shaped (U, Pu) mixed oxides in rat lung was analyzed after inhalation and intratracheal instillation. Their biological behaviour was relatively independent of particle shape and application route with only a few percent of radioactivity being transferred to other organs. In vivo and in vitro uptake and intracellular distribution in rat and bovine alveolar macrophages were analyzed as dependent on various parameters. In addition, detailed electron microscopic studies were performed demonstrating particles within membrane limited vacuoles as well as lying free in the cytoplasm. Under in vitro conditions the uptake process was finished after a few hours. After differential centrifugation of lung or macrophage homogenates the particles sedimented in the first (1000 g) fraction. (orig.) [de

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Health-Care Associated Mycobacterium bovis-BCG Infection in Cancer Patients without prior BCG Instillation.

    Science.gov (United States)

    Meije, Y; Martínez-Montauti, J; Caylà, J A; Loureiro, J; Ortega, L; Clemente, M; Sanz, X; Ricart, M; Santomà, M J; Coll, P; Sierra, M; Calsina, M; Vaqué, M; Ruiz-Camps, I; López-Sánchez, C; Montes, M; Ayestarán, A; Carratalà, J; Orcau, A

    2017-05-29

    Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is widely used as adjunctive therapy for superficial bladder cancer. Intravesical administration of BCG has been associated with systemic infection. Disseminated infection due to M. bovis is otherwise uncommon. After identification of three patients with health-care associated BCG infection (HCBCGI) who had never received intravesical BCG administration, an epidemiologic study was performed. All patients with HCBCGI in the Barcelona tuberculosis (TB) program were reviewed from January 1, 2005 to December 31, 2015 searching for infections caused by M. bovis-BCG. Patients with HCBCGI who had not received intravesical BCG instillation were selected and the source of infection was investigated. Nine oncology patients with infection caused by M. bovis-BCG were studied. All had permanent central venous catheters. Catheter maintenance was performed at four different outpatient clinics in the same room in which other patients underwent BCG instillations for bladder cancer without required biological precautions. All patients developed pulmonary TB, either alone or with extrapulmonary disease. Catheter-related infection was considered the mechanism of acquisition based on the epidemiologic association and positive catheter cultures for BCG in patients in whom mycobacterial cultures were performed. Physicians should be alerted to the possibility of TB due to nosocomially acquired, catheter-related infections with M. bovis-BCG in patients with indwelling catheters. This problem may be more common than expected in centers providing BCG therapy for bladder cancer without adequate precautions.

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

    Science.gov (United States)

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

    2016-07-01

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

  11. 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...

  12. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    Science.gov (United States)

    Lam, Chiu-wing; James, John T.

    2009-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

  13. 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.

  14. Systemic BCG-osis following intravesical BCG instillation for bladder carcinoma.

    Science.gov (United States)

    Liaw, Frank; Tan, Yan Yu; Hendry, David

    2017-10-01

    Intravesical instillation of Bacillus Calmette-Guérin (BCG) has been shown to be an effective form of immunotherapy for bladder cancer. This case report describes a patient who develops systemic BCG-osis following intravesical BCG instillation and demonstrates the importance of being aware of more severe complications associated with BCG immunotherapy.

  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. [Comparative study of the behavior of particulate emissions from diesel and gasoline engines in animal lungs: elimination rate and induction of benzo(a)pyrene hydroxylase and ethoxycoumarin de-ethylase].

    Science.gov (United States)

    Dehnen, W; Tomingas, R; Kouros, M; Mönch, W

    1985-03-01

    The emitted particulates of five diesel-engined and two gasoline-engined passenger cars were investigated for the elimination rate from hamster lungs after intratracheal instillation. In addition extracts of these particulates were studied for their influence on the mixed function oxidase activity (MFO; Benzo(a)pyrene Hydroxylase, Ethoxycoumarine Deethylase). Differences in the elimination rates of diesel soot and particulates from gasoline engines were not found. Compared with the blanc the extracts of diesel soot from two vehicles proved to give a moderate increase of the MFO activity, but a significant difference to the blanc was observed with the extracts of the gasoline engines. It should be mentioned that the effects were studied without taking into account the quantitative relations of the emissions in the ambient air. However, the amounts of particulates were extremely high in relation to the natural conditions. In the limits of our test model there is no indication of a higher toxicity of diesel-emissions.

  17. Effect of Kushen injection in combined with continuing nursing on the patients with instillation therapy after bladder cancer surgery

    Directory of Open Access Journals (Sweden)

    Rui-Xia Han

    2016-07-01

    Full Text Available Objective: To observe the effect of Kushen injection in combined with continuing nursing on the patients with instillation therapy after bladder cancer surgery. Methods: A total of 60 patients with bladder cancer who were admitted in our hospital from January, 2013 to January, 2015 for instillation therapy were included in the study and were randomized into the observation group and the control group. The patients in the two groups were given routine THP instillation therapy. On this basis, the patients in the observation group were given additional Kushen injection in combined with continuing nursing. The occurrence rate of adverse reactions during the chemotherapy period and the improvement of immunological indicators in the two groups were compared. SF-36 health survey scale was used to evaluate the living qualities. Results: After treatment, CD4+ and NK cell level in the observation group were significantly elevated, but CD8+ level was significantly reduced when compared with before treatment. CD4+, CD8+, and NK cell levels after treatment in the control group were not significantly different from those before treatment. The bladder irritation symptoms during the chemotherapy period in the observation group were significantly lighter than those in the control group. The occurrence rate of main adverse reactions during the chemotherapy period in the observation group was significantly lower than that in the control group. The living quality scores in the observation group were significantly higher than those in the control group. Conclusions: Kushen injection in combined with continuing nursing can effectively regulate the immunological function in patients with instillation therapy after bladder cancer surgery, reduce the occurrence rate of adverse reactions, and enhance the living qualities.

  18. A comparison between bupivacaine instillation versus ilioinguinal/iliohypogastric nerve block for postoperative analgesia following inguinal herniorrhaphy in children.

    Science.gov (United States)

    Casey, W F; Rice, L J; Hannallah, R S; Broadman, L; Norden, J M; Guzzetta, P

    1990-04-01

    This study compared the postoperative pain relief provided by simple instillation of bupivacaine into a hernia wound with that provided by ilioinguinal/iliohypogastric (IG/IH) nerve block. Sixty children undergoing inguinal hernia repair under general anesthesia were randomized to receive 0.25 ml/kg of 0.25% bupivacaine for either IG/IH nerve block or up to 0.5 ml/kg of the same solution for instillation nerve blocks. In the postanesthesia care unit (PACU), a trained blinded observer evaluated the patient's level of postoperative pain using a standardized 10-point objective pain scale. Fentanyl 1-2 micrograms/kg was administered intravenously to any child scoring 6 or more points on the pain scale. The difference in pain scores among the two groups were compared. The two groups were not significantly different in age, duration of surgery, or anesthesia. There was no significant difference between patients who received the two treatment modalities in their pain scores, analgesic requirements in the PACU, recovery times, and discharge times. These results demonstrate that the simple instillation of local anesthetics into a wound provides postoperative pain relief following hernia repair, which is as effective as that provided by intraoperative IG/IH nerve block.

  19. 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.

  20. Therapeutic effects and predictive factors for successful intravesical hyaluronic acid instillation in patients with interstitial cystitis/bladder pain syndrome

    Directory of Open Access Journals (Sweden)

    Cheng-Ling Lee

    2015-06-01

    Conclusion: Intravesical HA administrations improved IC symptoms, decreased bladder pain, and decreased frequency after four instillations, and decreased nocturia and increased bladder capacity after completion of all nine instillations. Low-grade glomerulation predicts successful outcome.

  1. Static and dynamic mechanics of the murine lung after intratracheal bleomycin

    Directory of Open Access Journals (Sweden)

    Papiris Spyridon

    2011-05-01

    Full Text Available Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 μL or bleomycin (2 mg/Kg in 50 μL saline were administered to C57BL/6 (n = 40 and Balb/c (n = 32 mice. Injury/fibrosis score, tissue volume density (TVD, collagen content, airway resistance (RN, tissue damping (G and elastance coefficient (H, hysteresivity (η, and area of pressure-volume curve (PV-A were determined after 7 and 21 days (inflammation and fibrosis stage, respectively. Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than

  2. Static and dynamic mechanics of the murine lung after intratracheal bleomycin

    Science.gov (United States)

    2011-01-01

    Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (n = 40) and Balb/c (n = 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (RN), tissue damping (G) and elastance coefficient (H), hysteresivity (η), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations

  3. Randomized controlled study of intraincisional infiltration versus intraperitoneal instillation of standardized dose of ropivacaine 0.2% in post-laparoscopic cholecystectomy pain: Do we really need high doses of local anesthetics-time to rethink!

    Science.gov (United States)

    Kaushal-Deep, Singh Mathuria; Anees, Afzal; Khan, Shehtaj; Khan, Mohammad Amanullah; Lodhi, Mehershree

    2018-01-16

    Earlier studies done to compare the efficacy of use of local anesthetics at intraperitoneal location versus intraincisional use had utilized equal amount of drugs at the two locations, usually 10-20 ml. Using this large amount of drug in the small space of intraincisional location as compared to similar amount of drug in large intraperitoneal space created an inadvertent bias in favor of patients receiving the drug intraincisionally so these patients naturally experienced less pain. To conduct a randomized, triple-blind, placebo-controlled study by standardizing dose of local anesthetic, to compare the effectiveness of intraperitoneal against intraincisional use of ropivacaine 0.2% for post-laparoscopic cholecystectomy pain relief. 294 patients underwent elective 4-port laparoscopic cholecystectomy. Patients were triple blindly randomized. All patients received ~ 23 ml of solution, of which 20 ml was given intraperitoneally (1 ml/cm; 16 ml along right hemi-dome and 4 ml in gall bladder fossa) and ~ 3 ml intraincisionally (1 ml/cm of length of incision). Solution was either normal saline or drug (0.2% ropivacaine) depending on the group [controls (n = 86), intraperitoneal group (n = 100), and intraincisional group (n = 108)]. 5 different pain scales were used for assessment of overall pain. Pain scores were assessed at 5 points of time. Patients in intraincisional group showed significantly less overall pain and rescue analgesia requirement (p  0.05); and shoulder pain was significantly less in intraperitoneal group (p < 0.05). The intraincisional use of injection ropivacaine at its minimum concentration of 0.2% in minimal doses of 1 ml/cm at the end of procedure provides significantly more post-operative analgesia as compared to intraperitoneal group and controls. However, for controlling shoulder pain, the use of intraperitoneal ropivacaine is desirable.

  4. In what type of interstitial cystitis/bladder pain syndrome is DMSO intravesical instillation therapy effective?

    Science.gov (United States)

    2015-01-01

    Background Dimethylsulfoxide (DMSO) is the most-used agent for intravesical instillation. We conducted this retrospective clinical study to determine in what type of the interstitial cystitis (IC)/bladder pain syndrome (BPS) DMSO was effective. Methods We combined DMSO with hydrodistension in 2003 and from 2004 we performed hydrodistension alone. Hydrodistension had been performed in 7 cases of IC/BPS with Hunner’s lesions (H group) and 7 cases of IC/BPS without Hunner’s lesions (non-H group), and they served as the control group (C group; n=14). There was also a DMSO group (D group; n=14) that consisted of an H group of 7 cases and an non-H group of 7 cases in which the hydrodistension had been immediately followed by intravesical instillation of 50% DMSO 50 mL. Before, and 2, 6, 12, 18, and 24 months (M) after the intervention, the patients were asked to complete a 4-day frequency-volume chart (FVC) and the O’Leary-Sant IC symptom index (ICSI) questionnaire and IC problem index (ICPI) questionnaire, and to rate their pain on a visual analogue scale (VAS). Results All parameters were improved after hydrodistension in both the C group and the D group. However, comparison of the C group and D group according to whether Hunner lesions were present showed that there were no significant differences in any of the postoperative parameters between the non-H groups in the C group and D group, but in the H groups, average and maximum voided volume were significantly higher and the ICSI, ICPI, and VAS scores were lower in the D group. Moreover, the significant differences increased with the duration of the postoperative period. Conclusions DMSO intravesical instillation therapy was useful in both maintaining and improving the effectiveness of hydrodistension in IC/BPS with Hunner lesions. However, DMSO did not have any particular efficacy in the treatment of IC/BPS in the absence of Hunner lesions. PMID:26816859

  5. Instilling Success in an Internship Program: A Dietetic Case Study

    Science.gov (United States)

    Shows, Amy R.; Killough, Jill E.; Jackson, Samantha; Lui, Janet

    2015-01-01

    Educators in the field of family and consumer science (FCS) must be able to foster intellectual curiosity and critical thinking skills in students (Schumacher, 2014), and internships are one way to do so. Internships are formal programs that provide practical experience for beginners in an occupation or profession. Interns are temporarily placed…

  6. Pulmonary pharmacokinetics of tulathromycin in swine. Part I: Lung homogenate in healthy pigs and pigs challenged intratracheally with lipopolysaccharide of Escherichia coli.

    Science.gov (United States)

    Villarino, N; Lesman, S; Fielder, A; García-Tapia, D; Cox, S; Lucas, M; Robinson, J; Brown, S A; Martín-Jiménez, T

    2013-08-01

    The objective of the study was to assess the pharmacokinetics of tulathromycin in lung tissue homogenate (LT) and plasma from healthy and lipopolysaccharide (LPS)-challenged pigs. Clinically healthy pigs were allocated to two dosing groups of 36 animals each (group 1 and 2). All animals were treated with tulathromycin (2.5 mg/kg). Animals in group 2 were also challenged intratracheally with LPS from Escherichia coli (LPS-Ec) 3 h prior to tulathromycin administration. Blood and LT samples were collected from all animals during 17-day post-tulathromycin administration. For LT, one sample from the middle (ML) and caudal lobes (CL) was taken. The concentration of tulathromycin was significantly lower in the ML after the intratracheal administration of LPS-E. coli (P lungs was rapid and persisted at high levels for 17-day postadministration. The distribution of the drug within the lung seems to be homogenous, at least between the middle and caudal lobes within dosing groups. The concentration versus time profile of the drug and pharmacokinetic parameters in two different lung areas (middle and caudal lobe) were consistent within the groups. The clinical significance of these findings is unknown. © 2012 John Wiley & Sons Ltd.

  7. The utilization of oropharyngeal intratracheal PAMP administration and bronchoalveolar lavage to evaluate the host immune response in mice.

    Science.gov (United States)

    Allen, Irving C

    2014-04-02

    The host immune response to pathogens is a complex biological process. The majority of in vivo studies classically employed to characterize host-pathogen interactions take advantage of intraperitoneal injections of select bacteria or pathogen associated molecular patterns (PAMPs) in mice. While these techniques have yielded tremendous data associated with infectious disease pathobiology, intraperitoneal injection models are not always appropriate for host-pathogen interaction studies in the lung. Utilizing an acute lung inflammation model in mice, it is possible to conduct a high resolution analysis of the host innate immune response utilizing lipopolysaccharide (LPS). Here, we describe the methods to administer LPS using nonsurgical oropharyngeal intratracheal administration, monitor clinical parameters associated with disease pathogenesis, and utilize bronchoalveolar lavage fluid to evaluate the host immune response. The techniques that are described are widely applicable for studying the host innate immune response to a diverse range of PAMPs and pathogens. Likewise, with minor modifications, these techniques can also be applied in studies evaluating allergic airway inflammation and in pharmacological applications.

  8. 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.

  9. DNA Damage Following Pulmonary Exposure by Instillation to Low Doses of Carbon Black (Printex 90) Nanoparticles in Mice

    DEFF Research Database (Denmark)

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

    2015-01-01

    We previously observed genotoxic effects of carbon black nanoparticles at low doses relative to the Danish Occupational Exposure Limit (3.5 mg/m3). Furthermore, DNA damage occurred in broncho-alveolar lavage (BAL) cells in the absence of inflammation, indicating that inflammation is not required...... for the genotoxic effects of carbon black. In this study, we investigated inflammatory and acute phase response in addition to genotoxic effects occurring following exposure to nanoparticulate carbon black (NPCB) at even lower doses. C57BL/6JBomTac mice were examined 1, 3, and 28 days after a single instillation...

  10. Investigation of the pathogenesis of Enterococcus cecorum after intravenous, intratracheal or oral experimental infections of broilers and broiler breeders

    DEFF Research Database (Denmark)

    Thoefner, Ida; Christensen, Jens Peter

    is known concerning transmission and pathogenesis in broilers and their parents. Consequently, a set of experimental E. cecorum infections were conducted in broiler breeders and broilers. The bacteria was inoculated at two doses using intravenous (IV), intratracheal (IT) and oral (PO) route of infection...

  11. Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat.

    Science.gov (United States)

    Lasfargues, G; Lison, D; Maldague, P; Lauwerys, R

    1992-01-01

    Alveolitis progressing to lung fibrosis has been reported in workers exposed to cobalt containing dust (e.g., tungsten carbide-cobalt mixture as produced by the hard metal industry) but rarely following exposure to pure cobalt dust (e.g., in cobalt-producing factories). We have previously demonstrated that tungsten carbide-cobalt mixture is more toxic toward rat alveolar macrophages in vitro than pure cobalt metal powder. The present study was undertaken to compare in female rats the acute pulmonary response (lung weight, lung histology, cellular and biochemical analyses of bronchoalveolar lavage fluid, and mortality) following the intratracheal instillation of pure cobalt (Co) particles (median particle size, d50:4 microns), pure tungsten carbide (WC) particles (d50:2 microns), tungsten carbide-cobalt (WC-Co) powder (d50:2 microns; cobalt 6.3%, tungsten 84%, carbon 5.4%) and crystalline silica (d50 less than 5 micron) used as pneumotoxic reference material. WC alone (15.67 mg/100 g body wt) behaves as an inert dust producing only a mild accumulation of macrophages in the alveolar duct walls. Co alone (1.0 mg/100 g) only causes a moderate inflammatory response. An identical amount of Co given as WC-Co mixture (16.67 mg/100 g; corresponding to 1.0 mg Co/100 g) produces a severe alveolitis and fatal pulmonary edema. Cellular and biochemical characteristics of bronchoalveolar lavage fluid collected 24 hr after the intratracheal instillation of WC (1.0 mg/100 g) or Co (0.06 mg/100 g) are not significantly different from those of control animals instilled with sterile saline. On the contrary, bronchoalveolar lavage fluid changes following administration of the WC-Co mixture (1.0 mg/100 g; corresponding to 0.06 mg Co/100 g) are very similar to those induced by crystalline silica (1.0 mg/100 g). The amount of cobalt excreted in urine is significantly higher when the animals are exposed to WC-Co powder as compared to an equivalent amount of pure cobalt particles

  12. Potential health impact on mice after nasal instillation of nano-sized copper particles and their translocation in mice.

    Science.gov (United States)

    Liu, Yang; Gao, Yuxi; Zhang, Lili; Wang, Tiancheng; Wang, Jiangxue; Jiao, Fang; Li, Wei; Liu, Ying; Li, Yufeng; Li, Bai; Chai, Zhifang; Wu, Gang; Chen, Chunying

    2009-11-01

    The purpose of this study is to evaluate the overall toxicity of nasal instilled nanoscale copper particles (23.5 nm) in mice. Pathological examination, target organs identification, and blood biochemical assay of experimental mice were carried out in comparison with micro-sized copper particles (17 microm). However, only in the high-dose group of copper nanoparticles (40 mg/kg body weight instilled for three times in one week), the body weight of mice were retarded and significant pathological changes were observed. There were hydropic degeneration around the central vein and the spotty necrosis of hepatocytes in the liver and swelling in the renal glomerulus, while, severe lesion associated with the decreased number of olfactory cells and the dilapidated laminated structure were also observed in the olfactory bulb. The serum biochemical assay also indicated the sign of renal and hepatic lesion. However, there were no obvious pathological and physiological damages in the mice after instilling different-sized copper nanoparticles with low dose of 1 mg/kg body weight. The retention and distribution of copper in various tissues show that the liver, kidneys and olfactory bulb are the main accumulated tissues for copper particles, which were determined by high sensitive element-specific technique of ICP-MS. The copper contents of the liver, kidneys and the olfactory bulb increase significantly at the group of 40 mg/kg compared to the control group, which is in agreement with the histological changes. Therefore, the data indicate that nasal inhaled copper particles at very high dosage can translocate to other organs and tissues and further induce certain lesions. The present results are helpful to get better understanding of the risk assessment and evaluation for copper nanoparticles.

  13. Quantitative Comparison of the Effect of 10% Phenylephrine Instillation and Manual Elevation in Patients with Involutional Blepharoptosis.

    Science.gov (United States)

    Pereira, Ivana Cardoso; Matayoshi, Suzana

    2017-01-01

    To compare the effect of 10% phenylephrine (PE) instillation and manual elevation (ME) on the upper eyelid position of the tested eye and the contralateral eye in patients with involutional blepharoptosis (IB). IB patients were submitted to two tests followed by observation of the effect on the contralateral eyelid: (1) ME of the more ptotic eyelid; and (2) instillation of two drops of 10% PE (phenylephrine test) in the more ptotic eye. The patients were filmed before and 5, 10, and 15 minutes after instillation. The upper eyelid margin reflex distance (MRD1) was measured using the software Image J, and the results were analyzed with the linear mixed-effects model. The study included 70 patients aged 44-86 years, 64 of whom were female (91.43%), divided into three groups: subjects with unilateral IB, subjects with bilateral IB, and controls. The eye submitted to instillation with 10% PE displayed significant elevation during the first 10 min: from 1.33 ± 0.66 mm to 2.06 ± 0.89 mm (unilateral group), from 1.26 ± 0.63 mm to 2.29 ± 0.86 mm (bilateral group), and from 3.12 ± 0.68 mm to 4.06 ± 0.92 mm (control group). MRD1 decreased in the contralateral eye in IB patients, significantly more so after the phenylephrine test: PE vs. ME = 18.9% versus 17.2% reduction in the unilateral group, and 13.6% versus 10.7% reduction in the bilateral group. The outcome was not influenced by IB severity and the concurrence of IB and eye dominance. Both ME and 10% PE affected the contralateral upper eyelid, but the response was significantly better with the latter.

  14. 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...

  15. 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.

  16. Current recommendations for bladder instillation therapy in the treatment of interstitial cystitis/bladder pain syndrome.

    Science.gov (United States)

    Colaco, Marc A; Evans, Robert J

    2013-10-01

    Bladder instillation therapy refers to the direct introduction of medication into the bladder and is a common treatment modality for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who have failed conservative and oral therapies. The current American Urological Association (AUA) recommendations list three medications as options for IC/BPS instillation therapy: dimethyl sulfoxide, heparin, and lidocaine. The purpose of this review is to examine the evidence behind the recommendations for these medications. We also examine several historical or experimental therapies that do not hold recommendations but are still used on rare occasion. Finally, we discuss our bladder instillation strategies as well as potential future research and development in intravesicular therapy.

  17. Floating Hydrogel with Self-Generating Micro-Bubbles for Intravesical Instillation

    Directory of Open Access Journals (Sweden)

    Tingsheng Lin

    2016-12-01

    Full Text Available Intravesical instillation is the main therapy for bladder cancer and interstitial cystitis. However, most drug solutions are eliminated from bladder after the first voiding of urine. To solve this problem, we proposed a floating hydrogel with self-generating micro-bubbles as a new delivery system. It floated in urine, avoiding the urinary obstruction and bladder irritation that ordinary hydrogels caused. In this study, we abandoned traditional gas-producing method like chemical decomposition of NaHCO3, and used the foamability of Poloxamer 407 (P407 instead. Through simple shaking (just like shaking SonoVue for contrast-enhanced ultrasound in clinical, the P407 solution will “lock” many micro-bubbles and float in urine as quickly and steadily as other gas producing materials. In vivo release experiments showed that drug was released continually from hydrogel for 10 h during the erosion process. Thus, the residence time of drug in bladder was prolonged and drug efficacy was improved. In vivo efficacy study using rabbit acute bladder injury model showed that prolonged drug residence time in bladder increased the efficiency of heparin in the protection of bladder mucosal permeability. Therefore, our floating hydrogel system with self-generating micro-bubbles was single-component, simply prepared and efficacy enhancing, successfully exempting users from worries on safety and clinical efficiency from bench to bedside.

  18. Serial measurement of tear meniscus by FD-OCT after instillation of artificial tears in patients with dry eyes.

    Science.gov (United States)

    Bujak, Matthew C; Yiu, Samuel; Zhang, Xinbo; Li, Yan; Huang, David

    2011-01-01

    To use Fourier-domain optical coherence tomography (FD-OCT) to study the effect of artificial tears on the tear meniscus in patients with dry eyes. The lower tear meniscus of 16 consecutive patients with dry eyes was imaged by an FD-OCT system (RTVue; Optovue, Inc., Fremont, CA). Baseline and five serial pairs of measurements were taken after the instillation of artificial tears (Optive; Allergan, Irvine, CA) at 1, 2, 5, 10, and 15 minutes. The lower meniscus height, depth, and area were measured with a computer caliper. Baseline meniscus measurements were 235.5 ± 150.0 μm, 138.1 ± 78.7 μm, and 0.020 ± 0.022 mm(2) for height, depth, and area, respectively. After instillation of artificial tears, all lower tear meniscus parameters remained significantly elevated for 5 minutes and returned to baseline by 10 minutes. FD-OCT is able to quantify a dramatic initial increase in tear meniscus, followed by a decay back to baseline values after approximately 5 minutes. FD-OCT may be useful in objectively quantifying the dynamic efficacy of dry eye treatments. Copyright 2011, SLACK Incorporated.

  19. 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.

  20. 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...

  1. Distribution assessment comparing continuous and periodic wound instillation in conjunction with negative pressure wound therapy using an agar-based model.

    Science.gov (United States)

    Rycerz, Anthony M; Slack, Paul; McNulty, Amy K

    2013-04-01

    Negative pressure wound therapy (NPWT) is a widely accepted and effective treatment for various wound types, including complex wounds. Negative pressure with instillation was initially used as a gravity-fed system whereby reticulated, open-cell foam in the wound bed was periodically exposed to cycles of soaking with instillation solution followed by NPWT. Recent publications have alluded to positive outcomes with continuous instillation, where fluid is delivered simultaneously with negative pressure. To evaluate the distribution of instillation solutions to wound beds in conjunction with negative pressure, agar-based models were developed and exposed to coloured instillation solutions to identify exposure intensity via agar staining. This model allowed comparison of continuous- versus periodic-instillation therapy with negative pressure. Continuous instillation at a rate of 30 cc/hour with negative pressure showed isolated exposure of instillation fluid to wound beds in agar wound models with and without undermining and tunnelling. In contrast, periodic instillation illustrated uniform exposure of the additive to the entire wound bed including undermined and tunnel areas, with increased staining with each instillation cycle. These findings suggest that periodic instillation facilitates more uniform exposure throughout the wound, including tunnels and undermining, to instillation solutions, thereby providing therapy consistent with the clinician-ordered treatment. © 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  2. 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.

  3. Dynamic MR imaging: Follow-up study after femoral head core decompression and rhBMP-2 instillation in patients with avascular necrosis of the femoral head; Dynamische Magnetresonanztomographie (MRT): Verlaufsbeobachtung nach Femurkerndekompression und Auffuellung mit rekombinantem, humanem Bone morphogenetic Protein-2 (rhBMP-2) bei avaskulaerer Femurkopfnekrose

    Energy Technology Data Exchange (ETDEWEB)

    Schedel, H. [Klinik Prof. Schedel, Kellberg (Germany); Schneller, A. [Humboldt-Universitaet, Berlin (Germany). Klinik fuer Allgemein- und Transplantationschirurgie; Vogl, T.; Mueller, H.F.; Maeurer, J.; Felix, R. [Humboldt-Universitaet, Berlin (Germany). Strahlenklinik und Poliklinik; Suedkamp, N. [Humboldt-Universitaet, Berlin (Germany). Unfall- und Wiederherstellungschirurgie; Eisenschenk, A. [Freie Univ. Berlin (Germany). Orthopaedische Klinik und Poliklinik

    2000-07-01

    Material and Methods: Six patients with avascular necrosis of the femoral head ARCO-stage I- or II-lesions were treated surgically by femoral head core decompression. Three of these patients were additionally treated with rhBMP-2-instillation. The progression or regression could be confirmed by T1- and T2-weighted spinecho-sequences (zero, four, ten, sixteen weeks and 24 months follow up). Results: Corresponding ARCO-classification with partly more sensitive measurement of vitality signs in comparison to the optical X-ray classification. The objective, quantitative measurement of signalintensity post contrast medium reduces the influence of experience and level of education. The dynamic sequences results are reproducable. (orig.) [German] Material und Methoden: Sechs Patienten mit avaskulaerer Nekrose des Femurkopfes des Stadiums I oder II nach ARCO wurden einer Femurkerndekompression unterzogen. Drei dieser Patienten erhielten zusaetzlich eine rhBMP-2-Auffuellung. Zum Zeitpunkt null, vier, zehn, sechszehn Wochen und 24 Monaten post OP erfolgte die kernspintomographische Untersuchung mit T1- und T2-gewichteten Sequenzen unter besonderer Beruecksichtigung der dynamischen Untersuchungssequenz nach Gabe von Gd-DTPA (Gadopentetsaeure, Dimegluminsalz; Magnevist {sup trademark}) zur Dokumentation der Signalintensitaetssteigerung pro Zeiteinheit in der Nekroseregion. Ergebnisse: Uebereinstimmende Stadienklassifikation nach ARCO mit zum Teil empfindlicherer Messung von Vitalitaetszeichen im Vergleich zu rein visuellen roentgenologischen Einteilung. Die objektive, quantitative Messung des Signalintensitaetssteigerungsverhaltens nach Kontrastmittelgabe im Bereich der Femurkopfnekrose kann den Einfluss von subjektiven Eigenschaften des Untersuchers (Erfahrung, Ausbildungsstand) reduzieren, wobei die Ergebnisse der Dynamiksequenzen objektiv reproduzierbar sind. (orig.)

  4. Impact of hydrochloric acid instillation on salvage of infected central venous catheters in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Madsen, Mette; Rosthøj, Steen

    2013-01-01

    Bacteraemia associated with indwelling central venous catheters (CVC) causes significant morbidity in children with cancer. Hydrochloric acid (HCl) instillations have been reported to salvage CVCs with antibiotic-refractory infection. We implemented this treatment in 2002. The impact on the survival of CVCs has been evaluated in a retrospective cohort study of children with acute lymphoblastic leukaemia (ALL). Children with newly diagnosed ALL during 1999-2005 having their first CVC inserted before (n = 16) and after (n = 24) the introduction of the procedure were studied. All bacteraemic episodes were reviewed, recording bacteriological findings and treatment, and the time to premature or planned removal of the CVC was determined. In the comparison cohort, 31.0% (9/29) of bacteraemic episodes led to removal of the CVC, compared to 5.5% (2/36) in the intervention cohort (p = 0.01). Thus, the rate of catheter loss due to infection fell from 56.3% (9/16) to 8.3% (2/24) after introducing HCl treatment (p = 0.0025). Overall, the premature catheter removal rate fell from 75.0% (12/16) to 45.8% (11/24) (p = 0.10). Analysed in a CUSUM plot the reduced frequency of premature CVC removal evidently coincided with the introduction of the procedure. In a subgroup analysis of 21 monobacterial infections with coagulase-negative staphylococci, a decrease in systemic and lock antibiotic therapy was found. No adverse events were noted. HCl instillations significantly reduced the need to remove and replace CVCs. The procedure is practical, appears to be safe, and may reduce the consumption of antibiotics.

  5. Estudo comparativo da acomodação residual após instilação de colírios de tropicamida a 1%, ciclopentolato a 1% e associação de tropicamida a 1% + ciclopentolato a 1% Comparative study of residual accommodation after the instillation of the following eye drops: 1% tropicamide, 1% cyclopentolate and 1% tropicamide + 1% cyclopentolate

    Directory of Open Access Journals (Sweden)

    Renato Klingelfus Pinheiro

    2000-12-01

    Outpatient Clinic of the Santa Casa-São Paulo, within the period of October 1997 to September 1988. The 46 patients were submitted to three complete ophthalmologic examinations. The potential of accommodation of each eye was tested as follows: 20 minutes after instillation of 1% tropicamide; 40 minutes after 1% cyclopentolate instiIlation and 30 minutes after 1% tropicamide plus 1% cyclopentolate, with an interval of 5 minutes between both drugs. Examination were performed with an interval of at least seven days between the tests. Results: There were no differences between the emmetropia, the hyperopia and the short myopia groups regarding all drugs (p > 0.005. 1% cyclopentolate and the association at the drugs caused statistically significant less residual accomodation, compared to 1% tropicamide in the hype- ropia and myopia groups. Conclusion: 1% cyclopentolate 1% and the association of the drugs are safe for the static refractometric examination in young patients with dark iris and without any type of eye disease, since they promote an average residual accomodation of 1.21 +/- 0.7 spherical diopters (SD in all studied groups.

  6. 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.

  7. 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.

  8. Mid-career construction counselling to instill spiritual awareness and ...

    African Journals Online (AJOL)

    This article reports on the value of career construction counselling for a black man facing a career crossroads. The participant was purposefully selected from a number of people participating in a career construction counselling course who had sought career counselling. An intrinsic, single-case study design was ...

  9. 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

  10. Instill Lean A3 Thinking into Healthcare IT Services

    Directory of Open Access Journals (Sweden)

    Jihong Zeng

    2014-08-01

    Full Text Available Healthcare information technology is a key enabler for care transformation to provide quality care at low cost and better population health.  Many healthcare organizations have established IT Program Management and adopted ITIL best practice to manage IT services. However, ITIL and traditional project management are heavily process oriented, and neither flexible nor effective enough for swift response to changing business demand. Lean methodologies are increasingly deployed by healthcare providers to improve workflow process management but only has limited use cases documented in healthcare IT service. This paper introduces the Lean A3 Thinking methodology and its value in identifying and eliminating wastes to provide agile and effective solutions in response to customer requests. We present a case study of applying Lean A3 Thinking to improve clinical informatics reporting service. The initial evaluation results are promising and indicate that both ITIL and Lean A3 Thinking focus on customer and service quality, complementing each other well. ITIL provides a framework for ITSM based on a set of best practice to manage IT services. Lean A3 Thinking specifies a set of framework and tools for improving quality of services and processes by eliminating wastes. Proper balance between Lean and ITIL principles for ITSM needs more research and further study.

  11. 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.

  12. 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.

  13. A Prospective, Multicenter, Double-Blind, Randomized Trial of Bladder Instillation of Liposome Formulation OnabotulinumtoxinA for Interstitial Cystitis/Bladder Pain Syndrome.

    Science.gov (United States)

    Chuang, Yao-Chi; Kuo, Hann-Chorng

    2017-08-01

    Intravesical instillation of liposomal formulated botulinum toxin A (lipotoxin) has shown therapeutic effects as treatment of refractory overactive bladder without needle injections. We assessed lipotoxin to treat refractory interstitial cystitis/bladder pain syndrome. This 2-center, double-blind, randomized, placebo controlled, physician initiated study enrolled patients with refractory interstitial cystitis/bladder pain syndrome. A total of 31 patients were assigned to intravesical instillation of lipotoxin (onabotulinumtoxinA 200 U with 80 mg sphingomyelin), 28 were assigned to onabotulinumtoxinA 200 U in normal saline and 31 were assigned to normal saline alone. The primary end point was the average change in O'Leary-Sant symptom scores, including ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index) between baseline and 4 weeks after treatment. Other end points included the average changes in a 3-day voiding diary, a visual analog scale for pain and a global response assessment of patient satisfaction. Improvements in the pain scale and O'Leary-Sant symptom scores occurred in all 3 groups by 4 weeks after treatment. Lipotoxin instillation was associated with a statistically significant decrease in O'Leary-Sant symptom scores (mean ± SD 7.38 ± 8.75), ICSI (4.00 ± 4.28), ICPI (3.35 ± 5.11) and the visual analog scale pain scale (1.64 ± 2.52), and an increase in the global response assessment (1.35 ± 1.28). However, there was no difference in improvement among the 3 groups. No significant adverse events were found in any group. Lipotoxin failed to demonstrate a positive proof of concept compared to onabotulinumtoxinA or placebo. However, a single intravesical instillation of lipotoxin was associated with decreased interstitial cystitis/bladder pain syndrome symptoms compared to baseline in patients with moderate to severe interstitial cystitis/bladder pain syndrome. The effect was likely due to a significant placebo

  14. Use of radioactively labelled bacteria in animal experiments. 4. Distribution of radioactivity in the mouse after intratracheal administration of labelled Pasteurella multocida germs

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    Flossmann, K.D.; Mueller, G.; Heilmann, P.; Finsterbusch, L.; Hubald, J. (Akademie der Landwirtschaftswissenschaften der DDR, Jena. Inst. fuer Bakterielle Tierseuchenforschung)

    1981-03-01

    Intratracheal administration of /sup 3/H-, /sup 14/C-, /sup 59/Fe- or /sup 125/I-labelled Pasteurella multocida germs to mice resulted in a more or less differentiated, nuclidedependent distribution of radioactivity in blood, spleen, liver, lung, kidney, and gastrointestinal tract, and was comparable to that following subcutaneous application. The elimination of the antigen from the lungs and other organs could be characterised by an e function, after having reached a certain level of distribution. Some of the antigen was persistent in the lung not less than 14 days. Extremely high activity concentration and persistence was recordable, following the use of /sup 59/Fe complete antigen. Phagocytosis of Pasteurella multocida germs through alveolar macrophages of the lung was secured by autoradiography. Most of the antigen seemed to be discharged from the lungs through the digestive tract. Antigen distribution recorded from immunized and non-immunized mice seemed to suggest that the fate of antigen applied was affected by the kind of immunization. No difference in antigen distribution between non-immunized and subcutaneously immunized animals were provable, following intratracheal antigen application, but is was clearly provable, following intratracheal immunization. Elimination of antigen from the lungs of intratracheally immunized animals was found to occur faster than it did from non-immunized animals.

  15. [Control of the rabbit's IOP after topic instillation of antiglaucomatic latanoprost and amino acid arginine with lysine mixture].

    Science.gov (United States)

    Veselovský, J; Oláh, Z; Veselá, A; Gressnerová, S

    2007-04-01

    To evaluate the effect of locally instilled 10% L-arginine.HCI and 10% L-lysine.2HC1.2H20 in 0.005% Latanoprost (Xalatane) mixture on the physiological IOP in rabbits. After instillation of the arginine and lysine in 0.005% latanoprost mixture into the left conjunctival sac of 5 female rabbits of the New Zealand White species the, IOP was measured at the time of instillation, and 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after the instillation. The right eye was used as the control. The mixture of arginine with lysine in 0.005% latanoprost decreased significantly the IOP value. The decrease had two peaks. The major decrease of the IOP was observed after 30 min. (3.1 mmHg) and after 24 h (5.0 mmHg) after instillation of this mixture. Between 120 min. and to 240 min., the mild decrease of the mean value of the IOP was found at the control eye as well. The mixture of arginine with lysine in 10 % concentration in 0.005 % latanoprost (Xalatane) decreased significantly the physiological IOP values in rabbits during the whole experiment. The decrease was significant in comparison both to the IOP of the control eye and to the effect of the amino acids arginine and lysine alone.

  16. Ventilator „Chirana Aura V“ In Two Models Of Neonatal Acute Lung Injury - A Pilot Study

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    Tomclkova L.

    2014-05-01

    Full Text Available In severe respiratory insufficiency, neonatal and pediatric patients should be ventilated artificially by a ventilator. Aim of this experimental study was to evaluate whether the newly developed ventilator Chirana Aura V may effectively ventilate the lungs of animals with two different models of acute lung injury: acute respiratory distress syndrome (ARDS induced by repetitive saline lavage and meconium aspiration syndrome (MAS induced by intratracheal instillation of neonatal meconium. The experiments were performed on 10 adult rabbits (New Zealand white. In ARDS group (n=5, the lungs were repetitively lavaged with saline (30 ml/kg until partial pressure of oxygen (PaO2 in arterial blood was under 26.7 kPa at inspiratory fraction of oxygen FiO2=1.0. In MAS group (n=5, animals were instilled 4 ml/kg of suspension of human meconium (25 mg/ml. When the model of acute lung injury was developed, animals were ventilated for additional 2 hours with pressure control ventilation (PCV regime by ventilator Chirana Aura V. Ventilatory parameters, blood gases, acid-base balance, end-tidal CO2, O2 saturation of hemoglobin, oxygenation indexes, ventilation efficiency index, dynamic lung compliance, and right-to-left pulmonary shunts were measured and calculated in regular time intervals. In both experimental groups, used ventilatory settings provided acceptable gas exchange within the period of observation. Thus, the results indicate that ventilator Chirana Aura V might be suitable for ventilation of animal models of acute lung injury. However, further pre-clinical investigation is needed before its use may be recommended in neonatal and/or pediatric patients with acute lung injury.

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

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    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

  18. Endometritis therapy in sows by intra uterine instillation of yeast cell wall solution

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    Lazarević M.

    2012-01-01

    Full Text Available On the basis of our investigations it was possible to conclude that intrauterine treatment of sows with puerperal uterine infections with sterile YCW (Yeast Cell Wall resulted in significant clinical improvement. The percent of recidivism was the lowest (10% in groups of sows treated with 10 and 20 g of YCW. The degree of bacterial CFU (Colony Forming Units reduction in samples of sows uterine flushings following instillation of YCW (5, 10 and 20 g was wery high and ranged from 1361 to 1444 times, while in sows treated with Lotagen 2% solution (100 mL this parametar was only 32. At the moment of weaning, piglets from sows treated with 10 and 20 g of YCW were heavier when compared to the control and Lotagen group and their DBWG (Daily Body Weight Gain was higher when compared to the Lotagen and control group. Treatment of sows by IU instillation of YCW did not influence the number of piglets in the next breeding cycle.

  19. Maintenance versus non-maintenance intravesical Bacillus Calmette-Guerin instillation for non-muscle invasive bladder cancer: A systematic review and meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Chen, Siteng; Zhang, Ning; Shao, Jialiang; Wang, Xiang

    2018-02-28

    It is not clear whether maintenance Bacillus Calmette-Guerin (BCG) is necessary for intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC). This systematic review and meta-analysis aimed to illustrate the effects of maintenance BCG for intermediate- or high-risk NMIBC. A comprehensive literature search of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov databases and International Clinical Trials Register (ICTRP) Search was conducted to identify relevant randomized controlled trials (RCTs) that have assessed the efficacy of maintenance or non-maintenance BCG therapy for patients with NMIBC. The maintenance group first received induction BCG instillations, and subsequently received BCG intravesical instillations regularly for at least 1 year, while the control group only received induction BCG instillations. Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Criteria. Ten RCTs were eligible in this systematic review. The meta-analysis showed that induction BCG followed by maintenance BCG instillation after transurethral resection (TUR) could reduce the risk ratios of tumor recurrence by 21% (RR = 0.79; 95% CI 0.70-0.89; P maintenance BCG. It could also reduce the risk ratios of tumor progression (RR = 0.81; 95% CI 0.68-0.97; P = 0.02). However, these pooled results should be considered with caution since the quality of evidences for outcomes ranged low. Subgroup analysis implied that different durations of maintenance BCG instillations might be one of the sources of potential clinical heterogeneity of included studies. Begg's funnel plot and Egger's test did not reveal any evidence of publication bias in this meta-analysis. Induction BCG followed by maintenance BCG instillation after TUR, compared with induction BCG along, can reduce the risk ratios of tumor recurrence and tumor progression, and prolong RFS. However, these results with a lower level of

  20. 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

  1. Negative Pressure Wound Therapy With Instillation: Review of Evidence and Recommendations.

    Science.gov (United States)

    Kim, Paul J; Attinger, Christopher E; Olawoye, Olayinka; Crist, Brett D; Gabriel, Allen; Galiano, Robert D; Gupta, Subhas; Lantis Ii, John C; Lavery, Lawrence; Lipsky, Benjamin A; Teot, Luc

    2015-12-01

    Negative pressure wound therapy with instillation (NPWTi) and dwell time is an adjunctive treatment modality for selected complex wounds. Because of the greater amount of research now available, a multidisciplinary expert panel comprising the fields of podiatry, plastic and general surgery, burn treatment, infectious diseases, and orthopedics was convened on July 11, 2015, to produce a summary of the data and recommendations on the use of NPWTi. The panel members each reviewed available published literature on NPWTi in the PubMed, Cochrane, and Google Scholar databases from 1 January 2012 up until 20 July 2015 using the string search term negative pressure wound therapy instillation provided by the panel moderator; there were no restrictions on the language or type of publication. Panel members discussed their experiences and worked to reach consensus on several predefined topics. NPWTi was found to be most appropriate for properly selected complex hosts or wounds such as patients with multiple comorbidities, patients with an American Society of Anesthesiology Classification ≥ 2, severe traumatic wounds, diabetic foot infections, and wounds complicated by invasive infection or extensive biofilm. NPWTi should not be used routinely to treat simple wounds or hosts without comorbidities.There is evidence that when NPWTi is added to standard of care in properly selected cases it provides better overall clinical outcomes than standard of care alone, even when including NPWT. Based on published evidence and panel member experience, the Panel recommends a dwell time - fluid briefly instilled into the wound and allowed to diffuse for a user-specified time - of 10-20 minutes followed by 2-4 hours of negative pressure at -125 mmHg, although larger wounds may need times of up to 6 hours. Normal saline (0.9%) is the preferred solution for NPWTi, except in special situations. NPWTi with dwell time is an adjunct to other standard principles of appropriate wound assessment and

  2. Evaluation of the respiratory route as a viable portal of entry for Salmonella in poultry via intratracheal challenge of Salmonella Enteritidis and Salmonella Typhimurium.

    Science.gov (United States)

    Kallapura, G; Morgan, M J; Pumford, N R; Bielke, L R; Wolfenden, A D; Faulkner, O B; Latorre, J D; Menconi, A; Hernandez-Velasco, X; Kuttappan, V A; Hargis, B M; Tellez, G

    2014-02-01

    Experimental and epidemiological evidence suggests that primary infection of Salmonella is by the oral-fecal route for poultry. However, the airborne transmission of Salmonella and similar enteric zoonotic pathogens has been historically neglected. Increasing evidence of Salmonella bioaerosol generation in production facilities and studies suggesting the vulnerabilities of the avian respiratory architecture together have indicated the possibility of the respiratory system being a potential portal of entry for Salmonella in poultry. Presently, we evaluated this hypothesis through intratracheal (IT) administration of Salmonella Enteritidis and Salmonella Typhimurium, as separate challenges, in a total of 4 independent trials, followed by enumeration of cfu recovery in ceca-cecal tonsils and recovery incidence in liver and spleen. In all trials, both Salmonella Enteritidis and Salmonella Typhimurium, challenged IT colonized cecae to a similar or greater extent than oral administration at identical challenge levels. In most trials, chickens cultured for cfu enumeration from IT-challenged chicks at same dose as orally challenged, resulted in an increase of 1.5 log higher Salmonella Enteritidis from ceca-cecal tonsils and a much lower dose IT of Salmonella Enteritidis could colonize ceca to the same extent than a higher oral challenge. This trend of increased cecal colonization due to IT challenge was observed with all trails involving week-old birds (experiment 2 and 3), which are widely considered to be more difficult to infect via the oral route. Liver-spleen incidence data showed 33% of liver and spleen samples to be positive for Salmonella Enteritidis administered IT (10(6) cfu/chick), compared with 0% when administered orally (experiment 2, trial 1). Collectively, these data suggest that the respiratory tract may be a largely overlooked portal of entry for Salmonella infections in chickens.

  3. Evaluation of the respiratory route as a viable portal of entry for Salmonella in poultry via intratracheal challenge of Salmonella Enteritidis and Salmonella Typhimurium1

    Science.gov (United States)

    Kallapura, G.; Morgan, M. J.; Pumford, N. R.; Bielke, L. R.; Wolfenden, A. D.; Faulkner, O. B.; Latorre, J. D.; Menconi, A.; Hernandez-Velasco, X.; Kuttappan, V. A.; Hargis, B. M.; Tellez, G.

    2014-01-01

    Experimental and epidemiological evidence suggests that primary infection of Salmonella is by the oral-fecal route for poultry. However, the airborne transmission of Salmonella and similar enteric zoonotic pathogens has been historically neglected. Increasing evidence of Salmonella bioaerosol generation in production facilities and studies suggesting the vulnerabilities of the avian respiratory architecture together have indicated the possibility of the respiratory system being a potential portal of entry for Salmonella in poultry. Presently, we evaluated this hypothesis through intratracheal (IT) administration of Salmonella Enteritidis and Salmonella Typhimurium, as separate challenges, in a total of 4 independent trials, followed by enumeration of cfu recovery in ceca-cecal tonsils and recovery incidence in liver and spleen. In all trials, both Salmonella Enteritidis and Salmonella Typhimurium, challenged IT colonized cecae to a similar or greater extent than oral administration at identical challenge levels. In most trials, chickens cultured for cfu enumeration from IT-challenged chicks at same dose as orally challenged, resulted in an increase of 1.5 log higher Salmonella Enteritidis from ceca-cecal tonsils and a much lower dose IT of Salmonella Enteritidis could colonize ceca to the same extent than a higher oral challenge. This trend of increased cecal colonization due to IT challenge was observed with all trails involving week-old birds (experiment 2 and 3), which are widely considered to be more difficult to infect via the oral route. Liver-spleen incidence data showed 33% of liver and spleen samples to be positive for Salmonella Enteritidis administered IT (106 cfu/chick), compared with 0% when administered orally (experiment 2, trial 1). Collectively, these data suggest that the respiratory tract may be a largely overlooked portal of entry for Salmonella infections in chickens. PMID:24570455

  4. Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

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    Angelino Julio Cariello

    2013-02-01

    Full Text Available PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO and S-nitroso-N-acetylcysteine (SNAC in a hydroxypropyl methylcellulose (HPMC matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each: Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05. All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

  5. Assessment of ocular surface toxicity after topical instillation of nitric oxide donors.

    Science.gov (United States)

    Cariello, Angelino Julio; Souza, Gabriela Freitas Pereira de; Lowen, Márcia Serva; Oliveira, Marcelo Ganzarolli de; Höfling-Lima, Ana Luisa

    2013-01-01

    To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

  6. Analgesic Efficacy of Intrarectal Instillation of Lidocaine Gel prior to Transrectal Ultrasound Guided Prostate Biopsy: A Prospective Randomized Trial

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    Yun, Tae Jin; Kim, Seung Hyup; Cho, Jeong Yeon [Seoul National University Hospital, Seoul (Korea, Republic of); Lee, Hak Jong; Lee, Sang Eun; Byun, Seok Soo [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Seong, Chang Kyu [Seoul National University Borame Hospital, Seoul (Korea, Republic of)

    2006-06-15

    To assess the analgesic efficacy of intrarectal lidocaine gel instillation prior to periprostatic nerve block during transrectal, ultrasound-guided prostate biopsies. Between March 2004 and October 2004, 203 consecutive patients for prostate biopsies were randomized into two groups. In 90 patients of group A, 10ml of 2% lidocaine gel was instilled intrarectally 10 minutes prior to periprostatic neurovascular bundle block, while 113 patients of group B received only periprostatic neurovascular bundle block without lidocaine gel instillation. Pain was assessed with the visual analogue pain scale, during periprostatic neurovascular bundle block (VAS 1), during the biopsy procedures (VAS 2) and 20 minutes after the procedure (VAS 3). The difference in VAS scores between patients in the two groups was evaluated with the unpaired t-test, with p < 0.05 considered significant. Patients in group A experienced statistically less pain during transrectal ultrasound guided prostate biopsy (VAS 2, 2.994 versus 3.903, p < 0.01). However, no significant difference in VAS values could be demonstrated during periprostatic neurovascular bundle block (VAS 1, 4.761 versus 5.133, p > 0.05) or at after 20 minutes after the procedure (VAS 3, 0.9778 versus 1.257, p > 0.05). Intrarectal instillation of lidocaine gel leads to significant additional analgesic efficacy during the biopsy procedure. It is a simple, safe and rapid technique that should be considered in all patients undergoing TRUS guided prostate biopsy

  7. Pretreatment Features to Influence Effectiveness of Intravesical Hyaluronic Acid Instillation in Refractory Interstitial Cystitis/Painful Bladder Syndrome

    Science.gov (United States)

    Kim, Aram; Lim, Bumjin; Song, Miho

    2014-01-01

    Purpose To determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect. Methods Thirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores ≥4 and total scores (symptom and bother scores) ≥13 on the pelvic pain and urgency/frequency (PUF) questionnaire and ≥12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a ≥2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation. Results The mean age was 57.0±1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed. Conclusions These results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation. PMID

  8. Intergenerational Transmission of Religious Giving: Instilling Giving Habits across the Life Course

    Directory of Open Access Journals (Sweden)

    Patricia Snell Herzog

    2016-07-01

    Full Text Available This paper investigates the research question: How do religious youth learn to give? While it is likely that youth learn religious financial giving from a variety of different sources, this investigation focuses primarily on how parents teach giving to their children. Supplementary data are also analyzed on the frequency in which youth hear extra-familial calls to give within their religious congregations. In focusing on parental transmission, the analysis identifies a number of approaches that parents report using to teach their children religious financial giving. It also investigates thoughts and feelings about religious financial giving by the children of these parents as a means of assessing the potential impacts of parental methods. Additionally, congregation member reflections on how they learned to give provide insights on giving as a process that develops across the life course, often instilled in childhood, but not appearing behaviorally until adulthood. As such, this paper contributes to a life course understanding of religious giving and has implications for giving across generations.

  9. 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.

  10. Radioautographic identification of central monoaminergic neurons after local micro-instillation of tritiated serotonin and norepinephrine in the cat

    International Nuclear Information System (INIS)

    Leger, Lucienne; Mouren-Mathieu, A.-M.; Descarries, Laurent.

    1978-01-01

    Monoaminergic neurons in nuclei raphe dorsalis and locus coeruleus of the cat may be visualized by radioautography after local micro-instillation of tritiated serotonin and noradrenaline. The concomitant administration of the appropriate tracer with the other biogenic amine in non radioactive form permits a specific identification of serotoninergic and catecholaminergic nerve cell bodies. A small contingent of presumptive serotoninergic neurons is thus demonstrated in the region of the locus coeruleus [fr

  11. Tumor associated macrophages polarization dictates the efficacy of BCG instillation in non-muscle invasive urothelial bladder cancer.

    Science.gov (United States)

    Suriano, Francesca; Santini, Daniele; Perrone, Giuseppe; Amato, Michela; Vincenzi, Bruno; Tonini, Giuseppe; Muda, Andrea; Boggia, Sara; Buscarini, Maurizio; Pantano, Francesco

    2013-11-05

    To evaluate the prognostic role of TAMs in patients affected by non-muscle invasive bladder cancer (NMIBC), undergone Trans Urethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) therapy. Data from 40 patients (36 men, 4 women), mean age 69 years (40-83 years), treated for NMIBC with TURB and BCG instillation were collected. Two different groups were considered: group with and group without bladder cancer recurrence. Correlations between immunofluorescence measured Mtot, M1 and M2 infiltration and clinicopathological parameters were evaluated using Spearman and Mann-Whitney methods. The recurrence-free survival rate was calculated using the Kaplan-Meier method. CD68 positive cells (Mtot) were observed in all specimens tested. High Mtot, M1 and M2 infiltration was observed in patients with disease recurrence, even before endovescical BCG instillation. Significant value for M2 infiltration (p = 0,042) was found calculating significativity between two group medians before BCG therapy. p = 0,072 and p = 0,180 were observed correlating median of Mtot and M1 between two groups of patients respectively. Values of p = 0,44, p = 0,23 and p = 0,64 from correlation between DFS and Mtot, M1 and M2 median in patients before endovescical BCG instillation, were calculated respectively. Comparing DFS and Mtot, M1 and M2 median in patients group after endovescical BCG instillation significant values were obtained (p = 0,020; p = 0,02; and p = 0,029 respectively). M2 tumor infiltration could be a prognostic value of recurrence in patients with NMIBC.

  12. 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.

  13. 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.

  14. Intratracheally Administered Pathogen-Associated Molecular Patterns Affect Antibody Responses of Poultry

    NARCIS (Netherlands)

    Ploegaert, T.C.W.; Vries Reilingh, de G.; Nieuwland, M.G.B.; Lammers, A.; Savelkoul, H.F.J.; Parmentier, H.K.

    2007-01-01

    Various potential immune-modulating microbially derived pathogen-associated molecular patterns (PAMP), or so called homotopes, are present in high concentrations in the environment of food animals. In previous studies, intravenously administered PAMP had variable effects on specific primary and

  15. Effect of nasal instillation of female urine or vaginal exudate on serum cortisol and prolactin levels in isolated and anesthetized male rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Mora, O A; García Castiñeiras, S; Ezquerra, C; Guisado, S

    1991-01-01

    Two male adult rhesus monkeys were used and caged individually. The room was temperature-controlled having a light-dark period of 12/12 hours. The animals were rapidly immobilized and immediately anesthetized with ketamine i. m. (10 mg/kg of body weight). They were bled four times at 15, 30, 45 and 60 mins after the ketamine injection, twice a week for 6 weeks. When necessary, maintenance doses of ketamine were administered. The serum levels of cortisol and prolactin after nasal instillation of a suspension of vaginal exudate showed lower values than in control conditions (nasal instillation of saline). The control levels of cortisol tended to increase up to 60 mins, whilst in experimental conditions (nasal instillation of female urine or vaginal exudate) did not show such an increase. Cortisol remained similar during the sampling and similar to the 15 mins control levels, but the difference is statistically significant only after instillation of vaginal exudate as compared with control. The levels of prolactin did not show significant variations during sampling either in control or after female urine instillation. However, the instillation of vaginal exudate decreased the prolactin levels at 15 mins which tended to recover the control levels up to 60 mins. These results support the hypothesis, discussed in a previous paper, that some chemical information from females suppresses or mitigates the effect of acute stress resulting from handling the animals before anesthesia.

  16. 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

  17. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

    OpenAIRE

    Li, Yu-Tao; He, Bei; Wang, Yu-Zhu; Wang, Jing

    2009-01-01

    Abstract To determine if nuclear factor-κB (NF-κB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model syste...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    BL/6BomTac) were anaesthetized with isoflurane and intratracheally instilled with saline containing 10% bronchoalveolar lavage (BAL) on gestation days 8, 11, 15 and 18. In addition, the early effects of the procedure were assessed in naive female mice. Control animals were not handled. Dams were......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 (C57...... instillation under isoflurane anaesthesia did not induce observable effects in pregnant mice or their offspring. We suggest that this procedure can be used as a means of exposure through the airways in studies of developmental toxicity....

  19. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

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

    2017-01-01

    21, CT was repeated before euthanasia. The trachea and epidermis were excised en bloc for histopathological evaluation. RESULTS: Insertion and correct placement of the disc was unproblematic in all animals. CT at day 14 confirmed a clear airway, appropriate placement of the disc, and full closure...

  20. Assessing the Feasibility of Replacing Standard-Dose Bacillus Calmette–Guérin Immunotherapy with Other Intravesical Instillation Therapies in Bladder Cancer Patients: A Network Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Cheng Wu

    2017-03-01

    Full Text Available Background: Bacillus Calmette–Guérin (BCG immunotherapy plays a key role in patients with bladder cancer. The shortage of intravesical BCG has motivated researchers to seek alternatives with equivalent efficacy If other alternative intravesical agents have equivalent efficacy compared to BCG, then it may be feasible to replace standard BCG with alternative options. Methods: We searched all relevant evidence in multiple sources and key data was extracted from included studies. Conventional and network meta-analysis were conducted so that pooled odds ratios (ORs for the event of tumor recurrence and progression can be computed. The relative efficacy of different intravesical instillation procedures was computed by pooled odds ratios and their 95% confidence or creditable intervals. Besides, several key model assumptions were evaluated in our analysis. Results: Three intravesical instillation procedures have the potential for preventing tumor recurrence: standard-dose BCG (BCG_SD, Epirubicin (EPI and Mitomycin C (MMC (ORs < 1. Patients with BCG SD also exhibited a decreased risk of tumor recurrence and progression compared to those with EPI. No significant difference in the risk of tumor recurrence or progression was detected between patients treated with BCG_ SD and those with low-dose BCG (BCG_LD. Results of SUCRA indicated that BCG_EPI, BCG_ MMC and BCG SD had higher rankings with respect to tumor recurrence and progression. Conclusions: BCG SD, EPI and MMC exhibited established efficacy for preventing tumor recurrence in postoperative BC patients. The efficacy of BCG may not be significantly reduced if standard dose was reduced to a lower level. However, there is no consensus suggesting that intravesical BCG with standard dose can be replaced by alternating or sequentially combined intravesical instillation therapies.

  1. Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis.

    Science.gov (United States)

    Shao, Yuan; Shen, Zhou-Jun; Rui, Wen-Bin; Zhou, Wen-Long

    2010-03-01

    To evaluate the efficacy of intravesical instillation of hyaluronic acid (HA) after hydrodistention for the treatment of patients with interstitial cystitis (IC) having small bladder capacity. A total of 47 patients with IC (aged 27-76 years) whose functional bladder capacity was less than 200 mL received bladder hydrodistention. Thereafter, 20 patients received intravesical instillation of 40 mg HA weekly in the first month and then monthly in the following 2 months. Sixteen patients received intravesical heparin instead and 11 patients received hydrodistention alone as the control. Mean voids per day, visual analog scale for pain, and functional bladder capacity were measured before hydrodistention and 3 and 6 months after hydrodistention in all 3 groups and 9 months after hydrodistention in HA and heparin groups. Two patients in the HA group and 1 in the heparin group failed to complete the treatment. Three months after hydrodistention, there was no improvement in the control group. Six and 9 months after hydrodistention, rate of improvement was significantly higher in the HA group than in the heparin group (77.8% vs 33.3%, P < .05; 50% vs 20%, P < .05). At 9 months, heparin treatment did not show any improvement. Improvement in voids per day (-1.8 +/- 2.5, P < .01), visual analog scale (-0.9 +/- 1.1, P < .01), and bladder capacity (16 +/- 18 mL, P < .01) was still significant in the HA group. Intravesical instillation of HA may obviously prolong the effect of bladder hydrodistention in patients with severe IC. Its effect was better than heparin. 2010 Elsevier Inc. All rights reserved.

  2. Can in vitro assays substitute for in vivo studies in assessing the pulmonary hazards of fine and nanoscale materials?

    Energy Technology Data Exchange (ETDEWEB)

    Sayes, Christie M.; Reed, Kenneth L. [DuPont Haskell Global Centers for Health and Environmental Sciences (United States); Subramoney, Shekhar; Abrams, Lloyd [DuPont Corporate Center for Analytical Services (United States); Warheit, David B., E-mail: David.B.Warheit@USA.dupont.co [DuPont Haskell Global Centers for Health and Environmental Sciences (United States)

    2009-02-15

    Risk evaluations for nanomaterials require the generation of hazard data as well as exposure assessments. Most of the validated nanotoxicity studies have been conducted using in vivo experimental designs. It would be highly desirable to develop in vitro pulmonary hazard tests to assess the toxicity of fine and nanoscale particle-types. However, in vitro evaluations for pulmonary hazards are known to have limited predictive value for identifying in vivo lung toxicity effects. Accordingly, this study investigated the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoparticle-types following exposures in rats. Initially, complete physicochemical characterization of particulates was conducted, both in the dry and wet states. Second, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle-types: carbonyl iron, crystalline silica, amorphous silica, nanoscale zinc oxide, or fine zinc oxide. Inflammation and cytotoxicity endpoints were measured at 24 h, 1 week, 1 month and 3 months post-instillation exposure. In addition, histopathological analyses of lung tissues were conducted at 3 months post-exposure. Pulmonary cell in vitro studies consisted of three different culture conditions at 4 different time periods. These included (1) rat L2 lung epithelial cells, (2) primary rat alveolar macrophages, and (3) alveolar macrophage-L2 lung epithelial cell co-cultures which were incubated with the same particles as tested in the in vivo study for 1, 4, 24, or 48 h. Cell culture fluids were evaluated for cytotoxicity endpoints and inflammatory cytokines at the different time periods in an attempt to match the biomarkers assessed in the in vivo study. Results of in vivo pulmonary toxicity studies demonstrated that instilled carbonyl iron particles produced little toxicity. Crystalline silica and amorphous silica particle exposures produced substantial inflammatory and cytotoxic effects initially, but

  3. Can in vitro assays substitute for in vivo studies in assessing the pulmonary hazards of fine and nanoscale materials?

    International Nuclear Information System (INIS)

    Sayes, Christie M.; Reed, Kenneth L.; Subramoney, Shekhar; Abrams, Lloyd; Warheit, David B.

    2009-01-01

    Risk evaluations for nanomaterials require the generation of hazard data as well as exposure assessments. Most of the validated nanotoxicity studies have been conducted using in vivo experimental designs. It would be highly desirable to develop in vitro pulmonary hazard tests to assess the toxicity of fine and nanoscale particle-types. However, in vitro evaluations for pulmonary hazards are known to have limited predictive value for identifying in vivo lung toxicity effects. Accordingly, this study investigated the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoparticle-types following exposures in rats. Initially, complete physicochemical characterization of particulates was conducted, both in the dry and wet states. Second, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle-types: carbonyl iron, crystalline silica, amorphous silica, nanoscale zinc oxide, or fine zinc oxide. Inflammation and cytotoxicity endpoints were measured at 24 h, 1 week, 1 month and 3 months post-instillation exposure. In addition, histopathological analyses of lung tissues were conducted at 3 months post-exposure. Pulmonary cell in vitro studies consisted of three different culture conditions at 4 different time periods. These included (1) rat L2 lung epithelial cells, (2) primary rat alveolar macrophages, and (3) alveolar macrophage-L2 lung epithelial cell co-cultures which were incubated with the same particles as tested in the in vivo study for 1, 4, 24, or 48 h. Cell culture fluids were evaluated for cytotoxicity endpoints and inflammatory cytokines at the different time periods in an attempt to match the biomarkers assessed in the in vivo study. Results of in vivo pulmonary toxicity studies demonstrated that instilled carbonyl iron particles produced little toxicity. Crystalline silica and amorphous silica particle exposures produced substantial inflammatory and cytotoxic effects initially, but

  4. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

    Science.gov (United States)

    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.

    2016-01-01

    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. PMID:26342468

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Eosinophilic lung inflammation in particulate-induced lung injury: technical consideration in isolating RNA for gene expression studies.

    Science.gov (United States)

    Kodavanti, U P; Jaskot, R H; Bonner, J; Badgett, A; Dreher, K L

    1996-01-01

    Particulate and other pollutant exposures are associated with lung injury and inflammation. The purpose of this study was to develop an approach by which intact RNA could be obtained from inflamed lung tissue from particulate-exposed animals in order to correlate injury with specific gene expression. Male Sprague Dawley (SD) and Fischer-344 (F-344) rats were intratracheally instilled with saline or residual oil fly ash (ROFA) particles, 8.3 mg/kg body weight in saline. At various time points following ROFA instillation, lungs were either lavaged or used for RNA isolation. ROFA exposure produced an increase in bronchoalveolar lavage fluid (BALF) neutrophils in both SD and F-344 rats. A time-dependent increase in eosinophils occurred only in SD rats but not in F-344 rats. Extraction of inflamed pulmonary tissue having a high influx of eosinophils for RNA using the conventional acid guanidinium thiocyanate phenol-chloroform (AGPC) procedure failed to provide undegraded RNA suitable for RT-PCR and Northern blot analysis of beta-actin mRNA expression. Mixing intact total RNA from saline control rat lungs with degraded RNA samples from inflamed lung yielded a gel profile of degraded RNA, indicating the presence of ribonuclease-like activity in the RNA extracted from lung tissues having eosinophil influx. Evidently, the conventional AGPC procedure failed to completely remove ribonuclease activity associated with ROFA-induced pulmonary eosinophil influx. This study reports a single-step modification to the AGPC extraction method that does not require additional reagents or additional precipitation steps for extracting undegraded RNA from nuclease-rich inflamed lung tissue. The aqueous layer resulting from mixing homogenate and chloroform is extracted a second time using an equal volume of AGPC buffer followed by addition of chloroform and centrifugation. The second aqueous phase is then treated as described in the conventional RNA extraction protocol. This simple and

  10. 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...

  11. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  12. 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)

  13. In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles.

    Science.gov (United States)

    Lu, Xiaoyan; Miousse, Isabelle R; Pirela, Sandra V; Moore, Jodene K; Melnyk, Stepan; Koturbash, Igor; Demokritou, Philip

    2016-01-01

    Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.

  14. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

    Directory of Open Access Journals (Sweden)

    Wang Yu-Zhu

    2009-08-01

    Full Text Available Abstract To determine if nuclear factor-κB (NF-κB activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs, and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-κB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC-labeled NF-κB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-κB and activator protein 1(AP-1 activity was detected by the electrophoretic motility shift assay (EMSA. Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA in bronchoalveolar lavage fluid (BALF and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 ± 3.30%. Analysis of respiratory function indicated that transfection of NF-κB decoy ODNs significantly impacted peak expiratory flow (PEF, and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-κB decoy ODNs smoke exposed mice. NF-κB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP 1α and monocyte chemoattractant protein 1(MCP-1 in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-κB decoy ODNs-treated mice showed significant increase in the

  15. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice.

    Science.gov (United States)

    Li, Yu-Tao; He, Bei; Wang, Yu-Zhu; Wang, Jing

    2009-08-25

    To determine if nuclear factor-kappaB (NF-kappaB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-kappaB can be blocked by intratracheal administration of NF-kappaB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-kappaB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-kappaB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-kappaB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-kappaB and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 +/- 3.30%. Analysis of respiratory function indicated that transfection of NF-kappaB decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-kappaB decoy ODNs smoke exposed mice. NF-kappaB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1alpha and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-kappaB decoy ODNs-treated mice showed

  16. 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.

  17. Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

    Science.gov (United States)

    Bezemer, Gillina F.G.; Bauer, Stephen M.; Oberdörster, Günter; Breysse, Patrick N.; Pieters, Raymond H.H.; Georas, Steve N.; Williams, Marc A.

    2011-01-01

    The biological effects of acute particulate air pollution exposure in host innate immunity remain obscure and have relied largely on in vitro models. We hypothesized that single acute exposure to ambient or engineered particulate matter (PM) in the absence of other secondary stimuli would activate lung dendritic cells (DC) in vivo and provide information on the early immunological events of PM exposure and DC activation in a mouse model naïve to prior PM exposure. Activation of purified lung DC was studied following oropharyngeal instillation of ambient particulate matter (APM). We compared the effects of APM exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and silver nanoparticles (AgP). We found that PM species induced variable cellular infiltration in the lungs and only APM exposure induced eosinophilic infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type cytokine response from naïve CD4+ T cells ex vivo. Cultures of primary peribronchial lymph node cells from mice exposed to APM and DEP also displayed a Th2-type immune response ex vivo. We conclude that exposure of the lower airway to various PM species induces differential immunological responses and immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness. PMID:21099199

  18. CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice.

    Science.gov (United States)

    Schneberger, D; Gordon, J R; DeVasure, J M; Boten, J A; Heires, A J; Romberger, D J; Wyatt, T A

    2015-04-01

    Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Previously, we have demonstrated that an endotoxin-independent component of swine barn dust extract (SBE) elevates lung chemokines in a protein kinase C (PKC)-dependent manner resulting in the significant formation of lung inflammatory cell infiltrates in a mouse model of SBE injury. In this study we test the ability of a CXCR1/CXCR2 antagonist, CXCL8(3-74)K11R/G31P (G31P) to block many of the features of lung-inflammation in response to challenge with SBE in an established mouse exposure system. Injection of G31P concurrent with SBE nasal instillation over a course of 3 weeks significantly reduced neutrophil accumulation in the lungs of barn dust exposed animals compared to those given SBE alone. There was a similar reduction in pro-inflammatory cytokines and chemokines IL-6, KC, and MIP-2 in SBE plus G31P-treated mice. In addition to excreted products, the receptors ICAM-1, CXCR1, and CXCR2, which all were elevated with SBE exposure, were also decreased with G31P treatment. SBE activation of PKCα and PKCε was reduced as well with G31P treatment. Thus, G31P was found to be highly effective at reducing several features of lung inflammation in mice exposed to barn dust extracts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome

    OpenAIRE

    Jung-Soo Pyo; Won Jin Cho

    2016-01-01

    Background/Aims: To assess the efficacy of intravesical hyaluronic acid (HA) and HA/chondroitin sulfate (CS) instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. Methods: A systematic literature search was performed using the keywords: ‘interstitial cystitis' or ‘painful bladder syndrome' or ‘bladder pain syndrome' and ‘hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS...

  20. EFFECT OF INSTILLED COMBUSTION-DERIVED ENVIRONMENTAL PARTICLES IN SPONTANEOUSLY HYPERTENSIVE RATS. PART II: PULMONARY RESPONSES

    Science.gov (United States)

    AbstractA consistent association between exposure to high concentrations of ambient particulate matter (PM) and excess cardiopulmonary-related morbidity and mortality has been observed in numerous epidemiological studies, across many different geographical locations. To elic...

  1. Sepse fatal após instilação intravesical de BCG: relato de caso Fatal sepsis after intravesical instillation of BCG: case report

    Directory of Open Access Journals (Sweden)

    Ulysses Vasconcellos de Andrade e Silva

    2011-03-01

    Full Text Available A instilação intravesical do bacilo de Calmette-Guérin (BCG é o tratamento de escolha para carcinoma de bexiga in situ ou tumores superficiais de bexiga de alto grau não invasivos. Este tratamento geralmente é bem tolerado, mas podem ocorrer complicações graves. Paciente idoso, coronariopata, portador de carcinoma superficial de bexiga de alto grau recidivado foi submetido à instilação intravesical de BCG, evoluindo com choque séptico. Recebeu antibioticoterapia de amplo espectro, tuberculostáticos, corticóide, aminas vasoativas, suporte ventilatório e tratamento hemodialítico, sem melhora. Faleceu nove dias após a instilação intravesical de BCG por insuficiência de múltiplos órgãos.Intravesical instillation of bacillus Calmette-Guérin (BCG is the treatment of choice for carcinoma in situ and non-invasive high-grade superficial tumors of the urinary bladder. This treatment is well tolerated overall, but serious complications can occur. An elderly man with coronary disease and recurrent high-grade superficial carcinoma of the bladder underwent intravesical instillation of BCG and developed septic shock. He received wide range antibiotics, tuberculostatic and vasoactive drugs, corticosteroids, mechanical ventilation and renal replacement therapy without improvement. He died nine days after the intravesical instillation of BCG because of multiple organ failure.

  2. Comparing Transcervical Intrauterine Lidocaine Instillation with Rectal Diclofenac for Pain Relief During Outpatient Hysteroscopy: A Randomized Controlled Trial

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    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.

  3. Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation.

    Science.gov (United States)

    Fangueiro, Joana F; Andreani, Tatiana; Fernandes, Lisete; Garcia, Maria L; Egea, Maria A; Silva, Amélia M; Souto, Eliana B

    2014-11-01

    The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Instilling positive beliefs about disabilities: pilot testing a novel experiential learning activity for rehabilitation students.

    Science.gov (United States)

    Silverman, Arielle M; Pitonyak, Jennifer S; Nelson, Ian K; Matsuda, Patricia N; Kartin, Deborah; Molton, Ivan R

    2018-05-01

    To develop and test a novel impairment simulation activity to teach beginning rehabilitation students how people adapt to physical impairments. Masters of Occupational Therapy students (n = 14) and Doctor of Physical Therapy students (n = 18) completed the study during the first month of their program. Students were randomized to the experimental or control learning activity. Experimental students learned to perform simple tasks while simulating paraplegia and hemiplegia. Control students viewed videos of others completing tasks with these impairments. Before and after the learning activities, all students estimated average self-perceived health, life satisfaction, and depression ratings among people with paraplegia and hemiplegia. Experimental students increased their estimates of self-perceived health, and decreased their estimates of depression rates, among people with paraplegia and hemiplegia after the learning activity. The control activity had no effect on these estimates. Impairment simulation can be an effective way to teach rehabilitation students about the adaptations that people make to physical impairments. Positive impairment simulations should allow students to experience success in completing activities of daily living with impairments. Impairment simulation is complementary to other pedagogical methods, such as simulated clinical encounters using standardized patients. Implication of Rehabilitation It is important for rehabilitation students to learn how people live well with disabilities. Impairment simulations can improve students' assessments of quality of life with disabilities. To be beneficial, impairment simulations must include guided exposure to effective methods for completing daily tasks with disabilities.

  5. Commentary on "The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature." Swietek N, Waldert M, Rom M, Schatzl G, Wiener HG, Susani M, Klatte T. Department of Urology, Medical University of Vienna, Vienna, Austria: J Urol 2012;188(3):748-53 [Epub 2012 Jul 20].

    Science.gov (United States)

    See, William A

    2013-07-01

    We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer. This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE(®), EMBASE(®) and Web of Science(®). The records of 740 patients from a total of 7 studies were finally analyzed. Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable. Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology. Copyright © 2013. Published by Elsevier Inc.

  6. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice.

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    P Padmini S J Khedoe

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD. However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE. METHODS: Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD. To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly. After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed. RESULTS: Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE. CONCLUSION: This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.

  7. The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice.

    Science.gov (United States)

    Khedoe, P Padmini S J; Wong, Man C; Wagenaar, Gerry T M; Plomp, Jaap J; van Eck, Miranda; Havekes, Louis M; Rensen, Patrick C N; Hiemstra, Pieter S; Berbée, Jimmy F P

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed. Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE. This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.

  8. A Study on Alternative Approaches to Instill Environmental Concerns in the Domain of Production Management of Industrial Firms

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    Ronaldo Manzan

    2013-10-01

    Full Text Available This article presents a comparative analysis of alternative models of production with environmental concerns that may lead to higher effectiveness in initiatives undertaken by industrial firms towards the development of more sustainable operations. The objective is to organize the knowledge on the subject of such models and provide guidelines that may help managers in selecting the most fitting approach for their business, according to the strategy and conditions of the firm. Among the presented models, the Cleaner Production model stands out for promoting the approach of nurturing the concurrent strengthening of quality, productivity, and sustainability in the existing manufacturing processes by dealing more comprehensively with factors internal to the firm that may be directly controlled by the managers.

  9. Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice

    DEFF Research Database (Denmark)

    Wallin, Håkan; Kyjovska, Zdenka O.; Poulsen, Sarah S.

    2016-01-01

    for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary...... instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside...

  10. Aspiration of activated charcoal elicits an increase in lung microvascular permeability.

    Science.gov (United States)

    Arnold, T C; Willis, B H; Xiao, F; Conrad, S A; Carden, D L

    1999-01-01

    Gastric decontamination with orally administered activated charcoal is the recommended treatment for many poisonings. However, ingestion of central nervous system depressants resulting in loss of protective airway reflexes may result in pulmonary aspiration of activated charcoal. Although activated charcoal has been reported to be an inert substance, evidence suggests that pulmonary aspiration of charcoal is associated with lung edema formation and pulmonary compromise. This study tested the hypothesis that intratracheal instillation of activated charcoal disrupts the integrity of the lung microvascular barrier. The capillary filtration coefficient (Kf,c), a sensitive measure of lung microvascular permeability, was determined isogravimetrically prior to and after intratracheal instillation of activated charcoal 0.04 g/kg (12% weight/vol solution, pH 7.4) or an equal volume of sterile water in isolated, perfused rat lungs. Arterial blood gas analysis was determined prior to and after tracheal instillation of activated charcoal or sterile water in a separate group of animals. Intratracheal instillation of activated charcoal resulted in a significant increase in pulmonary microvascular permeability compared to lungs treated with sterile water or control lungs (delta Kf,c = +0.21 +/- 0.076; -0.014 +/- 0.04; and -0.041 +/- 0.02 mL/min/cm H2O/100 g lung tissue, respectively, p animals administered activated charcoal compared to time-matched controls and animals administered sterile water. Intratracheal instillation of activated charcoal is associated with a significant increase in lung microvascular permeability and arterial blood gas derangements. The effects of activated charcoal on pulmonary microvascular barrier integrity may contribute to the lung edema formation and pulmonary compromise observed following clinical aspiration of activated charcoal.

  11. 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.

  12. Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome

    Directory of Open Access Journals (Sweden)

    Jung-Soo Pyo

    2016-09-01

    Full Text Available Background/Aims: To assess the efficacy of intravesical hyaluronic acid (HA and HA/chondroitin sulfate (CS instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. Methods: A systematic literature search was performed using the keywords: ‘interstitial cystitis' or ‘painful bladder syndrome' or ‘bladder pain syndrome' and ‘hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS. Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI and Problem Index (ICPI, frequency, nocturia, bladder volume, and voided urine volume. Results: Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315 and ICPI (MD -2.941, 95% CI -3.767 to -2.116. Similarly, the other outcomes were significantly improved. Conclusion: Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome.

  13. Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome.

    Science.gov (United States)

    Pyo, Jung-Soo; Cho, Won Jin

    2016-01-01

    To assess the efficacy of intravesical hyaluronic acid (HA) and HA/chondroitin sulfate (CS) instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. A systematic literature search was performed using the keywords: 'interstitial cystitis' or 'painful bladder syndrome' or 'bladder pain syndrome' and 'hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS). Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), frequency, nocturia, bladder volume, and voided urine volume. Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively) was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315) and ICPI (MD -2.941, 95% CI -3.767 to -2.116). Similarly, the other outcomes were significantly improved. Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome. © 2016 The Author(s) Published by S. Karger AG, Basel.

  14. Effect of nasal instillation of female urine or vaginal exudate on testosterone secretion in isolated and anesthetized male rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Mora, O A; García Castiñeiras, S; Guisado, S; Ezquerra, C

    1990-01-01

    Two male adult rhesus monkeys were individually placed in cages with a pulling device in order to immobilize the animals for anesthesia. The room was temperature-controlled having a light/dark period of 12/12 hours. The animals were rapidly immobilized and immediately anesthetized with ketamine i. m. (10 mg/kg of body weight). They were bled four times at 15, 30, 45, and 60 mins after the ketamine injection, twice a week during 6 weeks. When necessary, maintenance doses of ketamine were administered. The levels of serum testosterone in experimental conditions (nasal instillation of female urine or a suspension of vaginal exudate) showed significant lower values with respect to those in control conditions (saline instillation). The control levels of testosterone tend to increase up to 60 mins. The testosterone from samples obtained in experimental conditions did not show such an increase, remaining similar during the sampling and similar to the 15 min control levels that could be considered as basal. These results seem to point out some chemical information from females capable of modifying the pattern of secretion of testosterone of the males in the above mentioned experimental conditions.

  15. Comparative microscopic study of human and rat lungs after overexposure to welding fume.

    Science.gov (United States)

    Antonini, James M; Roberts, Jenny R; Schwegler-Berry, Diane; Mercer, Robert R

    2013-11-01

    Welding is a common industrial process used to join metals and generates complex aerosols of potentially hazardous metal fumes and gases. Most long-time welders experience some type of respiratory disorder during their time of employment. The use of animal models and the ability to control the welding fume exposure in toxicology studies have been helpful in developing a better understanding of how welding fumes affect health. There are no studies that have performed a side-by-side comparison of the pulmonary responses from an animal toxicology welding fume study with the lung responses associated with chronic exposure to welding fume by a career welder. In this study, post-mortem lung tissue was donated from a long-time welder with a well-characterized work background and a history of extensive welding fume exposure. To simulate a long-term welding exposure in an animal model, Sprague-Dawley rats were treated once a week for 28 weeks by intratracheal instillation with 2mg of a stainless steel, hard-surfacing welding fume. Lung tissues from the welder and the welding fume-treated rats were examined by light and electron microscopy. Pathological analysis of lung tissue collected from the welder demonstrated inflammatory cell influx and significant pulmonary injury. The poor and deteriorating lung condition observed in the welder examined in this study was likely due to exposure to very high levels of potentially toxic metal fumes and gases for a significant number of years due to work in confined spaces. The lung toxicity profile for the rats treated with welding fume was similar. For tissue samples from both the welder and treated rats, welding particle accumulations deposited and persisted in lung structures and were easily visualized using light microscopic techniques. Agglomerates of deposited welding particles mostly were observed within lung cells, particularly alveolar macrophages. Analysis of individual particles within the agglomerates showed that these

  16. 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

  17. Comparison of lung damage in mice exposed to black carbon particles and ozone-oxidized black carbon particles.

    Science.gov (United States)

    Chu, Hongqian; Shang, Jing; Jin, Ming; Li, Qian; Chen, Yueyue; Huang, Hongpeng; Li, Yuan; Pan, Yao; Tao, Xi; Cheng, Zhiyuan; Meng, Qinghe; Jia, Guang; Zhu, Tong; Wei, Xuetao; Hao, Weidong

    2016-12-15

    Black carbon (BC) is a key component of atmospheric particles and has a significant effect on human health. Oxidation could change the characteristics of BC and increase its toxicity. The comparison of lung damage in mice exposed to BC and ozone-oxidized BC (oBC) particles is investigated in this study. Mice which were intratracheally instilled with particles have a higher expression of IL-1β, IL-6 and IL-33 in bronchoalveolar lavage fluid (BALF). Also, the IL-6, IL-33 mRNA expression in the lung tissue of mice instilled with oBC was higher than that of mice instilled with BC. The expression of CD3 in the lung tissue of mice intratracheally instilled with oBC was higher than the mice distilled with BC. The pathology results showed that the lung tissue of mice instilled with oBC particles have much more inflammatory cells infiltration than that of mice treated with BC. It is believed that the PI3K-AKT pathway might be involved in the oBC particles caused lung damage. Results indicated that oBC particles in the atmosphere may cause more damage to health. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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......RNA levels were increased at all time point for the highest dose and 28 days post-exposure for the middle dose. DEP increased levels of DNA strand breaks in lung tissue for all doses 1 day post-exposure and after 28 days for mid- and high-dose groups. Pulmonary exposure to DEP induced transient inflammation...

  20. 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.

  1. Therapeutic Effect of C-Phycocyanin Extracted from Blue Green Algae in a Rat Model of Acute Lung Injury Induced by Lipopolysaccharide

    OpenAIRE

    Leung, Pak-on; Lee, Hao-Hsien; Kung, Yu-Chien; Tsai, Ming-Fan; Chou, Tz-Chong

    2013-01-01

    C-Phycocyanin (CPC), extracted from blue green algae, is a dietary nutritional supplement due to its several beneficial pharmacological effects. This study was conducted to evaluate whether CPC protects against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in rats. Rats were challenged with LPS (5?mg/kg body weight) intratracheally to induce ALI. After 3?h LPS instillation, rats were administrated with CPC (50?mg/kg body weight, i.p.) for another 3?h. Our results showed that post...

  2. 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

  3. 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.

  4. 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)

  5. [Fever, Hepatic Dysfunction and Interstitial Pneumonia Caused by Intravesical Bacillus Calmette-Guerin (BCG) Instillation after Urethral Bougie : A Case Report].

    Science.gov (United States)

    Nitta, Satoshi; Sakka, Shotaro; Endo, Tsuyoshi; Komine, Manabu; Tsutsumi, Masakazu; Nishiyama, Hiroyuki

    2017-10-01

    A 60-year-old man had a past history of urothelial carcinoma of the left renal pelvis treated with laparoscopic left total nephroureterectomy in October 2004. He underwent transurethral resection of the bladder tumor (TUR-Bt) twice for recurrence of urothelial carcinoma in the bladder in April 2014 and February 2015, and subsequently received intravesical Bacillus Calmette-Guerin (BCG) instillation at weekly intervalsfor prevention of recurrence. In November 2016, a year and a half after BCG induction, he received BCG therapy after urethral bougie to dilate the urethral stricture. After BCG therapy, he exhibited a continuously high fever. Immediate antituberculosis drug therapy in consideration of BCG sepsis failed to improve the symptoms, and all cultures from urine and blood were negative for mycobacterium tuberculosis. Serum liver enzyme was markedly elevated and chest CT showed diffuse interstitial shadows in both lower lungs. Thus, we considered that these symptoms were caused by a hypersensitivity reaction to BCG and started pulse steroid therapy. After pulse steroid therapy, body temperature, and hepatic function became normal and interstitial pneumonia subsided.

  6. Outcomes following intra-amniotic instillation with indigo carmine to diagnose prelabor rupture of membranes in singleton pregnancies: a single center experience.

    Science.gov (United States)

    Adekola, Henry; Gill, Navleen; Sakr, Sharif; Hobson, Deslyn; Bryant, David; Abramowicz, Jacques S; Soto, Eleazar

    2016-01-01

    To evaluate clinical outcomes of women with singleton pregnancies that underwent intra-amniotic dye instillation (amniodye test) following equivocal diagnosis of prelabor rupture of membranes (PROM). Records of 34 pregnant women who underwent amniodye test for equivocal PROM were reviewed. Comparisons of characteristics, amniotic fluid (AF) cultures, AF interleukin (IL)-6 concentrations, and placenta pathology results between women who tested positive and those who tested negative were performed. A sub-analysis of women who were amniodye test-negative was also performed. (1) Commonest indication for amniodye test was a typical history of PROM with positive conventional tests and persistently normal AF volume, (2) amniodye test-positive women had a shorter procedure-to-delivery interval (p = 0.008), and a greater proportion of histologic acute chorioamnionitis (p = 0.04) and funisitis (p = 0.01) than amniodye-negative women, and (3) in addition to similarities to women with amniodye-positive test, amniodye test-negative women who delivered <34 weeks, had a greater proportion of women with risk for preterm birth (p = 0.04), than their counterparts who delivered between 34 0/7 and 36 6/7 weeks. Equivocal diagnosis of PPROM should warrant an amniodye test to avoid iatrogenic intervention in women with intact amniotic membranes. AF analysis should be performed in amniodye test-negative women.

  7. 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.

  8. Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Mayer Paula

    2009-12-01

    Full Text Available Abstract Background Ambient particulate matter (PM-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (59Fe2O3 particles of 0.5 and 1.5 μm geometric mean diameter. Fe2O3 particles were examined for the induction of the release of interleukin 6 (IL-6 as pro-inflammatory and prostaglandin E2 (PGE2 as anti-inflammatory markers in cultured alveolar macrophages (AM from Wistar Kyoto (WKY rats. In addition, we exposed male WKY rats to monodispersed Fe2O3 particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight to examine in vivo inflammation. Results Particles of both sizes are insoluble extracellularly in the media but moderately soluble in AM with an intracellular dissolution rate of 0.0037 ± 0.0014 d-1 for 0.5 μm and 0.0016 ± 0.0012 d-1 for 1.5 μm 59Fe2O3 particles. AM exposed in vitro to 1.5 μm particles (10 μg/mL for 24 h increased IL-6 release (1.8-fold; p 2 synthesis (1.9-fold; p 2 synthesis (2.5-fold, p 2 synthesis by indomethacin caused a pro-inflammatory phenotype as noted by increased IL-6 release from AM exposed to 0.5 μm particles (up to 3-fold; p Conclusions Fe2O3 particle-induced neutrophilic inflammatory response in vivo and pro-inflammatory cytokine release in vitro might be modulated by intracellular soluble iron via PGE2 synthesis. The suppressive effect of intracellular released soluble iron on particle-induced inflammation has implications on how ambient PM-associated but soluble metals influence pulmonary toxicity of ambient PM.

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

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria

    2010-01-01

    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...

  10. Infection of the upper respiratory tract with seasonal influenza A(H3N2) virus induces protective immunity in ferrets against infection with A(H1N1)pdm09 virus after intranasal, but not intratracheal, inoculation.

    Science.gov (United States)

    Bodewes, Rogier; Kreijtz, Joost H C M; van Amerongen, Geert; Hillaire, Marine L B; Vogelzang-van Trierum, Stella E; Nieuwkoop, Nella J; van Run, Peter; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2013-04-01

    The clinical symptoms caused by infection with influenza A virus vary widely and depend on the strain causing the infection, the dose and route of inoculation, and the presence of preexisting immunity. In most cases, seasonal influenza A viruses cause relatively mild upper respiratory tract disease, while sometimes patients develop an acute severe pneumonia. Heterosubtypic immunity induced by previous infections with influenza A viruses may dampen the development of clinical symptoms caused by infection with influenza A viruses of another subtype, as is the case during influenza pandemics. Here we show that ferrets acquire protective immunity after infection of the upper respiratory tract with a seasonal influenza A(H3N2) virus against subsequent infection with influenza A(H1N1)pdm09 virus inoculated by the intranasal route. However, protective heterosubtypic immunity was afforded locally, since the prior infection with the A(H3N2) virus did not provide protection against the development of pneumonia induced after intratracheal inoculation with the A(H1N1)pdm09 virus. Interestingly, some of these animals developed more severe disease than that observed in naïve control animals. These findings are of interest in light of the development of so-called universal influenza vaccines that aim at the induction of cross-reactive T cell responses.

  11. Sensitivity of MRI in detecting alveolar infiltrates. Experimental studies; Sensitivitaet der MRT fuer alveolaere Infiltrate. Experimentelle Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Biederer, J.; Busse, I.; Grimm, J.; Reuter, M.; Heller, M. [Kiel Univ. (Germany). Klinikum fuer Diagnostische Radiologie; Muhle, C. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin; Freitag, S. [Kiel Univ. (Germany). Inst. fuer Medizinische Informatik und Statistik

    2002-08-01

    Purpose: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T{sub 1}- and T{sub 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{sub 2}-TSE and T{sub 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{sub 2}-HASTE and T{sub 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{sub 2}-weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30% at 100 ml (p<0.01) and 60% at 200 ml (p<0.01). With 2D- and 3D-GRE the infiltrates were not visible, although the lung parenchyma signal increase was statistically significant. On 2D-GRE the increase in signal intensity reached 0.74% (p=0.32) after 100 ml and 5.6% (p<0.01) after 200 ml for 3D-GRE: 2.2% [p=0.02] at 100 ml and 4.4% at 200 ml [p<0.001]. The CT controls revealed a significant increase of lung density of 17. H.E. at 100 ml (p=0.02) and 75 H.E. at 200 ml (p<0.01). Conclusions: MRI with T{sub 2}-weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to

  12. Intrapleural instillation of autologous blood for persistent air leak in spontaneous pneumothorax- is it as effective as it is safe?

    Directory of Open Access Journals (Sweden)

    Karangelis Dimos

    2010-08-01

    Full Text Available Abstract Objective The aim of the present study was to evaluate the efficacy of autologous blood pleurodesis in the management of persistent air leak in spontaneous pneumothorax. Patients and methods A number of 15 patients (10 male and 5 female were included in this prospective study between March 2005 and December 2009. The duration of the air leak exceeded 7 days in all patients. The application of blood pleurodesis was used as the last preoperative conservative method of treatment in 12 patients. One patient refused surgery and two were ineligible for operation due to their comorbidities. A blood sample of 50 ml was obtained from the patient's femoral vein and immediately introduced into the chest tube. Results A success rate of 27% was observed having the air leak sealed in 4 patients in less than 24 hours. Conclusion Despite our disappointingly poor outcome, the authors believe that the procedure's safety, convenience and low cost establish it as a worth trying method of conservative treatment for patients with the aforementioned pathology for whom no other alternative than surgery would be a choice.

  13. Fibrin glue instillation under skin flaps to prevent seroma-related morbidity following breast and axillary surgery.

    Science.gov (United States)

    Sajid, Muhammad S; Hutson, Kristian H; Rapisarda, Ignazio F; Bonomi, Riccardo

    2013-05-31

    Fibrin glue (FG) combines fibrinogen and thrombin, under the presence of factor XIII and calcium chloride, and produces a 'fibrin clot' as would occur through the natural clotting cascade. FG is thought to close over any small vessels including lymphatics that are too small for conventional surgical closure, thereby reducing seroma formation, seroma incidence and related comorbidities. To assess the evidence on the effectiveness of FG in people undergoing breast and axillary surgery and to establish whether FG is an efficient modality to prevent postoperative seroma and seroma-related outcomes. We searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register (9 December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2012), MEDLINE (9 December 2011), EMBASE (9 December 2011), LILACS (22 October 2012), SCI-E (22 October 2012), the World Health Organization's International Clinical Trial Registry (9 December 2011) and ClinicalTrials.gov (22 October 2012). Randomised controlled trials (RCTs) comparing the effectiveness of FG in terms of reducing the postoperative seroma incidence and related comorbidities in people undergoing breast and axillary surgery. At least two review authors independently scrutinised search results, selected eligible studies and extracted the data. The pooled analysis of the extracted data was achieved by the statistical analysis on Review Manager software. The quality of studies was assessed using The Cochrane Collaboration's 'Risk of bias' tool. The search of four standard electronic databases yielded 119 potentially relevant studies but only 18 RCTs involving 1252 people were found suitable for statistical analysis. There was significant heterogeneity among trials and the majority of trials were of poor quality. The use of FG under skin flaps following breast and axillary surgery failed to reduce the incidence of postoperative seroma (risk ratio (RR) 1.02; 95% Confidence Interval (CI) 0.90 to 1.16, P

  14. Ultrafine Particulate Matter Increases Cardiac Ischemia/Reperfusion Injury via Mitochondrial Permeability Transition Pore.

    Science.gov (United States)

    Ultrafine Particulate Matter (UFP) has been associated with increased cardiovascular morbidity and mortality. However, the mechanisms that drive PM associated cardiovascular disease and dysfunction remain unclear. We examined the impact of intratracheal instillation of 100 ᠊...

  15. Antigen-specific CD4 T cells are induced after intravesical BCG-instillation therapy in patients with bladder cancer and show similar cytokine profiles as in active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Julia Elsäßer

    Full Text Available Specific T cell immunity in patients with active tuberculosis is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used intravesical immunotherapy with attenuated live Bacille Calmette-Guérin (BCG in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards purified protein derivate (PPD and to study whether cytokine profiles differ depending on pre-existing immunity. Eighteen patients with non-muscle invasive bladder cancer were recruited during the BCG-induction course. Fifty-four healthy individuals served as controls. Interferon (IFN-γ and interleukin (IL-2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation using a rapid flow-cytometric whole blood immunoassay. Baseline levels of IFN-γ producing PPD-specific T cells were comparable to controls. T cells showed a 5-fold increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to 0.42%, p=0.0007. Systemic immunity was induced in all patients, although the increase was less pronounced in patients with pre-existing immunity. As in active TB, cytokine profiling during therapy revealed a lower percentage of multifunctional IFN-γ/IL-2 double-positive T cells compared to controls (60.2% vs. 71.9%, p=0.0003. Of note, when comparing patients with and without pre-existing immunity, cytokine profiles in patients with primary immunity were shifted towards IL-2 single producing T cells (p=0.02, whereas those in patients with pre-existing immunity were shifted towards IFN-γ single-positivity (p=0.01. In conclusion, systemic T cell responses were induced after BCG-therapy, and their kinetics and cytokine profile depended on pre-existing immunity. Decreased functionality is a typical feature of specific immunity in both patients with active tuberculosis and BCG

  16. NTP Toxicity Study Report on the atmospheric characterization, particle size, chemical composition, and workplace exposure assessment of cellulose insulation (CELLULOSEINS).

    Science.gov (United States)

    Morgan, Daniel L

    2006-08-01

    from 0.6 to 0.7 mum. The numbers of fibers in the respirable fractions ranged from 9.7 x 103 to 1.4 x 106 fibers/g of CI. The respirable particle fractions did not contain cellulose material and consisted mainly of fire retardants and small quantities of clays. The respirable fraction from one CI sample was administered by intratracheal instillation to male Fischer 344 rats at doses of 0, 0.625, 1.25, 2.5, 5, or 10 mg/kg body weight; the bronchoalveolar lavage (BAL) fluid cellularity was evaluated 3 days later. Based upon the relatively mild severity of the inflammatory response, a dose of 5 mg/kg body weight was selected for use in a subsequent 28-day study. Rats received CI, titanium dioxide (particle controls), or sterile saline (controls). BAL fluid was evaluated 1, 3, 7, 14, and 28 days after instillation, and lung histopathology was evaluated 14 and 28 days after treatment. CI caused a greater influx of inflammatory cells than titanium dioxide and caused significant increases in BAL fluid protein and lactate dehydrogenase. These CI-induced changes in BAL fluid parameters were transient and by day 14 were not significantly different than those observed in rats treated with titanium dioxide or phosphate-buffered saline. Unlike titanium dioxide, CI treatment caused a minimal to mild nonprogressive, minimally fibrosing granulomatous pneumonitis characterized by nodular foci of macrophages and giant cells. These results indicated that few respirable particles or fibers are likely generated during the CI application and that the acute pulmonary toxicity is minimal. The CI exposure assessment was conducted with 10 contractors located across the United States. Air samples of total dust and respirable dust were collected for scanning electron microscopy (SEM) to characterize any fibers in the dust. Two SEM air samples for each day of CI activities were collected from the installer and hopper operator. Bulk CI samples were collected and analyzed for metal, boron, and

  17. Influence of a Saccharomyces cerevisia fermentation product on the pathophysiological response to a combined intranasal bovine herpesvirus-1 and intratracheal Mannheimia haemolytica challenge in Holstein steers

    Science.gov (United States)

    The objective of this study was to determine the effects of supplementing a Saccharomyces cerevisiae fermentation product prototype (Prototype) on the pathophysiological response during a combined viral-bacterial respiratory challenge. Holstein steer calves (126.5±6.11kg; N=16) were completely rando...

  18. Illusions of Competence in Monitoring One's Knowledge During Study

    Science.gov (United States)

    Koriat, Asher; Bjork, Robert A.

    2005-01-01

    The monitoring of one's own knowledge during study suffers from an inherent discrepancy between study and test situations: Judgments of learning (JOLs) are made in the presence of information that is absent but solicited during testing. The failure to discount the effects of that information when making JOLs can instill a sense of competence…

  19. The effects of pentoxifylline on lung inflammation in a rat model of meconium aspiration syndrome.

    Science.gov (United States)

    Turhan, Ali Haydar; Atıcı, Aytuğ; Muşlu, Necati; Polat, Ayşe; Helvacı, İlter

    2012-06-01

    To examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

  20. Comparative study of respiratory tract immune toxicity induced by three sterilisation nanoparticles: silver, zinc oxide and titanium dioxide.

    Science.gov (United States)

    Liu, Huanliang; Yang, Danfeng; Yang, Honglian; Zhang, Huashan; Zhang, Wei; Fang, Yanjun; Lin, Zhiqing; Tian, Lei; Lin, Bencheng; Yan, Jun; Xi, Zhuge

    2013-03-15

    Silver, zinc oxide, and titanium dioxide nanoparticles are used as sterilisation materials to enhance the performance of disinfectants. We investigated the respiratory tract immune toxicity ("immunotoxicity") of these nanoparticles in vivo and in vitro, and we explored the relationships between particle size, particle shape, chemical composition, chemical stability and the toxicological effects of these typical nanoparticles in rats. In vivo, the rats were exposed to nanoparticles by intratracheal instillation. Exposure to nanoparticles caused an increase in oxidative injury to the lungs and disorders in regulating the cytokine network, which were detected in the bronchoalveolar lavage fluid, suggesting that oxidative stress might be important for inducing the respiratory immunotoxicity of nanoparticles. In vitro, the phagocytic function of alveolar macrophages (AMs) was dose-dependently reduced by nanoparticles, and ZnO nanoparticles induced greater cytotoxicity than the silver and titanium-dioxide nanoparticles, which were coincident with the results of multiple measurements, such as a cell viability assay by WST-8 and LDH measurements. Comparative analyses demonstrated that particle composition and chemical stability most likely had a primary role in the biological effects of different nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. 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

    Background: The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase...... 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...

  2. 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...... biopesticides in the future....

  3. 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...... instillation of the same particles had no effect on biomarkers of pulmonary oxidative stress and dilatory dysfunction in the aorta....

  4. Learning through Immersive Study: Contextualizing Music in the Elementary Music Classroom

    Science.gov (United States)

    Rifai, Ayah

    2016-01-01

    Music educators are part of a team charged with nurturing the development of the whole child. This includes instilling in students cognitive keys to essential life values that will be drawn on through adulthood. To help music educators attain this goal, this article encourages the inclusion of contexualized music units--immersive studies of…

  5. "Tone It down a Bit!": Euphemism as a Colonial Device in Australian Indigenous Studies

    Science.gov (United States)

    McGloin, Colleen

    2014-01-01

    In a previous article discussing the politics of language in Australian Indigenous Studies teaching and learning contexts, the author and her colleague stated their objective in writing that article was to ''instill'' a sense of the importance of the political nature of language to their student body (McGloin and Carlson 2013). They wanted to…

  6. Contributions of high mobility group box protein in experimental and clinical acute lung injury.

    Science.gov (United States)

    Ueno, Hiroshi; Matsuda, Tomoyuki; Hashimoto, Satoru; Amaya, Fumimasa; Kitamura, Yoshihiro; Tanaka, Masaki; Kobayashi, Atsuko; Maruyama, Ikuro; Yamada, Shingo; Hasegawa, Naoki; Soejima, Junko; Koh, Hidefumi; Ishizaka, Akitoshi

    2004-12-15

    This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.

  7. Pulmonary exposure to diesel exhaust particles induces airway inflammation and cytokine expression in NC/Nga mice

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Ken-ichiro; Yanagisawa, Rie [National Institute for Environmental Studies, Inhalation Toxicology and Pathophysiology Research Team, Tsukuba (Japan); Takano, Hirohisa [National Institute for Environmental Studies, Inhalation Toxicology and Pathophysiology Research Team, Tsukuba (Japan); Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan); Ichinose, Takamichi [Oita University of Nursing and Health Science, Department of Health Science, Oita (Japan); Shimada, Akinori [Tottori University, Department of Veterinary Pathology, Faculty of Agriculture, Tottori (Japan); Yoshikawa, Toshikazu [Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan)

    2005-10-01

    Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the effect of DEP on animal models with spontaneous allergic disorders has been far less intensively studied. The Nc/Nga mouse is known to be a typical animal model for human atopic dermatitis (AD). In the present study, we investigated the effects of repeated pulmonary exposure to DEP on airway inflammation and cytokine expression in NC/Nga mice. The animals were randomized into two experimental groups that received vehicle or DEP by intratracheal instillation weekly for six weeks. Cellular profiles of bronchoalveolar lavage (BAL) fluid and expressions of cytokines and chemokines in both the BAL fluid and lung tissues were evaluated 24 h after the last instillation. The DEP challenge produced an increase in the numbers of total cells, neutrophils, and mononuclear cells in BAL fluid as compared to the vehicle challenge (P<0.01). DEP exposure significantly induced the lung expressions of interleukin (IL)-4, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1{alpha} when compared to the vehicle challenge. These results indicate that intratracheal exposure to DEP induces the recruitment of inflammatory cells, at least partially, through the local expression of IL-4 and chemokines in NC/Nga mice. (orig.)

  8. In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

    Directory of Open Access Journals (Sweden)

    Martin Wiemann

    2018-03-01

    Full Text Available In vitro prediction of inflammatory lung effects of well-dispersed nanomaterials is challenging. Here, the in vitro effects of four colloidal amorphous SiO2 nanomaterials that differed only by their primary particle size (9, 15, 30, and 55 nm were analyzed using the rat NR8383 alveolar macrophage (AM assay. Data were compared to effects of single doses of 15 nm and 55 nm SiO2 intratracheally instilled in rat lungs. In vitro, all four elicited the release of concentration-dependent lactate dehydrogenase, β-glucuronidase, and tumor necrosis factor alpha, and the two smaller materials also released H2O2. All effects were size-dependent. Since the colloidal SiO2 remained well-dispersed in serum-free in vitro conditions, effective particle concentrations reaching the cells were estimated using different models. Evaluating the effective concentration–based in vitro effects using the Decision-making framework for the grouping and testing of nanomaterials, all four nanomaterials were assigned as “active.” This assignment and the size dependency of effects were consistent with the outcomes of intratracheal instillation studies and available short-term rat inhalation data for 15 nm SiO2. The study confirms the applicability of the NR8383 AM assay to assessing colloidal SiO2 but underlines the need to estimate and consider the effective concentration of such well-dispersed test materials.

  9. TRIAMCINОLON IN THE TREATMENT OF THE SIMPLE BACTERIAL CYSTITIS (EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Ya. V. Shikunova

    2013-01-01

    Full Text Available The problem of the bacterial cystitis treatment continues to be relevant among the urologists all over the world due to its prevalence rate and the complexity in its treatment. The goal of research: to study experimentally the influence of synthetic glucocorticoidtriamcinоlon on the inflammatory mucosa of the urinary bladder.Material. The experimental study was conducted on the outbred white reproductive rats-females. The main group of the animals (40 rats was exposed to simulation of the inflammatory mucosa of the urinary bladder. Triamcinоlon instillations (0.3 ml were performed on 20 rats. In the other group of rats the triamcinоlon instillation was added with intramuscular injection of antibiotics. There were two compari-son groups of rats with the simulated inflammatory mucosa of the urinary bladder. The first (20 rats re-ceived only intramuscular antibiotics injections and the second (20 rats received no treatment. The con-trol group of animals (10 rats received instillations of intact 0.9% NaCl.Methods. The bladder wall ultrastructure was analyzed by the method of transmission electronic microscopy.Rresults. According to the research data, decongestion of the swelling enchasing mass was observed after 5 days of triamcinоlon instillations both with antibiotics and without it in comparison with the inflammatory process without any treatment and with the antibiotics injections only. After 10 days this result in the main group was the same as in the control group. Infiltrating cells density in the main group after 7 days was obviously lower than in the comparison groups. The triamcinоlon injections induce neovasculogenesis and fibrogenesis, improve hemorheology in the vascular plexus of the urinary bladder mucosa. The results come up to a high level of statistical significance.Summary. The experimental data prove the safety of intravesical triamcialon instillation and its therapeutic effectiveness. 

  10. Locally instilled tumor necrosis factor α antisense oligonucleotide contributes to inhibition of TH 2-driven pulmonary fibrosis via induced CD4+ CD25+ Foxp3+ regulatory T cells.

    Science.gov (United States)

    Luo, Yi; Wang, Min; Pang, Zhonghua; Jiang, Fengtao; Chen, Jiangning; Zhang, Junfeng

    2013-01-01

    Anti-tumor necrosis factor α therapeutics has the potential to alleviate pulmonary fibrosis. However, the systemic administration of anti-tumor necrosis factor α agents has brought about contradictory results and frequent adverse effects, such as infections, immunogenicity and malignancies, amongst others. In the present study, we attempted the local administration of tumor necrosis factor α antisense oligonucleotide and evaluated the treatment effects on pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis mouse model. Flow cytometry for regulatory T cells, reverse transcriptase-polymerase chain reaction for crucial gene expression, western blotting for crucial protein products, immunofluorescent analysis for T(H)2 cells and myofibroblasts, as well as histology analysis for pathological examination, were used. By local administration of tumor necrosis factor α antisense oligonucleotide, we investigated whether tumor necrosis factor α expression in epithelial cells was significantly inhibited and extracellular matrix overexpression was dramatically reduced. These treatment effects were associated with induced regulatory T cells, reduced T(H)2 cells and generally decreased T(H)2-type cytokine expression. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of regulatory T cells in the blood, thymus or spleen was not affected. These findings demonstrate that local administration of tumor necrosis factor α antisense oligonucleotide contributes to anti-fibrotic action via a sustained up-regulated level of regulatory T cells, which inhibits T(H)2-biased responses, pro-fibrotic mediator production and extracellular matrix deposition, with no systemic immunosupression associated with systemically induced regulatory T cells. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Investigation of moxifloxacin loaded chitosan–dextran nanoparticles for topical instillation into eye: In-vitro and ex-vivo evaluation

    Science.gov (United States)

    Kaskoos, Raad A.

    2014-01-01

    Introduction: Management of ocular surface disease by conventional formulation is limited by poor residence of drug at cul-de-sac of eye. To overcome this limitation, prolonged released mucoadhesive chitosan (CS)–dextran sulfate (DS) nanoparticles (NPs) were investigated for the prolonged topical ophthalmic delivery of moxifloxacin (Mox). Methods: Formulation was optimized by 3-factors (CS, DS, and Mox concentration), 3-levels (−1, 0, +1) Box-Behnken design. Optimized formulation was characterized for various in-vitro attributes, including particles size, zeta potential, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, ocular tolerance test as well as antimicrobial activity. Results: Average hydrodynamic particle size of statistically optimized formulation was found to be 279.18 ± 15.63 nm with good polydispersity index, 0.367 ± 0.016 and positive zeta potential, +31.23 ± 1.32. NPs showed entrapment efficiency, 72.82 ± 3.6% and transmission electron microscopic analysis revealed a spherical shape of particles. Formulation exhibited biphasic release profile with an initial fast release (≈25% in 1st h) followed by sustained release (≈95% in next 24 h) following Korsmeyer–Peppas model with a nonFickian diffusion process. Mox loaded CS-DS NPs exhibited a significantly higher (P < 0.01), approximately 1.8-fold transcorneal permeation as well as significantly higher corneal retention (P < 0.01), around 4-5-fold when compared to free solution. Developed formulation exhibited safety profile comparable to normal saline, which was revealed by ocular tolerance test (Hen's egg test-chorioallantoic membrane). Mox-CS-DS NPs exhibited significantly high (P < 0.01) antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Conclusion: In-vitro and ex-vivo studies revealed that developed formulation could be a potential substitute for prolonged topical ocular delivery. PMID:25426437

  12. Polymer degradation and ultrafine particles: Potential inhalation hazards for astronauts

    Science.gov (United States)

    Ferin, J.; Oberdörster, G.

    When Teflon is heated the developing fumes produce in exposed humans an influenza-like syndrome (polymer fume fever) or also severe toxic effects like pulmonary edema, pneumonitis and death. The decomposition products and the resulting health effects are temperature-dependent. The toxic effects seem to be related to the ultrafine particulate fraction of the fume. To test the hypothesis that exposure to ultrafine particles results in an increased interstitialization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO 2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO 2 particles (˜20 nm diameter) access the pulmonary interstitium to a larger extent than fine particles (˜250 nm diameter) 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.

  13. Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer

    NARCIS (Netherlands)

    Hendricksen, Kees; van der Heijden, Antoine G.; Cornel, Erik B.; Vergunst, Henk; de Reijke, Theo M.; van Boven, Erika; Smits, Geert A. H. J.; Puri, Rajiv; Gruijs, Sigrid; Witjes, J. Alfred

    2009-01-01

    To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2

  14. The Influence of Active Participation and Organisation in Environmental Protection Activities on the Environmental Behaviour of Pupils: Study of a Teaching Technique

    Science.gov (United States)

    Baur, Armin; Haase, Hans-Martin

    2015-01-01

    Until now, many efforts in the area of environmental education, intended to instill consciously responsible behaviour into the general public in Germany, have failed. Several of the available intervention studies aimed at improving environmental behaviour of pupils with classroom tuition were able to show positive results, but there were often…

  15. 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

  16. 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

  17. Therapy of Murine Pulmonary Aspergillosis with Antibody-Alliinase Conjugates and Alliin▿

    Science.gov (United States)

    Appel, Elena; Vallon-Eberhard, Alexandra; Rabinkov, Aharon; Brenner, Ori; Shin, Irina; Sasson, Keren; Shadkchan, Yona; Osherov, Nir; Jung, Steffen; Mirelman, David

    2010-01-01

    Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The high morbidity and mortality rates as well as the poor efficacy of antifungal agents remain major clinical concerns. Allicin (diallyl-dithiosulfinate), which is produced by the garlic enzyme alliinase from the harmless substrate alliin, has been shown to have wide-range antifungal specificity. A monoclonal antibody (MAb) against A. fumigatus was produced and chemically ligated to the enzyme alliinase. The purified antibody-alliinase conjugate bound to conidia and hyphae of A. fumigatus at nanomolar concentrations. In the presence of alliin, the conjugate produced cytotoxic allicin molecules, which killed the fungus. In vivo testing of the therapeutical potential of the conjugate was carried out in immunosuppressed mice infected intranasally with conidia of A. fumigatus. Intratracheal (i.t.) instillation of the conjugate and alliin (four treatments) resulted in 80 to 85% animal survival (36 days), with almost complete fungal clearance. Repetitive intratracheal administration of the conjugate and alliin was also effective when treatments were initiated at a more advanced stage of infection (50 h). The fungi were killed specifically without causing damage to the lung tissue or overt discomfort to the animals. Intratracheal instillation of the conjugate without alliin or of the unconjugated monoclonal antibody significantly delayed the death of the infected mice, but only 20% of the animals survived. A limitation of this study is that the demonstration was achieved in a constrained setting. Other routes of drug delivery will be investigated for the treatment of pulmonary and extrapulmonary aspergillosis. PMID:19949059

  18. Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome.

    Science.gov (United States)

    Turhan, Ali Haydar; Atici, Aytuğ; Muşlu, Necati; Polat, Ayşe; Sungur, Mehmet Ali

    2016-05-01

    Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1β, IL-6, and IL-8 levels (p meconium-induced derangements.

  19. Cardiovascular effects of N-acetylcysteine in meconium-induced acute lung injury.

    Science.gov (United States)

    Mokra, D; Tonhajzerova, I; Pistekova, H; Visnovcova, Z; Drgova, A; Mokry, J; Calkovska, A

    2015-01-01

    Anti-inflammatory drugs are increasingly used for treatment of neonatal meconium aspiration syndrome (MAS), but their adverse effects are poorly known. Therefore, the aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine on cardiovascular parameters in an animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium suspension (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were given N-acetylcysteine (10 mg/kg, i.v.) or the same volume of saline. Changes in cardiovascular parameters (blood pressure, heart rate, and heart rate variability) were recorded over a 5-min course of solution administration, over 5 min after its end, and then hourly for 5 h. Oxidation markers (thiobarbituric acid-reactive substances (TBARS) and total antioxidant status) and aldosterone, as a non-specific marker of cardiovascular injury, were determined in plasma. Meconium instillation did not evoke any significant cardiovascular changes, but induced oxidative stress and elevated plasma aldosterone. N-acetylcysteine significantly reduced the mentioned markers of injury. However, its administration was associated with short-term increases in blood pressure and in several parameters of heart rate variability. Considering these effects of N-acetylcysteine, its intravenous administration in newborns with MAS should be carefully monitored.

  20. Estimation of Para Red Dye in Chilli Powder and Tomato Sauces by ...

    African Journals Online (AJOL)

    MICHAEL HORSFALL

    spectrophotometric method followed by thin layer chromatography technique and compared the results by single point and multiple ..... Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage. Fundam Appl Toxicol 22:103-112. Khanna, S. K., and Singh G. B., (1975).

  1. Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice

    DEFF Research Database (Denmark)

    Gosens, Ilse; Kermanizadeh, Ali; Jacobsen, Nicklas Raun

    2015-01-01

    O) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage...

  2. 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

  3. 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

    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...

  4. Management of difficult airway in intratracheal tumor surgery

    Directory of Open Access Journals (Sweden)

    Agarwal Surendra K

    2005-06-01

    Full Text Available Abstract Background Tracheal malignancies are usual victim of delay in diagnosis by virtue of their symptoms resembling asthma. Sometimes delayed diagnosis may lead to almost total airway obstruction. For difficult airways, not leaving any possibility of manipulation into neck region or endoscopic intervention, femorofemoral cardiopulmonary bypass can be a promising approach. Case Presentation We are presenting a case of tracheal adenoid cystic carcinoma (cylindroma occupying about 90% of the tracheal lumen. It was successfully managed by surgical excision of mass by sternotomy and tracheotomy under femorofemoral cardiopulmonary bypass (CPB. Conclusion Any patient with recurrent respiratory symptoms should be evaluated by radiological and endoscopic means earlier to avoid delay in diagnosis of such conditions. Femorofemoral cardiopulmonary bypass is a relatively safe way of managing certain airway obstructions.

  5. Biokinetics and effects of barium sulfate nanoparticles.

    Science.gov (United States)

    Konduru, Nagarjun; Keller, Jana; Ma-Hock, Lan; Gröters, Sibylle; Landsiedel, Robert; Donaghey, Thomas C; Brain, Joseph D; Wohlleben, Wendel; Molina, Ramon M

    2014-10-21

    Nanoparticulate barium sulfate has potential novel applications and wide use in the polymer and paint industries. A short-term inhalation study on barium sulfate nanoparticles (BaSO₄ NPs) was previously published [Part Fibre Toxicol 11:16, 2014]. We performed comprehensive biokinetic studies of ¹³¹BaSO₄ NPs administered via different routes and of acute and subchronic pulmonary responses to instilled or inhaled BaSO₄ in rats. We compared the tissue distribution of ¹³¹Ba over 28 days after intratracheal (IT) instillation, and over 7 days after gavage and intravenous (IV) injection of ¹³¹BaSO₄. Rats were exposed to 50 mg/m³ BaSO₄ aerosol for 4 or 13 weeks (6 h/day, 5 consecutive days/week), and then gross and histopathologic, blood and bronchoalveolar lavage (BAL) fluid analyses were performed. BAL fluid from instilled rats was also analyzed. Inhaled BaSO₄ NPs showed no toxicity after 4-week exposure, but a slight neutrophil increase in BAL after 13-week exposure was observed. Lung burden of inhaled BaSO₄ NPs after 4-week exposure (0.84 ± 0.18 mg/lung) decreased by 95% over 34 days. Instilled BaSO₄ NPs caused dose-dependent inflammatory responses in the lungs. Instilled BaSO₄ NPs (0.28 mg/lung) was cleared with a half-life of ≈ 9.6 days. Translocated ¹³¹Ba from the lungs was predominantly found in the bone (29%). Only 0.15% of gavaged dose was detected in all organs at 7 days. IV-injected ¹³¹BaSO₄ NPs were predominantly localized in the liver, spleen, lungs and bone at 2 hours, but redistributed from the liver to bone over time. Fecal excretion was the dominant elimination pathway for all three routes of exposure. Pulmonary exposure to instilled BaSO₄ NPs caused dose-dependent lung injury and inflammation. Four-week and 13-week inhalation exposures to a high concentration (50 mg/m³) of BaSO₄ NPs elicited minimal pulmonary response and no systemic effects. Instilled and inhaled BaSO₄ NPs were cleared quickly yet

  6. 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

  7. Cigarette smoke and bleomycin-induced pulmonary oxidative stress in rats

    OpenAIRE

    TEKE, TURGUT; MADEN, EMIN; KIYICI, AYSEL; KORKMAZ, CELALETTIN; GOK, MEHMET; OZER, FARUK; IMECIK, OKTAY; UZUN1, KURSAT

    2012-01-01

    Bleomycin causes pulmonary fibrosis by increasing free oxygen radicals. Cigarette smoke is a strong oxidant which adversely affects pulmonary tissue. We evaluated the effects of cigarette smoke administered with intratracheal bleomycin on pulmonary tissue. We studied 3 groups of rats (n=10): one group received intratracheal saline and served as a control; one received intratracheal bleomycin (IT) (0.5 U/100 g body weight, single dose on the first day), and one group received intratracheal ble...

  8. A Pilot Study: The Efficacy of Virgin Coconut Oil as Ocular Rewetting Agent on Rabbit Eyes

    Directory of Open Access Journals (Sweden)

    Haliza Abdul Mutalib

    2015-01-01

    Full Text Available Purpose. An open-label pilot study of virgin coconut oil (VCO was conducted to determine the safety of the agent as ocular rewetting eye drops on rabbits. Methods. Efficacy of the VCO was assessed by measuring NIBUT, anterior eye assessment, corneal staining, pH, and Schirmer value before instillation and at 30 min, 60 min, and two weeks after instillation. Friedman test was used to analyse any changes in all the measurable variables over the period of time. Results. Only conjunctival redness with instillation of saline agent showed significant difference over the period of time (P0.05. There were no changes in the NIBUT, limbal redness, palpebral conjunctiva redness, corneal staining, pH, and Schirmer value over the period of time for each agent (P>0.05. Conclusion. VCO acts as safe rewetting eye drops as it has shown no significant difference in the measurable parameter compared to commercial brand eye drops and saline. These study data suggest that VCO is safe to be used as ocular rewetting agent on human being.

  9. Sleep Patterns of Young Men and Women Enrolled at the United States Military Academy: Results from Year 1 of a 4-Year Longitudinal Study

    Science.gov (United States)

    2005-01-01

    searchers hope will lead to bener sleep hygiene among cadets. The importance of instilling good sleep habits in cadets at USMA and providing them with... Sleep Patterns of Young Men and Women Enrolled at the United States Military Academy: Results from Year 1 of a 4-Year Longitudinal Study Nita leWIs... Sleep patterns of young adults Bre different from those of other age groups .. This study eKamined sleep patterns of cadets during their first year

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Development and time-course of bleomycin-induced pulmonary fibrosis in NMRI mice

    Directory of Open Access Journals (Sweden)

    Jafarian-Dehkordi A.

    2007-04-01

    Full Text Available Bleomycin-induced pulmonary fibrosis is a widely used experimental model for human lung fibrosis. The severity of fibrosis varies among different strains of mice and investigation on different strains and finding the mechanisms of variation is important in understanding the pathogenesis of human lung fibrosis. In the present study, NMRI mice were used to investigate the severity and also time-course of bleomycin-induced pulmonary fibrosis in comparison with C57BL/6 mice. After single dose administration of intratracheal bleomycin, the fibrotic response was studied by biochemical measurement of collagen deposition and semiquantitative analysis of pathological lung changes. NMRI mice developed lung fibrosis from 1 to 4 week after bleomycin instillation, with significant increases in lung collagen content and significant morphological changes (P < 0.05. These findings indicate that NMRI mice might be suitable as an experimental model of bleomycin-induced lung fibrosis.

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

    DEFF Research Database (Denmark)

    Raun Jacobsen, Nicklas; Møller, Peter; Alstrup Jensen, Keld

    2009-01-01

    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...... 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 C-60 particles caused much weaker inflammatory responses...

  13. Pulmonary response, in vivo, to silicon carbide whiskers.

    Science.gov (United States)

    Vaughan, G L; Trently, S A; Wilson, R B

    1993-11-01

    Fischer rats were exposed to silicon carbide whiskers (SiCW), boron carbide whiskers (BCW), silicon carbide platelets (SiCP), or crocidolite asbestos separately administered by intratracheal instillation. SiCW proved to be the most toxic material within the test group. Dramatic increases in alveolar macrophage populations within 1 week of exposure to SiCW persisted for at least 28 days, evidence of the chronic inflammation observed in necropsies during the first months of the study. The most common finding in histological preparations of tissues taken from animals 18 months after exposure to SiCW was a high incidence (frequency > 0.85) of multiple pulmonary granulomas which occasionally occluded airways. Lesions associated with crocidolite were similar to those found with SiCW. Equivalent treatment with BCW and SiCP produced no significant histological changes within 18 months of exposure.

  14. The impact of microfluidic mixing of triblock micelleplexes on in vitro / in vivo gene silencing and intracellular trafficking

    Science.gov (United States)

    Feldmann, Daniel P.; Xie, Yuran; Jones, Steven K.; Yu, Dongyue; Moszczynska, Anna; Merkel, Olivia M.

    2017-06-01

    The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate carriers capable of complexing with nucleic acids for gene delivery. The objective of this study was to investigate micelleplex characteristics, their in vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL-PEG nanoparticles were prepared with batch reactor or microfluidic mixing techniques and characterized by various biochemical assays and in cell culture. Microfluidic nanoparticles showed a reduction of overall particle size as well as a more uniform size distribution when compared to batch reactor pipette mixing. Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular delivery of the microfluidic formulation and confirmed the ability to achieve mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted in a significantly more efficient (p production of well-defined polyplexes is required.

  15. 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...

  16. 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......Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which...... hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3...

  17. 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)

  18. 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

  19. Controlled release of carcinogens in heterotopic tracheal grafts

    Energy Technology Data Exchange (ETDEWEB)

    Pal, B.C.; Klein-Szanto, A.J.P.

    1981-01-01

    A major drawback of the conventional approaches to the study of the respiratory tract carcinogenesis by intratracheal injection or instillation is that neither the dose nor the target site can be accurately defined. The tracheal transplant model has been developed in our group to provide a solution to this problem. In this model, rodent tracheas are transplanted under the skin in the scapular region of the isogenic host. The transplants re-establish themselves in the host in 3 to 4 weeks and survive indefinitely. These tracheas can then be exposed to carcinogens in a controlled and quantitative fashion by using monolithic cylindrical pellets. The model has a good potential for establishing a more realistic dose-response relationship in respiratory tract carcinogenesis. However, the success of the model depends on the development of devices for release of carcinogens at a reproducible and predictable rate. This paper describes the various approaches to the solution of this problem.

  20. 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

  1. Paclitaxel-hyaluronic acid for intravesical therapy of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder: results of a phase I study.

    Science.gov (United States)

    Bassi, P F; Volpe, A; D'Agostino, D; Palermo, G; Renier, D; Franchini, S; Rosato, A; Racioppi, M

    2011-02-01

    Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guérin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guérin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guérin. A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guérin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guérin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs.

    Science.gov (United States)

    Holms, Carla Augusto; Otsuki, Denise Aya; Kahvegian, Marcia; Massoco, Cristina Oliveira; Fantoni, Denise Tabacchi; Gutierrez, Paulo Sampaio; Auler Junior, Jose Otavio Costa

    2015-08-01

    Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. Hypertonic saline infusion after intratracheal hydrochloric

  3. 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.

  4. 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

  5. Pulmonary alveolar and vascular morphometry after gel plug occlusion of the trachea in a fetal rabbit model of CDH.

    Science.gov (United States)

    Elattal, Ramy; Rich, Barrie S; Harmon, Carroll M; Muensterer, Oliver J

    2013-01-01

    Tracheal occlusion (TO) induces lung growth in congenital diaphragmatic hernia (CDH) but is also associated with drawbacks. We devised a temporary gel plug that induced lung growth when placed in the fetal trachea. This study evaluates the effects of temporary versus permanent TO on histologic radial alveolar count (RAC) and vascular morphometrics. Experimental CDH was created surgically in 64 New Zealand White rabbit fetuses on gestational day (GD) 24. On GD 27, these fetuses were randomized to intratracheal instillation of a fibrin gel plug (GP), tracheal suture ligation (SL), intratracheal instillation of normal saline (NS), or sham amniotomy (SH). Non-manipulated fetuses served as controls (NM). Histologic lung sections were assessed blindly for RAC and relative arterial adventitial thickness (%AT) as a variable for vascular remodelling. Results were statistically compared. RAC was significantly lower in the ipsilateral lung of SH fetuses than in the contralateral lung (p = 0.011). Mean RAC was higher after SL (p < 0.001) and GP (p = 0.03) compared to SH. Furthermore, %AT was higher in GP (50 ± 28, p < 0.001) and SL (45 ±2 6, p = 0.003) fetuses than in controls (36 ± 19). Temporary and permanent TO leads to increased RAC; this effect was more pronounced with permanent TO. Both interventions were associated with an increased %AT. These findings may explain the adverse clinical effects of TO, despite causing accelerated lung growth. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  6. 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.

  7. Didecyldimethylammonium chloride induces pulmonary inflammation and fibrosis in mice.

    Science.gov (United States)

    Ohnuma, Aya; Yoshida, Toshinori; Tajima, Haruka; Fukuyama, Tomoki; Hayashi, Koichi; Yamaguchi, Satoru; Ohtsuka, Ryoichi; Sasaki, Junya; Fukumori, Junko; Tomita, Mariko; Kojima, Sayuri; Takahashi, Naofumi; Takeuchi, Yukiko; Kuwahara, Maki; Takeda, Makio; Kosaka, Tadashi; Nakashima, Nobuaki; Harada, Takanori

    2010-11-01

    Didecyldimethylammonium chloride (DDAC) is used worldwide as a germicide, in antiseptics, and as a wood preservative, and can cause adverse pulmonary disease in humans. However, the pulmonary toxicity of DDAC has not yet been thoroughly investigated. Mice were intratracheally instilled with DDAC to the lung and the bronchoalveolar lavage (BAL) fluid and lung tissues were collected to assess dose- and time-related pulmonary injury. Exposure to 1500 μg/kg of DDAC caused severe morbidity with pulmonary congestive oedema. When the BAL fluid from survivors was examined on day 3 after treatment, exposure to 150 μg/kg of DDAC caused weakly induced inflammation, and exposure to 15μg/kg did not cause any visible effects. Next, we observed pulmonary changes that occurred up to day 20 after 150 μg/kg of DDAC exposure. Pulmonary inflammation peaked on day 7 and was confirmed by expression of interleukin-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and regulated upon activation, normal T-cell expressed and secreted in the BAL fluid; these changes were accompanied by altered gene expression of their chemokine (C-C motif) receptor (Ccr) 1, Ccr2, Ccr3, and Ccr5. Cytotoxicity evoked by DDAC was related to the inflammatory changes and was confirmed by an in vitro study using isolated mouse lung fibroblasts. The inflammatory phase was accompanied or followed by pulmonary remodeling, i.e., fibrosis, which was evident in the mRNA expression of type I procollagen. These results suggest that administering DDAC by intratracheal instillation causes pulmonary injury in mice, and occupational exposure to DDAC might be a potential hazard to human health. Copyright © 2009 Elsevier GmbH. All rights reserved.

  8. 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

  9. Ultrafine carbon black attenuates the antihypertensive effect of captopril in spontaneously hypertensive rats.

    Science.gov (United States)

    Zhang, Xinru; Chen, Yiyong; Wei, Hongying; Qin, Yu; Hao, Yu; Zhu, Yidan; Deng, Furong; Guo, Xinbiao

    2014-12-01

    Particulate matter (PM) has been associated with increased blood pressure (BP) by affecting renin-angiotensin system (RAS) on a systemic level in spontaneously hypertensive rats (SHR). RAS in SHR is also an important target for the angiotensin converting enzyme (ACE) inhibitors such as captopril. We aimed to determine if ultrafine carbon black (UCB) could affect antihypertensive effect of captopril in SHR. The rats were randomly divided into six groups. Group 1 did not receive intratracheal instillation; group 2 received saline instillation plus captopril administration; groups 3, 4 and 5 received 0.15 mg/kg, 0.45 mg/kg and 1.35 mg/kg UCB per instillation plus captopril administration, respectively; group 6 received 1.35 mg/kg UCB instillation only. Rats in the above groups were intratracheally instilled with saline or UCB once every two days for three times and captopril was administered to group 2-5 after the final UCB treatment, once a day for one week. The BP was measured 24 h after each intratracheal instillation. During captopril administration and 24 h after last captopril administration, we measured BP every two days for four times. Our results showed that UCB at the dose of 1.35 mg/kg induced pulmonary and systemic inflammation in SHR. Captopril reduced BP in rats exposed to 0, 0.15 and 0.45 mg/kg UCB seven and eleven days after the first UCB instillation, and had no effect on BP in rats exposed to 1.35 mg/kg UCB. Captopril also reduced angiotensin II (AngII) in rats exposed to saline. The reduction, however, was attenuated with increasing doses of UCB. We conclude that UCB attenuated the antihypertensive effect of captopril in SHR, and the effect was accompanied by a systemic increase in the concentration of AngII.

  10. The top ten list: lessons learned from teaching a study abroad course.

    Science.gov (United States)

    Kostovich, Carol T; Bermele, Charlene A

    2011-01-01

    In response to the need for culturally competent care, faculty can instill in students the desire to become culturally competent practitioners by providing the opportunity to participate in a short-term study abroad immersion experience. While this strategy is not considered cutting-edge or revolutionary, changing global dynamics warrant rethinking this curricular option. Nurse faculty conducted two short-term study abroad courses in Croatia. Students explored health care and nursing education in this Eastern European country and participated in a service-learning project. Based on their experiences, the authors offer five dos and five don'ts for planning and implementing a successful study abroad course.

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

    Science.gov (United States)

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

    2014-07-01

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

  12. N-acetylcysteine alleviates the meconium-induced acute lung injury.

    Science.gov (United States)

    Mokra, D; Drgova, A; Petras, M; Mokry, J; Antosova, M; Calkovska, A

    2015-01-01

    Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.

  13. Changes in Cardiac Autonomic Regulation after Acute Lung Exposure to Carbon Nano tubes: Implications for Occupational Exposure

    International Nuclear Information System (INIS)

    Magrini, A.; Pietroiusti, A.; Valentini, F.

    2012-01-01

    Carbon nano tubes (CNTs) are among the most relevant engineered nano materials (ENMs). Given the expected rise of exposure to ENMs, there is concern that they may adversely affect health of exposed people. Aim of the study was to test the hypothesis that single wall carbon nano tubes (SWCNTs) pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. We studied Wistar-Kyoto rats in which a telemetry transmitter for continuous arterial pressure (AP) and heart rate (HR) recordings was surgically implanted. SWCNTs dispersed in phosphate buffer saline (PBS) or PBS alone were randomly administered intratracheally. Immediately before, and 24 hours after each instillation a 30 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. In the control group, PBS instillation did not induce any significant changes. At variance the SWCNT exposure induced a significant reduction of baroreflex system (BRS) (3.5±0.6 versus 2.6±0.40 msec/mmHg) without significant changes in the occurrence of baroreflex sequences (7.5±0.47% versus 7.4± 0.38%). Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.

  14. In vivo genotoxicity of hard metal dust: induction of micronuclei in rat type II epithelial lung cells.

    Science.gov (United States)

    De Boeck, Marlies; Hoet, Peter; Lombaert, Noömi; Nemery, Benoit; Kirsch-Volders, Micheline; Lison, Dominique

    2003-11-01

    Inhalation of hard metal dust (WC-Co particles) has been associated with an increased risk for lung cancer in occupational settings. In vitro, WC-Co was genotoxic in human lymphocytes producing DNA strand breaks and micronuclei. The aim of the present study was to evaluate the in vivo genotoxic effects of WC-Co dust in rat type II pneumocytes. DNA breaks/alkali-labile sites (alkaline comet assay) and chromosome/genome mutations (micronucleus test) were assessed after a single intra-tracheal (i.t.) instillation of WC-Co, including dose-effect and time trend relationships. In addition, the alkaline comet assay was performed on cells obtained after broncho-alveolar lavage (BAL) and on peripheral blood mononucleated cells (PBMC). As pulmonary toxicity parameters, protein content, lactate dehydrogenase activity, total and differential cell count in BAL fluid were evaluated in parallel. In type II pneumocytes, WC-Co induced a statistically significant increase in tail DNA (12 h time point) and in micronuclei (72 h) after a single treatment with 16.6 mg WC-Co/kg body wt, a dose that produced mild pulmonary toxicity. This observation provides the first evidence of the in vivo mutagenic potential of hard metal dust. In PBMC, no increase in DNA damage or micronuclei was observed. This study indicates the potential to detect chromosome/genome mutations (micronuclei) in relevant target cells (type II pneumocytes) after i.t. instillation of a particle mixture.

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

    Science.gov (United States)

    Johansson, H K L; Hansen, J S; Elfving, B; Lund, S P; Kyjovska, Z O; Loft, S; Barfod, K K; Jackson, P; Vogel, U; Hougaard, K S

    2017-05-30

    The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase 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. Estrous cycle regularity was investigated by comparing vaginal smears before and after exposure to 67 μg of NM-400, whereas reproductive function was analyzed by measuring time to delivery of litters after instillation of 2, 18 or 67 μg of NM-400. Compared to normal estrous cycling determined prior to exposure, exposure to MWCNT significantly prolonged the estrous cycle during which exposure took place, but significantly shortened the estrous cycle immediately after the exposed cycle. No consistent effects were seen on time to delivery of litter or other gestational or litter parameters, such as litter size, sex ratio, implantations and implantation loss. Lung exposure to MWCNT interfered with estrous cycling. Effects caused by MWCNTs depended on the time of exposure: the estrous stage was particularly sensitive to exposure, as animals exposed during this stage showed a higher incidence of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation.

  16. 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.

  17. Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis

    Science.gov (United States)

    Redente, Elizabeth F.; Jacobsen, Kristen M.; Solomon, Joshua J.; Lara, Abigail R.; Faubel, Sarah; Keith, Rebecca C.; Henson, Peter M.; Downey, Gregory P.

    2011-01-01

    Fibrotic interstitial pneumonias are more prevalent in males of advancing age, although little is known about the underlying mechanisms. To evaluate the contributions of age and sex to the development of pulmonary fibrosis, we intratracheally instilled young (8–12 wk) and aged (52–54 wk) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration, and stereological quantification of fibrotic areas in histological sections. We also quantified proinflammatory and profibrotic chemokine and cytokine levels in the bronchoalveolar lavage fluid. Aged male mice developed more severe lung disease, indicated by increased mortality, increased collagen deposition, and neutrophilic alveolitis compared with aged female mice or young mice of either sex. Aged male mice also exhibited increased levels of transforming growth factor-β, IL-17A, and CXCL1 in their bronchoalveolar lavage fluid. Young male mice developed a more fibrotic disease after bleomycin instillation compared with female mice, regardless of age. There was no difference in fibrosis between young and aged female mice. Taken together, these findings suggest that the variables of advanced age and male sex contribute to the severity of pulmonary fibrosis in this model. Our findings also emphasize the importance of stratifying experimental groups on the basis of age and sex in experimental and epidemiological studies of this nature. PMID:21743030

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

    Science.gov (United States)

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

    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 23days. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Takemasa, Akihiro; Ishii, Yoshiki; Fukuda, Takeshi

    2012-12-01

    Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study. To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation. In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat. These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosis via inhibition of both TGF-β activation and inflammatory cell recruitment in the lung.

  20. Astragalus injection attenuates bleomycin-induced pulmonary fibrosis via down-regulating Jagged1/Notch1 in lungs.

    Science.gov (United States)

    Zhou, Yan; Liao, Shiping; Zhang, Zhongwei; Wang, Bo; Wan, Lihong

    2016-03-01

    Inhibition of Notch signalling is a potential therapeutic strategy for pulmonary fibrosis. This study was designed to investigate the antifibrosis effects and possible mechanism of astragalus injection (AI) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in male SD rats. All rats received daily intraperitoneally administration of dexamethasone (DEX, 3 mg/kg), astragalus injection (AI, 8 g/kg) or saline 1 day after bleomycin instillation daily for 28 days. Histological changes in the lung were evaluated by haematoxylin and eosin and Masson's trichrome staining. The expression of α-smooth muscle protein (α-SMA) was assayed by immunohistochemical (IHC). The mRNA and protein level of Jagged1, Notch1 and transforming growth factor-β1 (TGF-β1) was analysed by qPCR and Western blot. BLM-induced severe alveolitis and pulmonary fibrosis; together with significant elevation of α-SMA, TGF-β1, Jagged1 and Notch1. Astragalus injection (AI, 8 g/kg) administration notably attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of α-SMA, TGF-β1, Jagged1 and Notch1 in lungs. Astragalus injection (AI, 8 g/kg) may exert protective effects on bleomycin-induced pulmonary fibrosis via downregulating Jagged1/Notch1 in lung. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  1. Effects on Lung Function of Small-Volume Conventional Ventilation and High-Frequency Oscillatory Ventilation in a Model of Meconium Aspiration Syndrome.

    Science.gov (United States)

    Mikusiakova, L Tomcikova; Pistekova, H; Kosutova, P; Mikolka, P; Calkovska, A; Mokra, D

    2015-01-01

    For treatment of severe neonatal meconium aspiration syndrome (MAS), lung-protective mechanical ventilation is essential. This study compared short-term effects of small-volume conventional mechanical ventilation and high-frequency oscillatory ventilation on lung function in experimentally-induced MAS. In conventionally-ventilated rabbits, MAS was induced by intratracheal instillation of meconium suspension (4 ml/kg, 25 mg/ml). Then, animals were ventilated conventionally with small-volume (f-50/min; VT-6 ml/kg) or with high frequency ventilation (f-10/s) for 4 h, with the evaluation of blood gases, ventilatory pressures, and pulmonary shunts. After sacrifice, left lung was saline-lavaged and cells in bronchoalveolar lavage fluid (BALF) were determined. Right lung was used for the estimation of lung edema formation (wet/dry weight ratio). Thiobarbituric acid-reactive substances (TBARS), oxidative damage markers, were detected in lung tissue and plasma. Meconium instillation worsened gas exchange, and induced inflammation and lung edema. Within 4 h of ventilation, high frequency ventilation improved arterial pH and CO2 elimination compared with conventional ventilation. However, no other significant differences in oxygenation, ventilatory pressures, shunts, BALF cell counts, TBARS concentrations, or edema formation were observed between the two kinds of ventilation. We conclude that high frequency ventilation has only a slight advantage over small-volume conventional ventilation in the model of meconium aspiration syndrome in that it improves CO2 elimination.

  2. 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.)

  3. Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models

    Energy Technology Data Exchange (ETDEWEB)

    Costa, D.L.; Dreher, K.L. [US Environmental Protection Agency, Research Triangle Park, NC (United States). National Health and Environmental Effects Research Lab.

    1997-09-01

    Many epidemiologic reports associate ambient levels of particulate matter (PM) with human mortality and morbidity, particularly in people with preexisting cardiopulmonary disease (e.g., chronic obstructive pulmonary disease, infection, asthma). Because much ambient PM is derived from combustion sources, the hypothesis that the health effects of PM arise from anthropogenic PM that contains bioavailable transition metals was tested. The PM samples studied derived from three emission sources (two oil and one coal fly ash) and four ambient airsheds (St. Louis, MO, USA; Washington, DC (USA); Duesseldorf, Germany; and Ottawa, Canada). PM was administered to rats by intratracheal instillation in equimass or equimetal doses to address directly the influence of PM mass versus metal content on actual lung injury and inflammation. Results indicated that the lung dose of bioavailable transition metal, not instilled PM mass, was the primary determinant of the acute inflammatory response for both the combustion source and ambient PM samples. Residual oil fly ash, a combustion PM rich in bioavailable metal, and evaluated in rat model of cardiopulmonary disease (pulmonary vasculitis/hypertension) to ascertain whether the disease state augmented sensitivity to that PM. It is proposed that soluble metals from PM mediate the array of PM-associated injuries to the cardiopulmonary system of the healthy and at-risk compromised host.

  4. Effectiveness of transurethral resection under the control of photodynamic diagnosis and intravesical instillation of bacillus Calmette–Guérin in case of poorly differentiated non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    A. I. Rolevich

    2016-01-01

    Full Text Available Background. High-grade non-muscle-invasive bladder cancer (NMIBC is characterized by a high rate of recurrence, progression, and mortality associated with this disease. Organ-preserving treatment by transurethral resection and immunotherapy with bacillus Calmette-Guerin (BCG is an initial approach to therapy in these patients. However, the efficacy of such therapy is limited. This justifies the use of other methods of treatment, such as TUR under the control of photodynamic diagnosis (PDD. Aim of this study was to evaluate the effectiveness of therapeutic interventions in patients with high-grade NMIBC.Materials and methods. We have retrospectively analyzed results of follow-up of patients with primary or recurrent high-grade transitional cell NMIBC, treatment by TUR in conjunction with BCG or without it N.N. Alexandrov National Cancer Centre in the period from 2004 to 2013. In total, the study included 113 patients (27 women and 86 men, in the median age of 72 years. We have evaluated 5-year recurrence- and progression-free survival, analyzed an influence of prognostic factors and methods of treatment on the risk of recurrence and progression with Cox model and Kaplan–Meier method.Results. With a median of follow up of 59 (12–116 months the rates of 5-year recurrence- and progression-free survival were respectively 42.5 and 71.6 %. Statistically significant association with the risk of recurrence was observed in multivariate Cox regression analysis for recurrent tumors (hazard ratio (HR 2.73; 95 % confidence interval (CI 1.61–4.62 and immunotherapy with BCG (HR 0.56; 95 % CI 0.31–0.99. BCG significantly increased recurrence-free survival in patients with both primary tumors, and with recurrent ones. Significant factors in the multivariate analysis with regard to the risk of progression were suspicion for muscle-invasive tumors according to the cystoscopic picture (HR 3.36; 95 % CI 1.09–10.4, abnormal tumor-free bladder mucosa

  5. Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

    2016-03-15

    This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV{sub max} and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV{sub max} were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV{sub max} was 4.7. In 16 patients who underwent follow-up PET/CT, SUV{sub max} was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment.

  6. Effects of copy center particles on the lungs: a toxicological characterization using a Balb/c mouse model.

    Science.gov (United States)

    Pirela, Sandra; Molina, Ramon; Watson, Christa; Cohen, Joel M; Bello, Dhimiter; Demokritou, Philip; Brain, Joseph

    2013-08-01

    Printers and photocopiers release respirable particles into the air. Engineered nanomaterials (ENMs) have been recently incorporated into toner formulations but their potential toxicological effects have not been well studied. To evaluate the biological responses to copier-emitted particles in the lungs using a mouse model. Particulate matter (PM) from a university copy center was sampled and fractionated into three distinct sizes, two of which (PM0.1 and PM0.1-2.5) were evaluated in this study. The particles were extracted and dispersed in deionized water and RPMI/10% FBS. Hydrodynamic diameter and zeta potential were evaluated by dynamic light scattering. The toxicological potential of these particles was studied using 8-week-old male Balb/c mice. Mice were intratracheally instilled with 0.2, 0.6, 2.0 mg/kg bw of either the PM0.1 and PM0.1-2.5 size fractions. Fe2O3 and welding fumes were used as comparative materials, while RPMI/10% FBS was used as the vehicle control. Bronchoalveolar lavage (BAL) was performed 24 hours post-instillation. The BAL fluid was analyzed for total and differential cell counts, and biochemical markers of injury and inflammation. Particle size- and dose-dependent pulmonary effects were found. Specifically, mice instilled with PM0.1 (2.0 mg/kg bw) had significant increases in neutrophil number, lactate dehydrogenase and albumin compared to vehicle control. Likewise, pro-inflammatory cytokines were elevated in mice exposed to PM0.1 (2.0 mg/kg bw) compared to other groups. Our results indicate that exposure to copier-emitted nanoparticles may induce lung injury and inflammation. Further exposure assessment and toxicological investigations are necessary to address this emerging environmental health pollutant.

  7. 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

  8. N-acetylcysteine effectively diminished meconium-induced oxidative stress in adult rabbits.

    Science.gov (United States)

    Mokra, D; Drgova, A; Mokry, J; Antosova, M; Durdik, P; Calkovska, A

    2015-02-01

    Since inflammation and oxidative stress are fundamental in the pathophysiology of neonatal meconium aspiration syndrome (MAS), various anti-inflammatory drugs have been used in experimental and clinical studies on MAS. This pilot study evaluated therapeutic potential of N-acetylcysteine in modulation of meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated adult rabbits were intratracheally given 4 ml/kg of meconium (25 mg/ml) or saline (Sal, n = 6). Thirty minutes later, meconium-instilled animals were treated with intravenous N-acetylcysteine (10 mg/kg, Mec + NAC, n=6) or were non-treated (Mec, n = 6). All animals were oxygen-ventilated for additional 5 hours. Total and differential blood leukocyte counts were determined at baseline, and at 1, 3 and 5 h of the treatment. After sacrificing animals, left lung was saline-lavaged and total and differential cell counts in the bronchoalveolar lavage fluid were determined. Right lung was used for biochemical analyses and for estimation of wet-dry weight ratio. In lung tissue homogenate, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation (LPO) products, and total antioxidant status (TAS) were detected. In isolated lung mitochondria, TBARS, dityrosine, lysine-LPO products, thiol group content, conjugated dienes, and activity of cytochrome c oxidase were estimated. To evaluate systemic effects of meconium instillation and NAC treatment, TBARS and TAS were determined also in plasma. To evaluate participation of eosinophils in the meconium-induced inflammation, eosinophil cationic protein (ECP) was detected in plasma and lung homogenate. Meconium instillation increased oxidation markers and ECP in the lung and decreased TAS (all Pmeconium-induced inflammation and oxidative lung injury.

  9. Detection of tissue expander leakage by methylene blue instillation ...

    African Journals Online (AJOL)

    Background: Tissue expansion is an important and widely used technique of soft tissue reconstruction. Leakage of the expanders is one of the complications and it might at times be difficult to detect. Method and Conclusion: We used methylene blue stained saline for inflation of tissue expanders in 42 cases and found it to ...

  10. Ovine keratoconjunctivitis experimentally induced by instillation of Mycoplasma conjunctivae.

    Science.gov (United States)

    ter Laak, E A; Schreuder, B E; Kimman, T G; Houwers, D J

    1988-10-01

    Five sheep, free from Mycoplasma conjunctivae and ocular Chlamydia infection, were experimentally inoculated with M. conjunctivae and five more sheep were exposed to the infection by contact. Keratoconjunctivitis developed in all ten sheep. As in natural outbreaks of infectious keratoconjunctivitis (IKC), clinical signs were generally moderate and transient, and recurred in some sheep. M. conjunctivae was detected throughout the 53-day observation period. Clinical diagnosis was confirmed by histopathologic examination of three sheep. Moraxella ovis, found in six of the ten sheep before the start of the experiment, appeared to play no etiologic role in the development of IKC.

  11. Identifying service quality strengths and weaknesses using SERVQUAL: a study of dental services.

    Science.gov (United States)

    Kaldenberg, D; Becker, B W; Browne, B A; Browne, W G

    1997-01-01

    The goal of this study was to examine responses among dental patients to the most recent version of SERVQUAL, and to evaluate that instrument as a tool for measuring satisfaction in a dental practice. Items on the reliability and responsiveness dimensions produced the lowest satisfaction ratings, while improvements in providing services as promised and instilling confidence have the greatest potential for producing higher satisfaction among patients. Finally, using open-ended questions, we identified a number of patient events or experiences which caused either high or low scores on individual SERVQUAL items.

  12. A study on the role of apoptotic human umbilical cord mesenchymal stem cells in bleomycin-induced acute lung injury in rat models.

    Science.gov (United States)

    Liu, F-B; Lin, Q; Liu, Z-W

    2016-03-01

    We sought to determine whether normal human umbilical cord mesenchymal stem cells and apoptotic human umbilical cord mesenchymal stem cells play any role in the lung repair following bleomycin-induced lung injury in rat models. Umbilical cord mesenchymal stem cells were obtained from the umbilical cord following caesarian section from healthy normal babies. Plasmin deprivation method was used for culture of human umbilical cord mesenchymal stem cells and flow cytometry was used to identify cell surface antigen and activity of stem cells and apoptosis. The animal model of acute lung injury was established by a one-off intratracheal instillation of bleomycin (BLM) (5 mg/kg) and then normal stem cells and apoptotic stem cells were separately injected. Alveolar lavage fluid and lung tissue were collected for further analysis prior to the injury and at days 3, 7, 14 after administration of BLM. The number of neutrophils in the broncho alveolar lavage fluid (BALF) was counted; Bicinchoninic Acid (BCA) method was used for estimation of total protein content in alveolar lavage fluid; biochemical assay was used for estimation of myeloperoxidase (MPO) activity; hematoxylin and eosin (HE) staining of lung tissue was used for histopathology analysis; reverse transcription-polymerase chain reaction (RT-PCR) assay was used for the determination of interferon-gamma (INF-γ) and mRNA changes of interleukin-4 (IL-4) in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of cytokines TNF-α in the lung tissue. Apoptotic human umbilical cord mesenchymal stem cells were more effective in reducing lung neutrophil infiltration and total protein leakage in rat models of acute lung injury (ALI). There was also an improvement in the degree of vascular permeability, reduction in the level of proinflammatory cytokines, INF-γ gene level and boost in anti-inflammatory cytokine IL-4 levels which also helps in more effectively reducing the degree of injury in

  13. Toxic effects of different meconium fractions on lung function: new therapeutic strategies for meconium aspiration syndrome?

    Science.gov (United States)

    Saugstad, O D; Tølløfsrud, P A; Lindenskov, P; Drevon, C A

    2008-12-01

    To review and summarize experimental data examining the effects of different fractions of meconium, and to test the effect of albumin on meconium aspiration both as prophylactic and rescue treatment. Newborn piglets 2 to 5 days of age were made hypoxic and then instilled meconium or fractions of meconium intratracheally. Meconium-added albumin and albumin instilled after meconium were also tested. Lung function and inflammatory cytokines were measured. Both the lipid- and water-soluble fractions induce inflammation in the lungs with elevation of inflammatory cytokines. When meconium was mixed with albumin, the inflammatory effects of meconium were significantly ameliorated. Rescue therapy with intratracheal albumin 5 min after the meconium aspiration syndrome was induced also improved lung function. These results indicate that at least part of the symptoms seen in the meconium aspiration syndrome could be prevented by blocking the active substances of meconium such as bile acids and free fatty acids.

  14. Rubeola keratitis: a photographic study of corneal lesions.

    Science.gov (United States)

    Pavlopoulos, Georgios P; Giannakos, Georgios I; Theodosiadis, Panagiotis G; Moschos, Marilita M; Iliakis, Evangelos K; Theodosiadis, Georgios P

    2008-05-01

    Detailed description of the morphology of rubeola keratitis lesions is missing from textbooks and published reports. We performed a detailed analysis of rubeola keratitis lesions by using a photographic slit lamp and ophthalmic dyes. Thirty-four eyes of 17 male young adult patients with rubeola keratitis were examined. Patients were examined at 3.6 days after the development of rash. Ocular symptoms were recorded, and patients underwent complete ocular examination including photography of corneal lesions, with and without instillation of ophthalmic dyes (rose Bengal and fluorescein). Patients complained of foreign-body sensation (88%), photophobia (65%), tearing (65%), and burning sensation (47%). Visual acuity was unaffected (26%) or mildly affected (71%). Conjunctivitis was observed in 74% and keratitis in 100% of eyes. Corneal photographs were studied, and 4 types of corneal lesions were identified: small, punctate epithelial lesions staining only with rose Bengal (100%); small, round, or larger and irregular when they coalesced epithelial defects (100%); large or tiny filaments (39%); and target lesions (100%). Target lesions appeared when both dyes were instilled. The outline of target lesions stained with rose Bengal, and they consisted of a pattern of alternating concentric zones of staining with rose Bengal and fluorescein. Keratitis was strictly confined to the epithelium and resolved gradually in all patients without the appearance of complications. Rubeola keratitis in healthy young adults runs a benign course. Recognition of the specific to rubeola keratitis corneal target lesions could aid in the differential diagnosis and prevent the transmission of the disease.

  15. [Postoperative analgesia in children after hernioplasty. Wound infiltration with different concentrations of bupivacaine: a pilot study].

    Science.gov (United States)

    Bültmann, M; Streich, R; Risse, A; Falke, K J; Pappert, D

    1999-07-01

    Wound instillation seems to be an easy and preferable way to achieve postoperative analgesia in pediatric hernioplasty. This prospective, randomized and double-blinded pilot-study was initiated to gain preliminary information in order to define the appropriate concentration of local anaesthetic for efficient posthernioplastic analgesia. 29 children aged 3.1 to 13.7 (5.25 (3.8-8.2) years were randomly assigned to receive either 0.2 ml/kg bupivacaine 0.125% (n = 10), bupivacaine 0.25% (n = 10) or bupivacaine 0.5% (n = 9). The local anesthetic (LA) was instillated intraoperatively before wound closure above the external oblique muscle and below Scarpa's fascia. After entering the post-anesthetic care unit (PACU) pain was assessed by a trained nurse using the linear analogue pain scale (LAPS) in intervals of 15 min. Patients were observed in the PACU for 30-60 min. Pain was further evaluated for 5.5(3-6) h in the ward every hour. In day-only patients the parents were contacted 24 h postoperatively to obtain additional information. From the beginning of the observation period the 0.5% group tended to have less pain than the others in the PACU. The 0.125% and 0.25% group required earlier supplementary analgetics. In addition, the 0.5% group needed once (1/9) supplementary analgesics; the 0.25% group five times (5/10) and the 0.125% group six times (6/10). None of these results is statistically significant, though they appear to be clinically relevant. Wound instillation with 0.2 ml of bupivacaine 0.5% seems to be easy to perform, safe and efficient in controlling posthernioplastic pain. Because of the small numbers of patients included however, no statistically significant differences were observed between the groups. Neither in the LAPS on arrival and observation at the PACU nor in the need for supplementary analgesics. Despite lacking significance the clinical impression suggests a difference to be validated by larger studies. Our data implies that wound instillation

  16. 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...

  17. 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

  18. Effects of effluents of coal combustion and gasification upon lung structure and function. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, D.E.

    1980-01-01

    The overall objective of the proposed research is to correlate both structural and functional alterations in cells and tissues of the lung brought about by exposure to fluidized bed combustion and fixed bed gasification effluents and reagent grade oxides of metals known to be associated with coal combustion gasification. Projected milestones are described. Progress during the first year in setting up aerosol exposure facilities, intratracheal instillations, pulmonary mechanics, and morphometric examinations is reported. (DMC)

  19. Mechanism underlying acute lung injury due to sulfur mustard exposure in rats.

    Science.gov (United States)

    Xiaoji, Zhu; Xiao, Meng; Rui, Xu; Haibo, Chu; Chao, Zhao; Chengjin, Lian; Tao, Wang; Wenjun, Guo; Shengming, Zhang

    2016-08-01

    Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent. © The Author(s) 2014.

  20. Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    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/sup 0/C in the presence of /sup 35/S-sulfate. The labeled GAG were isolated and measured for /sup 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 /sup 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. Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Nikbakht, Jafar; Hemmati, Ali Asghar; Arzi, Ardeshir; Mansouri, Mohammad Taghi; Rezaie, Anahita; Ghafourian, Mehri

    2015-12-01

    Bleomycin (BLM), a chemotherapeutic agent is indicated in the management of some types of cancers. This drug produces a dose-dependent pulmonary fibrosis (PF) in most patients as well as experimental animals through oxidative injury. This study aimed to investigate the effect of gallic acid (GA), a polyphenolic compound, against PF-induce by BLM in rats. The rats were given GA orally at doses (50, 100, and 200 mg/kg/day) for 7 consecutive days before the administration of single intratracheal (it) instillation of BLM at 7.5 IU/kg. GA doses were continued for 21 days after BLM exposure. The regulatory effects of GA on BLM-induced pulmonary toxicity were determined by assaying oxidative stress biomarkers, lung and serum cytokine levels, and by histopathological examination of lung tissue. The results showed that intratracheal BLM administration significantly increased the inflammatory or fibrotic changes, collagen content, levels of malondialdehyde (MDA), and pro-inflammatory cytokines such as TNF-α and IL1β in lung. Also, it significantly decreased non-enzymatic (total thiol) and enzymatic (glutathione peroxidase (GPx)) antioxidant contents in the rats' lung tissue. However, oral administration of GA reversed all of these biochemical indices as well as histopathological alterations induced by BLM. Results of the present study demonstrate that GA, by its antioxidant properties, attenuates oxidative damage and fibrosis induced by BLM. Thus, an effective supplement with GA as an adjuvant therapy may be a very promising compound in reducing the side effects of BLM. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Background: The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison.Methods: Mice....... Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory...... and necrotic histological changes were observed, however, not in mice instilled with epoxy dust without CNT.Conclusions: Pulmonary deposition of epoxy dusts with and without CNT induced inflammation and DNA damage in lung tissue. There was no additive effect of adding CNT to epoxies for any of the pulmonary...

  3. Megakaryoblastic leukemia-1 is required for the development of bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Bernau, Ksenija; Ngam, Caitlyn; Torr, Elizabeth E; Acton, Benjamin; Kach, Jacob; Dulin, Nickolai O; Sandbo, Nathan

    2015-03-27

    Fibrosing disorders of the lung, such as idiopathic pulmonary fibrosis, are characterized by progressive extracellular matrix accumulation that is driven by myofibroblasts. The transcription factor megakaryoblastic leukemia-1 (MKL1) mediates myofibroblast differentiation in response to several profibrotic stimuli, but the role it plays in mediating pulmonary fibrosis has not been fully elucidated. In this study, we utilized mice that had a germline deletion of MKL1 (MKL1 (-,-)) to determine the role that MKL1 plays in the development of bleomycin-induced pulmonary fibrosis. Bleomycin or normal saline were intratracheally delivered to 9 to 12 week old female MKL1 (+,+) and MKL1 (-,-) mice. Mice were assessed for weight loss and survival to 28 days. Inflammatory responses were assessed through bronchoalveolar lavage at days 3 and 7 post-treatment. The development of pulmonary fibrosis was characterized using hydroxyproline assay and histological staining. MKL1 (+,+) and MKL1 (-,-) mouse lung fibroblasts were isolated to compare morphologic, gene expression and functional differences. MKL1 (-,-) mice demonstrated increased survival, attenuated weight loss, and decreased collagen accumulation compared to wild-type animals 28-days after intratracheal instillation of bleomycin. Histological analysis demonstrated decreased trichrome, smooth muscle α-actin, and fibronectin staining in MKL1(-,-) mice compared to MKL1 (+,+) controls. Differential cell counts from bronchoalveolar lavage demonstrated that there was attenuated neutrophilia 3 days after bleomycin administration, but no difference at day 7. Isolated mouse lung fibroblasts from MKL1 (-,-) mice had decreased contractility and deposited less fibronectin matrix compared to wild-type controls, suggesting a defect in key remodeling functions. Altogether, these data demonstrate that MKL1 plays a significant role in mediating the fibrotic response to bleomycin injury. Loss of MKL1 attenuated early neutrophil influx, as

  4. Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma

    Directory of Open Access Journals (Sweden)

    Lukacs Nicholas W

    2007-12-01

    Full Text Available Abstract Background While glucocorticoids are currently the most effective therapy for asthma, associated side effects limit enthusiasm for their use. Peroxisome proliferator-activated receptor-γ (PPAR-γ activators include the synthetic thiazolidinediones (TZDs which exhibit anti-inflammatory effects that suggest usefulness in diseases such as asthma. How the ability of TZDs to modulate the asthmatic response compares to that of glucocorticoids remains unclear, however, because these two nuclear receptor agonists have never been studied concurrently. Additionally, effects of PPAR-γ agonists have never been examined in a model involving an allergen commonly associated with human asthma. Methods We compared the effectiveness of the PPAR-γ agonist pioglitazone (PIO to the established effectiveness of a glucocorticoid receptor agonist, dexamethasone (DEX, in a murine model of asthma induced by cockroach allergen (CRA. After sensitization to CRA and airway localization by intranasal instillation of the allergen, Balb/c mice were challenged twice at 48-h intervals with intratracheal CRA. Either PIO (25 mg/kg/d, DEX (1 mg/kg/d, or vehicle was administered throughout the period of airway CRA exposure. Results PIO and DEX demonstrated similar abilities to reduce airway hyperresponsiveness, pulmonary recruitment of inflammatory cells, serum IgE, and lung levels of IL-4, IL-5, TNF-α, TGF-β, RANTES, eotaxin, MIP3-α, Gob-5, and Muc5-ac. Likewise, intratracheal administration of an adenovirus containing a constitutively active PPAR-γ expression construct blocked CRA induction of Gob-5 and Muc5-ac. Conclusion Given the potent effectiveness shown by PIO, we conclude that PPAR-γ agonists deserve investigation as potential therapies for human asthma.

  5. 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

  6. Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study.

    Science.gov (United States)

    Tanihara, Hidenobu; Inoue, Toshihiro; Yamamoto, Tetsuya; Kuwayama, Yasuaki; Abe, Haruki; Suganami, Hideki; Araie, Makoto

    2015-06-01

    To investigate the intra-ocular pressure (IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline. The mean IOP reduction was -5.2 mmHg for 0.2%, -6.4 mmHg for 0.4% and -2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were -6.8 mmHg for 0.2%, -7.3 mmHg for 0.4% and -4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo. Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Tyrosine Mutation in AAV9 Capsid Improves Gene Transfer to the Mouse Lung

    Directory of Open Access Journals (Sweden)

    Sabrina V. Martini

    2016-07-01

    Full Text Available Background/Aims: 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. Methods: 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. Results: 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. Conclusion: Our results provide the impetus for further studies to exploit the use of AAV9 vectors as a tool for pulmonary gene therapy.

  8. 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.

  9. Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis.

    Science.gov (United States)

    Conte, Enrico; Fagone, Evelina; Gili, Elisa; Fruciano, Mary; Iemmolo, Maria; Pistorio, Maria Provvidenza; Impellizzeri, Daniela; Cordaro, Marika; Cuzzocrea, Salvatore; Vancheri, Carlo

    2016-06-07

    In this study, the bleomycin model of pulmonary fibrosis was utilized to investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate therapeutic effects in a subset of mice, Ac-SDKP was administered one week after BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks later. Measurement of fluid and collagen content in the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and molecular analysis were performed. Compared to BLEO-treated mice, animals that received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality, weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage (histological evidence of lung injury), and fibrosis (collagen histological staining and soluble collagen content in the lung) at up to 21 days. Moreover, IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO-induced IL-17 and TGF-β expression in lung tissue. Importantly, α-SMA expression, the hallmark of myofibroblast differentiation, was also decreased. This is the first report showing not only a preventive protective role of Ac-SDKP but also its significant therapeutic effects in the bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.

  10. The antifibrotic effects of alveolar macrophages 5-HT2C receptors blockade on bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Elaidy, Samah M; Essawy, Soha S

    2016-12-01

    The most widespread chronic fibrosing lung disease is idiopathic pulmonary fibrosis. Lung serotonin (5-HT) content is increased during pulmonary fibrosis with the implication of 5-HT2 receptors in the pathogenesis. Serotonin plays important roles in alveolar macrophages function through 5-HT2C receptors activation. Numerous studies described the important role of 5-HT2A/B receptor blockers in suppressing different types of fibrosis as idiopathic pulmonary fibrosis. The current study pointed to examine the antifibrotic effects of RS-102221 and/or terguride through in vivo model of pulmonary fibrosis. Induction of pulmonary fibrosis was through a single dose of intra-tracheal bleomycin instillation (5mg/kg dissolved in phosphate buffer saline) in adult male albino Wistar rats. Next day of bleomycin instillation, intraperitoneal injection of RS-102221 (0.5mg/kg/d) and/or terguride (1.2mg/kg/d) were administered and continued for 14 days. Noticeable increase in 5-HT2C receptors expression was observed in fibrotic lung tissues with marked allocation belonging to alveolar macrophages. Either RS-102221 or terguride reduced the increments in lung water contents, grading of lung fibrosis, lung tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF- β1 ) and vascular endothelial growth factor (VEGF) levels in lung injury and fibrosis-induced by bleomycin. Moreover, collagen content and myofibroblasts-alpha smooth muscle actin (α-SМA) were significantly decreased. Additionally, the simultaneous administration of RS-102221 with terguride had a synergistic outcome compared to that obtained by individual monotherapy. These findings suggested the potential use of 5-HT2A/B/C antagonists as anti-fibrotic agents in lung fibrosis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  11. 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.

  12. 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

    and microlaryngoscopy, benign goitrous thyroid tissue was removed through a tracheal fissure during gestational week 35. Postoperatively the patient had stopped medication and was without any pulmonary symptoms. The child was delivered by cesarean section in gestational week 39. Apgar score was normal and the child has...

  13. THE PRODUCTION OF ANTIBODIES IN RABBITS BY A SIMPLIFIED INTRATRACHEAL METHOD.

    Science.gov (United States)

    Jones, F S

    1923-05-31

    The method described of producing antibodies by the administration of antigens through the larynx is simple. The results obtained, however, conform closely to those obtained through intraperitoneal injection. The procedure is relatively a safe one and may well be employed in experimental inoculations. The advantages of rapidity and painlessness are obvious. In addition, gross injury has not been observed. Injections may be repeated at frequent intervals without danger to the life of the animal. The tube illustrated in Text-fig. 1 extends a little over 1 cm. into the trachea. The tube designed for the guinea pig reaches 2 or 3 mm. below the glottis. While the doses indicated in the protocols are small, 7 to 10 cc. of liquid have been given to rabbits by means of the tube without ill effects. It has been shown by the injection of India ink that the material is well distributed throughout the lungs in both the rabbit and guinea pig. Under certain conditions it may be advisable to inject more deeply into the trachea, especially in the rabbit. The tube illustrated in Text-fig. 1 is not adaptable for this purpose. A cannula of larger diameter has proved of distinct advantage as a shield for introducing flexible catheters well down the trachea. A cannula 9 cm. long and 4 mm. in diameter when bent at an angle of 45 degrees may be passed through the larynx of a rabbit without difficulty. A No. 8 (French) woven or No. 10 soft rubber catheter may be inserted into the cannula beyond the bend before the tube is passed through the glottis. After the tube has entered the glottis the catheter then may be introduced as deeply as desired into the teachea. The metal cannula enables the operator to "feel" the glottis. From the experiments one seems justified in concluding that the results obtained by administering antigens by way of the trachea are about the same as those obtained by the intraperitoneal route. With the tubes described injury has been largely eliminated. The procedure is relatively a safe one.

  14. Comparison of Three Different Administration Positions for Intratracheal Beractant in Preterm Newborns with Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Ahmet Karadag

    2016-04-01

    Conclusion: In terms of efficacy and side effects, no important difference was observed between the recommended four position beractant application, the two position administration, and the neutral position.

  15. Differential infection efficiencies of peripheral lung and tracheal tissues in sheep infected with Visna/maedi virus via the respiratory tract.

    Science.gov (United States)

    McNeilly, Tom N; Tennant, Peter; Luján, Lluís; Pérez, Marta; Harkiss, Gordon D

    2007-02-01

    The main routes of transmission of Visna/maedi virus (VMV), an ovine lentivirus, are thought to be through ingestion of infected colostrum and/or milk or through inhalation of respiratory secretions. Whereas oral transmission appears to be mediated via epithelial cells within the small intestine, the mechanism of virus uptake in the respiratory tract is unknown. In addition, it is not known whether infection is mediated by cell-associated or cell-free VMV, previous studies having not addressed this question. Intratracheal (i.t.) injection of VMV is known to be a highly efficient method of experimental infection, requiring as little as 10(1) TCID(50) VMV for successful infection. However, using a tracheal organ culture system, we show here that ovine tracheal mucosa is relatively resistant to VMV, with detectable infection only seen after incubation with high titres of virus (> or =10(5) TCID(50) ml(-1)). We also demonstrate that i.t. injection results in exposure of both trachea and the lower lung and that the time taken for viraemia and seroconversion to occur after lower lung instillation of VMV was significantly shorter than that observed for tracheal instillation of an identical titre of virus (P=0.030). This indicates that lower lung and not the trachea is a highly efficient site for VMV entry in vivo. Furthermore, cell-free virus was identified within the lung-lining fluid of naturally infected sheep for the first time. Together, these results suggest that respiratory transmission of VMV is mediated by inhalation of aerosols containing free VMV, with subsequent virus uptake in the lower lung.

  16. Biological response to nano-scale titanium dioxide (TiO2): role of particle dose, shape, and retention.

    Science.gov (United States)

    Silva, Rona M; Teesy, Christel; Franzi, Lisa; Weir, Alex; Westerhoff, Paul; Evans, James E; Pinkerton, Kent E

    2013-01-01

    Titanium dioxide (TiO2) is one of the most widely used nanomaterials, valued for its highly refractive, photocatalytic, and pigmenting properties. TiO2 is also classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen. The objectives of this study were to (1) establish a lowest-observed-effect level (LOEL) for nano-scale TiO2, (2) determine TiO2 uptake in the lungs, and (3) estimate toxicity based on physicochemical properties and retention in the lungs. In vivo lung toxicity of nano-scale TiO2 using varying forms of well-characterized, highly dispersed TiO2 was assessed. Anatase/rutile P25 spheres (TiO2-P25), pure anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NB) were tested. To determine the effects of dose and particle characteristics, male Sprague-Dawley rats were administered TiO2 (0, 20, 70, or 200 μg) via intratracheal instillation. Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis 1 and 7 d post exposure. Despite abundant TiO2 inclusions in all exposed animals, only TiO2-NB displayed any significant degree of inflammation seen in BALF at the 1-d time point. This inflammation resolved by 7 d, although TiO2 particles had not cleared from alveolar macrophages recovered from the lung. Histological examination showed TiO2-NB produced cellular changes at d 1 that were still evident at d 7. Data indicate TiO2-NB is the most inflammatory with a LOEL of 200 μg at 1 d post instillation.

  17. Didecyldimethylammonium chloride induces pulmonary fibrosis in association with TGF-β signaling in mice.

    Science.gov (United States)

    Ohnuma-Koyama, Aya; Yoshida, Toshinori; Tajima-Horiuchi, Haruka; Takahashi, Naofumi; Yamaguchi, Satoru; Ohtsuka, Ryoichi; Takeuchi-Kashimoto, Yukiko; Kuwahara, Maki; Takeda, Makio; Nakashima, Nobuaki; Harada, Takanori

    2013-11-01

    Didecyldimethylammonium chloride (DDAC) is a representative dialkyl-quaternary ammonium compound that is used as a disinfectant against several pathogens and is also used in commercial, industrial, and residential settings. We previously investigated toxicity on air way system following single instillation of DDAC to the lungs in mice, and found that DDAC causes pulmonary injury, which is associated with altered antioxidant antimicrobial responses; the inflammatory phase is accompanied or followed by fibrotic response. The present study was conducted to monitor transforming growth factor-β (TGF-β) signaling in pulmonary fibrosis induced by DDAC. Mice were intratracheally instilled with DDAC and sacrificed 1, 3, or 7 days after treatment to measure TGF-β signaling. In order to further evaluate TGF-β signaling, we treated isolated mouse lung fibroblasts with DDAC. Fibrotic foci were observed in the lungs on day 3, and were widely extended on day 7, with evidence of increased α-smooth muscle actin-positive mesenchymal cells and upregulation of Type I procollagen mRNA. Developing fibrotic foci were likely associated with increased expression of Tgf-β1 mRNA, in addition to decreased expression of Bone morphogenetic protein-7 mRNA. In fibrotic lung samples, the expression of phosphorylated SMAD2/3 was considerably higher than that of phosphorylated SMAD1/5. In isolated lung fibroblasts, the mRNA levels of Tgf-β1 were specifically increased by DDAC treatment, which prolonged phosphorylation of SMAD2/3. These effects were abolished by treatment with SD208 - a TGF-βRI kinase inhibitor. The results suggest that DDAC induces pulmonary fibrosis in association with TGF-β signaling. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. Evaluation of Life and Death Studies Course on Attitudes Toward Life and Death Among Nursing Students

    Directory of Open Access Journals (Sweden)

    Huei-Lih Hwang

    2005-12-01

    Full Text Available The aim of this study was to evaluate attitudes toward life and death among nursing students after attending the life and death studies (LDS program. Both qualitative and quantitative methods were used to collect data. The pretest-posttest control group design randomly assigned students to an experimental (n = 47 or control group (n = 49. The 13-week course included lectures, video appraisal, games, simulations, films, books, assignments and group sharing. Statistical and content analysis were used to analyze qualitative and quantitative data. The findings showed a significant improvement in perception of the meaningfulness of life in four categories of improvement: expanded viewpoint, sadness about death, treating life sincerely, and instilling hope in life. The qualitative data indicated that a positive change in meaning of life was associated with interaction with others and self-reflection.

  19. Biological responses to diesel exhaust particles (DEPs depend on the physicochemical properties of the DEPs.

    Directory of Open Access Journals (Sweden)

    Eun-Jung Park

    Full Text Available Diesel exhaust particles (DEPs are the main components of ambient particulate materials, including polyaromatic hydrocarbons (PAHs, n-PAHs, heavy metals, and gaseous materials. Many epidemiological, clinical, and toxicological studies have shown that ambient particles, including DEPs, are associated with respiratory disorders, such as asthma, allergic rhinitis, and lung cancer. However, the relationship between the biological response to DEPs and their chemical composition remains unclear. In this study, we investigated the physicochemical properties of DEPs before toxicological studies, and then administered a single intratracheal instillation of DEPs to mice. The mice were then killed 1, 7, 14 and 28 days after DEP exposure to observe the biological responses induced by DEPs over time. Our findings suggest that DEPs engulfed into cells induced a Th2-type inflammatory response followed by DNA damage, whereas DEPs not engulfed into cells induced a Th1-type inflammatory response. Further, the physicochemical properties, including surface charge, particle size, and chemical composition, of DEPs play a crucial role in determining the biological responses to DEPs. Consequently, we suggest that the biological response to DEPs depend on cell-particle interaction and the physicochemical properties of the particles.

  20. Activation of Neutrophils by Nanoparticles

    Directory of Open Access Journals (Sweden)

    David M. Goncalves

    2011-01-01

    Full Text Available The use of nanoparticles (NPs has increased in the past few years in various fields, including defence, aerospace, electronics, biology, medicine, and so forth. and in applications such as diagnostic technology, bioimaging, and drug/gene delivery. Thus, human exposure to NPs and nanomaterials is unavoidable and will certainly expand in the future resulting in a growing interest in nanotoxicology, the study of toxicity of nanomaterials. A number of studies have reported the effects of NPs in respect to pulmonary inflammation by investigating in vitro activation of pulmonary cells with NPs and in vivo in a variety of models in which neutrophils appear to be the predominant leukocyte cell type in lungs and in bronchoalveolar lavages following inhalation or intratracheal instillation of NPs. Despite the fact that several studies have reported an increased number of neutrophils, the literature dealing with the direct activation of neutrophils by a given NP is poorly documented. This paper will summarize the current literature in this latter area of research and will end with a perspective view in which our laboratory will be involved in the following years.

  1. Long-term treatment with royal jelly improves bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Zargar, Hamid Reza; Hemmati, Ali Asghar; Ghafourian, Mehri; Arzi, Ardeshir; Rezaie, Anahita; Javad-Moosavi, Seyed Ali

    2017-01-01

    This study investigated the anti-fibrotic potential of royal jelly (RJ) powder against bleomycin-induced pulmonary fibrosis in rats. The rats were given RJ orally (25, 50, and 100 mg/kg per day) for 7 consecutive days before the administration of single intratracheal instillation of bleomycin (BLM) at 7.5 IU/kg. RJ doses were continued for 21 days after BLM exposure. Fibrotic changes in the lungs were studied by cell count and analysis of cytokine levels in the bronchoalveolar lavage fluid (BALF), histopathological examination, and assaying oxidative stress biomarkers in lung tissue. The results showed that BLM administration significantly increased the fibrotic changes, collagen content, and levels of malondialdehyde and decreased total thiol and glutathione peroxidase antioxidant contents in the rats' lung tissue. An increase in the level of cell counts and pro-inflammatory and pro-fibrotic cytokines such as TNF-α and TGF-β in BALF was observed. Also, it significantly decreased IFN-γ, an anti-fibrotic cytokine, in BALF. However, RJ (50 and 100 mg/kg) reversed all of these biochemical indices as well as histopathological alterations induced by BLM. The present study demonstrates that RJ, by its antioxidant and anti-inflammatory properties, attenuates oxidative damage and fibrosis induced by BLM.

  2. A Standardized Traditional Chinese Medicine Preparation Named Yejuhua Capsule Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Downregulating Toll-Like Receptor 4/Nuclear Factor-κB

    Directory of Open Access Journals (Sweden)

    Chu-Wen Li

    2015-01-01

    Full Text Available A standardized traditional Chinese medicine preparation named Yejuhua capsule (YJH has been clinically used in treatments of various acute respiratory system diseases with high efficacy and low toxicity. In this study, we were aiming to evaluate potential effects and to elucidate underlying mechanisms of YJH against lipopolysaccharide- (LPS- induced acute lung injury (ALI in mice. Moreover, the chemical analysis and chromatographic fingerprint study were performed for quality evaluation and control of this drug. ALI was induced by intratracheal instillation of LPS (5 mg/kg into the lung in mice and dexamethasone (5 mg/kg, p.o. was used as a positive control drug. Results demonstrated that pretreatments with YJH (85, 170, and 340 mg/kg, p.o. effectively abated LPS-induced histopathologic changes, attenuated the vascular permeability enhancement and edema, inhibited inflammatory cells migrations and protein leakages, suppressed the ability of myeloperoxidase, declined proinflammatory cytokines productions, and downregulated activations of nuclear factor-κB (NF-κB and expressions of toll-like receptor 4 (TLR4. This study demonstrated that YJH exerted potential protective effects against LPS-induced ALI in mice and supported that YJH was a potential therapeutic drug for ALI in clinic. And its mechanisms were at least partially associated with downregulations of TLR4/NF-κB pathways.

  3. An Inhaled Inhibitor of Myristoylated Alanine-Rich C Kinase Substrate Reverses LPS-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Yin, Qi; Fang, Shijing; Park, Joungjoa; Crews, Anne L; Parikh, Indu; Adler, Kenneth B

    2016-11-01

    Intratracheal instillation of bacterial LPS is a well-established model of acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Because the myristoylated alanine-rich C kinase substrate (MARCKS) protein is involved in neutrophil migration and proinflammatory cytokine production, we examined whether an aerosolized peptide that inhibits MARCKS function could attenuate LPS-induced lung injury in mice. The peptide, BIO-11006, was delivered at 50 μM via inhalation either just before intratracheal instillation of 5 μg of LPS into Balb/C mice, or 4, 12, 24, or 36 hours after LPS instillation. Effects of BIO-11006 were evaluated via analysis of mouse disease-related behavior, lung histology, bronchoalveolar lavage fluid total protein, neutrophil counts and percentages, cytokine (KC [CXCl1, mouse IL-8 equivalent] and TNF-α) expression, and activation of NF-κB in lung tissue. Treatment with aerosolized BIO-11006 at 0, 4, 12, 24, and even 36 hours after LPS instillation reversed the disease process: mouse behavior returned to normal after two treatments 12 hours apart with the inhaled peptide after LPS injury, whereas control LPS-instilled animals treated with PBS only remained moribund. Histological appearance of inflammation, bronchoalveolar lavage fluid protein levels, leukocyte and neutrophil numbers, KC and TNF-α gene and protein expression, and NF-κB activation were all significantly attenuated by inhaled BIO-11006 at all time points. These results implicate MARCKS protein in the pathogenesis of ALI/ARDS and suggest that MARCKS-inhibitory peptide(s), delivered by inhalation, could represent a new and potent therapeutic treatment for ALI/ARDS, even if administered well after the disease process has begun.

  4. Studies on the preparation and evaluation of colloidal chromic phosphate - 32P for possible therapeutic use

    International Nuclear Information System (INIS)

    Prabhakar, G.; Mehra, K.S.; Ramamoorthy, N.

    2001-01-01

    Radionuclide therapy has become the focus of recent attention in nuclear medicine, thanks to the emergence of new therapeutic radionuclides as well as the known prospects of local instillation approach and the exciting promise of targeted therapy concept. This has naturally led to a revived interest in the use of established products of earlier generation also, for example 32 P compounds. In response to such a demand of nuclear medicine physicians in India, 32 P labelled colloidal chromic phosphate suspension (CCPS) was prepared by suitable modifications to a reported procedure. 51 Cr was used as tracer for initial studies of standardisation, in order to avail the benefits of relatively greater ease and higher efficiency of assay of gamma activity at low levels. Recovery of the colloid and purification were accomplished by dialysis leading to about 60% radiochemical (RC) yield. The RC purity of the CCPS formulated in 30% dextrose solution was over 98% as assessed by paper chromatography. The particle size was below 5μM, with nearly 99% of the particles present in the size range of 0.6-2.5 μM. The stability of the colloid was found to be not less than 7 days, in terms of soluble phosphate content of the CCPS. The consistency of biological behaviour of CCPS was attempted to be studied by i.v. administration in test animals, although the envisaged end use is only by local instillation. The animal studies revealed prominent lung uptake (∼70%) indicating the presence of >10μM particles formed in vivo, most probably due to agglomeration in serum. The easy reliable preparation of CCPS in acceptable yield, purity and particle size distribution demonstrated in the present study, considered along with the added advantages of abundant, economic availability and convenient production logistics of no-carrier-added 32 P, would merit further investigations on CCPS and similar *M(III)-phosphate colloids for possible therapeutic applications. (author)

  5. Nervous system effects of dissolved and nanoparticulate cadmium in rats in subacute exposure.

    Science.gov (United States)

    Horváth, Edina; Oszlánczi, Gábor; Máté, Zsuzsanna; Szabó, Andrea; Kozma, Gábor; Sápi, András; Kónya, Zoltán; Paulik, Edit; Nagymajtényi, László; Papp, András

    2011-07-01

    Cadmium, a toxic heavy metal with various applications in technology, can affect people both by environmental (foodborne) and occupational (inhalation) exposure and can cause nervous system damage. To model this, rats were subacutely treated either with CdCl(2) solution per os (3.0 mg kg(-1) b.w.) or nanoparticulate CdO(2) (particle size ca 65 nm) by intratracheal instillation (0.04 mg kg(-1) b.w.) alone or in sequential combination. Nervous system effects were observed at different levels of function (open field behavior, cortical electrical activity, nerve action potential) and some general toxicological indicators were also measured. Three weeks of oral plus one week of intratracheal exposure caused significant reduction of body weight gain and open field motility. Lengthening of latency of sensory evoked potentials, observed in all treated rats, was also the most significant in the group receiving oral plus intratracheal treatment. Conduction velocity of the tail nerve was likewise decreased in all treated groups. Several of the effects pointed to a potentiating interaction between the two forms of Cd. Modeling environmental and occupational Cd exposure by oral and intratracheal application in rats was feasible, with results suggesting serious negative health effects in humans suffering such a combined exposure. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury.

    Science.gov (United States)

    Ogawa, Eileen N; Ishizaka, Akitoshi; Tasaka, Sadatomo; Koh, Hidefumi; Ueno, Hiroshi; Amaya, Fumimasa; Ebina, Masahito; Yamada, Shingo; Funakoshi, Yosuke; Soejima, Junko; Moriyama, Kiyoshi; Kotani, Toru; Hashimoto, Satoru; Morisaki, Hiroshi; Abraham, Edward; Takeda, Junzo

    2006-08-15

    Proinflammatory cytokines play an important role in ventilator-induced lung injury (VILI). High-mobility group box-1 (HMGB1) is a macrophage-derived proinflammatory cytokine that can cause lung injury. This study tested the hypothesis that HMGB1 is released in intact lungs ventilated with large Vt. A second objective was to identify the source of HMGB1. A third objective was to examine the effects of blocking HMGB1 on the subsequent development of VILI. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained from rabbits mechanically ventilated for 4 h with a small (8 ml/kg) versus a large (30 ml/kg) Vt. BALF was also obtained from rabbits with intratracheal instillation of anti-HMGB1 antibody before the initiation of large Vt ventilation. The concentrations of HMGB1 in BALF were fivefold higher in the large than in the small Vt group. Immunohistochemistry and immunofluorescence studies revealed expression of HMGB1 in the cytoplasm of macrophages and neutrophils in lungs ventilated with large Vt. Blocking HMGB1 improved oxygenation, limited microvascular permeability and neutrophil influx into the alveolar lumen, and decreased concentrations of tumor necrosis factor-alpha in BALF. These observations suggest that HMGB1 could be one of the deteriorating factors in the development of VILI.

  7. 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.

    Science.gov (United States)

    Dullin, Christian; dal Monego, Simeone; Larsson, Emanuel; Mohammadi, Sara; Krenkel, Martin; Garrovo, Chiara; Biffi, Stefania; Lorenzon, Andrea; Markus, Andrea; Napp, Joanna; Salditt, Tim; Accardo, Agostino; Alves, Frauke; Tromba, Giuliana

    2015-01-01

    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.

  8. Indoor secondary organic aerosols formation from ozonolysis of monoterpene: An example of d-limonene with ammonia and potential impacts on pulmonary inflammations.

    Science.gov (United States)

    Niu, Xinyi; Ho, Steven Sai Hang; Ho, Kin Fai; Huang, Yu; Cao, Junji; Shen, Zhenxing; Sun, Jian; Wang, Xiumei; Wang, Yu; Lee, Shuncheng; Huang, Rujin

    2017-02-01

    Monoterpene is one class of biogenic volatile organic compounds (BVOCs) which widely presents in household cleaning products and air fresheners. It plays reactive role in secondary organic aerosols (SOAs) formation with ozone (O 3 ) in indoor environments. Such ozonolysis can be influenced by the presence of gaseous pollutants such as ammonia (NH 3 ). This study focuses on investigations of ozone-initiated formation of indoor SOAs with d-limonene, one of the most abundant indoor monoterpenes, in a large environmental chamber. The maximum total particle number concentration from the ozonolysis in the presence of NH 3 was 60% higher than that in the absence of NH 3 . Both of the nuclei coagulation and condensation involve in the SOAs growth. The potential risks of pulmonary injury for the exposure to the secondary particles formed were presented with the indexes of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) expression levels in bronchoalveolar lavage fluid (BALF) upon intratracheal instillation in mice lung for 6 and 12h. The results indicated that there was 22-39% stronger pulmonary inflammatory effect on the particles generated with NH 3 . This is a pilot study which demonstrates the toxicities of the indoor SOAs formed from the ozonolysis of a monoterpene. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Nigella sativa, a traditional Tunisian herbal medicine, attenuates bleomycin-induced pulmonary fibrosis in a rat model.

    Science.gov (United States)

    Abidi, Anouar; Robbe, Alexandre; Kourda, Nadia; Ben Khamsa, Saloua; Legrand, Alexandre

    2017-06-01

    The present study investigated the effects of Nigella sativa oil (NSO) on bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary fibrosis (PF) was established by intratracheal instillation of BLM, and the effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was studied over a period of 50daysusing 1 H RMN analysis on the urine and broncho alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and fibrosis) and immunohistochemical (TGF-β1 density) changes were evaluated. Results found that the BLM group showed a significant increase in inflammatory index (II), fibrosis score (FS) and TGF-β1 distribution in the lung inflammatory infiltrate, accompanied by a decreased urinary secretion of Krebs cycle intermediates, including acetate, pyruvate, carnitine, trimethylamine-N-oxide and succinate. However, at the same time point, NSO treated rats had a reduced II and FS, and had an increased urinary secretion of histidine, fumarate, allantoin and malate. In conclusion, NSO treatment attenuated the effects of BLM-induced PF, by supporting lung, liver and kidney activity in resisting PF. These findings provide an insight into the preventive and therapeutic potential of NSO in the treatment of PF. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Evaluating the inhibitory potential of sulindac against the bleomycin-induced pulmonary fibrosis in wistar rats.

    Science.gov (United States)

    Verma, Ramesh; Brahmankar, Mahesh; Kushwah, Lokendra; Suresh, Balakrishnan

    2013-11-01

    The present study examined the protective effect of sulindac on bleomycin-induced lung fibrosis in rats. Animals were divided into saline group, bleomycin group (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally from day 1 to day 20). Bleomycin administration reduced the body weight, altered antioxidant status (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione) while it increased the lung weight, hydroxyproline content, collagen deposition and lipid peroxidation. However, simultaneous administration of sulindac improved the body weight, antioxidant status and decreased the collagen deposition in lungs. Moreover, the levels of inflammatory cytokine tumour necrosis factor-α increased in bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour necrosis factor-α were found reduced. Finally, histological evidence also supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The results of the present study indicate that sulindac can be used as an agent against bleomycin-induced pulmonary fibrosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. A comparative study of the effect of antiprostaglandins and steroids on aphakic cystoid macular oedema

    Directory of Open Access Journals (Sweden)

    Ahluwalia B

    1988-01-01

    Full Text Available The present double masked, randomized and placebo control study was carried out to compare the effects of steroids and an antiprostaglandin drug on aphakic cystoid macular oedema (ACME in 60 cases who underwent uneventful intracapsular lens extraction. These 60 eyes were equally divided into three groups depending on the type of prophylactic eye drop instilled viz. Placebo group (I, steroid group (11 and in-domethacin group (III. Angiographic incidence of ACME observed in groups I, II and III was 40%, 10% and I0%, respectively. It is concluded that prophylactic treatment with topical steroids or indomethacin have a definite role to play in reducing the incidence as well as severity of ACME. Hence, their use is recommended for the prophylaxis- of ACHE. However, to justify the superiority of indomethacin or dexamethasone over each other a large and long term compara-tive studs is suggested.

  12. A comparative study of Bilvadi Yoga Ashchyotana and eye drops in Vataja Abhishyanda (Simple Allergic Conjunctivitis).

    Science.gov (United States)

    Udani, Jayshree; Vaghela, D B; Rajagopala, Manjusha; Matalia, P D

    2012-01-01

    Simple allergic conjunctivitis is the most common form of ocular allergy (prevalence 5 - 22 %). It is a hypersensitivity reaction to specific airborne antigens. The disease Vataja Abhishyanda, which is due to vitiation of Vata Pradhana Tridosha is comparable with this condition. The management of simple allergic conjunctivitis in modern ophthalmology is very expensive and it should be followed lifelong and Ayurveda can provide better relief in such manifestation. This is the first research study on Vataja Abhishyanda. Patients were selected from the Outpatient Department (OPD), Inpatient Department (IPD), of the Shalakya Tantra Department and were randomly divided into two groups. In Group-A Bilvadi Ashchyotana and in Group-B Bilvadi eye drops were instilled for three months. Total 32 patients were registered and 27 patients completed the course of treatment. Bilvadi Ashchyotana gave better results in Toda, Sangharsha, Parushya, Kandu and Ragata as compared with Bilvadi Eye Drops in Vataja Abhishyanda.

  13. Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats.

    Science.gov (United States)

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

    2016-01-01

    With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs.

  14. Pressure-controlled ventilation attenuates lung microvascular injury in a rat model of activated charcoal aspiration.

    Science.gov (United States)

    Arnold, Thomas C; Zhang, Shu; Xiao, Feng; Conrad, Steven A; Carden, Donna L

    2003-01-01

    Previous animal data suggest that aspiration of activated charcoal is associated with pulmonary microvascular injury that may be related to excessive ventilator-induced airway pressures. The purpose of this study was to test the hypothesis that ventilator-induced airway trauma contributes to the lung vascular injury observed following activated charcoal aspiration. Capillary filtration coefficient (Kf,c), a sensitive measure of lung microvascular permeability, was determined isogravimetrically prior to and after intratracheal instillation of 0.4 ml/kg (12% weight/vol. solution, pH 7.4) activated charcoal oran equal volume of sterile water in isolated, perfused rat lungs in which ventilation was either pressure-controlled at 10cm H2O or volume-controlled at 5 ml/kg. There was significant lung injury in both activated charcoal groups regardless of ventilation method compared to control lungs or lungs administered sterile water (p activated charcoal as compared to traditional volume-controlled ventilation methods.

  15. 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.

  16. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

    International Nuclear Information System (INIS)

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-01-01

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO 2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema

  17. Suppression of RAGE and TLR9 by Ketamine Contributes to Attenuation of Lipopolysaccharide-Induced Acute Lung Injury.

    Science.gov (United States)

    Yang, Chunyan; Song, Yulong; Wang, Hui

    2017-06-01

    The present study aimed to investigate the protective role of ketamine in lipopolysaccharide (LPS)-induced acute lung injury (ALI) by the inhibition of the receptor for advanced glycation end products (RAGE) and toll-like receptor 9 (TLR9). ALI was induced in rats by intratracheal instillation of LPS (5 mg/kg), and ketamine (5, 7.5, and 10 mg/kg) was injected intraperitoneally 1 h after LPS administration. Meanwhile, A549 alveolar epithelial cells were incubated with LPS in the presence or absence of ketamine. After 24 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Ketamine posttreatment at doses of 5, 7.5, and 10 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, posttreatment with ketamine-inhibited inflammatory cells and inflammatory mediators including tumor necrosis factor-α, interleukin-6, and high-mobility group box 1 in BALF. Furthermore, we demonstrated that ketamine-inhibited LPS-induced RAGE and TLR9 protein up-expressions and the phosphorylation of I-κB-α and nuclear factor-κB (NF-κB) p65 in vivo and in vitro. The results presented here suggest that the protective mechanism of ketamine may be attributed partly to decreased production of inflammatory mediators through the inhibition of RAGE/TLR9-NF-κB pathway.

  18. In vitro and in vivo properties of a fully human IgG1 monoclonal antibody that combats multidrug resistant Pseudomonas aeruginosa

    Science.gov (United States)

    ADAWI, AZMI; BISIGNANO, CARLO; GENOVESE, TIZIANA; FILOCAMO, ANGELA; KHOURI-ASSI, CAMELLIA; NEVILLE, ANAT; FEUERSTEIN, GIORA Z.; CUZZOCREA, SALVATORE; NEVILLE, LEWIS F.

    2012-01-01

    The development of an anti-bacterial drug in the form of a monoclonal antibody (mAb) targeting an exposed virulence factor, represents an innovative therapeutic strategy. Consequently, a fully human IgG1 mAb (LST-007) targeting Pseudomonas aeruginosa (PA) flagellin type b was recombinantly expressed and characterized in vitro and in an infection model driven by a multidrug resistant (MDR) PA strain. LST-007 demonstrated a highly specific binding towards whole PA bacteria harboring flagellin type b and its recombinant counterpart, with a KD of 7.4×10−10 M. In bioactivity assays, LST-007 or titers of Cmax sera derived from pharmacokinetic studies, markedly attenuated PA motility in an equipotent manner. In vivo, parenteral LST-007 (20 mg/kg) given as a single or double-dosing paradigm post-infection, afforded survival (up to 75% at Day 7) in a lethal model of pneumonia driven by the intratracheal (i.t.) instillation of an LD80 of the MDR PA isolate. This protective effect was markedly superior to that of imipenem (30% survival at Day 7) and totally devoid with an irrelevant, human isotype mAb. These data lay credence that LST-007 may be a valuable adjunct to the limited list of anti-bacterials that can tackle MDR PA strains, thereby warranting its continued development for eventual clinical evaluation. PMID:22735858

  19. Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis.

    Science.gov (United States)

    De Langhe, Ellen; Cailotto, Frederic; De Vooght, Vanessa; Aznar-Lopez, Carolina; Vanoirbeek, Jeroen Alfons; Luyten, Frank Prosper; Lories, Rik Jozef Urbain

    2015-03-15

    Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ. We therefore studied the role of endogenous BMP signaling in bleomycin induced lung fibrosis. Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog +/LacZ ) mice by intratracheal instillation of bleomycin, or phosphate buffered saline as a control. Invasive pulmonary function tests were performed using the flexiVent® SCIREQ system. The mice were sacrificed and lung tissue was collected for analysis using histopathology, collagen quantification, immunohistochemistry and gene expression analysis. Nog +/LacZ mice are a known model of increased BMP signaling and were partially protected from bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen content and preservation of pulmonary compliance. In bleomycin-induced lung fibrosis, TGFβ and BMP signaling followed an inverse course, with dynamic activation of TGFβ signaling and repression of BMP signaling activity. Upon bleomycin exposure, active BMP signaling is decreased. Derepression of BMP signaling in Nog +/LacZ mice protects against bleomycin-induced pulmonary fibrosis. Modulating the balance between BMP and TGFβ, in particular increasing endogenous BMP signals, may therefore be a therapeutic target in fibrotic lung disease.

  20. N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.

    Science.gov (United States)

    Zhang, Yanlin; Zhao, Zanmei; Guan, Li; Mao, Lijun; Li, Shuqiang; Guan, Xiaoxu; Chen, Ming; Guo, Lixia; Ding, Lihua; Cong, Cuicui; Wen, Tao; Zhao, Jinyuan

    2014-01-01

    Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary, high levels of extracellular histones can be pathogenic in ALI caused by acid aspiration. By neutralizing extracellular histones, heparin/NAH can offer similar protection at the moderate doses. At the high dose, NAH provides better protection than heparin.

  1. Jinwei Tang modulates HDAC2 expression in a rat model of COPD.

    Science.gov (United States)

    Wu, Jianjun; Li, Xin; Qin, Yang; Cheng, Juan; Hao, Gaimei; Jin, Ruifeng; Zhu, Chenjun

    2018-03-01

    The aim of the present study was to investigate the effect of a Traditional Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2 (HDAC2) and its role in the regulation of corticosteroid resistance in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were divided into five groups (each n=10): COPD group, established by the intratracheal instillation of lipopolysaccharide and passive smoke exposure, and control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide groups. Lung function was measured, lung tissue histopathology was examined and HDAC2 expression in the lung was assessed by immunohistochemistry. In addition, protein levels of interleukin-8 (IL-8), tumor necrosis factor (TNF)-α and HDAC2 in lung homogenate were quantified by ELISA. The rat COPD model exhibited alterations of the ratio of forced expiratory volume in 0.2 sec (FEV 0.2 ) to the forced vital capacity, FEV 0.2 , dynamic compliance and airway resistance. HDAC2 expression was markedly reduced in the lung tissue of the COPD group compared with the control group, and treatment with Jinwei Tang + budesonide or theophylline + budesonide resulted in significant attenuation of the reduction of HDAC2 expression in the lungs (PTang + budesonide and theophylline + budesonide groups, IL-8 and TNF-α expression was significantly decreased (PTang modulates airway inflammation and may enhance the anti-inflammatory effect of glucocorticoid through the upregulation of HADC2 expression in a rat model of COPD.

  2. 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.

  3. Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice.

    Science.gov (United States)

    Hazarika, Surovi; Van Scott, Michael R; Lust, Robert M; Wingard, Christopher J

    2010-01-01

    Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intraperitoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K+ depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6±3.9% and 97.7±1.2% to 32±4% and 51±6%, respectively (p<0.05). The sensitivity to acetylcholine was likewise reduced (EC₅₀=0.26±0.05 μM vs. 1.09±0.16 μM, p<0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Evaluating the Ameliorative Potential of Quercetin against the Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ramesh Verma

    2013-01-01

    Full Text Available The current study deals with the effect of a dietary flavanoid quercetin on fibrotic lung tissue in rats. Bleomycin was administered by single intratracheal instillation to Wistar rats to induce lung fibrosis. The pathologies associated with this included significantly reduced antioxidant capacity, ultimately leading to protracted inflammation of the lung tissue. The hallmark of this induced fibrosis condition was an excessive collagen deposition in peribronchial and perialveolar regions of the lung. Oral quercetin treatment over a period of twenty days resulted in significant reversal of the pathologies. The antioxidant defense in lung tissue was revived. Moreover, activity of the collagenase MMP-7, which was high in fibrotic tissue, was seen restored after quercetin administration. Trichome staining of lung tissue sections showed high collagen deposition in fibrotic rats, which may be a direct result of increased mobilization of collagen by MMP-7. This was appreciably reduced in quercetin treated animals. These results point towards an important protective role of quercetin against idiopathic lung fibrosis, which remains a widely prevalent yet incurable condition in the present times.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Velat Şen

    2014-01-01

    Full Text Available 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.

  10. T cells suppress memory-dependent rapid mucous cell metaplasia in mouse airways

    Directory of Open Access Journals (Sweden)

    Hitendra S. Chand

    2016-10-01

    Full Text Available Abstract Background Airway epithelial cells (AECs are crucial for mucosal and adaptive immunity but whether these cells respond in a memory-dependent manner is poorly studied. Previously, we have reported that LPS intratracheal instillation in rodents causes extensive neutrophilic inflammation and airway epithelial cell hyperplasia accompanied by mucous cell metaplasia (MCM. And the resolution process required a period of 40 d for the inflammation to subside and the lung epithelia to resemble the non-exposed condition. Therefore, the present study investigated the memory-dependent response of airway epithelial cells to a secondary LPS challenge after the initial inflammation was resolved. Methods Airway epithelial and mucous cells were assessed in response to a secondary LPS challenge in F344/N rats, and in C57BL/6 wild-type (Foxn1WT and T cell-deficient athymic (Foxn1nu mice that were instilled with LPS or saline 40 d earlier. Epithelial expression of TLR4, EGFR, and phosphorylated-ERK1/2 (pERK were also analyzed. Results LPS-pretreated F344/N rats responded with elevated numbers of AECs after saline challenge and with 3-4-fold increased MCM following the LPS challenge in LPS- compared with saline-pretreated rats. LPS-pretreated rats showed 5-fold higher number of AECs expressing TLR4 apically than saline-pretreated rats. Also, the expression of EGFR was increased in LPS-pretreated rats along with the number of AECs with active or nuclear pERK, and the levels were further increased upon LPS challenge. LPS-pretreated Foxn1nu compared with Foxn1WT mice showed increased MCM and elevated levels of TLR4, EGFR, and nuclear pERK at 40 d after LPS instillation. LPS challenge further augmented MCM rapidly in Foxn1nu compared with Foxn1WT mice. Conclusion Together, these data suggest that AECs preserve an ‘innate memory’ that drives a rapid mucous phenotype via spatiotemporal regulation of TLR4 and EGFR. Further, T cells may suppress the sustained

  11. Effects of osteoinduction on bone regeneration in distraction: results of a pilot study.

    Science.gov (United States)

    Kroczek, A; Park, J; Birkholz, T; Neukam, F W; Wiltfang, J; Kessler, P

    2010-07-01

    Rate and frequency of distraction as well as stimulatory effects transmitted by growth factors and local gene therapy have a decisive influence on bone regeneration. In a pilot study we tested the effect of four different morphogenetic and mitotic proteins and a genetically transferred vector system on bone healing in continuous osteodistraction in a large animal experiment on 24 Goettingen mini-pigs. For this purpose bone morphogenetic protein (BMP-2), BMP-7, TGF-beta, IGF-1 and a liposome vector were instilled into the distraction gap. The animals were killed after 1-4 weeks of consolidation. Histological and radiological evaluations showed maximum bone formation after the application of BMP-2/7, whereas the application of TGF-beta, IGF-1 and the liposomal vector had only a limited effect on bone regeneration. The quantitative analysis demonstrated an average amount of bone in the distraction gap of 50% and 61% after instillation of BMP-2 and 7, respectively. The BMP-2 expression, however, was maximal after induction with the non-viral vector. Only after BMP-2/7 application could physical, radiographic and histological evidence of bone union be detected. In bone distraction with a short observation period the application of morphogenetic proteins seems to enhance bone regeneration significantly. Before application in humans further studies are necessary to measure the dose-effect relationship, the mode of application and the efficacy of different inductive proteins. The combination of osteodistraction with osteoinduction, however, could shorten treatment times dramatically. Copyright 2009 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Outdoor Education as Wilderness Studies.

    Science.gov (United States)

    Clark, Glenn

    1987-01-01

    Presents outline for introductory course designed to allow student exploration of outdoor opportunities and instill interest and basic knowledge. Includes nature trail development, edible wild plants, Adirondack/St. Lawrence geology, mountain climbing, fall camping, snowshoeing, cross-country skiing, winter camping, ice fishing, knots,…

  13. Ovine model for studying pulmonary immune responses

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Chanana, A.D.

    1984-11-25

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with /sup 125/I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables.

  14. Ovine model for studying pulmonary immune responses

    International Nuclear Information System (INIS)

    Joel, D.D.; Chanana, A.D.

    1984-01-01

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with 125 I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables

  15. 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

  16. Convectively Dominated Heparin Leakage From Multiple Catheter Designs: An In Vitro Experimental Study.

    Science.gov (United States)

    Barbour, Michael Coleman; Gow, Kenneth W; Aliseda, Alberto

    2018-03-16

    Central venous catheters (CVCs) are routinely filled with a heparin lock while not in use to avoid thrombus formation near the tip. However, heparin leakage is known to occur, and the lock effectiveness remains in question. It was recently shown that convective fluxes from the blood flow in the host vein transport the majority of locking solution away from the tip of hemodialysis catheters immediately after instillation. Combined with the low diffusivity of heparin, this results in concentrations of heparin at the catheter tip that are orders of magnitude lower than at instillation for the majority of the interdialytic phase, diminishing the antithrombotic effectiveness of the lock. In this study, heparin losses from three different CVCs with different tip designs are measured in a pulsatile flow loop. Planar laser-induced fluorescence and particle image velocimetry measurements of heparin concentration and fluid velocity are recorded downstream of the catheters and combined to evaluate heparin losses from each of the different catheter designs. Additionally, locking solution losses are measured from one catheter (Hickman) subjected to three different flow conditions. Heparin losses are shown to depend weakly on flow condition but be highly dependent on catheter design. Convective losses from the Hickman catheter, with no side holes, are minimal (1-2%), although losses from the other two catheter types, both with a number of side holes, are significantly higher (7%). These results indicate the potential to maintain a high concentration of locking solution during the interdialytic phase with proper catheter design, particularly focusing on side hole distribution and shape.

  17. 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

    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. Conclusion Two very different types of multiwalled CNTs had very similar pattern......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...

  18. 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...... that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors. Published by Elsevier Inc....

  19. 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 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....

  20. Transcriptomic Analysis Reveals Novel Mechanistic Insight into Murine Biological Responses to Multi-Walled Carbon Nanotubes in Lungs and Cultured Lung Epithelial Cells

    DEFF Research Database (Denmark)

    Poulsen, Sarah Søs; Jacobsen, Nicklas R.; Labib, Sarah

    2013-01-01

    responses of multiwalled carbon nanotubes (MWCNT) to those in vitro in cultured lung epithelial cells (FE1) at the global transcriptomic level. Primary size, surface area and other properties of MWCNT-XNRI -7 (Mitsui7) were characterized using DLS, SEM and TEM. Mice were exposed via a single intratracheal...... instillation to 18, 54, or 162 mu g of Mitsui7/mouse. FE1 cells were incubated with 12.5, 25 and 100 mu g/ml of Mitsui7. Tissue and cell samples were collected at 24 hours post-exposure. DNA microarrays were employed to establish mechanistic differences and similarities between the two models. Microarray...

  1. In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra

    2013-01-01

    J mice were exposed four times during gestation by intratracheal instillation of 67μg/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline...... mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring....

  2. 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

  3. Report of work performed by Dr. Ivancica Trosic in response to procurement request No. 4478H University of California, Los Alamos National Laboratory, Los Alamos, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Trosic, I. [Institut za Medicinska Istrazivanja i Medicinu Rada, Zagreb (Croatia)

    1994-07-01

    Rats were intratracheally instilled with polystyrene microspheres and/or asbestos particles (0.5 mg) suspended in PBS. Six animals from each group were dispatched n days 1, 7, 30, 80 and 150 days after their respective instillations. Their lungs were lavaged, and quantifications of lavaged fluorescent microspheres, analyses of distributions of microspheres in lung, phagocytes by type, quantification of unlavaged lung burdens of microspheres, and quantification of tracheobronchial lymph mode burdens of microspheres were performed. Data are presented herein describing lung retention kinetics of the microspheres, analyses of particle distributions in lung phagocytes over the course of alveolar phase clearlance, analyses of changes in the sizes of the lung`s population of free cells.

  4. Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Jacobsen, Nicklas Raun; Mortensen, Alicja

    2012-01-01

    with severity similar to Printex 90. The inflammatory response of NanoTiO(2) and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO(2) caused DNA damage in hepatic tissue 1 day after...... with and without NanoTiO(2). Methods: Mice received a single intratracheal instillation of 18, 54 and 162 mu g of NanoTiO(2) or 54, 162 and 486 mu g of the sanding dust from paint with and without NanoTiO(2). DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were...

  5. Factors Affecting Innovation Within Aeronautical Systems Center (ASC) Organizations - An inductive Study

    National Research Council Canada - National Science Library

    Feil, Eric

    2003-01-01

    In response to the Air Force transformation movement there is currently a lot of high level interest in instilling cultures that promote innovation and intelligent risk taking in Air Force organizations...

  6. Effect of Riboflavin/UVA Collagen Cross-linking on Central Cornea, Limbus and Intraocular Pressure. Experimental Study in Rabbit Eyes.

    Science.gov (United States)

    Kozobolis, Vassilios; Gkika, Maria; Sideroudi, Haris; Tsaragli, Efthymia; Lydataki, Stylliani; Naoumidi, Irini; Giatromanolaki, Alexandra; Mikropoulos, Dimitrios; Teus, Miguel; Labiris, Georgios

    The Purpose of present study was to investigate the effect of riboflavin/ultraviolet-A-induced collagen cross-linking (CXL) on central cornea, limbus and intraocular pressure (IOP). This was an animal experimental study. The right corneas of 10 rabbits were ultraviolet-A irradiated (3 mW/cm2 for 30 minutes) after de-epithelialization and instillation of 0.1% riboflavin / 20% Dextran drops. Left corneas served as controls. Samples were examined histologically one month postoperatively. Before and after treatment, IOP measurements were recorded bilaterally. At central cornea of eyes underwent CXL keratocyte repopulation, normal arrangement of collagen fibres and a statistically significant change in fibres diameter were detected, compared to controls. At limbus area, there were not any significant histological differences after CXL. There was no statistically significant difference between pre- and postoperative IOP in all eyes.

  7. Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study.

    Science.gov (United States)

    Vandermeer, G; Chamy, Y; Pisella, P-J

    2018-02-01

    Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the Optical Quality Analyzing System, Visiometrics (OQAS). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an ocular surface disease index (OSDI) score >23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there were no significant variations in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204, Pvision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a reduction

  8. [Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study].

    Science.gov (United States)

    Vandermeer, G; Chamy, Y; Pisella, P-J

    2018-03-01

    Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in the quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the OQAS (Optical Quality Analyzing System, Visiometrics). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an Ocular Surface Disease Index (OSDI) score>23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient's preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there was no significant variation in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204; Pvision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a

  9. Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint

    Directory of Open Access Journals (Sweden)

    Saber Anne

    2012-02-01

    Full Text Available Abstract Background Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2, pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2. Methods Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO2 or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control. Results There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points. Conclusions Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

  10. Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint.

    Science.gov (United States)

    Saber, Anne Thoustrup; Jacobsen, Nicklas Raun; Mortensen, Alicia; Szarek, Józef; Jackson, Petra; Madsen, Anne Mette; Jensen, Keld Alstrup; Koponen, Ismo K; Brunborg, Gunnar; Gützkow, Kristine Bjerve; Vogel, Ulla; Wallin, Håkan

    2012-02-02

    Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2. Mice received a single intratracheal instillation of 18, 54 and 162 μg of NanoTiO2 or 54, 162 and 486 μg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control. There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points. Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

  11. A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study.

    Science.gov (United States)

    Lin, Xiaona; Wei, Minling; Li, T C; Huang, Qiongxiao; Huang, Dong; Zhou, Feng; Zhang, Songying

    2013-10-01

    To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Asherman's syndrome. Retrospective cohort study of 107 women with Asherman's syndrome who were treated with hysteroscopic division of intrauterine adhesions. After hysteroscopic adhesiolysis, 20 patients had intrauterine balloon inserted, 28 patients had intrauterine contraceptive device (IUD) fitted, 18 patients had hyaluronic acid gel instilled into the uterine cavity, and 41 control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases, and the effect of hysteroscopic adhesiolysis was scored by the American Fertility Society classification system. Both the intrauterine balloon group and the IUD group achieved significantly (Pintrauterine balloon or intrauterine device is more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  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. A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits.

    Directory of Open Access Journals (Sweden)

    Françoise Brignole-Baudouin

    Full Text Available We investigated in a rabbit model, the eye distribution of topically instilled benzalkonium_(BAK chloride a commonly used preservative in eye drops using mass spectrometry imaging. Three groups of three New Zealand rabbits each were used: a control one without instillation, one receiving 0.01%BAK twice a day for 5 months and one with 0.2%BAK one drop a day for 1 month. After sacrifice, eyes were embedded and frozen in tragacanth gum. Serial cryosections were alternately deposited on glass slides for histological (hematoxylin-eosin staining and immunohistological controls (CD45, RLA-DR and vimentin for inflammatory cell infiltration as well as vimentin for Müller glial cell activation and ITO or stainless steel plates for MSI experiments using Matrix-assisted laser desorption ionization time-of-flight. The MSI results were confirmed by a round-robin study on several adjacent sections conducted in two different laboratories using different sample preparation methods, mass spectrometers and data analysis softwares. BAK was shown to penetrate healthy eyes even after a short duration and was not only detected on the ocular surface structures, but also in deeper tissues, especially in sensitive areas involved in glaucoma pathophysiology, such as the trabecular meshwork and the optic nerve areas, as confirmed by images with histological stainings. CD45-, RLA-DR- and vimentin-positive cells increased in treated eyes. Vimentin was found only in the inner layer of retina in normal eyes and increased in all retinal layers in treated eyes, confirming an activation response to a cell stress. This ocular toxicological study confirms the presence of BAK preservative in ocular surface structures as well as in deeper structures involved in glaucoma disease. The inflammatory cell infiltration and Müller glial cell activation confirmed the deleterious effect of BAK. Although these results were obtained in animals, they highlight the importance of the safety

  14. Novel multisensor probe for monitoring bladder temperature during locoregional chemohyperthermia for nonmuscle-invasive bladder cancer: technical feasibility study

    NARCIS (Netherlands)

    Cordeiro, Ernesto R.; Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional

  15. STUDY OF SINGLE DOSE CARBOPROST IN TERMINATING PREGNANCY

    Directory of Open Access Journals (Sweden)

    Sudhavani

    2016-11-01

    Full Text Available INTRODUCTION Medical termination of pregnancy. It also called induced abortion. It is the medical way of getting rid of unwanted pregnancy. Efficacy of the methods in achieving complete abortion is needed. The aim of the study is to evaluate induction abortion interval when intracervical prostaglandin-E2 gel was followed by carboprost IM injections. MATERIALS AND METHODS This was a prospective study for a period of 2 years. 50 cases were randomly selected from the patients attending the Gynaecology Outpatient Department seeking termination of pregnancy between 10-14 weeks of gestation. Patients are divided into 3 groups, Group - I: (25 intracervical application of 500 μg PGE2 gel, Group - II: Study group (25 500 μg PGE2 gel was instilled intracervically. After 12 hours, carboprost injections were given intramuscularly at 3 rd hourly intervals. RESULTS Results were analysed in both the groups according to age, parity, reason for seeking abortion, preinduction cervical status, cervical dilatation after 12 hours in group I and in group II induction abortion interval, incidence of incomplete abortion and incidence of side effects. CONCLUSION Carboprost intramuscular injections 3 rd hourly found to be an effective and safe method of terminating pregnancy with induction abortion interval 19.8 hours in primi and 19.3 hours in multi with a success rate of 100%.

  16. A study of the barrier function of the upper respiratory tract covering epithelium in the event of combined respiratory tract injuries

    International Nuclear Information System (INIS)

    Ivanov, Z.; Kolev, K.; Dermendzhiev, Kh.; Nikolova, M.; Kantardzhiev, V.

    1976-01-01

    Functional and morphologic impairment of upper respiratory tract mucous membranes after chronic exposure to the three major occupational noxious agents in ore mining - radon-222, silica dust, and respirable dust - has been studied experimentally. Over a 6-month period, rats were given daily treatments, with the agents applied either individually or in combination. Radon-222 (at 1 x 10 -10 Ci/l, corresponding to the maximum permissible concentrotion in uranium mine atmospheres) and respirable dust (dispersed silicogen at 100 mg/m 3 ) were administered four hours daily in toxicological chambers. Monodisperse silica dust was given by tracheal tube, at 50 mg in 1 ml of saline per rat. At the end of the treatment period, the barrier function of the respiratory epithelium was tested, and found to have been affected, by measuring beta radioactivity in blood following introduction into -the animal's nasopharynx of a 32 P-labelled staphylococcus culture. The most severe degree if impairment was found to result from simultaneous exposure to radon and respirable dust. Any of ti'e agents given individually caused a similar degree of impairment. Intratracheal administration of silicic acid anhydride appeared to have no deleterious consequences. The evidence for functional impairment was supported by histologic findings, indicating Jevelopment of ulcerous bronchitis, metaplasia of cylindrical epithelium, etc., after both individual and combined radon exposure. (A.B.)

  17. Human Resource Slack as an Antecedent to Instilling the Entrepreneurial Mindset within Department of Defense Organizations

    Science.gov (United States)

    2003-03-01

    additional debt or equity capital). Though there has been very little research comparing the three types of slack, Cheng and Kesner found...levels of uncertainty (Evans, 1991; Fiegenbaum and Karnani, 1991; Genus , 1995; Porter, 1980; Sanchez, 1995; Wernerfelt and Karnani; 1984). Firms...Issues 14:68-84. Genus , A. 1995. Flexible Strategic Management. London: Chapman and Hall. Greenley, G.E. and M. Oktemgil. 1998. “A comparison

  18. Improving public perceptions by instilling objectivity in decisions to waive procurement regulations

    OpenAIRE

    Potter, Kenyon

    2006-01-01

    Third Annual Acquisition Research Symposium The following article is taken as an excerpt from the proceedings of the annual Acquisition Research Program. This annual event showcases the research projects funded through the Acquisition Research Program at the Graduate School of Business and Public Policy at the Naval Postgraduate School. Featuring keynote speakers, plenary panels, multiple panel sessions, a student research poster show and social events, the Annual Acquisition Research Sy...

  19. Instilling safety culture in the passenger rail transport industry within the South African context

    Directory of Open Access Journals (Sweden)

    Khulumane (John Maluleke

    2013-07-01

    Full Text Available South Africa has two major rail operators that constitute the rail transport industry. These are Transnet Freight Rail (TFR, which operates freight and the Passenger Rail Agency of South Africa (PRASA. Although the Railway Safety Regulator (2011:29 reported the year on year declining trend of collisions, the main concern is that the costs incurred for each year’s incidents is escalating. This article is concerned with the declining safety standards of these operators as evidenced by 742 collisions recorded during the 2011/2012 financial year for both operators. The focus is mainly on collisions during the movement of rolling stock within the PRASA environment. The analysis of the occurrences is narrowed down, with the emphasis on the province of Gauteng. In the analysis of the causes of these collisions, the problems that led to the root causes of these collisions is reported. Of critical importance is that every transport operator is faced with the challenges of how to effectively respond to the basic transport needs and requirements of the travelling public. The transport users’ need is to travel between the two geographical points. During the journey between these geographical points, the operator has safety and security requirements and must provide a reliable, accessible and affordable transport system. As the travelling public becomes more affluent, the transport needs become open ended and require much more rational public choices. The rail transport system remains a vital or indispensable business sector of the economy. By investing in new technology, rolling stock and infrastructure, we woud see an increase in innovation, competitiveness, and an elevated standard of living.

  20. 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

    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

  1. Management of the open abdomen using negative pressure wound therapy with instillation in severe abdominal sepsis

    Directory of Open Access Journals (Sweden)

    Pablo Sibaja

    2017-01-01

    NPWT-I in patients with severe abdominal sepsis had promising results, since we obtained higher fascia closure rates, lower mortality and reduced hospital and ICU length of stay with no complications due to this therapeutic approach.

  2. Battling Ecophobia: Instilling Activism in Nonscience Majors when Teaching Environmental Issues

    Science.gov (United States)

    Bloom, Mark A.; Holden, Molly

    2011-01-01

    When learning about large-scale environmental problems such as climate change, species extinctions, overpopulation, and habitat destruction, students can become hopelessly dismayed and experience ecophobia--a state of mind in which the student is fearful of the looming environmental problems but senses that there is nothing that can be done to…

  3. Delayed healing at transurethral resection of bladder tumour sites after immediate postoperative mitomycin C instillation

    DEFF Research Database (Denmark)

    Aagaard, Mark F; Mogensen, Karin; Hermann, Gregers G

    2014-01-01

    The most common reactions to mitomycin C are dysuria and drug-related palmar and genital desquamation. This report describes two cases of delayed healing of the mucosa at resection sites after transurethral resection of bladder tumours, most likely due to immediate postoperative mitomycin C...

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  5. Pulmonary Fibrosis in BALB/c Mice Caused by Long-Term Instillation of Bleomycin

    OpenAIRE

    NAKAJIMA, Masamitsu

    1992-01-01

    It is well-known that bleomycin-induced pulmonary fibrosis is difficult to produce in BALB/c mice. To see whether bleomycin could induce pulmonary fibrosis in BALB/c mice, we repeatedly administered this drug through the airway for 10 consecutive days. Our experiment clearly showed that fibrosis can be induced, although it was rather mild, and also suggested that the bronchiolar and alveolar epithelia are the primary sites of injury. We believe this experimental model may be useful in studyin...

  6. Instilling Literacy through Developmental Module Approach (DMA) Towards Orang Asli Pupils in Malaysia

    Science.gov (United States)

    Dali, Mohd Hasani; Shaari, Abdull Shukur; Ghazali, Mohd Izam; Yusoff, Nuraini

    2012-01-01

    Development of module has great impact on literacy today. This paper highlights the challenges and experiences of the researchers in an academic institution where the research project which initially began as part of an academic research initiative expanded to helping a marginalized community in need. Literacy pedagogy has to be relevant to the…

  7. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

    DEFF Research Database (Denmark)

    Bourdon, Julie A; Saber, Anne T; Jacobsen, Nicklas R

    2012-01-01

    Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo.......Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo....

  8. Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case–control study

    Science.gov (United States)

    Ciani, Oriana; Arendsen, Erik; Romancik, Martin; Lunik, Richard; Costantini, Elisabetta; Di Biase, Manuel; Morgia, Giuseppe; Fragalà, Eugenia; Roman, Tomaskin; Bernat, Marian; Guazzoni, Giorgio; Tarricone, Rosanna; Lazzeri, Massimo

    2016-01-01

    Objectives To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). Setting A European Union-based multicentre, retrospective nested case–control study. Participants 276 adult women treated for RUTIs starting from 2009 to 2013. Interventions Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). Primary and secondary outcome measures The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. Results 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥5. Conclusions Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. Trial registration number NCT02016118. PMID:27033958

  9. Newsmaking on drugs: a qualitative study with journalism professionals.

    Science.gov (United States)

    Mastroianni, Fabio C; Noto, Ana Regina

    2008-09-01

    Drugs are a frequent subject in the news media. Despite the existence of an important dynamic interplay between the print media, public opinion, and public policies, studies on these relationships are still scarce regarding the drug issue. The objective of this study is to understand the newsmaking process regarding drugs from the vantage point of Brazilian journalism professionals. Using qualitative research, semistructured interviews were conducted among an intentional sample of 22 professionals who write news stories and articles about drugs in nationwide news media. Interviewees mentioned illegality and crime as the main factors leading to the production of stories and articles. They claimed that by instilling fear among readers, newspapers and magazines tend to increase their audiences and/or sales. Most interviewees considered the coverage of drugs in Brazil as weak. Main problems reported include lack of knowledge on the subject, and not enough time to prepare the stories. It was concluded that the newsmaking process regarding drugs undergoes a series of interferences that compromise the content of the stories, therefore social strategies are needed in order to improve the quality of the material published in Brazil.

  10. 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

  11. Case Study: Rocket Mail--Using Historic Articles as Case Studies in Physics and Engineering

    Science.gov (United States)

    Brown, Todd; Brown, Katrina

    2014-01-01

    In the early 1900s science magazines were published with a goal of interesting and exciting the public about science and technology. Articles described technology that was possible and perhaps even tested, but never embraced because of practical limitations. Articles were written in an effort to instill creativity in the reader and to stimulate…

  12. Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice

    Directory of Open Access Journals (Sweden)

    Wakako Yamada

    2008-09-01

    Full Text Available Wakako Yamada1, Sadatomo Tasaka1, Hidefumi Koh1, Mie Shimizu1, Yuko Ogawa1, Naoki Hasegawa1, Taku Miyasho2, Kazuhiro Yamaguchi1, Akitoshi Ishizaka11Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, JapanBackground: Toll-like receptors (TLRs represent a conserved family of innate immune recognition receptors. Among TLRs, TLR4 is important for the recognition of Gram-negative bacteria, whereas TLR2 recognizes cell wall constituents of Gram-positive microorganisms, such as peptidoglycan (PGN.Methods: To evaluate the role of TLR4 in the pathogenesis of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide; LPS or PGN, we compared inflammatory cell accumulation in bronchoalveolar lavage (BAL fluid and lung pathology between C3H/HeJ (TLR4 mutant and wild-type C3H/HeN mice. The levels of proinflammatory cytokines and chemokines in plasma and BAL fluid and nuclear factor-κB (NF-κB translocation in the lung were also evaluated.Results: In C3H/HeJ mice, LPS-induced neutrophil emigration was significantly decreased compared with C3H/HeN mice, whereas PGN-induced neutrophil emigration did not differ. Differential cell count in BAL fluid revealed comparable neutrophil recruitment in the alveolar space. In TLR4 mutant mice, LPS-induced upregulation of tumor necrosis factor-alpha (TNF-α, KC, and CXCL10 in plasma and BAL fluid was attenuate, which was not different after PGN. NF-κB translocation in the lung was significantly decreased in C3H/HeJ compared with C3H/HeN mice, whereas PGN-induced NF-κB translocation was not different.Conclusion: These results suggest that TLR4 mediates inflammatory cascade induced by Gram-negative bacteria that is locally administered.Keywords: rodent, TLR4, endotoxin, neutrophils, NF-κB

  13. CpG-ODN Facilitates Effective Intratracheal Immunization and Recall of Memory against Neoantigen-Expressing Alveolar Cells

    Directory of Open Access Journals (Sweden)

    Mathias Riehn

    2017-09-01

    Full Text Available Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA exclusively in alveolar type II epithelial cells. This model is characterized by the absence of functional endogenous T cell responses upon OVA neoantigen induction. Standard DNA and protein vaccination protocols resulted in the accumulation of high numbers of antigen-specific CD8 T cells in the lung. However, clearance of antigen-expressing cells was not achieved. To overcome this tolerance, we induced inflammatory conditions by coapplication of the TLR ligands LPS and CpG-ODN during intrapulmonary vaccinations. Both ligands induced high numbers of neoantigen-specific T cells in the lung. However, only coapplication of CpG-ODN was sufficient to establish functional cytotoxic responses resulting in the elimination of neoantigen presenting target cells. Remarkably, CpG-ODN was also crucial for functional memory responses upon re-induction of the neoantigen. The results highlight the need of TLR9 co-stimulation for overcoming tolerization, which might be a key factor for therapeutic interventions.

  14. Effects of asphalt fume condensate exposure on acute pulmonary responses

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.Y.C.; Barger, M.W.; Castranova, V. [Health Effects Lab. Div., National Inst. for Occupational Safety and Health, Morgantown, WV (United States); Kriech, A.J. [Heritage Research Group, Indianapolis, IN (United States)

    2000-10-01

    The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. Methods: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-{alpha} and IL-1 production by AM were assayed to monitor AM function. Results: In vitro AFC exposure at <200 {mu}g/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-{alpha} release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control

  15. Development and validation of a highly sensitive LC-MS/MS method for quantification of IC87114 in mice plasma, bronchoalveolar lavage and lung samples: Application to pharmacokinetic study.

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Lee, Yong-Chul; Kim, So-Ri; Chae, Han-Jung

    2014-02-01

    IC87114 is a selective PI3Kδ inhibitor. A simple, sensitive and reliable LC-MS/MS method with rapid sample preparation was developed and validated for the determination of IC87114 in mouse plasma, bronchoalveolar lavage, and lung. Chromatographic separation was achieved using an Agilent Zorbax Eclipse XDB-C18 column (150mm×2.1mm internal diameter, 3.5μm particle size). Mass spectrometric detection was conducted by electrospray ionization in positive ion multiple reaction monitoring modes. The calibration curve was linear over a concentration range of 0.01-1000ng/mL for plasma/BAL and 0.1-250ng/mL for lung tissue. Recoveries were as high as 97.29%, 102.81% and 89.70% for plasma, BAL fluid and lung sample, respectively. The lower limit of quantification was 0.01ng/mL. Intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all concentrations. Finally, the method was successfully used in a pharmacokinetic study that measured IC87114 in mouse plasma, BAL fluid and lung tissue after administration of a single 1mg/kg intratracheal dose of IC87114. The percentage change for incurred sample reanalysis (ISR) was within ±15.0% and met the acceptance criteria for ISR. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Spectroscopic studies and thermal analysis of mononuclear metal complexes with moxifloxacin and 2,2‧-bipyridine and their effects on acute lung injury induced by hydrochloric acid in rats

    Science.gov (United States)

    El-Hamid, S. M. Abd; El-Demerdash, R. S.; Arafat, H. F. H.; Sadeek, S. A.

    2017-12-01

    The article describes the interaction of Y(III), Zr(IV), La(III), Ce(IV) and U(VI) with moxifloxacin hydrochloride and 2,2‧-bipyridine. Characterization of complexes was made by elemental analyses, molar conductivity, magnetic moment measurements and spectral measurements e.g. IR, UV-Vis., 1H NMR and mass as well as thermal analyses (TG and DTG). The molar conductivity shows that the complexes are electrolytes nature. Spectroscopic investigation of the solid complexes studied here indicate that moxifloxacin hydrochloride and 2,2‧-bipyridine are coordinated to the metal ions in a neutral bidentate manner. After complete characterization, the chemical formulae of the complexes were established. The calculated bond length and force constant, F(Udbnd O), in the uranyl complex are 1.756 Å and 637.90 Nm-1, respectively. Kinetic and thermodynamic parameters were determined using Coats-Redfern and Horowitz-Metzger equations. Establishment of hydrochloric acid that induce acute lung injury (ALI) in rats by intratracheal administration through damaging the alveolar epithelium and activation of the neutrophil and subsequent oxidative stress by increasing malondialdehyde (MDA), tumor necrosis factor (TNF-α) and neutrophil, which were confirmed by histopathological investigation while decreasing in antioxidant enzymes and lymphocytes. Whereas treatment with mixed-ligand metal complexes significantly decrease MDA, TNF-α and neutrophils and increase antioxidant and lymphocytes.

  17. Short-term mechanisms of toxic action of airborne particulates underlie dose-rate dependent health risks and support control of one-hour airborne particle levels

    Energy Technology Data Exchange (ETDEWEB)

    Michaels, R.A.; Kleinman, M.T.

    1999-07-01

    Twenty-four-hour airborne particle mass levels permissible under the NAAQS have been associated with mortality and morbidity in communities, motivating reconsideration of the standard. Reports of shorter-term mechanisms of toxic action exerted by airborne PM and PM constituents are emerging. The mechanisms are diverse, but have in common a short time frame of toxic action, from minutes to hours. In view of documented PM excursions also lasting minutes to hours, this study inquires whether such short-term mechanisms might contribute to explaining daily morbidity and mortality. Toxicology experiments have demonstrated the harmfulness of brief exposure to PM levels in the range of observed excursions. This suggests that toxicological processes initiated by short-term inhalation of PM may exert clinically important effects, and that weak associations of 24-hour-average particle mass with mortality and morbidity may represent artifacts of stronger, shorter-term associations whose full magnitude remains to be quantified. In one study, the area of lung surface developing lesions was elevated in rats breathing the same four-hour dose of aerosols, when the four-hour average rate of aerosol delivery included a short-term (five-minute) burst fifty percent above the average dose rate. Elevations were observed with each of two aerosols tested. The magnitude of the effect was higher with one of the two aerosols, whose dose rate included four excursions rather than just one excursion. Particulate matter inhaled or instilled intratracheally has produced morbidity in animals, including apnea and electrophysiological effects in dogs. Other studies reveal that PM can kill rats via electrophysiological and possibly other mechanisms. PM has also adversely affected asthmatic people in controlled clinical settings during exercise or, in one study, at rest.

  18. Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats: Part 1.

    Science.gov (United States)

    Kreyling, Wolfgang G; Holzwarth, Uwe; Haberl, Nadine; Kozempel, Ján; Hirn, Stephanie; Wenk, Alexander; Schleh, Carsten; Schäffler, Martin; Lipka, Jens; Semmler-Behnke, Manuela; Gibson, Neil

    2017-05-01

    Submicrometer TiO 2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40-400 μg/kg BW) of 48 V-radiolabeled, pure TiO 2 anatase nanoparticles ([ 48 V]TiO 2 NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [ 48 V]TiO 2 NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [ 48 V]TiO 2 NP accumulations were found in liver (95.5%ID after one day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [ 48 V]TiO 2 NP content in blood decreased rapidly after 24 h while the distribution in other organs and tissues remained rather constant until day-28. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (IV injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to test the common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes. This hypothesis is disproved by this series of studies.

  19. CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of silica-induced lung fibrosis in mice.

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    Fangwei Liu

    Full Text Available BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-β during the fibrotic stage in silica-induced lung fibrosis. CONCLUSION/SIGNIFICANCE: Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.

  20. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction

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    Joseph J. Janicki

    2016-03-01

    Full Text Available Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  1. Induced pluripotent stem cells inhibit bleomycin-induced pulmonary fibrosis in mice through suppressing TGF-β1/Smad-mediated epithelial to mesenchymal transition

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    Yan Zhou

    2016-11-01

    Full Text Available Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS cells have been considered as an ideal resource for stem cell-based therapy. Although an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF-β1 signaling pathway, and epithelial to mesenchymal transition (EMT during bleomycin (BLM-induced lung fibrosis. A single intratracheal instillation of BLM (5 mg/kg was performed to induce pulmonary fibrosis in C57BL/6 mice. Then, iPS cells (c-Myc-free were administrated intravenously at 24 h following BLM instillation. Three weeks after BLM administration, pulmonary fibrosis was evaluated. As expected, treatment with iPS cells significantly limited the pathological changes, edema, and collagen deposition in lung tissues of BLM-induced mice. Mechanically, treatment with iPS cells obviously repressed the expression ratios of matrix metalloproteinase-2 (MMP-2 to its tissue inhibitor -2 (TIMP-2 and MMP-9/TIMP-1 in BLM-induced pulmonary tissues. In addition, iPS cell administration remarkably suppressed BLM-induced up-regulation of pulmonary inflammatory mediators, including tumor necrosis factor-α, interleukin (IL-1β, IL-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and prostaglandin E2. We further demonstrated that transplantation of iPS cells markedly inhibited BLM-mediated activation of TGF-β1/Mothers against decapentaplegic homolog 2/3 (Smad2/3 and EMT in lung tissues through up-regulating epithelial marker E-cadherin and down-regulating mesenchymal markers including fibronectin, vimentin and α-smooth muscle actin. Moreover, in vitro, iPS cell-conditioned medium (iPSC-CM profoundly inhibited TGF-β1-induced EMT signaling pathway in mouse

  2. GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition

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    Xiao-Ming Zhou

    2017-12-01

    Full Text Available Objective: Idiopathic pulmonary fibrosis is an irreversible and progressive fibrotic lung disease that leads to declines in pulmonary function and, eventually, respiratory failure and has no effective treatment. Gly-His-Lys (GHK is a tripeptide involved in the processes of tissue regeneration and wound healing and has significant inhibitory effects on transforming growth factor (TGF-β1 secretion. The effect of GHK on fibrogenesis in pulmonary fibrosis and the exact underlying mechanism have not been studied previously. Thus, this study investigated the effects of GHK on bleomycin (BLM-induced fibrosis and identified the pathway that is potentially responsible for these effects.Methods: Intratracheal injections of 3 mg/kg BLM were administered to induce pulmonary fibrosis in C57BL/6 mice. GHK was administered intraperitoneally at doses of 2.6, 26, and 260 μg/ml/day every other day from the 4th to the 21st day after BLM instillation. Three weeks after BLM instillation, pulmonary injury and pulmonary fibrosis was evaluated by the hematoxylin-eosin (HE and Masson’s trichrome (MT staining. Chronic inflammation index was used for the histological assessments by two pathologists blindly to each other. Tumor necrosis factor (TNF-α and IL-6 levels in BALF and myeloperoxidase (MPO activity in lung extracts were measured. For the pulmonary fibrosis evaluation, the fibrosis index calculated based on MT staining, collagen deposition and active TGF-β1 expression detected by ELISA, and the expression of TGF-β1, α-smooth muscle actin (SMA, fibronectin, MMP-9, and TIMP-1 by western blotting. The epithelial mesenchymal transition index, E-cadherin, and vimentin was also detected by western blot. The statistical analysis was performed by one-way ANOVA and the comparison betwe