Sample records for repeated intratracheal instillations

  1. Tissue distribution of indium after repeated intratracheal instillations of indium-tin oxide into the lungs of hamsters. (United States)

    Tanaka, Akiyo; Hirata, Miyuki; Matsumura, Nagisa; Kiyohara, Yutaka


    The aim of this study was to analyze the tissue distribution of indium after intratracheally instilling indium-tin oxide (ITO) into the lungs of hamsters. Male Syrian hamsters received an intratracheal dose of 3 mg/kg or 6 mg/kg of ITO particles containing 2.2 mg/kg or 4.5 mg/kg of indium, twice weekly for 8 weeks. In parallel, control hamsters received only an intratracheal dose of distilled water. A subset of hamsters was euthanized periodically throughout the study from 8 up to 78 weeks after the final instillation. The distribution of indium in the lungs, liver, kidneys and spleen, as well as pathological changes in the liver, kidneys, and spleen, was determined. The contents of indium in the lungs in the two ITO groups gradually decreased over the 78-week observation period, with elimination half-lives of approximately 142 weeks for the 3 mg/kg ITO group and 124 weeks for the 6 mg/kg ITO. The indium concentrations in the liver, kidneys, and spleen gradually increased throughout the observation period. Although foci of the lesions were observed histopathologically in the extrapulmonary organs among the two ITO groups, the control group showed similar lesions. The results clearly demonstrate that the clearance of indium from the body is extremely slow after intratracheal instillation in hamsters.

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

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    Angela Maria Rizzo

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

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

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    Vogel Ulla


    Full Text Available Abstract 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 nanoparticles distributed over a period of 3 weeks and were killed 24 h after the last dose. One group of mice were given a single intratracheal dose and were killed after 1 h. Results The instilled nanoparticles were found in lung macrophages already 1 h after a single instillation. In mice instilled treated repeatedly during 3 weeks, the load was substantial. Ultrastructurally, AMG silver enhanced gold nanoparticles were found in lysosome-/endosome-like organelles of the macrophages and analysis with AMG, ICP-MS and NAA of the liver revealed an almost total lack of translocation of nanoparticles. In mice given repeated instillations of 2 nm gold nanoparticles, 1.4‰ (by ICP-MS to 1.9‰ (by NAA of the instilled gold was detected in the liver. With the 40 nm gold, no gold was detected in the liver (detection level 2 ng, 0.1‰ except for one mouse in which 3‰ of the instilled gold was found in the liver. No gold was detected in any liver of mice instilled with 100 nm gold (detection level 2 ng, 0.1‰ except in a single animal with 0.39‰ of the dose in the liver. Conclusion We found that that: (1 inert gold nanoparticles, administered intratracheally are phagocytosed by lung macrophages; (2 only a tiny fraction of the gold particles is translocated into systemic circulation. (3 The translocation rate was greatest with the 2 nm gold particles.

  4. Comparison of functional biochemical, and morphometric alterations in the lungs of four rat strains and hamsters following repeated intratracheal instillation of crocidolite asbestos (United States)

    Four rat strains and hamsters were exposed to 0.7mg crocidolite asbestos/g lung once/wk for 3weeks by intratracheal instillation (IT). Pulmonary function, biochemistry, and morphometry were evaluated at 3 and 6-months after IT. Each rat strain, but not the hamster, exhibited ele...

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

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


    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...... nanoparticles distributed over a period of 3 weeks and were killed 24 h after the last dose. One group of mice were given a single intratracheal dose and were killed after 1 h. Results The instilled nanoparticles were found in lung macrophages already 1 h after a single instillation. In mice instilled treated...

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

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


    -induced response, such as inflammation during gestation, leads to secondary effects in the fetus. Time-mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Nanopure water) or one of three concentrations (2.75, 13.5 or 67μg in 40μl Nanopure water) of carbon black Printex 90 (CB...

  7. In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats. (United States)

    Naya, Masato; Kobayashi, Norihiro; Ema, Makoto; Kasamoto, Sawako; Fukumuro, Masahito; Takami, Shigeaki; Nakajima, Madoka; Hayashi, Makoto; Nakanishi, Junko


    Titanium dioxide (TiO₂) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO₂ nanoparticles was evaluated in vivo using the comet assay after a single or repeated intratracheal instillation in rats. The nanoparticles were instilled intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated instillation group) into male Sprague-Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO₂ groups. In the comet assay, there was no increase in % tail DNA in any of the TiO₂ groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO₂ nanoparticles in the anatase crystal phase are not genotoxic following intratracheal instillation in rats. Copyright © 2011 Elsevier Inc. All rights reserved.

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

  9. Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice. (United States)

    Li, Yufeng; Li, Jungang; Yin, Jilei; Li, Wenxin; Kang, Cheng; Huang, Qing; Li, Qingnuan


    This work reported the systematic influence of titanium dioxide nanoparticles (TiO2 NPs) with a diameter of 3 nm on mice. Mice were repeated intratracheally instilled with TiO2 NPs, once per-week for 4 consecutive weeks, at total dose of 13.2 mg/kg. At 28 days post-instillation, the biochemical parameters in broncboalveolar lavage fluid (BALF) and brain homogenate as well as histopathologic changes of tissues were examined to describe the subacute toxicity of instilled TiO2 NPs. The results showed that instilled TiO2 NPs could induce lung damage, and change the permeability of alveolar-capillary barrier. The TiO2 NPs were able to get access to blood circulation and reach extrapulmonary tissues, then lead to injury at the different level, such as liver and kidney. Our results also indicated that TiO2 NPs might pass through the blood-brain barrier (BBB), and induce the brain injury through oxidative stress response.

  10. Subacute pulmonary toxicity of copper indium gallium diselenide following intratracheal instillations into the lungs of rats. (United States)

    Tanaka, Akiyo; Hirata, Miyuki; Shiratani, Masaharu; Koga, Kazunori; Kiyohara, Yutaka


    The aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8-wk-old rats. Male Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined. None of the CIGS-treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg-treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS-treated groups, and the severity of these lesions worsened with the passage of time. The present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats.

  11. [Clinical efficacy of porcine pulmonary surfactant combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome]. (United States)

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


    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 (pneonatal MAS is effective and superior to PS alone treatment.

  12. Increased monocyte actin polymerization in rat blood after intratracheal instillation of air pollution particles. (United States)

    Adams, Rachel A; Al-Mosawi, Ameena; Bérubé, Kelly; Jones, Tim; Higgins, Timothy; Evans, Shelley-Ann


    Exposure to particulate air pollution is associated with an increased risk of cardiovascular disease. The mechanism by which exposure increases risk is poorly understood but could involve changes in the flow properties of blood. The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on leukocyte flow properties by measurement of polymorphonucleocyte (PMN) and monocyte actin polymerisation. Rats were exposed to particulate air pollution by intratracheal instillation of PM10. Blood was collected from test and control animals at 3 days (n=10) and 6 weeks (n=10) after dust instillation. Partial differential leukocyte counts were performed. The intracellular F-actin content of blood PMNs and monocytes was determined by staining with FITC-phalloidin and flow cytometric determination of mean florescence intensity (MFI). There were no significant changes in PMN MFI (p=0.369, ANOVA) or cell counts (p=0.753, ANOVA). There was a significant increase in monocyte MFI (p=0.004, ANOVA) and a decrease in monocyte cell count (p=0.003, ANOVA) in instilled rats. Intratracheal instillation of air pollution particles resulted in an increase in blood monocyte actin polymerisation, which may cause trapping of monocytes. This could be a mechanism by which exposure to air pollution increases the risk of cardiovascular disease.

  13. Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats

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    Nadine Haberl


    Full Text Available Silver nanoparticles (AgNP are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH, total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF. Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold and total protein (1.3-fold levels as well as in neutrophil numbers (60-fold of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations.

  14. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies (United States)


    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. PMID:20226088

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

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    Yamamoto Kazuhiro


    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.

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

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    Morimoto, Yasuo, E-mail:; 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)


    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.

  17. 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


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

  18. Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (kosa). (United States)

    Naota, Misaki; Shiotsu, Shizuka; Shimada, Akinori; Kohara, Yukari; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa


    Asian sand dust (ASD) events are associated with an increase in pulmonary morbidity and mortality. The number of ASD events has increased rapidly in the east Asian region since 2000. To study the chronic lung toxicity of ASD, saline suspensions of low doses (200 and 400 µg) and high doses (800 and 3,000 µg) of ASD were intratracheally instilled into ICR mice. Animals were sacrificed at 24 hr, 1 week, or 1, 2, or 3 months after instillation. Histopathological examination revealed that ASD induced acute inflammation at 24 hr after instillation. The acute inflammation was transient and subsided at 1 week and 1 month after instillation. At 2 and 3 months after instillation, focal infiltration of lymphocytes with accumulation of epithelioid macrophages, which is a suggestive finding of transformation to granuloma, and granuloma formation were occasionally observed. Aggregation of macrophages containing particles was observed in the pulmonary lymph nodes at 3 months after instillation in high-dose groups. Prolonged inflammatory foci (granuloma) and presence of ASD particles in pulmonary lymph nodes would have a chance to induce immunological modulation leading to adverse health effects in the exposed animals.

  19. [Metabonomic study of plasma after intratracheally instilling titanium dioxide nanoparticles in rats]. (United States)

    Wang, Shu; Tang, Meng; Zhang, Ting; Huang, Ming-ming; Lei, Hao; Yang, Yang; Lu, Min-yu; Kong, Lu; Xue, Yu-ying


    1H magnetic resonance (1H MR) spectroscopic technique in combination with pattern recognition technique were applied to analyze toxic effects of rats which were intratracheally instilled with titanium dioxide nanoparticles (nano-TiO2) as well as to detect the target organs and biomarkers associated with the toxic effects. Twenty-four SD male rats were divided into 4 groups randomly which were high dose group (40 mg/kg nano-TiO2), moderate dose group (4 mg/kg nano-TiO2), low dose group (0.4 mg/kg nano-TiO2) and control group (0.9% NaCl solution) respectively, there were six rats per group. All rats were exposed to the object by single intratracheally instilling at a volume of 0.1 ml/100 g. After one week observation, 1H MR spectra of plasma were measured and analyzed by principal component analysis. Histopathologic examination for tissues such as heart, lung, liver, and kidney were performed simultaneously. The relative content of lactate [(37.86+/-2.58)x10(-3)], citrate [(2.21+/-0.45)x10(-3)], choline [(7.74+/-0.76)x10(-3)] and creatine [(4.17+/-1.15)x10(-3)] in high dose group were significantly decreased as compared with those [(52.07+/-5.12)x10(-3), (3.01+/-0.21)x10(-3), (9.28+/-0.78)x10(-3), (8.59+/-2.64)x10(-3)] in control group (t values were -6.024, -3.177, -3.374, -4.215 respectively, Pkidney and heart were the target organs of rats which were intratracheally instilling titanium dioxide nanoparticles. Lactate, pyruvate, glucose, citrate, choline and creatine can be presumed as the biomarkers when searching the target organs of the toxic effects.

  20. Assessment of oxidative stress induced by gold nanorods following intra-tracheal instillation in rats. (United States)

    Lingabathula, Harikiran; Yellu, Narsimhareddy


    Gold nanorods (GNRs) are used for their wide variety of applications in various industries. There is a little availability of data related to toxicity and ecological implications of these GNRs. The study evaluated the oxidative stress induction following intra-tracheal instillation of 1 and 5 mg/kg b.w. doses of 10 and 25 nm GNRs by estimating various oxidative stress markers including lipid peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and total antioxidant capacity (TAC) after 1 day, 1 week, 1 month, and 3 months post exposure periods. The results have shown increased MDA levels and decreased GSH levels following 1 day and 1 week post exposure periods, indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels were significantly decreased following exposure of both 10 and 25 nm GNRs after 1 day and 1 week after exposures, indicating the inhibition of antioxidant defense mechanisms. Moreover, the 10 nm GNRs at 5 mg/kg dose displayed greater changes in all the estimated parameters, representing dose and size based induction of oxidative stress by GNRs. In contrast, a little change was observed during 1 month and 3 months post exposure periods, may be due to recovery. Finally, the GNRs induced dose-size-dependent oxidative stress induction by various oxidative stress markers following intra-tracheal instillation in rats.

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

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    Yoshiura, Yukiko, E-mail:; 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)


    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.

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

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    Peters Annette


    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

  3. Pathological features of different sizes of nickel oxide following intratracheal instillation in rats. (United States)

    Ogami, Akira; Morimoto, Yasuo; Myojo, Toshihiko; Oyabu, Takako; Murakami, Masahiro; Todoroki, Motoi; Nishi, Kenichiro; Kadoya, Chikara; Yamamoto, Makoto; Tanaka, Isamu


    Focusing on the "size" impact of particles, the objective of this study was to analyze morphological and qualitative changes over time in the development of inflammation and collagen deposition in lung tissue after intratracheal instillation of two sizes of nickel oxide in rats, in comparison with the results of instillation of crystalline silica and titanium dioxide. The fine-sized nickel oxide sample (nNiOm: median diameter of agglomerated particles 0.8 microm) was prepared from crude particles of nickel oxide (median diameter of primary particle 27 nm) by liquid-phase separation. Another samples of micrometer-sized nickel oxide (NiO: median diameter of particles 4.8 microm), crystalline silica (Min-U-SIL-5; geometric mean diameter 1.6 microm, geometric standard deviation [GSD] 2.0), and TiO(2) (geometric mean diameter 1.5 microm, GSD 1.8) were also used. Well-sonicated samples of 2 mg per 0.4 ml saline or saline alone (control) were intratracheally instilled into Wistar rats (males, 10 wk old). Bronchoalveolar lavage fluid (BAL)F and lung tissue were examined at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo after instillation, from 5 rats of each group. Histopathological findings showed that the infiltration of macrophages or polymorphonuclear cells and the alveolitis in rats treated with nNiOm were remarkable over time and similar to the effects of crystalline silica. The numbers of total cells in BALF and the percentage of plymorphonuclear leukocytes (PMNs) also increased in the nNiOm group and silica group. The point counting method (PCM) showed a significant increase of inflammatory area, with the peak at 3 mo after instillation in the nNiOm group. In contrast, NiO treatment showed only a slight inflammatory change. Collagen deposition in two regions in the lung tissue (alveolar duct and pleura) showed an increasing collagen deposition rate in nNiOm at 6 mo. Our results suggest that submicrometer nano-nickel oxide is associated with greater toxicity, as for crystalline

  4. Assessment of pulmonary toxicity of gold nanorods following intra-tracheal instillation in rats. (United States)

    Lingabathula, Harikiran; Yellu, Narsimhareddy


    The present investigation was aimed to evaluate the pulmonary toxicity of 10 and 25nm gold nanorods (GNRs) following intra-tracheal instillation in rats using bronchoalveolar lavage (BAL) fluid and lung histopathological analysis. The GNRs displayed that the dose-dependent toxicity via elevated lactate dehydrogenase leakage, alkaline phosphatase, lipid peroxidation and total microprotein levels in BAL fluids after 1day, 1 week and 1 month post exposure periods. All the parameters were returned to normal values after 3 months post exposure period may be due to recovery. The rat lung histopathology displayed that accumulation of macrophages, inflammatory response and tissue thickening for both sizes of GNRs. 10nm GNRs increased all BAL fluid parameters significantly following 1day, 1 week and 1 month post exposure periods whereas 25nm GNRs have shown similar effects but less extent. These investigations proposed that the dose and size dependent pulmonary toxicity of GNRs. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Toxicity Evaluation following Intratracheal Instillation of Iron Oxide in a Silica Matrix in Rats

    Directory of Open Access Journals (Sweden)

    Alina Mihaela Prodan


    Full Text Available Iron oxide-silica nanoparticles (IOSi-NPs were prepared from a mixture of ferrous chloride tetrahydrate and ferric chloride hexahydrate dropped into a silica xerogel composite. The structure and morphology of the synthesized maghemite nanoparticles into the silica xerogel were analysed by X-ray diffraction measurements, scanning electron microscopy equipped with an energy dispersive X-ray spectrometer, and transmission electron microscopy. The results of the EDAX analysis indicated that the embedded particles were iron oxide nanoparticles. The particle size of IOSi-NPs calculated from the XRD analysis was estimated at around 12.5 nm. The average size deduced from the particle size distribution is 13.7 ± 0.6 nm, which is in good agreement with XRD analysis. The biocompatibility of IOSi-NPs was assessed by cell viability and cytoskeleton analysis. Histopathology analysis was performed after 24 hours and 7 days, respectively, from the intratracheal instillation of a solution containing 0.5, 2.5, or 5 mg/kg IOSi-NPs. The pathological micrographs of lungs derived from rats collected after the intratracheal instillation with a solution containing 0.5 mg/kg and 2.5 mg/kg IOSi-NPs show that the lung has preserved the architecture of the control specimen with no significant differences. However, even at concentrations of 5 mg/kg, the effect of IOSi-NPS on the lungs was markedly reduced at 7 days posttreatment.

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    He Xiao; Zhang Haifeng; Ma Yuhui; Bai Wei; Zhang Zhiyong; Ding Yayun; Zhao Yuliang; Chai Zhifang [CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Lu Kai, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail: [School of Biological Science and Engineering, South China University of Technology, Guangzhou 510641 (China)


    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.

  8. Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area

    Directory of Open Access Journals (Sweden)

    Kommineni C


    Full Text Available Abstract Background The production and use of nanoparticles is growing rapidly due to the unique physical and chemical properties associated with their nano size and large surface area. Since nanoparticles have unique physicochemical properties, their bioactivity upon exposure to workers or consumers is of interest. In this study, the issue of what dose metric (mass dose versus surface area dose is appropriate for toxicological studies has been addressed. Rats were exposed by intratracheal instillation to various doses of ultrafine or fine TiO2. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium basis. Results The findings of the study show that on a mass basis the ultrafine particles caused significantly more inflammation and were significantly more cytotoxic than the fine sized particles. However, when doses were equalized based on surface area of particles delivered, the ultrafine particles were only slightly more inflammogenic and cytotoxic when compared to the fine sized particles. Lung burden data indicate that ultrafine TiO2 appears to migrate to the interstitium to a much greater extent than fine TiO2. Conclusion This study suggests that surface area of particles may be a more appropriate dose metric for pulmonary toxicity studies than mass of particles.

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

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts


    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.

  10. Pathological study of acute pulmonary toxicity induced by intratracheally instilled Asian sand dust (kosa). (United States)

    Naota, Misaki; Mukaiyama, Toru; Shimada, Akinori; Yoshida, Atushi; Okajima, Mina; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa


    The objective of this study was to investigate acute lung toxicity caused by Asian sand dust. Simulated Asian sand dust collected from the Tennger desert in China (CJ-2 particles) and Asian sand dust collected from the atmosphere in Japan (Tottori particles) were used. Saline suspensions of 50, 200, 800, and 3,000 µg Asian sand dust were intratracheally instilled to ICR mice. Localized accumulation of the dust particles was observed in the bronchioles and the alveoli of the lung tissues; acute inflammatory changes characterized by infiltration of macrophages and neutrophils were observed around the particles. Degenerated alveolar walls and bronchial epithelial cells, as well as a weakened positive immunolabeling for laminin, were observed to be associated with particle attachment. Positive immunolabelings for interleukin-6, tumor necrosis factor-α inducible nitric oxide synthase, and dimeric copper- and zinc-containing superoxide dismutase were observed mainly in the inflammatory cells in the lesions; these findings were not observed in the controls or in areas lacking lesions. These results suggest that Asian sand dust particles caused damage to the lung tissue through a direct physical effect. In addition, secondary released cytokines and oxidative stress generated in the lesion may be involved in the development of the acute lung toxicity.

  11. [Health effects of solar cell component material. Toxicity of indium compounds to laboratory animals determined by intratracheal instillations]. (United States)

    Tanaka, Akiyo; Hirata, Miyuki


    Owing to the increasing interest being paid to the issue of the global environment, the production of solar cells has increased rapidly in recent years. Copper indium gallium diselenide (CIGS) is a new efficient thin film used in some types of solar cell. Indium is a constitutive element of CIGS thin-film solar cells. It was thought that indium compounds were not harmful until the beginning of the 1990s because there was little information regarding the adverse health effects on humans or animals arising from exposure to indium compounds. After the mid-1990s, data became available indicating that indium compounds can be toxic to animals. In animal studies, it has been clearly demonstrated that indium compounds cause pulmonary toxicity and that the dissolution of indium compounds in the lungs is considerably slow, as shown by repeated intratracheal instillations in experimental animals. Thus, it is necessary to pay much greater attention to human exposure to indium compounds, and precautions against possible exposure to indium compounds are paramount with regard to health management.

  12. 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.


    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...... for the study of oxidative damage induced by particulate matter. (C) 2003 Elsevier Science (USA). All rights reserved....

  13. Transcriptomic and histopathology changes in rat lung after intratracheal instillation of polymers. (United States)

    Carthew, Philip; Fletcher, Samantha; White, Andrew; Harries, Helen; Weber, Klaus


    The lung toxicity of inhalable polymer materials is normally carried out by evaluation of the histopathology responses of rat lungs to repeat, nose-only, exposures of an inhalable aerosol of material in a 13-wk subchronic repeat dose toxicity study. The introduction of transcriptomics into toxicology has allowed the comparison of histopathological responses in target organs, after exposure, with the "signature" of gene expression ( Waters et al., 2003 ), characteristic of the pathology processes known to be involved in the response to inhaled particulates. The transcriptomic and histopathological changes have been examined in a dose response study of the rat lung to intratracheally administered acrylate polymer solutions at time points equivalent to those used in a 13-wk inhalation study with an additional 13-wk recovery period. The doses administered in the intratracheal study were equivalent to the total doses achieved in a comparable 13-wk inhalation study. The changes in gene expression were found to be dose dependent, as was the histopathology. The changes in regulation of the genes expressed were also consistent with the histopathological responses, such as acute and chronic inflammation, commonly observed with inhalation exposure of the rat lungs to polymers. Functional classification of the genes affected highlight changes in inflammatory and immune response combined with macrophage recruitment, as well as cell adhesion and matrix formation. This would suggest a degree of tissue remodeling and is consistent with the histopathology observed. With further confirmation of the consistency of this response, the use of a transcriptomic approach in toxicology may be valuable in defining "signature" markers for the acute and chronic inflammation induced by polymers, or other inhalables, deposited in the lung. Osteopontin, in particular, a gene implicated in granuloma formation during chronic tissue damage, was significantly upregulated at high levels of exposure to

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


    The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48V-radiolabeled [48V]TiO2 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 [48V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 40-240 μg·kg-1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48V-ions not bound to TiO2-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 [48V]TiO2-nanoparticles present in liver and kidneys remained constant (0.03%). [48V]TiO2-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 [48V]TiO2-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [48V]TiO2-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 TiO2-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health

  15. Cardiovascular effects in rats after intratracheal instillation of metal welding particles. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Andrea L Armstead

    Full Text Available 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.

  17. Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C(60) fullerenes. (United States)

    Fujita, Katsuhide; Morimoto, Yasuo; Endoh, Shigehisa; Uchida, Kunio; Fukui, Hiroko; Ogami, Akira; Tanaka, Isamu; Horie, Masanori; Yoshida, Yasukazu; Iwahashi, Hitoshi; Nakanishi, Junko


    The use of C(60) fullerenes is expected to increase in various industrial fields. Little is known about the potential toxicological mechanism of action of water-soluble C(60) fullerenes. In our previous research, gene expression profiling of the rat lung was performed after whole-body inhalation exposure to C(60) fullerenes to gain insights into the molecular events. These DNA microarray-based data closely matched the pathological findings that C(60) fullerenes caused no serious adverse pulmonary effects under the inhalation exposure condition. Taking advantage of this, we attempted to characterize time-dependent changes in the gene expression profiles after intratracheal instillation with C(60) fullerenes at different dosages and to identify the candidate expressed genes as potential biomarkers. The hierarchical cluster analysis revealed that the up- or downregulation of genes after intratracheal instillation with 1.0 mg C(60) fullerene particles in rat lung tissue was significantly over-represented in the "response to stimulus" and "response to chemical stimulus" categories of biological processes and in the "extracellular space" category of the cellular component. These results were remarkable for 1 week after the instillation with C(60) fullerenes. In the lung tissues instilled with 1.0 mg C(60) fullerene particles, many representative genes involved in "inflammatory response," such as the Cxcl2, Cxcl6, Orm1, and Spp1 genes, and in "matrix metalloproteinase activity," such as the Mmp7 and Mmp12 genes, were upregulated for over 6 months. The expression levels of 89 and 21 genes were positively correlated with the C(60) fullerene dose at 1 week and 6 months after the instillation, respectively. Most of them were involved in "inflammatory response", and the Ccl17, Ctsk, Cxcl2, Cxcl6, Lcn6, Orm1, Rnase9, Slc26a4, Spp1, Mmp7, and Mmp12 genes were overlapped. Meanwhile, the expression levels of 16 and 4 genes were negatively correlated with the C(60) fullerene dose

  18. Ultrastructural changes in the air-blood barrier in mice after intratracheal instillations of Asian sand dust and gold nanoparticles. (United States)

    Rattanapinyopituk, Kasem; Shimada, Akinori; Morita, Takehito; Togawa, Masako; Hasegawa, Tatsuya; Seko, Yoshiyuki; Inoue, Kenichiro; Takano, Hirohisa


    The purpose of this study was to investigate a possible translocation pathway of intratracheally instilled gold nanoparticles after the induction of acute pulmonary injury by Asian sand dust. ICR mice were intratracheally instilled with 800μg Asian sand particles (CJ-2 particles) 24h before instillation of 50-nm gold nanoparticles. Lungs from mice treated with Asian sand particles and gold nanoparticles showed an acute focal inflammation with an increased expression of proinflammatory cytokines (IL-6 and TNF-α) and oxidative stress markers (Cu/Zn SOD and iNOS) in alveolar macrophages, type I alveolar epithelial cells, and endothelial cells at the alveolar walls. Electron microscopy revealed a destruction of the alveolar walls with an increased number of endocytic vesicles in the cytoplasm of both type I epithelial cells and endothelial cells; gold nanoparticles were demonstrated in these endocytic vesicles. These findings suggest that translocation of the exposed nanoparticles may be enhanced in the lung tissues with acute inflammatory changes. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Metabonomic studies of biochemical changes in the serum of rats by intratracheally instilled TiO2 nanoparticles. (United States)

    Tang, Meng; Zhang, Ting; Xue, Yuying; Wang, Shu; Huang, Mingming; Yang, Yang; Lu, Minyu; Lei, Hao; Kong, Lu; Wang, Yiqing; Pu, Yuepu


    In vivo behavior of nanoparticles and interactions between nanoparticles and organisms are key components of nanotoxicology. In this study, the biochemical compositions of rat serum exposed to TiO2 nanoparticles (nano-TiO2) by intratracheal instillation at low (0.8 mg/kg), medium (4 mg/kg) and high doses (20 mg/kg) were investigated using 1H-NMR techniques with pattern recognition methods. Serum biochemical assays, as well as histopathological and transmission electron microscopy (TEM) examinations of tissues were performed. 1H-NMR spectra and pattern recognition analyses of nano-TiO2 treated animals showed increased serum levels of ketone bodies, choline, low density lipoprotein (LDL), alanine and GLU, and decreased levels of lactate, creatine and pyruvate. Clinical chemistry analyses of serum showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. Furthermore, TEM provided an analysis of particle-related structural changes of the lungs, liver and kidneys, and revealed that the localization of nanoparticles within cells induced apoptosis. The damage to the target organs was associated with the perturbation of energy metabolism. Serum 1H-NMR spectra, in combination with pattern recognition techniques, proved to be an efficient and simple metabonomic method to depict the metabolic changes produced by intratracheally-instilled nano-TiO2.

  20. Intratracheal Instillation of High Dose Adenoviral Vectors Is Sufficient to Induce Lung Injury and Fibrosis in Mice (United States)

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


    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

  1. 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.


    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...

  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


    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. Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation. (United States)

    Chen, Rui; Zhang, Lili; Ge, Cuicui; Tseng, Michael T; Bai, Ru; Qu, Ying; Beer, Christiane; Autrup, Herman; Chen, Chunying


    The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly.

  4. 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


    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.

  5. Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment. (United States)

    Máté, Zsuzsanna; Horváth, Edina; Kozma, Gábor; Simon, Tímea; Kónya, Zoltán; Paulik, Edit; Papp, András; Szabó, Andrea


    Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.

  6. The induction of lipid peroxidation during the acute oxidative stress response induced by intratracheal instillation of fine crystalline silica particles in rats. (United States)

    Fukui, Hiroko; Endoh, Shigehisa; Shichiri, Mototada; Ishida, Noriko; Hagihara, Yoshihisa; Yoshida, Yasukazu; Iwahashi, Hitoshi; Horie, Masanori


    Crystalline silica (SiO2) is an important material for industry but is considered potentially carcinogenic. Inhalation of a crystalline SiO2 aerosol may contribute to serious lung diseases. Crystalline SiO2 particles are commonly used as a positive control in toxicity assays of particulate materials (e.g. nanoparticles). Crystalline SiO2 induces oxidative stress resulting in lipid peroxidation, but the acute oxidative stress response in the lung is not well understood. Lipid peroxidation during the acute stage of oxidative stress after instillation of crystalline SiO2 into rats was examined by bronchoalveolar lavage fluid (BALF) analysis. The levels of 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acid (HODE) in the BALF were measured using liquid chromatography coupled to quadrupole mass spectrometry. The concentration of the antioxidant protein heme oxygenase-1 (HO-1) in the BALF was determined using enzyme-linked immunosorbent assay. Intratracheal instillation of crystalline SiO2 increased the level of HODE and HO-1 in BALF at 24 h after administration. The levels of HODE and HO-1 returned to baseline at 72 h after instillation. Lactate dehydrogenase leakage was observed only after 1 h instillation. These results suggest that the contribution of oxidative stress to the pulmonary toxicity of crystalline SiO2 is minimal in the early acute stage after exposure. © The Author(s) 2014.

  7. Rat strain differences in levels and effects of chronic inflammation due to intratracheal instillation of quartz on lung tumorigenesis induced by DHPN. (United States)

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


    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.

  8. Sclerotherapy of simple hepatic cysts by repeated aspiration and alcohol instillation. (United States)

    Yan-Hong, Feng; Lin-Xue, Qian; Hai-Ma, Gong; Qing, Zhang; Yu, Gui; Xiangdong, Hu


    The efficacy and safety of traditional alcohol sclerotherapy procedures are controversial in the management of large simple hepatic cysts. In this study, we aimed to develop and evaluate a novel alcohol sclerotherapy procedure, termed repeated aspiration and alcohol instillation sclerotherapy, for the treatment of simple hepatic cysts. A prospective, double-blind, randomized study was performed. Sixty-seven patients with large simple hepatic cysts were randomized into two groups to receive either single-session alcohol retention sclerotherapy (alcohol was instilled into the cyst cavity, kept for 20 minutes and aspirated) or repeated aspiration and alcohol instillation sclerotherapy (instillation of 30-70 ml of alcohol and immediate aspiration with repetition 3 to 6 times until the estimated alcohol concentration exceeded 80%). The cyst volume reduction was calculated to compare the efficacy of the two procedures. We evaluated the safety of the procedure by monitoring side effects and assaying blood alcohol concentrations at 0, 0.5, 1, 2 and 3 hours after sclerotherapy. The cyst volume reduction in patients undergoing repeated aspiration and alcohol instillation sclerotherapy was significantly higher than that in those receiving alcohol-retention sclerotherapy. The concentration of alcohol in the last aspirated cyst fluid was correlated with the mean volume reduction in patients undergoing repeated aspiration and alcohol instillation sclerotherapy but not in the alcohol-retention group. Only minor side effects occurred in both groups. Although elevated blood alcohol concentration was noted in all patients, it declined to normal levels within 2-3 hours after treatment. There were no significant differences in blood alcohol concentration between the two groups. Repeated aspiration and alcohol instillation sclerotherapy is superior to single-session alcohol-retention sclerotherapy in the management of large simple hepatic cysts.

  9. 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


    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....../mouse/exposure; once a week for 10 weeks). Inflammation was determined by counting cells in bronchoalveolar lavage fluid. Serum Amyloid A3 (Saa3) expression and glutathione status were determined in lung tissue. Plaque progression was assessed in the aorta and the brachiocephalic artery. The effect of vasoactive...

  10. Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions. (United States)

    Shimada, Akinori; Kohara, Yukari; Naota, Misaki; Kobayashi, Yoshimi; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa


    Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mortality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD. A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase. A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions. These findings suggest that collagen deposition resulting from the altered regulation of extracellular matrix is associated with granuloma formation in the lungs of mice treated with ASD.

  11. Repeated measurements of dynamic tear distribution on the ocular surface after instillation of artificial tears. (United States)

    Wang, Jianhua; Aquavella, James; Palakuru, Jayachandra; Chung, Suk


    To determine the repeatability of real-time optical coherence tomography (OCT) measurements of tear film thickness (TFT) and variables of tear film menisci. Forty eyes were imaged with a custom-built, real-time OCT to obtain heights, curvatures, and cross-sectional areas of upper and lower tear menisci simultaneously. The central TFT was indirectly determined as the difference between the combined thickness of the central cornea and tear film and the true corneal thickness obtained after instillation of artificial tears. Dynamic tear distribution was determined by OCT imaging immediately and 5, 20, 40, and 60 minutes after tear instillation. Measurements taken after two blinks of one eye at each visit were repeated on the next day. Measurements from the companion eye were made on separate days. There were no significant differences between the two measurements of each variable made on consecutive days. At baseline, upper tear meniscus variables were strongly correlated with the comparable lower meniscus variables. However, there were no significant correlations between TFT and any tear meniscus variable. Immediately after instillation of artificial tears, all measured variables increased significantly. TFT, upper and lower menisci heights, and upper meniscus area remained elevated for at least 5 minutes. In addition there were significant correlations between TFT and the lower tear meniscus height and area. The custom-built OCT showed good repeatability and holds promise in measuring the dynamic distribution of artificial tears on the ocular surface.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  13. Persistent inflammation and tumour response in rats after intratracheal installation of high doses of coal dusts, Ti dioxide and quartz; Chronische Entzuendung und Tumorbildung in Ratten nach intratrachealer Instillation hoher Dosen von Kohlenstaeuben, Titandioxid und Quarz

    Energy Technology Data Exchange (ETDEWEB)

    Borm, P.J.A.; Hoehr, D.; Steinfartz, Y.; Zeittraeger, I.; Albrecht, C. [Heinrich-Heine Univ., Duesseldorf (Germany). Medizinisches Inst. fuer Umwelthygiene


    The aim of this study was to investigate persistent inflammation and tumor response in the rat after intratracheal instillation of two coal dust samples and other dust preparations. Female Wistar rats (190 gr) were instilled with ground lean coal (60 mg), coal mine dust (60 mg), DQ12 quartz (5 mg) and fine (60 mg) and ultrafine (30 mg) TiO{sub 2}. After 129 weeks rats were killed, tumors detected by macroscopy, and inflammation by immunohistochemistry using specific antibody staining for macrophages and granulocytes. Increased alveolar macrophages (AM) and interstitial granulocytes were still present in dust treated animals. Both AM and granulocytes per surface area were related to tumor incidence when all materials were plotted in one graph, and can be interpreted as effects of overload. Differences in tumor formation between fine and ultrafine TiO{sub 2}, despite similar inflammatory response, are probably caused by a direct effect of ultrafine TiO{sub 2} after interstitialisation. It is concluded that coal dust is another poorly soluble, non-toxic dust, which at high enough dose-rate causes overload, inflammation and tumor response in the rat. (orig.) [German] Das Ziel dieser vorliegenden Studie war die Untersuchung der persistierenden Entzuendung und Tumorantwort in Ratten nach der intratrachealen Instillation von zwei verschiedenen Kohlenstaeuben und anderer Staubpraeparationen. Weiblichen Wistarratten (190 g) wurde Kohlenstaub (Quarzgehalt <0,1%, 60 mg), Gesteinsstaub (Quarzgehalt 16,7%, 60 mg), DQ12 Quarz (5 mg) sowie feinen (60 mg) und ultrafeinen (30 mg) Titandioxid instilliert. Nach 129 Wochen wurden die Ratten getoetet, die Lungen makroskopisch auf Tumoren untersucht und die Entzuendung nach spezifischer Antikoerperfaerbung gegen Makrophagen und neutrophile Granulozyten immunohistochemisch bestimmt. Ein Anstieg an Alveolarmakrophagen (AM) und interstitiellen Granulozyten wurde in den staubbehandelten Ratten nachgewiesen. Die Zahl der AM und der

  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 (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. 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:; 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:; 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)


    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

  16. Intratracheal budesonide supplementation in addition to surfactant improves pulmonary outcome in surfactant-depleted newborn piglets. (United States)

    Yang, Chia-Feng; Lin, Chih-Hsueh; Chiou, Shr-Yun; Yang, Yi-Chiang; Tsao, Pei-Chen; Lee, Yu-Sheng; Soong, Wen-Jue; Jeng, Mei-Jy


    Severe respiratory distress syndrome (RDS) is still a major cause of mortality and morbidity in premature infants. The combined use of intratracheal corticosteroid and surfactant in severe RDS, which bypasses the systemic circulation, may not only help recruit the lungs but also alleviates pulmonary inflammation without an increase in systemic adverse effects. Twelve newborn piglets received repeated pulmonary saline lavage to create surfactant-depleted lungs that mimic neonatal RDS, and then were randomly grouped into a control group (standard intratracheal instillation of surfactant-Survanta 100 mg/kg); and a budesonide (Bude) group (intratracheal instillation with the mixed suspension of Budesonide 0.25 mg/kg and Survanta 100 mg/kg). Blood samples were examined, and the observation period was 24 hr. The results showed that oxygenation was significantly better in Bude group compared to the control group over time (P = 0.016). The proinflammatory cytokines tumor necrosis factor-α and interleukin-1 β showed a reduced trend in the Bude group, but was not significantly different from the control group (P > 0.05). Comparing the histological lung injury scores, the Bude group had a significantly lower score than the control group at both dependent and non-dependent sites (P surfactant seems to results in a sustained improvement in pulmonary outcome over 24 hr. Copyright © 2012 Wiley Periodicals, Inc.

  17. Artificial pulmonary surfactant as a carrier for intratracheally instilled insulin. (United States)

    Ji, Ying; Liu, Chen; Pei, Yuan-Ying


    The relative bioavailabilities and effects on lung injury alleviation of 4 insulin- artificial pulmonary surfactant (INS-APS) preparations were studied in normal rats. The relationship between the minimal surface tension (Gamma(min )) of INS-APS and the absorption of insulin was also investigated. Four formulations of APS [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/lecithin/palmitic acid (PA), DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl), DPPC/L-alpha-phosphatidyl-DL-glycerol sodium salt (PG), DPPC/Tyl] were prepared by thin-film sonication method and direct sonication. The Gamma(min ) of 4 APS dispersions was examined with and without INS by pulsating with a bubble surface tensiometer. In vivo experiments were performed in which serum glucose change and the insulin level were measured by an enzymatic glucose reagent kit and a radioimmunology assay kit after IT to rats. The reduction in lung injury by INS-APS following 7 d of consecutive administration was evaluated by the pulmonary edema index (the weight ratio of wet lung to dry lung) and histopathology examination. The Gamma(min ) of all APS dispersions were below 10 mN/m. There was no significant difference (P> 0.05) between the Gamma(min ) of APS and the corresponding INS-APS. In vivo experiments showed a significant glucose level decrease and insulin absorption increase (P 0.05) between INS/DPPC/Tyl, INS/ DPPC/PG, and the control group. The pulmonary edema indices and histopathological observation indicated that INS-APS could alleviate lung injury. The most potent hypoglycemic effect and insulin absorption increase in this study were obtained with INS/DPPC/Tyl. According to the results, there was a linear correlation between the Gamma(min ) and relative bioavailability of INS-APS, suggesting a possible effect of the Gamma(min ) of carriers on the in vivo absorption of insulin. APS, DPPC/Tyl, and DPPC/PG dispersions might be the most efficient insulin pulmonary delivery carriers in achieving a lower Gamma(min ), enhancing insulin absorption, and decreasing lung injury.

  18. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

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


    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...


    Auer, J; Gates, F L


    In the preceding pages we have submitted evidence which shows that a simple intratracheal injection of a solution in a normally breathing rabbit penetrates within a few seconds to the alveoli, chiefly those of the left lower lobe; that absorption is rapid and well maintained; and that the procedure may be repeated effectively a number of times even with a substance like adrenalin which decreases absorption. It was also shown that absorption of adrenalin from the lung could be obtained at a time when double the dose given intramuscularly exerted no blood pressure effect whatever, and that absorption could still take place after the development of pulmonary edema, when there was an undoubted dilution of the injected solution with a serum-containing liquid and when a diminution of the absorptive field had occurred. The solution injected, after reaching the alveoli, is probably largely taken up by the capillaries of the pulmonary veins. This is indicated by the great rapidity with which an intratracheal injection of adrenalin may cause a rise of blood pressure. In numerous instances, for example, the pressure began to rise less than 5 seconds after the completion of an injection, equaling and even surpassing in rapidity of effect an intramuscular injection. Absorption by the lymphatics probably plays a secondary part, an assumption rendered all themore likely if we consider that lymph nodes are interpolated in the lymphatic pulmonary path, where the bed of the lymph stream becomes greatly widened and the current slowed. Injection into the lungs, however, offers another advantage due to the vascular arrangement of the absorbing field which could be of value therapeutically. Absorption of liquids injected into the lung probably takes place largely through the capillaries of the pulmonary veins; to a slight extent possibly through the capillaries of the bronchial veins which empty partly into the pulmonary veins, partly into the azygos veins; and probably some absorption

  20. 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


    Effects of maternal pulmonary exposure to carbon black (Printex 90) on gestation, lactation and DNA strand breaks were evaluated. Time-mated C57BL/6BomTac mice were exposed by inhalation to 42 mg/m3 Printex 90 for 1 h/day on gestation days (GD) 8–18, or by four intratracheal instillations on GD 7...

  1. 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.


    We investigated the inflammatory response, acute phase response and genotoxic effect of diesel exhaust particles (DEPs, NIST1650b) following a single intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 µg/mouse and were killed 1, 3 and 28 days post-exposure. Vehicle controls a...

  2. Joint Intratracheal Surfactant-Antibacterial Therapy in Experimental Pseudomonas-Induced Pneumonia. (United States)

    Birkun, Alexei A; Kubyshkin, Anatoly V; Novikov, Nikolai Y; Krivorutchenko, Yuri L; Fedosov, Michael I; Postnikova, Olga N; Snitser, Anatoly A


    The application of an exogenous pulmonary surfactant as a carrier for intratracheally administered antimicrobials represents a promising therapeutic modality that is still on its way to clinical practice. Owing to its ability to decrease surface tension, exogenous surfactant may enhance delivery of antibiotics into foci of pulmonary infection, thus increasing efficiency and safety of topical antimicrobial therapy in bacterial lung diseases. To assess potential interactions between exogenous surfactant and amikacin in vitro, and to study the effects of their joint intratracheal instillation in rats with acute pneumonia caused by Pseudomonas aeruginosa. The antibacterial and surface-active properties of amikacin (Amicil, Kievmedpreparat, Ukraine), porcine pulmonary surfactant (Suzacrin, Docpharm, Ukraine), and their combination were studied in vitro using standard microbiologic procedures and modified Pattle method (estimation of bubble diameter). Similar methods were utilized to study bacterial contamination of lungs and blood, and to assess the surface activity of bronchoalveolar wash (BAW) in 119 Wistar rats, including infected (intratracheal introduction of P. aeruginosa ATCC 27853) and noninfected animals. Histopathologic findings, differential leukocyte counts, and oxygenation parameters were recorded. Antibacterial and surface-active properties of the surfactant and amikacin remained unimpaired in vitro. In rats anti-pseudomonal and anti-inflammatory effects of the surfactant-amikacin mixture were more pronounced (psurfactant-amikacin therapy of Pseudomonas-induced pneumonia may suggest further clinical trials.

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

    Energy Technology Data Exchange (ETDEWEB)

    Becak DP, Holland NA; Shannahan, Jonathan H.


    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.

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

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki


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

  5. Alleviating effects of artificial tear instillation on S-1-induced ocular toxicity in dogs. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Koji Sugioka


    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

  7. Enhanced bioavailability of opiates after intratracheal administration

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  8. Short-term effects of intratracheal installations of yttrium barium copper oxide

    Energy Technology Data Exchange (ETDEWEB)

    London, J.E.; Newkirk, L.R.; Lehnert, B.E.


    Inhalation exposures to the new high-temperature ({Tc}) superconductor (SC) materials can occur during manufacturing and fabrication processes. In this exploratory study, we examined the pulmonary response to the deposition of an yttrium barium copper oxide SC powder. Groups of Sprague-Dawley rats were intratracheally instilled with either 10 mg or 20 mg of SC in phosphate-buffered saline (PBS) or with PBS only. The animals were sacrificed 60 days later for histopathologic assessments of their lungs. Lung lesions in the 10-mg SC group were found mainly in alveolar ducts and proximal alveoli. The lesions consisted of variably sized foci of interstitial thickening involving accumulations of macrophages. These interstitial aggregates were often times centered around one or more extracellular crystals, which, presumably, were retained SC product. Trichome stains also demonstrated the presence of fibrosis in the walls of alveoli surrounding the granulomas. Similar interstitial-macrophage accumulations and fibrosis were observed in rats instilled with 20 mg of SC. However, alveolus like structures lined by ciliated cuboidal epithelium near interstitial granulomas were additionally found in the lungs of some of the animals in this latter group. These results suggest SC material of the yttrium barium copper oxide type may represent a potential exposure hazard to the lung.

  9. Intratracheal Seal Disc: A Novel Tracheostoma Closure Device. (United States)

    Christiansen, Karen J; Moeslund, Niels; Lauridsen, Henrik; Devantier, Louise; Rohde, Marianne C; Kjærgaard, Benedict; Pedersen, Michael


    Tracheostomy decannulation is accompanied by several clinical concerns due to air leakage. In this study, we introduced a novel tracheostoma closure device that facilitates the use of noninvasive ventilation, improvement of pulmonary function, and vocalization in the newly decannulated patient. The biosafety and feasibility of the device were evaluated in an animal model. Five Danish Landrace pigs were subjected to tracheostomy followed by decannulation and insertion of the tracheostoma closure device. Correct placement of the device was ensured by flexible tracheoscopy. The device consisted of an intratracheal silicone seal disc fixated by a cord through the stoma to an external part. At day 14, computed tomography (CT) was performed before the device was extracted. With the pulling of a cord, the disc unraveled into a thin thread and was extracted through the stoma. At day 21, CT was repeated before euthanasia. The trachea and epidermis were excised en bloc for histopathological evaluation. 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 of the tracheostoma. Extraction was successful in one animal but complicated in the remaining animals. There was histological evidence of healing after the foreign body placement. The study demonstrated that the tracheostoma closure device is feasible and biosafe in a porcine animal model, but the design and quality of the materials need to be improved before clinical trials. Copyright © 2017 by Daedalus Enterprises.

  10. 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


    .5 and 25μg on a range of parameters. However, mice that survived a high dose (50μg; 2.7mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results......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...... prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100μg; ≥1.4mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6μg; ≥0.3mg/kg) elicited acute toxicity in terms of reduced weight gain...

  11. Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats


    Dunnick, Katherine M.; Morris, Anna M.; Badding, Melissa A.; Barger, Mark; Stefaniak, Aleksandr B.; Sabolsky, Edward M.; Leonard, Stephen S.


    Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. Du...

  12. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats (United States)


    Background Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. Methods On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry. Results TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema. Conclusions TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages. PMID:22849372

  13. 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: [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)


    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

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

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    Alexandre Robbe


    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.

  15. Instillation versus inhalation of multiwalled carbon nanotubes: exposure-related health effects, clearance, and the role of particle characteristics. (United States)

    Silva, Rona M; Doudrick, Kyle; Franzi, Lisa M; TeeSy, Christel; Anderson, Donald S; Wu, Zheqiong; Mitra, Somenath; Vu, Vincent; Dutrow, Gavin; Evans, James E; Westerhoff, Paul; Van Winkle, Laura S; Raabe, Otto G; Pinkerton, Kent E


    Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague-Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses.

  16. Acute intratracheal Pseudomonas aeruginosa infection in cystic fibrosis mice is age-independent

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    Munder Antje


    Full Text Available Abstract Background Since the discovery of the human CFTR gene in 1989 various mouse models for cystic fibrosis (CF have been generated and used as a very suitable and popular tool to approach research on this life-threatening disease. Age related changes regarding the course of disease and susceptibility towards pulmonary infections have been discussed in numerous studies. Methods Here, we investigated CftrTgH(neoimHgu and Cftrtm1Unc-Tg(FABPCFTR1Jaw/J CF mice and their non-CF littermates during an acute lung infection with Pseudomonas aeruginosa for age dependent effects of their lung function and immune response. Mice younger than three or older than six months were intratracheally infected with P. aeruginosa TBCF10839. The infection was monitored by lung function of the animals using non-invasive head-out spirometry and the time course of physiological parameters over 192 hours. Quantitative bacteriology and lung histopathology of a subgroup of animals were used as endpoint parameters. Results Age-dependent changes in lung function and characteristic features for CF like a shallower, faster breathing pattern were observed in both CF mouse models in uninfected state. In contrast infected CF mice did not significantly differ from their non-CF littermates in susceptibility and severity of lung infection in both mouse models and age groups. The transgenic Cftrtm1Unc-Tg(FABPCFTR1Jaw/J and their non-CF littermates showed a milder course of infection than the CftrTgH(neoimHgu CF and their congenic C57Bl/6J non-CF mice suggesting that the genetic background was more important for outcome than Cftr dysfunction. Conclusions Previous investigations of the same mouse lines have shown a higher airway susceptibility of older CF mice to intranasally applied P. aeruginosa. The different outcome of intranasal and intratracheal instillation of bacteria implies that infected CF epithelium is impaired during the initial colonization of upper airways, but not in

  17. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies. (United States)

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


    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.

  18. Intratracheal heparin improves plastic bronchitis due to sulfur mustard analog. (United States)

    Houin, Paul R; Veress, Livia A; Rancourt, Raymond C; Hendry-Hofer, Tara B; Loader, Joan E; Rioux, Jacqueline S; Garlick, Rhonda B; White, Carl W


    Inhalation of sulfur mustard (SM) and SM analog, 2-chloroethyl ethyl sulfide (CEES), cause fibrinous cast formation that occludes the conducting airways, similar to children with Fontan physiology-induced plastic bronchitis. These airway casts cause significant mortality and morbidity, including hypoxemia and respiratory distress. Our hypothesis was that intratracheal heparin, a highly cost effective and easily preserved rescue therapy, could reverse morbidity and mortality induced by bronchial cast formation. Sprague-Dawley rats were exposed to 7.5% CEES via nose-only aerosol inhalation to produce extensive cast formation and mortality. The rats were distributed into three groups: non-treated, phosphate-buffered saline (PBS)-treated, and heparin-treated groups. Morbidity was assessed with oxygen saturations and clinical distress. Blood and bronchoalveolar lavage fluid (BALF) were obtained for analysis, and lungs were fixed for airway microdissection to quantify the extent of airway cast formation. Heparin, given intratracheally, improved survival (100%) when compared to non-treated (75%) and PBS-treated (90%) controls. Heparin-treated rats also had improved oxygen saturations, clinical distress and airway cast scores. Heparin-treated rats had increased thrombin clotting times, factor Xa inhibition and activated partial thromboplastin times, indicating systemic absorption of heparin. There were also increased red blood cells (RBCs) in the BALF in 2/6 heparin-treated rats compared to PBS-treated control rats. Intratracheal heparin 1 hr after CEES inhalation improved survival, oxygenation, airway obstruction, and clinical distress. There was systemic absorption of heparin in rats treated intratracheally. Some rats had increased RBCs in BALF, suggesting a potential for intrapulmonary bleeding if used chronically after SM inhalation. © 2014 Wiley Periodicals, Inc.

  19. Severe airway epithelial injury, aberrant repair and bronchiolitis obliterans develops after diacetyl instillation in rats.

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    Scott M Palmer


    Full Text Available Bronchiolitis obliterans (BO is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA, a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1 to determine if DA, delivered by intratracheal instillation (ITI, would lead to the development of BO in rats and 2 to characterize epithelial regeneration and matrix repair after ITI of DA.Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg or sterile water (vehicle control by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets.

  20. Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2. (United States)

    Rosenblum Lichtenstein, Jamie H; Molina, Ramon M; Donaghey, Thomas C; Hsu, Yi-Hsiang H; Mathews, Joel A; Kasahara, David I; Park, Jin-Ah; Bordini, André; Godleski, John J; Gillis, Bruce S; Brain, Joseph D


    After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multiple-dosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single- or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1α, MIP-1β, TNF-α, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiple- than in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.

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

    Directory of Open Access Journals (Sweden)

    Matsunaga Hirofumi


    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.

  2. Negative pressure wound therapy with instillation: the current state of the art. (United States)

    Wolvos, Tom A


    Traditional negative pressure wound therapy (NPWT) has revolutionized the treatment of complex wounds for nearly 20 years. A decade ago, a modification of the original system added intermittent automated instillation of topical wound irrigation solutions to traditional negative pressure wound therapy. This combined therapy, termed negative pressure wound therapy with instillation (NPWTi), has been shown to be effective in the treatment of a variety of complex wounds. Negative pressure wound therapy with instillation has been shown to reduce bioburden and biofilms present in wounds helping heal clinically infected wounds. It has also been used with success to jump-start stalled wounds, in relieving wound pain and treating infected foreign bodies including infected orthopedic hardware and some types of exposed abdominal wall mesh. The system includes a foam dressing placed in the wound covered by a semi-occlusive drape. A tubing placed over a hole cut in the drape connects the foam dressing to a pump run by a computerized microprocessor that delivers negative pressure to the dressing and wound. A preset volume of instillation fluid is automatically delivered via the instillation tubing to the wound. The fluid is held in the foam to bathe the wound for a predetermined time period. Negative pressure is then re-started draining the irrigation fluid and any wound exudate into a collection canister. The entire sequence is automated and consists of three phases: (1) fluid instillation; (2) holding for a period of time in the wound, which is fully expanded since the negative pressure is off during this phase; and then (3) a cycle of continuous negative pressure. The entire sequence repeats itself automatically. Typically the dressing is changed three times a week. The variables involved in treating patients with negative pressure wound therapy with instillation included: the indicated wound types; the system settings; the choice of the irrigation solution and the duration

  3. The use of intratracheal pulmonary ventilation and partial liquid ventilation in newborn piglets with meconium aspiration syndrome. (United States)

    Onasanya, Babatunde I.; Rais-Bahrami, Khodayar; Rivera, Oswaldo; Seale, Winslow R.; Short, Billie L.


    OBJECTIVE: To determine whether intratracheal pulmonary ventilation (ITPV) combined with partial liquid ventilation (PLV) improves oxygenation and ventilation at lower mean airway and peak inspiratory pressures when compared with conventional mechanical ventilation in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, randomized, interventional study. SETTING: Animal Research Laboratory at the Children's National Medical Center, Washington, DC. SUBJECTS: Twenty newborn piglets, 1 to 2 wks of age, 1.8-2.8 kg in weight. INTERVENTION: The animals were anesthetized, paralyzed, and intubated with a 4.0 mm (internal diameter) endotracheal tube via a tracheostomy and were ventilated. Catheters were placed in the femoral artery and vein. Seven milliliters per kilogram of 20% human meconium was insufflated into the lungs over 30 mins. Dynamic pulmonary compliance was measured before and after instillation of meconium. Animals were ventilated to maintain arterial blood gases in a normal range, that is, pH = 7.35-7.45, Paco(2) = 40-45 torr (5.3-6.0 kPa), and Pao(2) = 70-90 torr (9.3-12.0 kPa). Ventilator settings were increased as needed to a maximum setting of Fio(2) = 1.0, peak inspiratory pressure (PIP) = 40 cm H(2)O, positive end-expiratory pressure = 5 cm H(2)O, and intermittent mandatory ventilation = 60 bpm. After a period of stabilization, 30 mL/kg of perflubron (Liquivent; Alliance Pharmaceutical Corp., San Diego, CA) was given intratracheally over 30 mins and the animals were randomized to either ITPV or control group. Measurements and RESULTS: Arterial blood gases were taken every 30 mins, and ventilatory settings were adjusted to achieve the targeted blood gas parameters. The animals' temperature, arterial blood pressure, heart rate, and oxygen saturation were monitored continuously. There was a significant decrease in the dynamic pulmonary compliance measurements in both groups immediately after meconium instillation. Compliance measurements

  4. Toxicokinetics of ochratoxin A in rat following intratracheal administration. (United States)

    Breitholtz-Emanuelsson, A; Fuchs, R; Hult, K


    The toxicokinetic parameters of ochratoxin A in rat following intratracheal administration of 50 ng ochratoxin A/g body weight were studied. The absorption of ochratoxin A from the lungs was very efficient. The elimination pattern of the toxin was studied by the analysis of blood samples. The biological half-life of ochratoxin A was 127 h and the calculated apparent volume of distribution equalled 168 ml/kg. The bioavailability of the toxin was very high, 98%. The plasma clearance of the toxin was 0.92 ml/kg.h.

  5. Conventional and toxicogenomic assessment of the acute pulmonary damage induced by the instillation of Cardiff PM10 into the rat lung. (United States)

    Wise, H; Balharry, D; Reynolds, L J; Sexton, K; Richards, R J


    There is strong epidemiological evidence of association between PM10 (particulate matter with an aerodynamic diameter less than or equal to 10 microm) and adverse health outcomes including death and increased hospital admissions for cardiopulmonary conditions. Ambient PM10 surrogates such as diesel exhaust particles (DEP), a common component of UK PM10 have been shown to induce lung inflammation in both humans and rodents. To date, few studies have reported on the toxicological response of UK PM10 in experimental animals. This study examines the pulmonary toxicological responses in male Sprague Dawley rats following the intratracheal instillation of Cardiff urban PM10. A mild but significant change in lung permeability was observed in the lung post-instillation of a high (10 mg) dose of the whole PM10 as adjudged by increases in lung to body weight ratio and total acellular lavage protein. Such effects were less marked following instillation of a water-soluble fraction (80% of the total mass) but histological examination showed that lung capillaries were swollen in size with this treatment. In conclusion, conventional toxicological, histological and toxicogenomic studies have indicated that Cardiff PM10 exhibits low bioreactivity in the form of mild permeability changes. Differential gene expression was observed when the lung was treated with whole PM10, containing durable particles, in comparison with the water-soluble fraction of PM10 that was devoid of particles. Such changes were linked to different histopathological events within the lung.

  6. Distribution of a 20-mer phosphorothioate oligonucleotide, CGP69846A (ISIS 5132), into airway leukocytes and epithelial cells following intratracheal delivery to brown-norway rats. (United States)

    Danahay, H; Giddings, J; Christian, R A; Moser, H E; Phillips, J A


    To evaluate the pulmonary distribution of CGP69846A (ISIS 5132), a phosphorothioate oligonucleotide, following intra-tracheal (i.t.) instillation into Brown-Norway rats. The pharmacokinetic profile of [3H]-CGP69846A was investigated following i.t. instillation into both naive and inflamed airways of Brown-Norway rats. The cellular distribution was determined using autoradiography, immunohistochemistry and flow cytometry/fluorescence microscopy, in inflamed airways. CGP69846A displayed a dose-dependent lung retention following i.t. administration which was unaffected by local inflammation. Autoradiography and immunohistochemistry showed distribution to alveolar macrophages, eosinophils, bronchial and tracheal epithelium and alveolar cells. Studies with [FITC]-CGP69846A demonstrated a preferential association of oligonucleotide with leukocytes in bronchial lavage fluid of: macrophages > eosinophils = neutrophils > lymphocytes. The dose-dependency of lung retention together with cell-specific uptake suggests that the lung can be used as a local target for antisense molecules with potentially minimal systemic effects. Furthermore, the preferential targeting of macrophages and the airway epithelium by oligonucleotides may represent rational cellular targets for antisense therapeutics.

  7. Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis. (United States)

    Timmers, Michael S; Graafland, Niels; Bernards, Alexandra T; Nelissen, Rob G H H; van Dissel, Jaap T; Jukema, Gerrolt N


    In a retrospective, case-control cohort study an assessment was made of the clinical outcome of patients with osteomyelitis treated with a new modality of negative pressure wound therapy, so called negative pressure instillation therapy. In this approach, after surgical debridement, a site of osteomyelitis is treated with negative pressure of at least 300 mmHg applied through polyvinyl alcohol dressing. The polyvinyl alcohol foam is irrigated through the tubes three times a day with a polyhexanide antiseptic solution. In 30 patients (14 males; mean age 52 [range, 26-81]) admitted between 1999 and 2003 with osteomyelitis of the pelvis or lower extremity, we assessed time to wound closure, number of surgical procedures and rate of recurrence of infection as well as need for rehospitalizations. For comparison, a control group of 94 patients (males, 58; mean age 47 [range, 9-85]), matched for site and severity of osteomyelitis, was identified in hospital records between 1982 and 2002. These patients underwent standard surgical debridement, implantation of gentamicin polymethylmethacrylate beads and long-term intravenous antibiotics. In the Instillation group the rate of recurrence of infection was 3/30 (10%), whereas 55/93 (58.5%) of the controls had a recurrence (p<0.0001). Moreover, in those treated with instillation the total duration of hospital stay was shorter and number of surgical procedures smaller as compared with the controls (all p<0.0001). We conclude that in posttraumatic osteomyelitis negative pressure instillation therapy reduces the need for repeated surgical interventions in comparison with the present standard approach.

  8. 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.

  9. Assessment of eye drop instillation technique in glaucoma patients

    Directory of Open Access Journals (Sweden)

    Beatriz Fiuza Gomes

    Full Text Available ABSTRACT Purpose: To study the technique of eye drop instillation in glaucoma patients and identify independent factors that may influence their performance. Methods: In this cross-sectional study, 71 consecutive patients with glaucoma or ocular hypertension, self-administering topical anti-glaucoma medications for ≥6 months were evaluated. All patients instilled a tear substitute into the eye with the worst eyesight using the technique normally used at home. The following parameters were evaluated: age, number of years receiving treatment with ocular hypotensive eye drops, time spent to instill the first drop, number of drops instilled, correct location of the eye drops, contact of the bottle with the eye, closing of the eyelids or occlusion of the tear punctum, and asepsis of the hands. Results: The mean age of the patients was 66 ± 10.8 years, and patients were on ocular hypotensive drugs for 11.3 ± 7.3 (range, 2-35 years. Only 28% of the patients were able to correctly instill the eye drops (squeeze out 1 drop and instill it into the conjunctival sac without bottle tip contact. Touching the tip of the bottle to the globe or periocular tissue occurred in 62% of the patients. In 49% of the patients, the eye drops fell on the eyelids or cheek. Two or more drops were squeezed by 27% of the patients. Conclusions: The majority of glaucoma patients were unable to correctly instill eye drops. Age was an independent factor associated with eye drop instillation performance.

  10. 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.


    The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal...... 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...... and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung...

  11. 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


    Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric...

  12. 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


    transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also...... differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3h post-exposure declining to base-levels by 3d, increasing again at 14d, and then persisting to 42d post-exposure. Thus, this single CBNP exposure that was equivalent...... to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42d post-exposure, raising concern over the chronic effects of CBNP exposure....

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

    African Journals Online (AJOL)

    Objective. The objective of this study was to describe the effect of normal saline instillation (NSI) on cardiorespiratory parameters in intubated cardiothoracic patients. Methods. A comparative design was employed to meet the study objectives. Simple random sampling was used to assign patients to study groups, namely a ...

  14. Late sensory function after intraoperative capsaicin wound instillation

    DEFF Research Database (Denmark)

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


    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...... 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...... treatment. RESULTS: Twenty (100%) capsaicin and 16 (76%) placebo-treated patients were seen at the 2 1/2 year follow-up. Hyperalgesia was seen in five capsaicin- vs. one placebo-treated patient (P=0.2). The mechanical detection threshold was significantly increased on the operated side in the capsaicin vs...

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

    Directory of Open Access Journals (Sweden)

    Keng Lim Ng


    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.

  16. Corneal sensitivity after topical bromfenac sodium eye-drop instillation

    Directory of Open Access Journals (Sweden)

    Yanai K


    Full Text Available Kaori Yanai,1 Jane Huang,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Purpose: To evaluate the safety of bromfenac sodium eye drops from the standpoint of corneal sensitivity and tear secretion in healthy controls following instillation for 1 month. Methods: A prospective single-blind parallel clinical study was conducted in 20 eyes of ten healthy volunteers with no history of ocular or systemic allergic disease, dry eye, contact lens wear, or ocular surgery. Participants were instructed to instill either bromfenac sodium or artificial tears in each eye twice daily for 28 days. Corneal sensitivity tested using a Cochet–Bonnet esthesiometer was evaluated before and immediately after instillation at 7, 14, and 28 days after the initiation of treatment. Tear secretion was also evaluated by Schirmer's eye test before and at 28 days. Results: No significant difference in mean corneal sensitivity and tear-secretion rate was observed between the bromfenac and artificial-tear treatment groups at any time. Conclusion: These results indicate that bromfenac sodium eye drops are safe with respect to corneal sensitivity and tear secretion in subjects with a normal ocular surface condition. Further evaluation is still necessary to determine whether bromfenac is safe in pathological conditions, such as inflammatory disorders and postsurgical cases. Keywords: bromfenac sodium, cornea, sensitivity, tear, nonsteroidal anti-inflammatory drug

  17. A novel and simple method for endotracheal intubation of mice

    NARCIS (Netherlands)

    Spoelstra, E. N.; Ince, C.; Koeman, A.; Emons, V. M.; Brouwer, L. A.; van Luyn, M. J. A.; Westerink, B. H. C.; Remie, R.

    Endotracheal intubation in mice is necessary for experiments involving intratracheal instillation of various substances, repeated pulmonary function assessments and mechanical ventilation. Previously described methods for endotracheal intubation in mice require the use of injection anaesthesia to

  18. Impaired resolution of inflammatory response in the lungs of JF1/Msf mice following carbon nanoparticle instillation

    Directory of Open Access Journals (Sweden)

    De Angelis Martin


    Full Text Available Abstract Background Declined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD. Carbon nanoparticles (CNP are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1 mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution. Methods 5 μg, 20 μg and 50 μg CNP (Printex 90 were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 μg dosage. Inflammation was assessed using histology, bronchoalveolar lavage (BAL analysis and by a panel of 62 protein markers. Results 24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN respectively while the 5 μg represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3, and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3 were significantly decreased at day 3 (72.9 × 10E3 and day 7 (48.5 × 10E3 but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3 and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3 compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte

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

    NARCIS (Netherlands)

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


    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

  20. Tissue uptake, distribution and excretion of brevetoxin-3 after oral and intratracheal exposure in the freshwater turtle Trachemys scripta and the diamondback terrapin Malaclemys terrapin. (United States)

    Cocilova, Courtney C; Flewelling, Leanne J; Bossart, Gregory D; Granholm, April A; Milton, Sarah L


    Harmful algal blooms (HABs) occur nearly annually off the west coast of Florida and can impact both humans and wildlife, resulting in morbidity and increased mortality of marine animals including sea turtles. The key organism in Florida red tides is the dinoflagellate Karenia brevis that produces a suite of potent neurotoxins referred to as the brevetoxins (PbTx). Despite recent mortality events and rehabilitation efforts, still little is known about how the toxin directly impacts sea turtles, as they are not amenable to experimentation and what is known about toxin levels and distribution comes primarily from post-mortem data. In this study, we utilized the freshwater turtle Trachemys scripta and the diamondback terrapin, Malaclemys terrapin as model organisms to determine the distribution, clearance, and routes of excretion of the most common form of the toxin, brevetoxin-3, in turtles. Turtles were administered toxin via esophageal tube to mimic ingestion (33.48μg/kg PbTx-3, 3×/week for two weeks for a total of 7 doses) or by intratracheal instillation (10.53μg/kg, 3×/week for four weeks for a total of 12 doses) to mimic inhalation. Both oral and intratracheal administration of the toxin produced a suite of behavioral responses symptomatic of brevetoxicosis. The toxin distributed to all organ systems within 1h of administration but was rapidly cleared out over 24-48h, corresponding to a decline in clinical symptoms. Excretion appears to be primarily through conjugation to bile salts. Histopathological study revealed that the frequency of lesions varied within experimental groups with some turtles having no significant lesions at all, while similar lesions were found in a low number of control turtles suggesting another common factor(s) could be responsible. The overall goal of this research is better understand the impacts of brevetoxin on turtles in order to develop better treatment protocols for sea turtles exposed to HABs. Copyright © 2017 Elsevier B

  1. Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2-chloroethyl ethyl sulfide, a mustard gas analog. (United States)

    Gadsden-Gray, Jessica; Mukherjee, Shyamali; Ogunkua, Olugbemiga; Das, Salil K


    Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog and a chemical warfare agent is known to cause massive damage to lung. The purpose of this study was to determine whether intratracheal CEES infusion causes neuronal damage. Histological, immunohistochemical, and Western blot studies indicated that CEES treatment caused dose-dependent increases in blood cell aggregation, microglial cell number, microglial activation, and brain inflammation. In addition, an increased expression of α-synuclein and a decreased expression of the dopamine transporter were observed. The results indicate that intratracheal CEES infusion is associated with changes in brain morphology mediated by an increase in α-synuclein expression, leading to neurotoxicity in a guinea pig model. These changes may be mediated by oxidative stress. Furthermore, the present study indicates for the first time that intratracheal infusion of a single dose of CEES can cause neuroinflammation, which may lead to neurological disorders in later part of life. Copyright © 2011 Wiley Periodicals, Inc.

  2. In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Valnemulin in an Experimental Intratracheal Mycoplasma gallisepticum Infection Model


    Xiao, Xia; Sun, Jian; Yang, Tao; Fang, Xi; Wu, Dong; Xiong, Yan Q.; Cheng, Jie; Chen, Yi; Shi, Wei; Liu, Ya-Hong


    Valnemulin, a semisynthetic pleuromutilin antibiotic derivative, is greatly active against Mycoplasma. The objective of our study was to evaluate the effectiveness of valnemulin against Mycoplasma gallisepticum in a neutropenic intratracheal model in chickens using a pharmacokinetic/pharmacodynamic (PK-PD) method. The PK of valnemulin after intramuscular (i.m.) administration at doses of 1, 10, and 20 mg/kg of body weight in M. gallisepticum-infected neutropenic chickens was evaluated by liqu...

  3. Systemic BCG-osis following intravesical BCG instillation for bladder carcinoma. (United States)

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


    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.

  4. VAWCM-Instillation Improves Delayed Primary Fascial Closure of Open Septic Abdomen

    Directory of Open Access Journals (Sweden)

    Qingsong Tao


    Full Text Available Background. Failure to achieve delayed primary fascial closure (DPFC is one of the main complications of open abdomen (OA, certainly when abdominal sepsis is present. This retrospective cohort study aims to evaluate the effect of combined therapy of vacuum-assisted mesh-mediated fascial traction and topical instillation (VAWCM-instillation on DPFC in the open septic abdomen. Methods. The patients with abdominal sepsis who underwent OA using VAWCM were included and divided into the instillation and noninstillation (control groups. The DPFC rate and other outcomes were compared between the two groups. Results. Between 2007 and 2013, 73 patients with open septic abdomen were treated with VAWCM-instillation and 61 cases with VAWCM-only. The DPFC rate in the instillation group was significantly increased (63% versus 41%, P=0.011. The mortality with OA was similar (24.6% versus 23%, P=0.817 between the two groups. However, time to DPFC (P=0.003 and length of stay in hospital (P=0.022 of the survivals were significantly decreased in the instillation group. In addition, VAWCM-instillation (OR 1.453, 95% CI 1.222–4.927, P=0.011 was an independent influencing factor related to successful DPFC. Conclusions. VAWCM-instillation could improve the DPFC rate but could not decrease the mortality in the patients with open septic abdomen.

  5. VAWCM-Instillation Improves Delayed Primary Fascial Closure of Open Septic Abdomen. (United States)

    Tao, Qingsong; Ren, Jianan; Ji, Zhenling; Liu, Shengli; Wang, Baochai; Zheng, Yu; Gu, Guosheng; Wang, Xinbo; Li, Jieshou


    Background. Failure to achieve delayed primary fascial closure (DPFC) is one of the main complications of open abdomen (OA), certainly when abdominal sepsis is present. This retrospective cohort study aims to evaluate the effect of combined therapy of vacuum-assisted mesh-mediated fascial traction and topical instillation (VAWCM-instillation) on DPFC in the open septic abdomen. Methods. The patients with abdominal sepsis who underwent OA using VAWCM were included and divided into the instillation and noninstillation (control) groups. The DPFC rate and other outcomes were compared between the two groups. Results. Between 2007 and 2013, 73 patients with open septic abdomen were treated with VAWCM-instillation and 61 cases with VAWCM-only. The DPFC rate in the instillation group was significantly increased (63% versus 41%, P = 0.011). The mortality with OA was similar (24.6% versus 23%, P = 0.817) between the two groups. However, time to DPFC (P = 0.003) and length of stay in hospital (P = 0.022) of the survivals were significantly decreased in the instillation group. In addition, VAWCM-instillation (OR 1.453, 95% CI 1.222-4.927, P = 0.011) was an independent influencing factor related to successful DPFC. Conclusions. VAWCM-instillation could improve the DPFC rate but could not decrease the mortality in the patients with open septic abdomen.

  6. Comparison of mydriatic efficacy of spray application and drop instillation of tropicamide 1%. (United States)

    Akman, A; Aydin, P


    To determine whether the mydriatic efficacy of spray application of tropicamide 1% is comparable to drop instillation of tropicamide 1%, and to compare the ocular discomfort caused by these methods. Thirty-four healthy volunteers were randomly assigned to one of two groups, and received either a single drop of tropicamide 1% eye drops or a single puff of tropicamide 1% spray into open eyes. Pupil diameters were measured from anterior segment images taken using a Topcon Imagenet system at baseline and at the fifth, tenth and fifteenth minute after drug administration. Ocular discomfort experienced with each method was also compared. Repeated measures analysis of variance revealed that a statistically significant increase in pupil diameter was achieved with both application methods over time (p tropicamide 1% spray was 1.45 +/- 0.56, and for tropicamide 1% eye drops was 2.71 +/- 0.67. This difference was statistically significant (p tropicamide 1% spray is similar to that of conventional tropicamide 1% eye drops, and spray application causes less ocular discomfort.

  7. Instilling fear makes good business sense: unwarranted hysterectomies in Karnataka. (United States)

    Xavier, Teena; Vasan, Akhila; S, Vijayakumar


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

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

    Directory of Open Access Journals (Sweden)

    Omar M Aboumarzouk


    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. Factors affecting eye drop instillation in glaucoma patients with visual field defect.

    Directory of Open Access Journals (Sweden)

    Tomoko Naito

    Full Text Available To investigate the success rate of eye drop instillation in glaucoma patients with visual field defect as well as non-glaucoma volunteers. Factors that may affect the success rate of eye drop instillation were also evaluated.A prospective, observational study.Seventy-eight glaucoma patients and 85 non-glaucoma volunteers were recruited in this study.Open angle glaucoma patients with visual field defect as well as non-glaucoma volunteers were asked to video record their procedures of eye drop instillation using a 5-mL plastic bottle of artificial tear solution. Success of eye drop instillation was judged on video based on the first one drop of solution successfully applied on the cornea, by two investigators.Success rate of eye drop instillation in glaucoma patients and non-glaucoma volunteers. Factors related to success rate of eye drop instillation, such as visual field defect and clinical characteristics, were also analyzed using multivariable logistic regression.No significant deference in mean age was observed between two groups (glaucoma: 64.5 ± 14.4 years, non-glaucoma: 60.9 ± 14.1 years, P = 0.1156. Success rate of eye drop instillation was significantly lower (P = 0.0215 in glaucoma patients (30/78; 38.5% than in non-glaucoma volunteers (48/85; 56.5%. The most frequent reason of instillation failure in glaucoma patients was touching the bulbar conjunctiva, cornea, eyelid or eyelashes with the tip of the bottle (29.5%. Multivariable logistic regression analysis identified lower corrected visual acuity (VA (≤ 1.0; odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.04-0.93, P = 0.0411, lower mean deviation (MD (< -12 dB; OR = 0.20, 95% CI 0.05-0.86, P = 0.0307 and visual field defect (VFD in the inferior hemifield (OR = 0.11, 95% CI 0.02-0.34, P < 0.001 to be significantly related to instillation failure in glaucoma patients.Success rate of eye drop instillation was significantly lower in glaucoma patients than in non

  10. VAWCM-Instillation Improves Delayed Primary Fascial Closure of Open Septic Abdomen


    Qingsong Tao; Jianan Ren; Zhenling Ji; Shengli Liu; Baochai Wang; Yu Zheng; Guosheng Gu; Xinbo Wang; Jieshou Li


    Background. Failure to achieve delayed primary fascial closure (DPFC) is one of the main complications of open abdomen (OA), certainly when abdominal sepsis is present. This retrospective cohort study aims to evaluate the effect of combined therapy of vacuum-assisted mesh-mediated fascial traction and topical instillation (VAWCM-instillation) on DPFC in the open septic abdomen. Methods. The patients with abdominal sepsis who underwent OA using VAWCM were included and divided into the instilla...

  11. Immunological and Physiological Differences Between Layer- and Broiler Chickens after Concurrent Intratracheal Administration of Lipopolysaccharide and Human Serum Albumin

    NARCIS (Netherlands)

    Parmentier, H.K.; Vries Reilingh, de G.; Freke, P.; Koopmanschap, R.E.; Lammers, A.


    Layers and broilers were concurrently intratracheally challenged with 0.5 mg Lipopolysaccharide (LPS) and 0.1 mg Human Serum Albumin (HuSA) at 3 weeks of age. Specific total and isotype-specific (IgM, IgG, IgA) Antibody (Ab) responses to HuSA during 3 weeks following immunization, cellular in vitro

  12. 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.


    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.

  13. Comparison of the local pulmonary distribution of nanoparticles administered intratracheally to rats via gavage needle or microsprayer delivery devices. (United States)

    Zhang, Guihua; Shinohara, Naohide; Oshima, Yutaka; Kobayashi, Toshio; Imatanaka, Nobuya; Kawaguchi, Kenji; Gamo, Masashi


    Intratracheal administration methods are used to conduct toxicological assessments of inhaled nanoparticles (NPs), and gavage needles or microsprayers are common intratracheal delivery devices. The NP suspension is delivered in a liquid state via gavage needle and as a liquid aerosol via microsprayer. The differences in local pulmonary NP distribution (called the microdistribution) arising from the different states of the NP suspension cause differential pulmonary responses; however, this has yet to be investigated. Herein, using microbeam X-ray fluorescence microscopy, we quantitatively evaluated the TiO2 pulmonary microdistribution (per mesh: 100 μm × 100 μm) in lung sections from rats administered an intratracheal dose of TiO2 NPs (6 mg kg-1 ) via gavage needle or microsprayer. The results revealed that: (i) using a microsprayer appears to reduce the variations in TiO2 content (ng mesh-1 ) among rats (e.g., coefficients of variation, n = 3, microsprayer vs gavage needle: 13% vs 30%, for the entire lungs); (ii) TiO2 appears to be deposited less in the right middle lobes than in the rest of the lung lobes, irrespective of the chosen intratracheal delivery device; and (iii) similar TiO2 contents (ng mesh-1 ) and frequencies are deposited in the lung lobes of rats administered TiO2 NPs via gavage needle or microsprayer. This suggests that the physical state of the administered NP suspension does not markedly alter TiO2 pulmonary microdistribution. The results of this investigation are important for the standardization of intratracheal administration methods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Adjuvant intravesical instillation for primary T1G3 bladder cancer: BCG versus MMC in Korea. (United States)

    Cho, In-Chang; Kim, Eun Kyoung; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Park, Weon Seo; Lee, Kang Hyun


    To compare the efficacy of bacillus Calmette-Guerin (BCG) and mitomycin-C (MMC) intravesical instillation for primary T1G3 bladder cancer (BC). This retrospective study included 107 patients with newly diagnosed primary T1G3 BC who were treated by transurethral resection (TUR) plus intravesical instillation. The BCG group was administered BCG-RIVM (2×10(8) colony forming unit) instilled once weekly for 6 weeks, or the same regimen as induction therapy followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy. The MMC group was administered MMC (30 mg) in six weekly instillations, or the same regimen with subsequent monthly instillations for one year. We evaluated differences between these agents in disease recurrence-free survival and disease progression rate at the time of recurrence. The mean observation period was 24.3±28.6 months. The BCG and MMC groups comprised 53 patients (49.5%) and 54 patients (50.5%), respectively. During the observation period, recurrences developed in 61 patients (57.0%). The median time to recurrence for the BCG and MMC arm were 24.0 and 26.0 months, respectively. There were no significant differences for recurrence-free survival between the two groups (log-rank p=0.616). At the time of recurrence, 9.4% (5 out of 53) of patients in the BCG arm and 7.4% (4 out of 54) patients in the MMC arm also experienced by disease progression (p=1.000). There were no statistically significant differences regarding recurrence and disease progression rate at the time of recurrence between the two adjuvant treatments in primary T1G3 BC. Thus, large prospective studies in Asian population are required.

  15. Intraluminal instillation of urokinase and autologous plasma: a method to unblock occluded central venous ports

    Directory of Open Access Journals (Sweden)

    Henze Guenter


    Full Text Available Abstract Background Therapeutic use and effective function of recombinant urokinase (r-UK for occluded ports need the presence of plasminogen. Methods As a therapeutic proof of principle, we demonstrate that the use of r-UK and autologous plasma effectively reestablishes the function of occluded central venous ports (CVP resistant to routine management of catheter occlusion. Five patients with occluded ports resistant to the routine management were treated. Results All patients were successfully treated with thrombolytic therapy using intraluminal instillation of r-UK and autologous plasma. Conclusion Instillation of r-UK and autologous plasma is a safe and effective method for management of CVP occlusion.

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

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


    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.

  17. Does prior instillation of a topical anaesthetic alter the pupillary mydriasis produced by tropicamide (0.5%)? (United States)

    Haddad, David E; Rosenfield, Mark; Portello, Joan K; Krumholz, David M


    It is common clinical practice to instill a topical anaesthetic prior to the instillation of a mydriatic agent into the eye. The main rationale for using the anaesthetic is to increase corneal permeability, so that more of the mydriatic agent reaches the receptor sites within the anterior chamber. It addition, as mydriatics generally cause stinging, prior use of an anaesthetic should reduce the degree of discomfort. The aim of the present study was to determine whether the efficacy of mydriasis produced by an antimuscarinic agent is enhanced by prior instillation of a topical anaesthetic. The study was performed using a double-masked protocol on 20 healthy young subjects. One drop of either proparacaine (proxymetacaine) (0.5%) or isotonic saline was instilled into the eye, followed by one drop of tropicamide (0.5%). Pupil diameter was measured using a customized photographic device at 0, 10, 20, 30 and 60 min following drug instillation. Additionally, subjects were asked to rate the degree of discomfort following the instillation of each drop on a scale from 0 (no discomfort) to 10 (agony). There was no significant difference in either the rate of onset of mydriasis, or the maximum pupil diameter achieved between the two conditions. The mean change in pupil diameter produced by tropicamide after the instillation of saline or proparacaine was 2.31 and 2.28 mm, respectively. The mean discomfort scores following instillation of saline and proparacaine were 1.15 and 1.65, respectively, while mean discomfort scores following the instillation of tropicamide after saline or proparacaine were 4.00 and 0.85, respectively. Instillation of a topical anaesthetic does significantly reduce the degree of discomfort produced by the instillation of tropicamide. However, it does not produce any significant increase in either the magnitude or rate of onset of mydriasis.

  18. 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


    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

  19. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Shi Z


    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

  1. Liberal-Democratic States Should Privilege Parental Efforts to Instil Identities and Values (United States)

    Robinson, Andrew M.


    Liberal-democratic states' commitments to equality and personal autonomy have always proven problematic with respect to state regulation of relations between parents and children. In the parental authority literature, positions have varied from invoking children's interests to argue for limitations on parental efforts to instil identities and…

  2. 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


    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...... instillation of the bladder....

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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. [Our experience with 1 mg BCG vaccine instillation in T1 stage cancer of the bladder]. (United States)

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


    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.

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

    NARCIS (Netherlands)

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

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

  6. 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


    We have studied the effect of ropivacaine for combined port site and mesosalpinx infiltration, and peritoneal instillation on pain, nausea and vomiting after laparoscopic sterilization, in a double-blind, placebo-controlled study in 80 patients. The total dose of ropivacaine was 285 mg. All...

  7. 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

  8. Intracellular changes in rat hepatocytes after intratracheal administration of highly dispersed silicon dioxide and uridine effects on these changes. (United States)

    Lebkova, N P; Baranov, V I


    Rat hepatocytes were examined under electron microscope at early terms after intratracheal administration of highly dispersed silicon dioxide powder against the background of uridine treatment. Penetration of powder particles into hepatocyte cytoplasm, nuclei, mitochondria, and peroxisomes and development of bacteria in these cells were observed. Uridine reduced the destructive effect of powder on the organelles, increased glycogen content in hepatocytes, and inhibited the formation of capsulated bacterial forms in these cells.

  9. Co-instillation of nano-solid magnesium hydroxide enhances corneal permeability of dissolved timolol. (United States)

    Nagai, Noriaki; Ogata, Fumihiko; Otake, Hiroko; Kawasaki, Naohito; Nakazawa, Yosuke; Kanai, Kazutaka; Okamoto, Norio; Shimomura, Yoshikazu


    We prepared magnesium hydroxide (MH) nanoparticles by a bead mill method, and investigated whether the co-instillation of MH nanoparticles improves the low transcorneal penetration of water-soluble drugs, such as the anti-glaucoma eye drug timolol maleate (TM). MH particle size was decreased by the bead mill treatment to a mean particle size of 71 nm. In addition, the MH nanoparticles were highly stable. Next, we demonstrated the effect of MH nanoparticles on the corneal surface. MH shows only slight solubility in lacrimal fluid, and the instillation of MH nanoparticles for 14 days did not affect the behavior (balance of secretion and excretion) of the lacrimal fluid in rabbit corneas. Moreover, there was no observable corneal toxicity of MH nanoparticles, and treatment with MH nanoparticles enhanced the intercellular space ratio in the eyes of rats. MH alone did not permeate into the cornea; however, the co-instillation of MH nanoparticles and dissolved TM (nMTFC) enhanced the corneal penetration of TM. In addition, the intraocular pressure (IOP)-reducing effect of nMTFC was significantly higher than those of the TM solution or the co-instillation of MH microparticles and TM. In conclusion, we found that MH nanoparticles enhance the corneal penetration of dissolved TM with no observable corneal stimulation or obstruction of the nasolacrimal duct by the MH nanoparticles. It is possible that the co-instillation of MH nanoparticles may provide a useful way to improve the bioavailability of water-soluble drugs in the ophthalmic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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


    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.

  11. 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: [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)


    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.

  12. In vivo pharmacokinetic/pharmacodynamic profiles of valnemulin in an experimental intratracheal Mycoplasma gallisepticum infection model. (United States)

    Xiao, Xia; Sun, Jian; Yang, Tao; Fang, Xi; Wu, Dong; Xiong, Yan Q; Cheng, Jie; Chen, Yi; Shi, Wei; Liu, Ya-Hong


    Valnemulin, a semisynthetic pleuromutilin antibiotic derivative, is greatly active against Mycoplasma. The objective of our study was to evaluate the effectiveness of valnemulin against Mycoplasma gallisepticum in a neutropenic intratracheal model in chickens using a pharmacokinetic/pharmacodynamic (PK-PD) method. The PK of valnemulin after intramuscular (i.m.) administration at doses of 1, 10, and 20 mg/kg of body weight in M. gallisepticum-infected neutropenic chickens was evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Real-time PCR (RT-PCR) was used for quantitative detection of M. gallisepticum. The ratio of the 24-h area under the concentration-time curve divided by the MIC (AUC24/MIC) correlated well with the in vivo antibacterial effectiveness of valnemulin (R(2) = 0.9669). The AUC24/MIC ratios for mycoplasmastasis (a reduction of 0 log10 color-changing unit [CCU] equivalents/ml), a reduction of 1 log10 CCU equivalents/ml, and a reduction of 2.5 log10 CCU equivalents/ml are 28,820, 38,030, and 56,256, respectively. In addition, we demonstrated that valnemulin at a dose of 6.5 mg/kg resulted in a reduction of 2.5 log10 CCU equivalents/ml. These investigations provide a solid foundation for the usage of valnemulin in poultry with M. gallisepticum infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


    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.

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


    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.

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

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


    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. Treating Fasciotomy Wounds with Negative Pressure Wound Therapy with Instillation and Dwell Time (NPWTi-d)


    Lee, Priscilla


    Acute compartment syndrome (ACS) is a serious complication of lower-extremity trauma caused by accidents or post-procedure complications. ACS is characterized by increased pressure within the compartment, resulting in reduced blood flow, tissue hypoxia, and tissue necrosis. Fasciotomies to relieve pressure and debridement of necrotic tissue comprise primary treatment. My purpose is to present initial experience using negative pressure wound therapy with instillation and dwell time (NPWTi-d)* ...

  18. Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation. (United States)

    Peters, Kenneth M; Hasenau, Deborah; Killinger, Kim A; Chancellor, Michael B; Anthony, Michele; Kaufman, Jonathan


    Intravesical instillation of liposomes is a potentially new therapeutic option for subjects with interstitial cystitis/bladder pain syndrome (IC/BPS). The aim of this study was to explore the safety and clinical outcomes of 4 weekly instillations of sphingomyelin liposomes in an open-label cohort of subjects with IC/BPS. Fourteen symptomatic IC/BPS subjects were treated with intravesical liposomes once a week for 4 weeks. Safety measurements included laboratory specimen collection, vital signs, post-void residual, and assessment of adverse events (AEs). Efficacy measurements included pain visual analog scales (VAS), voiding diaries, global response assessments (GRAs), and O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI and ICPI). No treatment-related AEs were reported at any time over the course of the study. Urgency VAS scores significantly decreased at 4 weeks (p = 0.0029) and 8 weeks (p = 0.0112) post-treatment. Pain VAS scores significantly decreased at 4 weeks post-treatment (p = 0.0073). Combined ICSI and ICPI scores improved significantly at 4 and 8 weeks (p = 0.002 for both time points) post-treatment. Responses to GRA showed improvement at 4 weeks post-instillation. No significant decrease in urinary frequency was found. Sphingomyelin liposome instillations were well tolerated in subjects with IC/BPS with no AEs attributed to the test article. Treatment was associated with improvements in pain, urinary urgency, and overall symptom scores. Placebo-controlled clinical trials are needed to assess this potential therapy for IC/BPS.

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

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    Kawagoe, Koh; Kawana, Takashi (Tokyo Univ. (Japan). Faculty of Medicine)


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

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

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    Sahu S


    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.

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

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    Renzo Colombo


    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.

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

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    F. Ravenna


    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.

  3. Efficacy of oropharyngeal lidocaine instillation on hemodynamic responses to orotracheal intubation. (United States)

    Sun, Hsiao-Lun; Wu, Tzong-Jeng; Ng, Chen-Chuan; Chien, Chih-Cheng; Huang, Chi-Cheng; Chie, Wei-Chu


    To determine whether oropharyngeal instillation of lidocaine after anesthetic induction modifies the hemodynamic response to intubation. Prospective, randomized, double-blind, placebo-controlled study. Operating room of a university hospital. 56 ASA physical status I and II adult patients scheduled for elective surgery requiring orotracheal intubation and general anesthesia. Patients were randomized to receive oropharyngeal instillation with either 5 mL 2% lidocaine (n = 28, lidocaine group) or 5 mL normal saline (n = 28, control group) 45 seconds after anesthetic induction bolus. Orotracheal intubation was attempted three minutes later. Systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded at baseline, just before intubation, and for three minutes postintubation at one-minute intervals. Occurrence of adverse events such as arrhythmias, ischemic changes in electrocardiography, and bronchospasm after intubation were also documented. All postintubation values of SBP, DBP, MAP, and HR were significantly lower in the lidocaine group than the control group (P < 0.01). In both groups, postintubation HRs were significantly higher than baseline values (P < 0.05). More patients (P < 0.001) became hypertensive postintubation in the control group (14/28, 50%) than the lidocaine group (2/28, 7%). Oropharyngeal instillation of lidocaine for three minutes before intubation attenuates the cardiovascular responses to intubation.

  4. Immunological and Physiological Differences Between Layer- and Broiler Chickens after Concurrent Intratracheal Administration of Lipopolysaccharide and Human Serum Albumin


    Parmentier, H. K.; Vries Reilingh, de, G.; Freke, P.; Koopmanschap, R.E.; Lammers, A.


    Layers and broilers were concurrently intratracheally challenged with 0.5 mg Lipopolysaccharide (LPS) and 0.1 mg Human Serum Albumin (HuSA) at 3 weeks of age. Specific total and isotype-specific (IgM, IgG, IgA) Antibody (Ab) responses to HuSA during 3 weeks following immunization, cellular in vitro mitogen responses to Concanavalin A (Con A) and specific cellular responses in vitro to different dosages of HuSA, blood serotonin (5-HT) levels, plasma Corticosterone (CORT) levels at 6 weeks of a...

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

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    Papiris Spyridon


    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

  6. Static and dynamic mechanics of the murine lung after intratracheal bleomycin (United States)


    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

  7. Kinetics and dissolution of intratracheally administered nickel oxide nanomaterials in rats. (United States)

    Shinohara, Naohide; Zhang, Guihua; Oshima, Yutaka; Kobayashi, Toshio; Imatanaka, Nobuya; Nakai, Makoto; Sasaki, Takeshi; Kawaguchi, Kenji; Gamo, Masashi


    The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body. Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was determined using artificial lysosomal fluid, artificial interstitial fluid, hydrogen peroxide solution, pure water, and saline. In addition, macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants. The wire-like NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4 × 10-3 and 4.9 × 10-3/h). The largest irregular-shaped NiO nanoparticles hardly dissolved in any solution, including artificial lysosomal fluid (7.8 × 10-5/h). Pulmonary clearance rate constants, estimated using a one-compartment model, were much higher for the NiO nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped NiO nanoparticles, but not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO nanoparticles were excreted in the first 24

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

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    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)


    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

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

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    Jack V Greiner


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

  10. Treating Fasciotomy Wounds with Negative Pressure Wound Therapy with Instillation and Dwell Time (NPWTi-d). (United States)

    Lee, Priscilla


    Acute compartment syndrome (ACS) is a serious complication of lower-extremity trauma caused by accidents or post-procedure complications. ACS is characterized by increased pressure within the compartment, resulting in reduced blood flow, tissue hypoxia, and tissue necrosis. Fasciotomies to relieve pressure and debridement of necrotic tissue comprise primary treatment. My purpose is to present initial experience using negative pressure wound therapy with instillation and dwell time (NPWTi-d)* to treat fasciotomy wounds in two patients. NPWTi-d provides automated, volumetric control of instilled topical wound solutions with a dwell time in combination with negative pressure wound therapy (NPWT). Patient 1, a 33-year-old male injured in a motorcycle accident, developed ACS within 24 hours of hospitalization. Prior treatments included wet-to-dry dressings and NPWT†. In the latter course of treatment, NPWTi-d was applied; 40 ml of normal saline (NS) were instilled with a ten-minute dwell time, followed by four hours of NPWT at ‑125 mmHg. After five days of NPWTi‑d, granulation tissue covered the bone. Four days later, the patient was discharged home. The wound continued to improve and, at the last recorded visit, was completely closed. Patient 2, a 44-year-old male, developed right lower extremity ACS due to complications post cardiac surgery. NPWT was initiated in the hospital and continued post-discharge to a nursing home. The patient was readmitted to the hospital with a right leg wound infection that was surgically debrided. NPWTi-d was then applied; 60 ml of NS were instilled with a ten-minute dwell time, followed by 3.5 hours of NPWT at -125 mmHg. After ten days of NPWTi-d, granulation tissue covered the bone. In Patient 2, NPWTi-d improved the likelihood of healing in a malnourished patient who had been critically ill by promoting granulation tissue over exposed bone. The use of NPWTi-d with NS contributed to positive outcomes for both patients. *V

  11. [Biological effect of fullerene (C60) to lung by inhalation or instillation]. (United States)

    Ogami, Akira; Morimoto, Yasuo; Myojo, Toshihiko; Oyabu, Takako


    Fullerene (C60) is a newly generated nanoparticle that has a soccer-ball structure with 60 carbon atoms. Fullerenes are expected to have a multitude of uses, for example as energy device materials or information technology materials. The biological effects of nanoparticles are now being discussed, and there are ongoing animal studies using various nanoparticles. Here we review some reports about the toxicity of C60, and in addition we present the results of our 2-year follow up studies of instillation and inhalation of C60 via the trachea.

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

    DEFF Research Database (Denmark)

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


    BACKGROUND: The laparoscopic technique has many advantages compared with open surgery for symptomatic cholecystolithiasis. Despite these advantages, many patients complain about shoulder pain (SP) after laparoscopic cholecystectomy. The purpose of this review was to evaluate intraperitoneal...... instillation (IPI) of saline and local anesthesia (LA) to minimize SP. METHODS: A search of the literature was conducted using PubMed and Excerpta Medica Database (EMBASE). Eligibility criteria were: randomized clinical trials (RCT) evaluating IPI of saline and/or LA to minimize incidence or severity of SP...

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


    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.

  14. Feasibility of drug delivery to the eye's posterior segment by topical instillation of PLGA nanoparticles

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    Kohei Tahara


    Full Text Available We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs. Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan (CS and glycol chitosan (GCS, which are mucoadhesive polymers, and polysorbate 80 (P80 were used as surface modifiers, and have been reported to increase the association of NPs with cells. Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal, non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.

  15. Effect of gel-instillation sonography on Doppler ultrasound findings in endometrial polyps. (United States)

    Van Den Bosch, T; Van Schoubroeck, D; Luts, J; Bignardi, T; Condous, G; Epstein, E; Leone, F P; Testa, A C; Valentin, L; Van Huffel, S; Bourne, T; Timmerman, D


    Saline infusion sonohysterography has been reported to suppress the color signal within the endometrium at color or power Doppler evaluation. The aim of this study was to evaluate if gel-instillation sonography (GIS) affects the power Doppler signal in patients with endometrial polyps. Ultrasound volumes of the uterus, obtained by three-dimensional ultrasound imaging of 25 women with histologically confirmed endometrial polyps, were assessed offline by six gynecologists with a special interest in gynecological ultrasound. Each woman contributed four volumes: one gray-scale volume and one power Doppler volume before GIS, and one gray-scale volume and one power Doppler volume at GIS. Power Doppler features before and after gel infusion were compared. At unenhanced ultrasound a pedicle artery was seen in 27-46% of cases, whereas, after gel infusion the examiners reported a pedicle artery in 30-46% of cases (Exact McNemar's test P-values ranged from 0.50 to 1.00). The level of agreement between unenhanced ultrasound and GIS ranged from 59 to 91% (Cohen's kappa values ranged from 0.17 to 0.79). There was no tendency for a pedicle artery to be identified less often at GIS than before gel instillation. Gel infusion does not affect the power Doppler signal in patients with endometrial polyps. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

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

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    Lazarević M.


    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.

  17. Categorical evaluation of the ocular irritancy of cosmetic and consumer products by human ocular instillation procedures. (United States)

    Gao, Yang; Kanengiser, Bruce E


    The assessment of ocular irritation potential is an important part of safety testing for cosmetic and consumer products. The purpose of this investigation was to examine ocular irritancy levels elicited in humans by various categories of a specific class of cosmetic and consumer products that have a potential to enter the eye inadvertently during use. Test materials assessed belonged to one of seven categories, which included liquid makeup, shampoo, baby wash, mascara, eye makeup remover, powder eye shadow, and facial cleanser. These test materials were evaluated by human ocular instillation, followed by examinations, for which subjective perceptions of irritation were recorded, and component areas of ocular tissues were individually examined for inflammation and for the area and density of fluorescein staining patterns at 30 seconds and at 5, 15, 60, and 120 minutes post-instillation. Subjective and objective ocular irritation scores of 410 eyes were analyzed by product classification. Average score levels were determined for subjective responses, inflammation, and fluorescein staining patterns. This investigation determined that irritation levels of the evaluated test materials varied markedly with respect to product category, type of ocular irritation, and ocular tissue, demonstrating that these factors are important considerations for the prediction of the ocular irritancy of a test material.

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


    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.

  19. 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)


    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.

  20. Transient anuria requiring nephrostomy after intravesical bacillus Calmette-Guérin instillations for superficial bladder cancer. (United States)

    Kaneko, Tomoyuki; Fujita, Kiichiro; Homma, Yukio


    A 76-year-old man received intravesical bacillus Calmette-Guérin (BCG) instillations for recurrent superficial bladder cancer. He had undergone right nephroureterectomy for right renal pelvic cancer 9 months previously. He presented with anuria and left hydronephrosis after the fourth instillation, with serum creatinine increasing up to 15.7 mg/dL. Percutaneous nephrostomy was indwelled, and antegrade pyelography showed left vesicoureteral obstruction. There was no sign of recurrent bladder cancer or ureteral cancer. He started spontaneous voiding on day 4 and the nephrostomy was removed on day 8. Most of the side-effects of intravesical BCG therapy are minor, and major adverse reactions are rare. Life-threatening ureteral obstruction would be a rare complication of BCG immunotherapy. Although BCG intravesical instillation after nephroureterectomy is a common practice, special care should be taken of renal function in patients with unilateral kidney during BCG therapy.

  1. [Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor]. (United States)

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


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

  2. Evaluation of the efficacy and safety of a new device for eye drops instillation in patients with glaucoma. (United States)

    Junqueira, Daniela M; Lopes, Flavio S; de Souza, Fabiola C; Dorairaj, Syril; Prata, Tiago S


    This study evaluated the efficacy and safety of a new device (Eyedrop(®)) designed for eye drop instillation in patients with and without glaucoma. This prospective study included consecutive patients with glaucoma and healthy participants. After a complete eye examination and determination of baseline intraocular pressure (IOP), topical hypotensive medication was introduced in both eyes, and the Eyedrop(®) delivery device (a plastic device in which the bottle with eye drops is inserted) was made available to all participants (with video and written instructions) for use in one eye, randomly chosen. In the second phase, all patients were evaluated by an experienced examiner for IOP determination, investigation of possible associated side effects, and ease of instilling eye drops (by a visual analog scale [VAS]; 0-10). Thirty two participants (mean age 42.3±16.2 years) were evaluated. Of these, 44% had glaucoma. There was no significant difference in mean IOP variation when comparing the eye using (-3.9±2.9 mmHg) or not using the device (-3.3±2.6 mmHg; P=0.36). The subjective rating of the facility of drops instillation was significantly higher with the Eyedrop(®) applicator (VAS =7.6±1.6) than without it (VAS =6.2±1.8; P5) among participants without prior experience with eye drop instillation (78.6% [11/14]) versus those already experienced (66.7% [12/18]). No difference in the frequency of side effects or in the distribution pattern of fluorescein between eyes was observed (P≥0.63). Eyedrop(®) received a better subjective response regarding the ease of instillation of hypotensive eye drops compared to traditional instillation, especially in patients with no previous experience with eye drops. Using the device did not result in any loss of hypotensive effect or increase in the frequency of side effects.

  3. 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

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

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    Ivana Cardoso Pereira


    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

  5. The evolution of negative pressure wound therapy: negative pressure wound therapy with instillation. (United States)

    Wolvos, Tom


    Complex wounds pose a considerable burden to patients and the health-care system. The development of negative pressure wound therapy (NPWT) has revolutionised the treatment of these wounds. NPWT helps create a favourable wound healing environment by removing infectious material, decreasing oedema and promoting perfusion and granulation tissue formation. Additionally, NPWT has been reported to help reduce time to wound closure and length of hospital stay. Modifications of this foundation of wound care have added intermittent instillation with a dwell time to NPWT (NPWTi-d). This new system offers more comprehensive wound care through automated wound irrigation, allowing more control over the wound environment and the opportunity to deliver topical wound solutions directly to the affected tissues. A comparison between the two therapies, NPWT and NPWTi-d, is described, and two real-world applications of NPWTi-d are presented.

  6. 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


    BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro......, 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...... 4975) after open mesh groin hernia repair in 41 adult male patients. The primary end-point was average daily visual analog scale (VAS) pain scores during the first week after surgery assessed as area under the curve (AUC). Pain was recorded twice daily in a pain diary for 4 wk. Physical examination...

  7. The use of electrochemically activated saline as a uterine instillation in pony mares : article

    Directory of Open Access Journals (Sweden)

    C.H. Annandale


    Full Text Available Twelve pony mares were randomly assigned to either a control or a treatment group and inseminated with fresh, raw semen from a single stallion of known fertility in a cross-over trial design. Pregnancy was diagnosed by transrectal ultrasound 12-14 days post-ovulation and then terminated by administration of a luteolytic dose of cloprostenol. Treatment mares received a uterine instillation of 100 m of electrochemically activated (ECA saline 4-12 hours post-insemination. Control mares received no treatment post-insemination. Per cycle pregnancy rate was 58.3 % in the control group and 50 % in the treatment group. There was no statistical difference (P = 1.000 in pregnancy rate between the 2 groups. The principles of ECA and applications of ECA saline are discussed.

  8. Bronchoscopic management of bronchopleural fistula with intrabronchial instillation of glue (N-butyl cyanoacrylate

    Directory of Open Access Journals (Sweden)

    Rakesh K Chawla


    Full Text Available Context: Bronchopleural fistula (BPF is a communication between the pleural space and bronchial tree. Materials and Methods: A series of 9 cases are reported where BPF was identified and managed with intrabronchial instillation of glue (N-butyl-cyanoacrylate through a video bronchoscope. Results: Out of 9 patients the BPF was successfully sealed in 8 cases (88.88%. In 1 patient of postpneumonectomy, the fistula was big, that is >8 mm who had a recurrence after the procedure. In one case of pyopneumothorax the leak reduced slowly and it took us 14 days to remove the intercostal drainage tube. Rest of the patients had a favorable outcome. No complications were observed in a follow-up of 6 months. Conclusions: In our opinion, it is a cost-effective, viable, and safe alternative compared with costly, time-consuming, and high-risk surgical procedures.

  9. Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain.

    Directory of Open Access Journals (Sweden)

    Joanna Seiffert

    Full Text Available Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP and citrate-capped; 0.1 mg/Kg in Brown-Norway (BN and Sprague-Dawley (SD rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.

  10. Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain. (United States)

    Seiffert, Joanna; Hussain, Farhana; Wiegman, Coen; Li, Feng; Bey, Leo; Baker, Warren; Porter, Alexandra; Ryan, Mary P; Chang, Yan; Gow, Andrew; Zhang, Junfeng; Zhu, Jie; Tetley, Terry D; Chung, Kian Fan


    Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.

  11. 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

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    Ömer Gülpinar


    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.

  12. Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder. (United States)

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


    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.

  13. 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)


    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

  14. 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.


    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...

  15. Mini-open vacuum-assisted closure therapy with instillation for debilitated and septic patients with pleural empyema. (United States)

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


    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

  16. Inflation lung mechanics deteriorates markedly after saline instillation and open endotracheal suctioning in mechanically ventilated healthy piglets. (United States)

    Cunha-Goncalves, Doris; Perez-de-Sá, Valéria; Ingimarsson, Jónas; Werner, Olof; Larsson, Anders


    Non-bronchoscopic bronchoalveolar lavage is an alternative to diagnostic bronchoscopy in pediatric patients, as fiberoptic bronchoscopes with aspiration channels are too large for small infants. There are many variations of the method in clinical practice, and saline instillation followed by open endotracheal suctioning is still commonly used. Lung function can deteriorate with these procedures, and we have investigated the effects on lung mechanics and oxygenation in healthy piglets. The lungs of anesthetized and mechanically ventilated piglets were recruited with CPAP 35 cmH2O. Thereafter we instilled 5 ml of saline into the endotracheal tube, followed by three breaths from the ventilator. Saline was retrieved through a suction catheter wedged far distally in the airway. The procedure was followed by a new recruitment maneuver. Complete inspiratory/expiratory pressure - volume loops (PV-loops) were obtained just before and 5 min after saline instillation. Arterial blood gases were collected at equivalent times in 14 similar piglets submitted to exactly the same procedure. The inspiratory limb of the PV-loops changed markedly, as the lower inflection point was displaced towards higher pressures (P=0.004), and hysteresis measured at 15 and 30 cmH2O increased (P=0.004 and P=0.012, respectively). Although PaO2 decreased significantly (P=0.001), values after saline instillation/suctioning were still in the high normal range, that is, 22.2 +/- 2.6 kPa. Opening pressures of the lungs increase markedly after saline instillation/suctioning in healthy piglets. In this situation, adequate recruitment maneuvers and PEEP might prevent lung collapse and deteriorations in arterial oxygenation. (c) 2006 Wiley-Liss, Inc.

  17. Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits. (United States)

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


    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.

  18. Intratracheal Gene Delivery of SERCA2a Ameliorates Chronic Post-Capillary Pulmonary Hypertension: A Large Animal Model. (United States)

    Aguero, Jaume; Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos G; Fish, Kenneth M; Kohlbrenner, Erik; Hammoudi, Nadjib; Kho, Changwon; Lee, Ahyoung; Ibáñez, Borja; García-Alvarez, Ana; Zsebo, Krisztina; Maron, Bradley A; Plataki, Maria; Fuster, Valentin; Leopold, Jane A; Hajjar, Roger J


    Pulmonary hypertension (PH) is characterized by pulmonary arterial remodeling that results in increased pulmonary vascular resistance, right ventricular (RV) failure, and premature death. Down-regulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) in the pulmonary vasculature leads to perturbations in calcium ion (Ca(2+)) homeostasis and transition of pulmonary artery smooth muscle cells to a proliferative phenotype. We assessed the feasibility of sustained pulmonary vascular SERCA2a gene expression using aerosolized delivery of adeno-associated virus type 1 (AAV1) in a large animal model of chronic PH and evaluated the efficacy of gene transfer regarding progression of pulmonary vascular and RV remodeling. A model of chronic post-capillary PH was created in Yorkshire swine by partial pulmonary vein banding. Development of chronic PH was confirmed hemodynamically, and animals were randomized to intratracheal administration of aerosolized AAV1 carrying the human SERCA2a gene (n = 10, AAV1.SERCA2a group) or saline (n = 10). Therapeutic efficacy was evaluated 2 months after gene delivery. Transduction efficacy after intratracheal delivery of AAV1 was confirmed by β-galactosidase detection in the distal pulmonary vasculature. Treatment with aerosolized AAV1.SERCA2a prevented disease progression as evaluated by mean pulmonary artery pressure, vascular resistance, and limited vascular remodeling quantified by histology. Therapeutic efficacy was supported further by the preservation of RV ejection fraction (p = 0.014) and improvement of the RV end-diastolic pressure-volume relationship in PH pigs treated with aerosolized AAV1.SERCA2a. Airway-based delivery of AAV vectors to the pulmonary arteries was feasible, efficient, and safe in a clinically relevant chronic PH model. Vascular SERCA2a overexpression resulted in beneficial effects on pulmonary arterial remodeling, with attendant improvements in pulmonary hemodynamics and RV performance, and might offer

  19. Effects of intratracheal exposure of 2-chloroethyl ethyl sulfide (CEES) on the activation of CCAAT-enhancer-binding protein (C/EBP) and its protection by antioxidant liposome. (United States)

    Roy, Somdutta Sinha; Mukherjee, Shyamali; Das, Salil K


    Exposure of 2-chloroethyl ethyl sulfide (CEES) to guinea pigs causes lung injury by infiltration of neutrophils in interstitial lung spaces. A unique MAPK-regulated transcription factor, C/EBP (CCAAT-enhancer-binding protein), regulates the expression of intracellular adhesion molecule-1 (ICAM-1), involved in recruiting neutrophils in lung. The present study was to determine if CEES exposure causes activation of C/EBP, in particular the predominant β-isoform and if so whether it can be prevented by intratracheal delivery of an antioxidant liposome containing N-acetyl cysteine and tocopherols. Lung injury was developed in guinea pigs by intratracheal exposure of CEES (0.5 mg/kg). The antioxidant liposome was given intratracheally 5 min after CEES exposure, and the animals were sacrificed after 30 days. CEES exposure caused a 2.3-fold increase in the activation of C/EBP accompanied with a 45% and 121% increase in the protein level of C/EBP β and ICAM-1, respectively, and this effect was counteracted by the antioxidant liposome. © 2016 Wiley Periodicals, Inc.

  20. To compare the incubation period following intratracheal and subcutaneous inoculation of bovine leukosis virus infected lymphocytes and to study their clearance from the circulation. (United States)

    Roberts, D H; Lucas, M H; Wibberley, G


    The migration of fluorescein isothiocyanate labelled lymphocytes through the tracheobronchial mucosa has been studied in cattle. Following intratracheal inoculation of labelled non-infected autologous lymphocytes and bovine leukosis virus (BLV) infected heterologous (presumed allogeneic) lymphocytes, the labelled lymphocytes appeared in the blood circulation between 4 and 7 days post inoculation. Following intravenous inoculation of labelled autologous lymphocytes, the cells could be detected in the circulation for 10 days post inoculation whereas BLV infected and non-infected heterologous lymphocytes could be detected for only 2 days. The migration of BLV-infected heterologous lymphocytes through the tracheobronchial mucosa caused a delay in the appearance of labelled lymphocytes in the circulation and a corresponding delay in the appearance of BLV antibodies. Comparison was made of the effect of two different routes of inoculation, subcutaneous and intratracheal on the incubation period as indicated by the detection of antibody. Subcutaneous inoculation of 1 X 10(4), 5 X 10(3), 1 X 10(3) of lymphocytes from a BLV infected cow caused seroconversion whereas 5 X 10(2) cells did not. Intratracheal inoculation of 5 X 10(3) cells caused sero-conversion. One animal did not develop BLV antibody until 30 weeks after inoculation although BLV could be isolated from the blood at 24 and 26 weeks post inoculation.

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


    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

  2. Intravaginal instillation of gonadotropin-releasing hormone analogues with an absorption enhancer induced a surge of luteinizing hormone in lactating dairy cows. (United States)

    Wijma, R; Stangaferro, M L; Masello, M; Elmetwally, M A; Granados, G E; Amovilli, F; Giordano, J O


    Our objectives were to evaluate circulating LH concentrations after intravaginal (IVG) instillation of GnRH analogs in lactating dairy cows. In 2 experiments, lactating Holstein cows (experiment 1: n = 32; experiment 2: n = 47) received the experimental treatments 48 h after the first of 2 PGF2α treatments given 12 h apart and 7 d after a modified Ovsynch protocol (GnRH at -7 d, PGF2α at -24 h, PGF2α at -56 h, GnRH at 0 h). In experiment 1, cows were stratified by parity and randomly allocated to receive the following treatments: 2 mL of saline IVG (SAL, n = 6), 100 µg of gonadorelin (Gon) i.m. (G100-IM, n = 5), and 100 (G100, n = 7), 500 (G500, n = 8), or 1,000 µg of Gon IVG (G1000, n = 7). In experiment 2, treatments were SAL (n = 8), G100-IM (n = 8), G1000 (n = 7), 1,000 µg of Gon plus 10% citric acid (CA) IVG (G1000CA, n = 8), 80 µg of buserelin IVG (B80, n = 8), and 80 µg of buserelin plus 10% CA IVG (B80CA, n = 8). In both experiments, blood was collected every 15 min from -15 min to 4 h, and every 30 min from 4 to 6 h after treatment. Data for area under the curve (AUC), mean LH concentrations, and time to maximum LH concentration were analyzed by ANOVA with (mean LH only) or without repeated measures using PROC MIXED of SAS (version 9.4, SAS Institute Inc., Cary, NC). The proportion of cows with a surge of LH was evaluated with Fisher's exact test using PROC FREQ of SAS. In both experiments, LH concentrations were affected by treatment, time, and the treatment by time interaction. In experiment 1, the AUC for LH and maximum LH concentration were greatest for the G100-IM treatment and were greater for the G1000 than for the SAL and G500 treatments. The proportion of cows with an observed surge of LH was 100 and 0% for cows that received Gon i.m. and IVG, respectively. In experiment 2, the AUC and maximum LH concentrations were greater for the G100-IM, G1000CA, and B80CA treatments than for the other IVG treatments. The proportion of cows with a surge

  3. Gel instillation sonohysterography (GIS) and saline contrast sonohysterography (SCSH): comparison of two diagnostic techniques. (United States)

    Bij de Vaate, A J M; Brölmann, H A M; van der Slikke, J W; Emanuel, M H; Huirne, J A F


    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.

  4. Instilling a soul in your organization without losing yours to it. (United States)

    Stegall, M Scott


    Health-care professionals are accustomed to struggling with ethical considerations brought about by advances in the medical sciences. How aware are these professionals of the ethical dilemmas created by advances in the management sciences? Deeply embedded in organizational and departmental changes are theories, paradigms, and philosophies that often are understood poorly even by their promoters. Although these system changes can occur at glacial speed, they also can be glacial in their effects on an organization's culture. Are individuals aware that the latest implemented management fad is changing their behaviors? By becoming mindful of the potential ramifications of change, individuals increase their ability to behave in a civil manner--that is, ethically choosing to embrace or resist the change. By acting within their own sphere of influence, civil individuals at all levels of the organization collectively instill a soul in their organization rather than losing their own souls to it. This article is adapted from a commencement speech presented to graduates of an executive health-care administration program. Most of these graduates were a mixture of hospital department heads, middle managers, and a few medical and hospital executives. Each year, I distribute my current version of this teaching note or mini-lecture to students completing my leadership class in hope that it will help them put in perspective the appropriate use of the management sciences they intensely study.

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

    Directory of Open Access Journals (Sweden)

    Patricia Snell Herzog


    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.

  6. Videotaped evaluation of eyedrop instillation in glaucoma patients with visual impairment or moderate to severe visual field loss. (United States)

    Hennessy, Amy L; Katz, Joanne; Covert, David; Protzko, Colleen; Robin, Alan L


    Objectively evaluate the ability of visually disabled glaucoma patients to successfully administer a single drop onto their eye. Prospective, observational study. Experienced glaucoma patients with Early Treatment of Diabetic Retinopathy Study visual acuity (VA) of ≤ 6/18 (≤ 20/60) ≥ 1 eye, or moderate or severe visual field damage in ≥ 1 eye. Subjects were "low vision" (20/60 ≤ VA 6 months. Subjects used a mean of 1.9 ± 1.1 bottles of intraocular pressure-lowering medications to treat their glaucoma. Seventy-six percent (155/204) of subjects had severe visual field damage, with a mean deviation of -14.5 ± 8.0. Twenty-six percent (54/204) had acuity of ≤ 20/200 in ≥ 1 eye, and subjects had a mean logarithm of minimal angle of resolution acuity of 0.8 ± 0.9. Seventy-one percent of subjects were able to get a drop onto the eye; only 39% instilled 1 drop onto the eye without touching the ocular surface, instilling a mean 1.4 ± 1.0 drops, using 1.2 ± 0.6 attempts. Of the 142 subjects who denied touching the bottle to the ocular surface, 24% did touch the bottle to the eye. Multiple factors were tested for ability to predict successful application of an eyedrop; however, only age (visually impaired glaucoma patients, we evaluated the difficulty this population has instilling eyedrops, most important, the use of multiple drops per instillation, potential contamination of a chronically used bottle, and poor patient understanding of the situation. Ability to self-administer eyedrops and cost considerations of wasted drops must be thought out before institution of glaucoma therapy. Efforts to determine better methods of eyedrop administration need to be undertaken. Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  7. Utilizing the VeraFlo™ Instillation Negative Pressure Wound Therapy System with Advanced Care for a Case Study. (United States)

    Driver, Rita K


     Mankind has always suffered wounds throughout time due to trauma, disease, and lifestyles. Many wounds are non-healing and have continued to be challenging. However, utilizing advanced wound care treatments, such as negative pressure wound treatment with instillation and dwell time (NPWTi-d), has proven beneficial. NPWTi-d is indicated in a variety of wounds, such as trauma, surgical, acute, pressure injuries, diabetic foot ulcers, and venous leg ulcers. Bacteria and bioburden interrupts wound healing by increasing the metabolic needs, ingesting, and robbing the necessary nutrients and oxygen. Instillation therapy is the technique of intermittently washing out a wound with a liquid solution. The mechanism of action is instilling fluid into the wound bed, soaking for a determined time, loosening and cleaning of exudate, contaminants, and/or infection, removing fluid via negative pressure, thus promoting tissue growth.  The patient was diagnosed with a large lymphedema mass on the right upper thigh. Surgical removal of the lymphedema mass was indicated due to interference with quality of life. After a failed flap and surgical debridement, NPWTi-d with normal saline was implemented.  The patient had excellent results, with obvious forming of red, beefy granulation, epithelization tissue development, and a cleaner, healthier wound bed. Settings for the NPWTi-d was 18 minutes dwell time, every 2.5 hours with a constant pressure of 125 mm/hg pressure.  The NPWTi-d demonstrated to be an instrumental treatment in supporting and stimulating healing. Early application of the treatment with normal saline as the instillation fluid prepared the previously failed wound for quicker healing.

  8. Intraoperative instillation of ropivacaine during the placement of sub-muscular cosmetic breast implants: Is there a clinical benefit? (United States)

    Picard, F; Niddam, J; De Runz, A; Chaouat, M; Mimoun, M; Boccara, D


    The sub-muscular placement of cosmetic breast implants leads to substantial pain due to the muscular distention. The aim of this study was to assess the efficiency of intraoperative ropivacaine instillation to reduce postoperative pain the day after surgery. We conducted a prospective, controlled, single-blinded study comparing the intraoperative instillation of 7.5mg of ropivacaine through Redon drains with the standard procedure in 72 patients undergoing sub-muscular cosmetic breast augmentation for the first time. Pain at the awakening on postoperative day 1 was 4.8 on a simple numeric pain scale in the treatment group and 5.1 in the control group (P>0.05). On postoperative day 3, pain at awakening was 3.7 in both groups (P>0.05), and on postoperative day 5, pain was 2.8 in the treatment group and 2.7 in the control group (P>0.05). Local instillation of ropivacaine in the implant pocket during surgery did not decrease postoperative pain on day 1, day 3 and day 5. From now on, we are able to tell to patients that the postoperative pain after sub-muscular cosmetic breast implants surgery is about 5/10 on postoperative day 1, 4/10 at day 3 and 3/10 at day 5. Level II. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Negative Pressure Wound Therapy With Instillation and Dwell Time Used to Treat Infected Orthopedic Implants: A 4-patient Case Series. (United States)

    Dettmers, Robert; Brekelmans, Wouter; Leijnen, Michiel; van der Burg, Boudewijn; Ritchie, Ewan


    Infection following orthopedic implants for bone fixation or joint replacement is always serious and may require removal of the osteosynthetic material. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is an emerging therapy for the treatment of complex wounds, including infected wounds with osteosynthetic material. The purpose of this case study was to evaluate the outcomes of 4 patients (1 man, 3 women; age range 49 to 71 years) with a postoperative wound infection (POWI) following fracture repair and internal fixation. All patients were at high risk for surgical complications, including infections. Standard infection treatments (antibiotics) had been unsuccessful. Based on the available literature, a NPWTi-d protocol was developed. Following surgical debridement, wounds were instilled with polyhexanide biguanide with a set dwell time of 15 minutes, followed by continuous NPWTi-d of -125 mm Hg for 4 hours. The system was changed every 3 to 4 days until sufficient granulation tissue was evident and negative pressure without instillation could be used. Systemic antibiotics were continued in all patients. Granulation tissue was found to be sufficient in 12 to 35 days in the 4 cases, no recurrence of infection was noted, and the osteosynthesis material remained in place. No adverse events were observed. Research is needed to compare the safety and effectiveness of this adjunct treatment in the management of challenging wounds to other patient and wound management approaches.

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

    Directory of Open Access Journals (Sweden)

    Honglei Chen

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

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

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


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

  12. Pulmonary clearance kinetics and extrapulmonary translocation of seven titanium dioxide nano- and submicron materials following intratracheal administration in rats. (United States)

    Shinohara, Naohide; Oshima, Yutaka; Kobayashi, Toshio; Imatanaka, Nobuya; Nakai, Makoto; Ichinose, Takayuki; Sasaki, Takeshi; Kawaguchi, Kenji; Zhang, Guihua; Gamo, Masashi


    We evaluated and compared the pulmonary clearance kinetics and extrapulmonary translocations of seven titanium dioxide (TiO2) nano- and submicron particles with different characteristics, including size, shape and surface coating. Varying doses of TiO2 nano- and submicron particles dispersed in 0.2% disodium phosphate solution were intratracheally administered to male F344 rats. The rats were euthanized under anesthesia for 3, 28 and 91 days after administration. Ti levels in pulmonary and various extrapulmonary organs were determined using inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). The lungs, including bronchoalveolar lavage fluid (BALF), contained 55-89% of the administered TiO2 dose at 3 days after administration. The pulmonary clearance rate constants, estimated using a one-compartment model, were higher after administration of 0.375-2.0 mg/kg body weight (bw) (0.016-0.020/day) than after administration of 3.0-6.0 mg/kg bw (0.0073-0.013/day) for six uncoated TiO2. In contrast, the clearance rate constant was 0.011, 0.0046 and 0.00018/day following administration of 0.67, 2.0 and 6.0 mg/kg bw TiO2 nanoparticle with Al(OH)3 coating, respectively. Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner. Furthermore, the translocation of TiO2 from the lungs to the thoracic lymph nodes after 91 days was higher when Al(OH)3 coated TiO2 was administered (0.93-6.4%), as compared to uncoated TiO2 (0.016-1.8%). Slight liver translocation was observed (kidney, spleen and brain.

  13. Intraperitoneal instillation of polihexanide produces hypotension and vasodilation: in vivo and in vitro study in rats. (United States)

    Frieling, Helge; Gründling, Matthias; Lauer, Kai-Steffen; Wendt, Michael; Hachenberg, Thomas; Hackenberg, Thomas; Lehmann, Christian; Pavlovic, Dragan


    Treatment of peritonitis may include abdominal lavage with a local disinfectant polihexanide, available as 0.04% solution, which is often accompanied by hypotension. We examined the effects of peritoneal installation of polihexanide or NaCl 0.9% (10 ml each, for 10 min; polihexanide n=5, NaCl n=5) on mean arterial pressure in healthy rats and, using intravital microscopy, measured in seven other animals the diameter of terminal ileum submucosal arterioles and venules before and after local superfusion with polihexanide. Furthermore, in an in vitro isometric preparation of rat thoracic aortal rings, with and without endothelium, we tested the effects of cumulative concentrations of polihexanide on vascular basic tension and on tension elicited by phenylephrine and KCl. It was found that polihexanide peritoneal instillation produced a decrease in mean arterial pressure, while superfusion with polihexanide caused local vasodilation of intestinal wall blood vessels. In vitro, polihexanide produced endothelium-dependent relaxation in the preparations pre-contracted with phenylephrine (EC(50), polihexanide 0.04% solution 2.53+/-0.16 vs. 1.36+/-0.16, n=4, P<0.05; polihexanide 4.02+/-0.12 vs. 3.21+/-0.10, n=12, P<0.001;+ vs. - endothelium, respectively; -log g%) which (in aortae +endothelium) could be attenuated by either N(G)-nitro-L-arginine methyl ester, a nitric oxide generation inhibitor, or 1H-(1,2,4)oxodiazolo-(4,3-a)quinoxalin-1-one, an inhibitor of guanylyl cyclase. The relaxing effect of polihexanide (aortae -endothelium) was not affected by K(+)-channel blocking agents charybdotoxin, tetraethylammoniumchloride, glibenclamide or 4-aminopyridine, while polihexanide had no effects on 40-mM KCl contractions. This implies that polihexanide may promote nitric oxide liberation, potassium channel activation and vasodilation that may result in hypotension.

  14. Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation. (United States)

    Win-Shwe, Tin-Tin; Sone, Hideko; Kurokawa, Yoshika; Zeng, Yang; Zeng, Qin; Nitta, Hiroshi; Hirano, Seishiro


    Dendrimers are highly branched spherical nanomaterials produced for use in diagnostic and therapeutic applications such as a drug delivery system. The toxicological profiles of dendrimers are largely unknown. We investigated the in vivo effects of nasal exposure to polyamidoamine (PAMAM) dendrimers on their effects on neurological biomarkers in the mouse brain. A single dose of PAMAM dendrimers (3 or 15μg/mouse) was intranasally administered to 8-week old male BALB/c mice. Twenty-four hours after administration, the olfactory bulb, hippocampus, and cerebral cortex were collected and potential biomarkers in the blood and brain were examined using blood marker, microarray and real-time RT-PCR analyses. No remarkable changes in standard serum biochemical markers were observed in the blood. A microarray analysis showed the alterations of the genes expression level related to pluripotent network, serotonin-anxiety pathway, TGF-beta receptor signaling, prostaglandin synthesis-regulation, complement-coagulation cascades, and chemokine-signaling pathway and non-odorant GPCR signaling pathways in brain tissues. Brain derived-neurotrophic factor mRNA was up-regulated in the hippocampus and cerebral cortex in mice treated with a high dose of dendrimers. These findings suggest that PAMAM dendrimers may reach the brain via the systemic circulation or an olfactory nerve route after intranasal instillation, and indicate that a single intranasal administration of PAMAM dendrimers may potentially lead to neuronal effects by modulating the gene expression of brain-derived neurotrophic factor signaling pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Honesty through repeated interactions. (United States)

    Rich, Patricia; Zollman, Kevin J S


    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Repeated Infections in Children (United States)

    ... he/she have ear tubes?What are the dangers of my child’s repeated infections?Should my child ... affect you or your baby through your breast milk.December 2017December editorial staffHip Problems in ...

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


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


    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. Spectral-domain optical coherence tomography study on dynamic changes of human tears after instillation of artificial tears. (United States)

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


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

  19. Outcome of bone marrow instillation at fracture site in intracapsular fracture of femoral neck treated by head preserving surgery. (United States)

    Verma, Nikhil; Singh, M P; Ul-Haq, Rehan; Rajnish, Rajesh K; Anshuman, Rahul


    The aim of present study is to evaluate the outcome of bone marrow instillation at the fracture site in fracture of intracapsular neck femur treated by head preserving surgery. This study included 32 patients of age group 18-50 years with closed fracture of intracapsular neck femur. Patients were randomized into two groups as per the plan generated via The two groups were Group A (control), in which the fracture of intracapsular neck femur was treated by closed reduction and cannulated cancellous screw fixation, and Group B (intervention), in which additional percutaneous autologous bone marrow aspirate instillation at fracture site was done along with cannulated cancellous screw fixation. Postoperatively the union at fracture site and avascular necrosis of the femoral head were assessed on serial plain radiographs at final follow-up. Functional outcome was evaluated by Harris hip score. The average follow-up was 19.6 months. Twelve patients in each group had union and 4 patients had signs of nonunion. One patient from each group had avascular necrosis of the femoral head. The average Harris hip score at final follow-up in Group A was 80.50 and in Group B was 75.73, which was found to be not significant. There is no significant role of adding on bone marrow aspirate instillation at the fracture site in cases of fresh fracture of intracapsular neck femur treated by head preserving surgery in terms of accelerating the bone healing and reducing the incidence of femoral head necrosis. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  20. Intraperitoneal sub-diaphragmatic instillation of bupivacaine plus morphine for reducing postoperative shoulder pain after gynecologic endoscopy. (United States)

    Sutchritpongsa, Pavit; Chaipakdi, Pakprapa; Sirimai, Korakot; Chalermchokcharoenkit, Amphan; Tanmahasamut, Prasong


    Gynecologic endoscopic surgery is a minimally invasive surgical technique for treatment of various gynecologic diseases. When compared to conventional laparotomy, this procedure has advantages in many aspects such as reduced postoperative pain, short hospital stay, and decreased morbidity associated with laparotomy. However 15 to 30% of the patients experienced moderate or severe postoperative shoulder pain. Methods to minimize postoperative shoulder pain after gynecologic endoscopy are essential to maximize the quality of life of the patients. To evaluate the benefit of intraperitoneal instillation of bupivacaine plus morphine for reducing postoperative shoulder pain incidence after gynecologic endoscopy. A randomized clinical trial was conducted in 158 patients undergoing laparoscopic procedures. The patients were randomly assigned to receive either 0.5% bupivacaine hydrochloride 20 mL mixed with morphine 3 mg (study group) or normal saline (control group) instillation to subdiaphragmatic area before finishing the procedure. Shoulder pain was evaluated at immediate post-operative time, and at 12 and 24 hours from the termination of surgery. The data of requested analgesic drugs after surgery was also recorded. Baseline characteristics were comparable between the two groups. Diagnosis, laparoscopic procedures, and duration of operation were also comparable. There were comparable proportions of patients reporting shoulder pain at 12 and 24 hours between the study and control group (30.4% and 30.4% at 12 hours, and 11.3% and 21.5% at 24 hours, respectively). Median pain scores at 12 and 24 hours were comparable between the study and control group (3 and 2 at 12 hours, and 4 and 4 at 24 hours, respectively). Requirement of analgesics was slightly greater among control than study group, but without statistical significance (17.7% and 24.1% respectively). Intraperitoneal instillation of bupivacaine plus morphine had no efficiency for reducing postoperative shoulder

  1. Is bladder tumor location associated with prostate cancer detection after intravesical bacillus Calmette-Guérin instillation?

    Directory of Open Access Journals (Sweden)

    Sungwoo Hong

    Full Text Available The aim of this study was to evaluate the effect of bladder tumor (BT location on prostate cancer (PCa detection in patients with elevated PSA levels after intravesical BCG instillation.Between February 2004 and January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder cancer (NMIBC patients whose PSA level were elevated (≥3 ng/ml after a 6 week course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline. Differences in PCa detection according to the BT location [bladder neck and/or trigone (Group 1, n = 22 vs. other locations (Group 2, n = 37] were evaluated. The Fisher's exact test and the Mann-Whitney U test were used to evaluate the association between categorical and continuous variables, respectively.A total of 14 patients (23.7% were diagnosed with PCa. The mean ± standard deviation (SD PSA before intravesical BCG instillation and prostate biopsy were 1.36±1.04 ng/ml in Group 1 and 1.09±1.12 ng/ml in Group 2 (P = 0.633, and 6.05±3.57 ng/ml in Group 1 and 5.13±3.88 ng/ml in Group 2 (P = 0.378, respectively. Interestingly, whereas PCa was detected upon biopsy in only one patient in Group 1 (4.5%, 13 cases were detected in Group 2 (35.1% (P = 0.009.PCa detection after intravesical BCG was highly associated with BT location. Prostate biopsy should therefore be considered when PSA level is elevated after BCG instillation and his BT is located far from the bladder neck.

  2. Allowing repeat winners


    Marco D. Huesch; Richard Brady


    Unbiased lotteries seem the least unfair and simplest procedures to allocate scarce indivisible resources to those with equal claims. But, when lotteries are repeated, it is not immediately obvious whether prior winners should be included or excluded. As in design questions surrounding single-shot lotteries, considerations of self-interest and distributive social preferences may interact. We investigate preferences for allowing participation of earlier winners in sequential lotteries. We foun...

  3. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

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

    Directory of Open Access Journals (Sweden)

    A. V. Kurinnoy


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

  5. Intraperitoneal Instillation of Lidocaine Improves Postoperative Analgesia at Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Trial. (United States)

    Patel, Ruchira; Carvalho, Jose C A; Downey, Kristi; Kanczuk, Marcelo; Bernstein, Paul; Siddiqui, Naveed


    Cesarean delivery is a commonly performed procedure worldwide. Despite improvements in balanced multimodal analgesia, there remains a proportion of women for whom postoperative pain relief and patient satisfaction are still inadequate. Intraperitoneal instillation of local anesthetic has been shown to be effective in reducing postoperative pain after abdominal surgery. We sought to investigate the effect of intraperitoneal instillation of lidocaine on postcesarean delivery pain as part of a multimodal analgesia regimen. We studied women scheduled for elective cesarean delivery under spinal anesthesia. Spinal anesthesia was performed with 0.75% hyperbaric bupivacaine, fentanyl, and morphine. At the end of the cesarean delivery, immediately before parietal peritoneum or fascia closure, patients were randomized to receive either lidocaine (20 mL 2% lidocaine with epinephrine) or placebo (20 mL normal saline) instilled into the peritoneal cavity. The primary outcome was pain score on movement at 24 hours. Secondary outcomes were pain score at rest and on movement at 2, 24, and 48 hours; maternal satisfaction score; analgesic consumption; incidence of nausea, vomiting, and itching; and return of bowel function. Two hundred four women were recruited. Baseline characteristics were similar between the lidocaine and placebo groups. Pain scores at 24 hours postcesarean delivery on movement (parameter estimate 0.02 [95% confidence interval {CI} -0.14 to 0.18]; P = .823) and at rest (parameter estimate 0.00 [95% CI -0.32 to 0.33]; P = .986) were similar in both groups. Pain scores at 2 hours postcesarean delivery on movement (parameter estimate -0.58 [95% CI -0.90 to -0.26]; P = .001) and at rest (parameter estimate -1.00 [95% CI -1.57 to -0.43]; P = .001) were lower in the lidocaine group. Subgroup analysis of patients with peritoneum closure revealed significantly lower pain scores at 24 hours on movement (parameter estimate -0.33 [95% CI -0.64 to -0.03]; P = .032) in the

  6. 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


    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.

  7. Mechanical ventilation and the role of saline instillation in suctioning adult intensive care unit patients: an evidence-based practice review. (United States)

    Caparros, Alyssa Camille S


    Saline instillation in suctioning mechanically ventilated patients remains a common practice in the intensive care unit (ICU). Many respiratory therapists and nurses are using saline with suctioning without an adequate knowledge of the current evidence-based research to guide this practice. The purpose of this study was to determine if this routine method is beneficial or harmful to the patients and provide evidence-based practice recommendations that will serve as a guide for practice. This is a comprehensive review on the use of saline instillation in suctioning mechanically ventilated adult ICU patients. Database such as CINAHL, MEDLINE, Cochrane, PsycINFO, and national guidelines are extracted for the review of literature. The study population consists of patients 18 years or older, who are intubated or have a tracheostomy in place, requiring mechanical ventilation, and who are admitted in the ICU. Although most of the evidence suggests not to use saline when suctioning, there are various limitations to the studies such as small sample size, settings, inconsistencies in data collection, or not enough or outdated research clinical trials, which calls for further studies. This study does not support the use of saline instillation when suctioning an artificial airway. Further clinical trials are crucial to effectively determine if saline instillation use with suctioning an artificial airway is deemed harmful, which can be strictly enforced as a mandatory clinical guideline for all hospitals to include in their standardized protocol to not use saline instillation with suctioning.

  8. Serial measurement of tear meniscus by FD-OCT after instillation of artificial tears in patients with dry eyes. (United States)

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


    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.

  9. Repeatability of Cryogenic Multilayer Insulation (United States)

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


    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  10. Repeatability of Cryogenic Multilayer Insulation (United States)

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


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

  11. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

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


    NAKAJIMA, Masamitsu


    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...

  13. Repeat Customer Success in Extension (United States)

    Bess, Melissa M.; Traub, Sarah M.


    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  14. Repeated judgment sampling: Boundaries

    Directory of Open Access Journals (Sweden)

    Johannes Muller-Trede


    Full Text Available This paper investigates the boundaries of the recent result that eliciting more than one estimate from the same person and averaging these can lead to accuracy gains in judgment tasks. It first examines its generality, analysing whether the kind of question being asked has an effect on the size of potential gains. Experimental results show that the question type matters. Previous results reporting potential accuracy gains are reproduced for year-estimation questions, and extended to questions about percentage shares. On the other hand, no gains are found for general numerical questions. The second part of the paper tests repeated judgment sampling's practical applicability by asking judges to provide a third and final answer on the basis of their first two estimates. In an experiment, the majority of judges do not consistently average their first two answers. As a result, they do not realise the potential accuracy gains from averaging.

  15. Allowing repeat winners

    Directory of Open Access Journals (Sweden)

    Marco D. Huesch


    Full Text Available Unbiased lotteries seem the least unfair and simplest procedures to allocate scarce indivisible resources to those with equal claims. But, when lotteries are repeated, it is not immediately obvious whether prior winners should be included or excluded. As in design questions surrounding single-shot lotteries, considerations of self-interest and distributive social preferences may interact. We investigate preferences for allowing participation of earlier winners in sequential lotteries. We found a strong preference for exclusion, both in settings where subjects were involved, and those where they were not. Subjects who answered questions about both settings did not differ in their tendency to prefer exclusion. Stated rationales significantly predicted choice but did not predict switching of choices between the two settings.

  16. Pilot safety study of intrabronchial instillation of bone marrow-derived mononuclear cells in patients with silicosis. (United States)

    Morales, Marcelo M; Souza, Sérgio A L; Loivos, Luiz Paulo; Lima, Marina A; Szklo, Amir; Vairo, Leandro; Brunswick, Taís H K; Gutfilen, Bianca; Lopes-Pacheco, Miquéias; Araújo, Alberto J; Cardoso, Alexandre P; Goldenberg, Regina C; Rocco, Patricia R M; Fonseca, Lea M B; Lapa e Silva, José R


    Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis. We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18-50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s 40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 × 10(7) cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation. No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration. Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. CLINICAL TRIALS. NCT01239862 Date of Registration: November 10, 2010.

  17. Impact of hydrochloric acid instillation on salvage of infected central venous catheters in children with acute lymphoblastic leukaemia. (United States)

    Madsen, Mette; Rosthøj, Steen


    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.

  18. Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning. (United States)

    Mazzoli-Rocha, Flavia; Carvalho, Giovanna M C; Lanzetti, Manuella; Valença, Samuel S; Silva, Luiz F F; Saldiva, Paulo H N; Zin, Walter A; Faffe, Débora S


    We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund


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

  20. To Repeat or Not to Repeat a Course (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.


    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  1. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    Directory of Open Access Journals (Sweden)

    Kuiper Jan


    Full Text Available Abstract Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV with either a low tidal volume (Vt of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis. Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. Conclusions During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of

  2. Comparison of the effectiveness of mydriasis by two instillation methods of combined 0.75% tropicamide and 2.5% phenylephrine eye drop in preterm infants. (United States)

    Phamonvaechavan, Pittaya; Chutasmit, Kanya; Damrongrak, Parichat; Koukiatkul, Supanna; Wongkiatkajorn, Tassanee; Ngerncham, Sopapan


    To compare the effectiveness and safety of two instillation methods of combined 0.75% tropicamide and 2.5% phenylephrine at 0, 5 minutes (min) with the same combined regimen at 0,30 minutes in preterm infants. A prospective, cross-over, randomized controlled trial was performed to compare 0, 5-min instillation (Method A) of combined 0.75% tropicamide and 2.5% phenylephrine with 0, 30-min instillation (Method B) of the same regimen. Forty-two preterm infants scheduled for screening retinopathy of prematurity (ROP) were randomly assigned to two groups. Group 1 was defined as preterms applied by Method A at first examination then by Method B 1-4 weeks apart whereas vice versa in Group 2. Pupil size, heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were recorded before and after eye-drop instillation. Mean time to 7-mm pupil size was no statistically significant difference between the two methods (Method A 46.47 min, Method B 46.58 min; p = 0.894). Method B has mean longer time to maintain 7-mm pupil size than Method A (Method A 67.67 min, Method B 75.33 min); but not statistically significant different (p = 0.323). HR, SBP and DBP were not significant change between the two methods. Both instillation methods produced consistently sufficient mydriasis and safety for evaluation peripheral fundus. Method B has slight longer mydriatic effect than Method A; thus giving more time to evaluate infant's eye for ophthalmologists.

  3. Nifty Nines and Repeating Decimals (United States)

    Brown, Scott A.


    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  4. All-photonic quantum repeaters (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Pierre Machu


    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.

  6. Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage. (United States)

    Aguirre, Tanira A S; Aversa, Vincenzo; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J


    Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45μmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Paulo Gelman Vaidergorn


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

  8. 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


    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

  9. 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


    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

  10. Anti-TNP-forming cells in bronchus-associated lymphoid tissue (BALT) and paratracheal lymph node (PTLN) of the rat after intratracheal priming and boosting with TNP-KLH. (United States)

    van der Brugge-Gamelkoorn, G J; Claassen, E; Sminia, T


    The aim of the present study was to elucidate the role of the paratracheal lymph node (PTLN) and bronchus-associated lymphoid tissue (BALT) in the generation of antigen-specific antibody-forming cells after intratracheal administration of trinitrophenyl-conjugated keyhole limpet haemocyanin (TNP-KLH). Priming as well as boosting resulted in the occurrence of specific antibody-forming cells in the PTLN, in BALT and in the lung. No anti-TNP-forming cells were observed in Peyer's patch, mesenteric lymph node and popliteal lymph node. From the data on the kinetics of anti-TNP-forming cells, it is concluded that intratracheal administration of antigen leads to a locally confined plasmacellular reaction. This suggests that the migrating and/or homing capacities of memory cells generated in the lung environment (PTLN, BALT) differ from those generated in the gut. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3514441

  11. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul


    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  12. Repeated DNA sequences in fungi

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, S.K.


    Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10 to 20 percent repeated DNA sequences. There are approximately 100 to 110 copies of repeated DNA sequences of approximately 4 x 10/sup 7/ daltons piece size of each. Repeated DNA sequence homoduplexes showed on average 5/sup 0/C difference of T/sub e/50 (temperature at which 50 percent duplexes dissociate) values from the corresponding homoduplexes of unfractionated whole DNA. It is suggested that a part of repetitive sequences in fungi constitutes mitochondrial DNA and a part of it constitutes nuclear DNA. (auth)

  13. Tumor incidence was not related to the thickness of visceral pleural in female Syrian hamsters intratracheally administered amphibole asbestos or manmade fibers. (United States)

    Adachi, S; Kawamura, K; Kimura, K; Takemoto, K


    Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.

  14. 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


    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.

  15. The effect of negative pressure wound therapy with periodic instillation using antimicrobial solutions on Pseudomonas aeruginosa biofilm on porcine skin explants. (United States)

    Phillips, Priscilla L; Yang, Qingping; Schultz, Gregory S


    Negative pressure wound therapy with instillation (NPWTi) is increasingly used as an adjunct therapy for a wide variety of infected wounds. However, the effect of NPWTi on mature biofilm in wounds has not been determined. This study assessed the effects of NPWTi using saline or various antimicrobial solutions on mature Pseudomonas aeruginosa biofilm using an ex vivo porcine skin explant biofilm model. Treatment consisted of six cycles with 10-minute exposure to instillation solution followed by 4 hours of negative pressure at -125 mm Hg over a 24-hour period. NPWTi using saline reduced bacterial levels by 1-log (logarithmic) of 7-log total colony-forming units (CFUs). In contrast, instillation of 1% povidone iodine (2-log), L-solution (3-log), 0·05% chlorhexidine gluconate (3-log), 0·1% polyhexamethylene biguanide (4-log), 0·2% polydiallyldimethylammonium chloride (4-log) and 10% povidone iodine (5-log), all significantly reduced (P porcine skin explants, these ex vivo model data suggest that NPWTi with delivery of active antimicrobial agents enhances the reduction of CFUs by increasing destruction and removal of biofilm bacteria. These results must be confirmed in human studies. © 2013 The Authors. International Wound Journal © 2013 John Wiley & Sons Ltd and Inc.

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

    Directory of Open Access Journals (Sweden)

    Sussan S. Mohammadi


    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.

  17. A Case Review Series of Christiana Care Health System’s Experience with Negative Pressure Wound Therapy Instillation (United States)

    Gallagher, Kathy E; Tinkoff, Glen H; Cipolle, Mark


    Acute and chronic wounds afflict a multitude of patients to varying degrees. Wound care treatment modalities span the spectrum of technological advancement and with that differ greatly in cost. Negative pressure wound therapy (NPWT) can now be combined with instillation and dwell time (NPWTi-d). This case review series of 11 patients in a community hospital setting provides support for the utilization of NPWTi-d. Additionally, current literature on the use of NPWTi-d in comparison to NPWT will be reviewed.  We highlight three specific cases. The first case is a 16-year-old male who was shot in the left leg. He suffered a pseudoaneurysm and resultant compartment syndrome. This required a fasciotomy and delayed primary closure. To facilitate this, NPWTi-d was employed and resulted in a total of four operative procedures before closure 13 days after admission. Next, a 61-year-old uncontrolled diabetic female presented with necrotizing fasciitis of the lower abdomen and pelvis. She underwent extensive debridement and placement of NPWTi-d with Dakin’s solution. A total of four operative procedures were performed including delayed primary closure six days after admission. Finally, a 48-year-old female suffered a crush injury with internal degloving. NPWTi-d with saline was utilized until discharge home on postoperative day 12. NPWTi-d, when compared to NPWT, has been reported to lead to a decrease in time to operative closure, hospital length of stay, as well as operative procedures required. The cost-benefit analysis in one retrospective review noted a $1,400 savings when these factors were taken into account. This mode of wound care therapy has significant benefits that warrant the development of a prospective randomized controlled trial to further define the improvement in quality-of-life provided to the patient and the reduction of potential overall healthcare costs. PMID:27980886

  18. Efficiency of repeated network interactions

    NARCIS (Netherlands)

    Timmer, Judith B.; Mandjes, M.R.H.


    In this paper we consider a network with interactions by two users. Each of them repeatedly issues download requests on the network. These requests may be unsuccessful due to congestion or non-congestion related errors. A user decides when to cancel a request (that is, what his impatience threshold

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


    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.

  20. Pentapeptide Repeat Proteins and Cyanobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Buchko, Garry W.


    Cyanobacteria are unique in many ways and one unusual feature is the presence of a suite of proteins that contain at least one domain with a minimum of eight tandem repeated five-residues (Rfr) of the general consensus sequence A[N/D]LXX. The function of such pentapeptide repeat proteins (PRPs) are still unknown, however, their prevalence in cyanobacteria suggests that they may play some role in the unique biological activities of cyanobacteria. As part of an inter-disciplinary Membrane Biology Grand Challenge at the Environmental Molecular Sciences Laboratory (Pacific Northwest National Laboratory) and Washington University in St. Louis, the genome of Cyanothece 51142 was sequenced and its molecular biology studied with relation to circadian rhythms. The genome of Cyanothece encodes for 35 proteins that contain at least one PRP domain. These proteins range in size from 105 (Cce_3102) to 930 (Cce_2929) kDa with the PRP domains ranging in predicted size from 12 (Cce_1545) to 62 (cce_3979) tandem pentapeptide repeats. Transcriptomic studies with 29 out of the 35 genes showed that at least three of the PRPs in Cyanothece 51142 (cce_0029, cce_3083, and cce_3272) oscillated with repeated periods of light and dark, further supporting a biological function for PRPs. Using X-ray diffraction crystallography, the structure for two pentapeptide repeat proteins from Cyanothece 51142 were determined, cce_1272 (aka Rfr32) and cce_4529 (aka Rfr23). Analysis of their molecular structures suggests that all PRP may share the same structural motif, a novel type of right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a square tower with four distinct faces. Each pentapeptide repeat occupies one face of the Rfr-fold with four consecutive pentapeptide repeats completing a coil that, in turn, stack upon each other to form “protein skyscrapers”. Details of the structural features of the Rfr-fold are reviewed here together with a discussion for the possible role of end

  1. A new modified fluorescein strip: Its repeatability and usefulness in tear film break-up time analysis. (United States)

    Pult, H; Riede-Pult, B H


    To (i) analyze the repeatability of fluorescein instillation from a modified fluorescein strip (MFS) compared to a standard fluorescein strip (FS), and to (ii) observe its usefulness in the measurement of the fluorescein break-up time (FBUT) in comparison to the Tearscope (NIBUT). In-vitro: Intra- and inter-observer repeatability in fluorescein instillation from the MFS and FS was evaluated by fluorescence analysis (n=10, each). In-vivo: BUT of the right eye of 20 randomly selected subjects (mean age 43.3±11.5, range=21-60 years, 8 males, 12 females) was measured by use of the Tearscope and MFS. Subjects were grouped by the Ocular Surface Disease Index (OSDI) score into 8 OSDI+ and 12 OSDI- by a cut-off value of 15. In-vitro: Intra-observer 95% limit of agreement (LoA) of the MFS was similar to the FS LoA in observer 1 (O1), but better than the FS LoA in observer (O2) (MFS: O1: LoA=±1.98 mW; p=0.179; O2: ±2.71; 0.442; FS: O1: ±1.71; 0.246; O2: ±4.11; 0.512). Inter-observer LoA in fluorescence was better in MFS (±1.42; 0.111) than in FS (±3.71; 0.003). In-vivo: MFS-BUT was significantly shorter than the NIBUT (p=0.002), but significantly correlated (r=0.864, p<0.001). NIBUT and MFS-BUT were significant discriminators (p<0.001) of OSDI±(0.948/8s and 0.938/5s [AUC/cut-off value]; NIBUT and MFS-BUT, respectively). The MFS was better in the repeatability of fluorescein instillation than the FS. NIBUT and MFS-BUT were good discriminators of dry eye symptoms, but differ in their cut-off values. Copyright © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  2. A repeating fast radio burst (United States)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.


    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  3. [Successful treatment of hemorrhagic cystitis after radiation therapy with intravesical instillation of aluminium hydroxide gel and magnesium hydroxide: report of a case]. (United States)

    Kawamura, Norihiko; Kakuta, Yoichi; Fukuhara, Sinichiro; Imazu, Tetsuo; Hara, Tsuneo; Yamaguchi, Seiji


    A 77-year-old man was admitted to our hospital due to macrohematuria and bladder tamponade. Bladder hemorrhage caused by radiation therapy had not improved after bladder lavage, intravesical drip infusion, medication of hemostatics, and transurethral coagulation. Bladder hemorrhage had completely disappeared 7 days after the intravesical instillation of 50-100 ml aluminium hydroxide gel and magnesium hydroxide for an hour per day. This method is easy and can be performed without complications. This method might be useful as first-line therapy in the case of severe bladder hemorrhage.

  4. 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


    μg/mouse. Mice were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific q......PCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (±1.3 fold; p...

  5. Assessment of carvacrol for control of avian aspergillosis in intratracheally challenged chickens in comparison to voriconazole with a reference on economic impact. (United States)

    Tartor, Y H; Hassan, F A M


    This study was designed to investigate the efficacy of essential oils as an alternative prophylaxis and treatment for avian aspergillosis. The in vitro susceptibility of Aspergillus fumigatus strains to antifungal drugs and carvacrol, thymol, eugenol, thymoquinone and cinnamon was determined using the macrodiffusion and microdilution methods. Carvacrol has antifungal activity in comparison to voriconazole (VCZ) (MIC 0·5, 0·25 μg ml(-1) respectively). While cinnamon, euganol, thymol and thymoquinone displayed moderate to weak inhibitory activity. For the efficacy study, five groups of 10-day-old chicks (n = 48) were infected intratracheally either with A. fumigatus conidia or saline (negative control). Chicks in carvacrol prophylactic and treatment (CRPT) group were fed for 10 days beginning from hatch with carvacrol (200 mg kg(-1) per diet) supplemented diets. VCZ (VCZT:20 mg kg(-1) body weight (BW)), carvacrol treatment (CRT, CRPT) was started upon appearance of the first clinical signs and continued for 10 days. Birds were monitored for an additional 15 days following treatment. Fungal burden and therapeutic efficacy were assessed by survival, BW, quantitative (q) culture (CFU), quantitative real-time PCR (qPCR) and histopathological changes at several time points. Serum biochemical changes were also assessed. VCZT, CRPT, CRT in comparison to the sham-treated (SHAM) group have prolonged survival (87·5, 83·4, 79·2, 41·7% respectively). In VCZT and CRPT, a significant reduction in clinical signs, lesions, CFU and qPCR counts to the limit of detection were observed. CRPT has the lowest BW reduction, economic losses and significant low total cholesterol levels. Carvacrol has a promising potential to be used as a prophylactic and treatment against A. fumigatus. Prognosis of avian aspergillosis is often poor due to delayed diagnosis and treatment failure. However, the widespread uses of azole prophylaxis in birds are thought to be the major driver of

  6. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz


    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  7. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy


    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  8. Effect of mydriasis induced by topical 0.5% tropicamide instillation on the corneal biomechanical properties in healthy individuals measured by ocular response analyzer. (United States)

    Oltulu, Refik; Satirtav, Gunhal; Altunkaya, Orhan; Bitirgen, Gulfidan; Okka, Mehmet


    This observational study aims to investigate the effects of tropicamide (0.5%) on corneal biomechanical properties, with the ocular response analyzer (ORA), in healthy individuals. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) measurements of 38 (21 female and 17 male) healthy individuals, before and after 30 min of 0.5% tropicamide instillation, were performed by using the ORA. The mean CH, CRF, IOPg and IOPcc measurements of the eyes were 10.2 ± 1.9 mmHg, 10.3 ± 2.1 mmHg, 15.7 ± 3.4 mmHg, 16.4 ± 3.3 mmHg pre-tropicamide, and 10.4 ± 1.7 mmHg, 10.3 ± 2.1 mmHg, 15.3 ± 3.4 mmHg, 15.8 ± 2.7 mmHg post-tropicamide, respectively. The differences between the pre- and post-tropicamide measurements of the eyes were insignificant (p = 0.184, p = 0.659, p = 0.294, p = 0.150, respectively; paired t-test). A tropicamide instillation does not lead to significant changes in the corneal biomechanical properties. Therefore, it can be used safely in disease, i.e. in the diagnosis and follow-up ORA as it does not cause any change.

  9. Solid-state power converter repeatability analysis

    CERN Document Server

    Dal Gobbo, Anthony; Aguglia, Davide


    This paper presents a method for evaluating power converter repeatability. The focus is on solid-state switch mode power converter for which the most problematic non-repeatability sources are the jitter of the drivers and of the switches leading to output voltage pulses bad repeatability. Both driver and switch turn-on and turn-off delay dispersion have been measured. These measurements confirm that the delay is Gaussian distributed and that the repeatability prediction method is valid.

  10. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  11. Repeated expansion in burn sequela. (United States)

    Pitanguy, Ivo; Gontijo de Amorim, Natale Ferreira; Radwanski, Henrique N; Lintz, José Eduardo


    This paper presents a retrospective study of the use of 346 expanders in 132 patients operated at the Ivo Pitanguy Clinic, between the period of 1985 and 2000. The expanders were used in the treatment of burn sequela. In the majority of cases, more than one expander was used at the same time. In 42 patients, repeated tissue expansion was done. The re-expanded flaps demonstrated good distension and viability. With the increase in area at each new expansion, larger volume expanders were employed, achieving an adequate advancement of the flaps to remove the injured tissue. The great advantage of using tissue re-expansion in the burned patient is the reconstruction of extensive areas with the same color and texture of neighboring tissues, without the addition of new scars.

  12. ProRepeat: an integrated repository for studying amino acid tandem repeats in proteins

    NARCIS (Netherlands)

    Luo, H.; Lin, K.; David, A.; Nijveen, H.; Leunissen, J.A.M.


    ProRepeat ( is an integrated curated repository and analysis platform for in-depth research on the biological characteristics of amino acid tandem repeats. ProRepeat collects repeats from all proteins included in the UniProt knowledgebase, together with 85

  13. 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.


    BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro......, 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...... 4975) after open mesh groin hernia repair in 41 adult male patients. The primary end-point was average daily visual analog scale (VAS) pain scores during the first week after surgery assessed as area under the curve (AUC). Pain was recorded twice daily in a pain diary for 4 wk. Physical examination...

  14. Effets de l’administration intramusculaire du butorphanol et de l’instillation oculaire du tropicamide sur l’ouverture pupillaire et la pression intraoculaire chez le chien‎


    Grillot, Aure-Eline


    Le but de cette étude était d’évaluer chez le chien sédaté par le butorphanol si la mydriase induite par l’instillation de tropicamide était retardée, et si l’augmentation de la pression intraoculaire (PIO) par le butorphanol était renforcée par celle-ci. Douze chiens Beagles sains ont reçu une injection intramusculaire de butorphanol 0,2 mg/kg ou de NaCl 0,9%. Des mesures du diamètre pupillaire et de la PIO ont été réalisées sur les yeux de chaque chien dont un tiré au sort ayant reçu une in...

  15. Recommendations on negative pressure wound therapy with instillation and antimicrobial solutions - when, where and how to use: what does the evidence show? (United States)

    Back, David A; Scheuermann-Poley, Catharina; Willy, Christian


    Infections of contaminated or colonised acute or chronic wounds remain a grave risk for patients even today. Despite modern surgical debridement concepts and antibiotics, a great need exists for new therapies in wound management. Since the late 1990s, advantageous effects of negative pressure wound therapy (NPWT) have been combined with local antiseptic wound cleansing in the development of NPWT with instillation (NPWTi). This article summarises the current scientific knowledge on this topic. MEDLINE literature searches were performed on the subject of negative pressure wound and instillation therapy covering publications from the years 1990 to 2013 (36 peer-reviewed citations) and regarding randomised controlled trials (RCTs) covering wound care with bone involvement (27 publications) or soft-tissue wounds without bone participation (11 publications) from 2005 to 2012. The use of NPWTi in the therapy of infected wounds appears to be not yet widespread, and literature is poor and inhomogeneous. However, some reports indicate an outstanding benefit of NPWTi for patients, using antiseptics such as polyhexanide (concentration 0·005-0·04%) and acetic acid (concentration 0·25-1%) in acute and chronic infected wounds and povidone-iodine (10% solution) as prophylaxis in contaminated wounds with potential viral infection. Soaking times are recommended to be 20 minutes each, using cycle frequencies of four to eight cycles per day. Additionally, the prophylactic use of NPWTi with these substances can be recommended in contaminated wounds that cannot be closed primarily with surgical means. Although first recommendations may be given currently, there is a great need for RCTs and multicentre studies to define evidence-based guidelines for an easier approach to reach the decision on how to use NPWTi. © 2013 The Authors. International Wound Journal © 2013 John Wiley & Sons Ltd and Inc.

  16. Repeated Maxima of Sunspot Cycles (United States)

    Krivodubskij, V.


    The explanation for the observed phenomenon of repeated maxima of sunspot cycles is proposed. Key roles in the proposed scenarioplay two tides of toroidal field from the lower base of the solar convection zone (SCZ) to the surface. Deep toroidal field is excited due to Ω-effectnear the bottom of the SCZ at the beginning of the cycle. Then this field is transported to the surface due to combined acting of magnetic buoyancy,magnetic ∇ρ-flow and turbulent diamagnetism in the equatorial domain. Over time the magnetic fragments can be seen as bipolar spots in themiddle latitudes in the "royal zone". This first wave of toroidal field, which is directed up, gives the main maximum activity spots. However, theunderlying toroidal field in the high-latitude polar domains at the beginning of the cycle is blocked by directed downward magnetic∇ρ-pumping and turbulent diamagnetism. Directed to the equator deep meridional flow replaces this field to the low latitudes (the equatorialdomain) during about 1 - 2 years. After that the turn of floating this "retarded" field to surface (second tide of toroidal field). Coming to the surfaceat low latitudes this second portion of toroidal field leads to second sunspot maximum.

  17. Repeats and EST analysis for new organisms

    Directory of Open Access Journals (Sweden)

    Jonassen Inge


    Full Text Available Abstract Background Repeat masking is an important step in the EST analysis pipeline. For new species, genomic knowledge is scarce and good repeat libraries are typically unavailable. In these cases it is common practice to mask against known repeats from other species (i.e., model organisms. There are few studies that investigate the effectiveness of this approach, or attempt to evaluate the different methods for identifying and masking repeats. Results Using zebrafish and medaka as example organisms, we show that accurate repeat masking is an important factor for obtaining a high quality clustering. Furthermore, we show that masking with standard repeat libraries based on curated genomic information from other species has little or no positive effect on the quality of the resulting EST clustering. Library based repeat masking which often constitutes a computational bottleneck in the EST analysis pipeline can therefore be reduced to species specific repeat libraries, or perhaps eliminated entirely. In contrast, substantially improved results can be achived by applying a repeat library derived from a partial reference clustering (e.g., from mapping sequences against a partially sequenced genome. Conclusion Of the methods explored, we find that the best EST clustering is achieved after masking with repeat libraries that are species specific. In the absence of such libraries, library-less masking gives results superior to the current practice of using cross-species, genome-based libraries.

  18. Strengthening concept learning by repeated testing (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars


    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system. PMID:24313425

  19. 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


    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

  20. 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 (United States)

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


    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 (purinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

  1. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A


    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  2. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan


    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  3. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan


    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  4. [Comparison of the effectiveness between long-term instillation of mitomycin C and short-term prophylaxis with MMC or bacille Calmette-Guérin. Study of patients with non-muscle-invasive urothelial cancer of the urinary bladder]. (United States)

    Isbarn, H; Budäus, L; Pichlmeier, U; Conrad, S; Huland, H; Friedrich, M G


    Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment. A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy. The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant. Long

  5. A Comparison of DWI Repeaters and Non-repeaters Who Attended a Level I Rehabilitation Program. (United States)

    Landrum, James W.; Windham, Gerald O.


    Compares behavioral and demographic characteristics of drunk drivers with repeated arrests and drivers not having repeated arrests, after attending an alcohol education program. Previous public drunkeness and previous drunk driving arrests were strong predictors of repeat arrests and were judged useful in screening offenders for rehabilitation…

  6. Finding and Characterizing Repeats in Plant Genomes. (United States)

    Nicolas, Jacques; Peterlongo, Pierre; Tempel, Sébastien


    Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available software that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, many methods have been used or developed for this large class of sequences. They are representative of the range of tools available for other classes of repeats and we have provided a whole section on this topic as well as a selection of the main existing software. In order to better understand how they work and how repeats may be efficiently found in genomes, it is necessary to look at the technical issues involved in the large-scale search of these structures. Indeed, it may be hard to keep up with the profusion of proposals in this dynamic field and the rest of the chapter is devoted to the foundations of the search for repeats and more complex patterns. The second section introduces the key concepts that are useful for understanding the current state of the art in playing with words, applied to genomic sequences. This can be seen as the first stage of a very general approach called linguistic analysis that is interested in the analysis of natural or artificial texts. Words, the lexical level, correspond to simple repeated entities in texts or strings. In fact, biologists need to represent more complex entities where a repeat family is built on more abstract structures, including direct or inverted small repeats, motifs, composition constraints as well as ordering and distance constraints between these elementary blocks. In terms of linguistics, this corresponds to the syntactic level of a language. The last section introduces concepts and practical tools that can be used to reach this syntactic level in biological sequence analysis.

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

    DEFF Research Database (Denmark)

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


    Exposure to high aspect ratio nanomaterials, such as multi-walled carbon nanotubes (MWCNTs) may be associated with increased risk of atherosclerosis, pulmonary disease, and cancer. In the present study, we investigated the cardiovascular and pulmonary health effects of 10 weeks of repeated oral...... or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only...

  8. The child accident repeater: a review. (United States)

    Jones, J G


    The child accident repeater is defined as one who has at least three accidents that come to medical attention within a year. The accident situation has features in common with those of the child who has a single accident through simple "bad luck", but other factors predispose him to repeated injury. In the child who has a susceptible personality, a tendency for accident repetition may be due to a breakdown in adjustment to a stressful environment. Prevention of repeat accidents should involve the usual measures considered appropriate for all children as well as an attempt to provide treatment of significant maladjustment and modification of a stressful environment.

  9. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P


    suicidal behavior. The results showed that three fourths of the patients attempted suicide more than once (62% nonfatal and 14% fatal outcome). The sex distribution was about the same among the first-evers as among the repeaters. Most repeaters were younger people in their twenties and thirties...... that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood...

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

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


    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.

  11. Proximal bowel T-tube drainage and local instillation of N-acetyl cysteine: A modified approach to management of meconium ileus

    Directory of Open Access Journals (Sweden)

    Bhattacharyaya S


    Full Text Available Various surgical procedures are described and practiced for operative management of uncomplicated meconium ileus. In our series, we have tried an approach of minimally invasive procedure to minimize the operative stress in already sick neonates. Ten cases of meconium ileus operated between 01/01/2003 to 21/06/2004 were screened. Three cases presented with complications like peritonitis (2 and volvulus (1 and so were not included in this study. Seven cases were uncomplicated. Out of them three were managed conservatively. Operative management by minilaparotomy - enterotomy and T-tube insertion was done in the remaining four cases, which did not resolve by conservative approach. In this group, patients passed stool by approximately seventh day (range - sixth to eight day. Oral feeds begun on approximately ninth day (range - eighth to tenth day. All four babies survived. This approach of minilaprotomy, T-tube insertion and N acetyl cysteine instillation, could be of significant benefit in an already sick neonate. Also, T- tube helps in post- operative bowel decompression, distal bowel wash and check dye study

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

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


    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.

  13. Effect of mydriasis induced by topical instillations of 0.5% tropicamide on the anterior segment in normotensive dogs using ultrasound biomicroscopy. (United States)

    Dulaurent, Thomas; Goulle, Frédéric; Dulaurent, Alice; Mentek, Marielle; Peiffer, Robert Louis; Isard, Pierre-François


    To determine the effect of 0.5% tropicamide and the resultant mydriasis on the anterior segment in normotensive dogs using ultrasound biomicroscopy. Twenty-four dogs without ocular disease underwent ultrasound biomicroscopic examination of both the eyes under general anesthesia. Pharmacologic mydriasis was induced in the right eye of each dog by the topical instillation of 0.5% tropicamide. Ultrasound biomicroscopic examinations were performed and the anatomical parameters of the anterior segment were evaluated including the geometric iridocorneal angle (ICA) - formed by the plane of the iris root and the internal corneoscleral limbus - the width of the opening of the ciliary cleft (CC), the width of the mid-CC, the length of the CC, and the anterior chamber (AC) depth (distance between the corneal endothelium and the anterior lens capsule). Mydriasis resulting from the topical use of 0.5% tropicamide is associated with an increase in the geometric ICA and a decrease in the opening of the CC, without any effect on the width of the mid-CC, or on the length of the CC, or on the AC depth. Mydriasis induced by topical 0.5% tropicamide results in modification of the anterior segment which may influence the drainage of aqueous humor. © 2012 American College of Veterinary Ophthalmologists.

  14. CDC Vital Signs: Preventing Repeat Teen Births (United States)

    ... text version SOURCE: Adapted from Trussell J in Contraceptive Technology, 2011, and FDA Office of Women’s Health ... about how to avoid repeat births with both male and female teens. ...

  15. DNA repair in the trinucleotide repeat disorders. (United States)

    Jones, Lesley; Houlden, Henry; Tabrizi, Sarah J


    Inherited diseases caused by unstable repeated DNA sequences are rare, but together represent a substantial cause of morbidity. Trinucleotide repeat disorders are severe, usually life-shortening, neurological disorders caused by nucleotide expansions, and most have no disease-modifying treatments. Longer repeat expansions are associated with genetic anticipation (ie, earlier disease onset in successive generations), although the differences in age at onset are not entirely accounted for by repeat length. Such phenotypic variation within disorders implies the existence of additional modifying factors in pathways that can potentially be modulated to treat disease. A genome-wide association study detected genetic modifiers of age at onset in Huntington's disease. Similar findings were seen in the spinocerebellar ataxias, indicating an association between DNA damage-response and repair pathways and the age at onset of disease. These studies also suggest that a common genetic mechanism modulates age at onset across polyglutamine diseases and could extend to other repeat expansion disorders. Genetic defects in DNA repair underlie other neurodegenerative disorders (eg, ataxia-telangiectasia), and DNA double-strand breaks are crucial to the modulation of early gene expression, which provides a mechanistic link between DNA repair and neurodegeneration. Mismatch and base-excision repair are important in the somatic expansion of repeated sequences in mouse models of trinucleotide repeat disorders, and somatic expansion of the expanded CAG tract in HTT correlates with age at onset of Huntington's disease and other trinucleotide repeat disorders. WHERE NEXT?: To understand the common genetic architecture of trinucleotide repeat disorders and any further genetic susceptibilities in individual disorders, genetic analysis with increased numbers of variants and sample sizes is needed, followed by sequencing approaches to define the phenotype-modifying variants. The findings must

  16. Archaeal Nucleosome Positioning by CTG Repeats


    Sandman, Kathleen; Reeve, John N.


    DNA shape recognition determines the preferred binding sites for sequence-independent DNA binding proteins, and here we document that archaeal histones assemble archaeal nucleosomes in vitro centered preferentially within (CTG)6 and (CTG)8 repeats, close to junctions with flanking mixed-sequence DNA. Archaeal nucleosomes were not positioned by (CTG)4-, (CTG)5-, or (CTG)3AA(CTG)3-containing DNA sequences. The features of CTG repeat-containing sequences that direct eucaryal nucleosome positioni...

  17. Blockwise Repeated Burst Error Correcting Linear Codes

    Directory of Open Access Journals (Sweden)

    B.K. Dass


    Full Text Available This paper presents a lower and an upper bound on the number of parity check digits required for a linear code that corrects a single sub-block containing errors which are in the form of 2-repeated bursts of length b or less. An illustration of such kind of codes has been provided. Further, the codes that correct m-repeated bursts of length b or less have also been studied.

  18. Monitoring plant phenology using digital repeat photography. (United States)

    Crimmins, Michael A; Crimmins, Theresa M


    Repeated observations of plant phenology have been shown to be important indicators of global change. However, capturing the exact date of key events requires daily observations during the growing season, making phenologic observations relatively labor intensive and costly to collect. One alternative to daily observations for capturing the dates of key phenologic events is repeat photography. In this study, we explored the utility of repeat digital photography for monitoring phenologic events in plants. We provide an illustration of this approach and its utility by placing observations made using repeat digital imagery in context with local meteorologic and edaphic variables. We found that repeat photography provides a reliable, consistent measurement of phenophase. In addition, digital photography offers advantages in that it can be mathematically manipulated to detect and enhance patterns; it can classify objects; and digital photographs can be archived for future analysis. In this study, an estimate of greenness and counts of individual flowers were extracted by way of mathematic algorithms from the photo time series. These metrics were interpreted using meteorologic measurements collected at the study site. We conclude that repeat photography, coupled with site-specific meteorologic measurements, could greatly enhance our understanding environmental triggers of phenologic events. In addition, the methods described could easily be adopted by citizen scientists and the general public as well as professionals in the field.

  19. Digital repeat analysis; setup and operation. (United States)

    Nol, J; Isouard, G; Mirecki, J


    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  20. Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal (United States)

    Beaver, Jill M.; Lai, Yanhao; Rolle, Shantell J.; Liu, Yuan


    DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively. We showed that PCNA stimulated LIG I activity on a nick across a small template loop during BER in a duplex (CAG)20 repeat tract promoting small repeat deletions. Surprisingly, we found that during BER in a hairpin loop, PCNA promoted reannealing of the upstream flap of a double-flap intermediate, thereby facilitating the formation of a downstream flap and stimulating FEN1 cleavage activity and hairpin removal. Our results indicate that PCNA plays a critical role in preventing CAG repeat expansions by modulating the structures of dynamic DNA via cooperation with BER enzymes. We provide the first evidence that PCNA prevents CAG repeat expansions during BER by promoting CAG repeat deletion and removal of a TNR hairpin. PMID:27793507

  1. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)


    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  2. Risk factors for repeat abortion in Nepal. (United States)

    Thapa, Shyam; Neupane, Shailes


    To examine the incidence of and risk factors for repeat abortion in Nepal. Data were analyzed from a survey of 1172 women who had surgical abortions between December 2009 and March 2010 in 2 clinics in Kathmandu, Nepal. Bivariate and multivariate logistic regressions were performed to estimate odds ratios for the risk factors. Among the respondents, 32.3% (95% confidence interval, 29.6-34.9) had repeat abortions. This incidence rose sharply with age and parity, and was higher among those with no intention of having a future child, those attaining primary or secondary level education, and those attending the non-governmental sector clinic. Women with repeat abortion were similar to those with 1 abortion in terms of contraceptive practice. Among women not using contraceptives at the time of the unintended pregnancy, the 3 most commonly cited reasons were ill health, non-compliance with the method intended for use, and dislike of the method. Women with repeat abortion showed a pattern of contraceptive acceptance immediately after the procedure similar to that of women who had 1 abortion. Repeat abortion is emerging as a major public health issue in Nepal, with implications for counseling and provision of abortion, and for family planning services. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  3. The effectiveness of ayurvedic oil-based nasal instillation (Nasya) medicines in the treatment of facial paralysis (Ardita): a systematic review. (United States)

    Vivera, Manuel Joseph; Gomersall, Judith Streak


    Ardita (facial paralysis) is a medical condition that disfigures or distorts the facial appearance of the sufferer causing facial asymmetry and malfunction. Ardita patients may benefit from considering alternative treatments such as Ayurveda, including Taila Nasya (nasal instillation of medicated oil). To synthesize the best available evidence on the effectiveness of different Nasya oils in the treatment of Ardita. Studies conducted on adult sufferers (18-70 years) of Ardita (chronic or acute) in any setting were considered. Studies including participants who were pregnant or suffered allergic rhinitis, fever, intracranial tumor/hemorrhage and bilateral facial palsy were excluded. Standalone treatment of Nasya (at all dosages and frequencies) compared to Nasya in combination with other Ayurvedic treatments was considered. Comparisons between different interventions including Taila Nasya alone, Taila Nasya in combination with other Ayurvedic interventions and Ayurvedic interventions that did not include Taila Nasya were also considered. Changes in Ardita symptoms, including facial distortion, speech disorders and facial pain, were measured. All quantitative study designs (experimental, quasi-experimental and observational) were considered. Relevant studies were identified following a comprehensive literature search. References provided within these key studies identified additional resources. Indian universities were also contacted for results of Ardita studies undertaken in their institutions.A three-step search strategy aimed to find studies of published and unpublished studies was undertaken. Studies published in the English language were considered for inclusion, irrespective of publication date/year. Following an initial limited search of MEDLINE and CINAHL, the text words contained in the title and abstract, and of the index terms used to describe each articles were analyzed. From the identified keywords and index terms, searches were undertaken across all

  4. 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: [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)


    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.

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


    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

  6. Photometric Repeatability of Scanned Imagery: UVIS (United States)

    Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia


    We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

  7. simple sequence repeats (EST-SSR)

    African Journals Online (AJOL)



    Jan 19, 2012 ... repeats (EST-SSR) markers characterized by new bioinformatic criteria reveal high genetic similarity in sugarcane (Saccharum spp.) breeding lines. Kittipat Ukoskit1*, Penjun Thipmongkolcharoen1 and Prasert Chatwachirawong2. 1Department of Biotechnology, Faculty of Science and Technology, ...

  8. FRB 121102: A Starquake-induced Repeater? (United States)

    Wang, Weiyang; Luo, Rui; Yue, Han; Chen, Xuelei; Lee, Kejia; Xu, Renxin


    Since its initial discovery, the fast radio burst (FRB) FRB 121102 has been found to be repeating with millisecond-duration pulses. Very recently, 14 new bursts were detected by the Green Bank Telescope during its continuous monitoring observations. In this paper, we show that the burst energy distribution has a power-law form which is very similar to the Gutenberg–Richter law of earthquakes. In addition, the distribution of burst waiting time can be described as a Poissonian or Gaussian distribution, which is consistent with earthquakes, while the aftershock sequence exhibits some local correlations. These findings suggest that the repeating FRB pulses may originate from the starquakes of a pulsar. Noting that the soft gamma-ray repeaters (SGRs) also exhibit such distributions, the FRB could be powered by some starquake mechanisms associated with the SGRs, including the crustal activity of a magnetar or solidification-induced stress of a newborn strangeon star. These conjectures could be tested with more repeating samples.

  9. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander


    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly...

  10. [Preventive maintenance of repeated ischemic insults]. (United States)

    Gavrilenko, A V; Kuklin, A V; Kravchenko, A A; Agafonov, I N


    In the review we offer analysis of the effectiveness of carotid endarterectomy in treatment of post-functional apoplexy or stroke patients. Published results of the researches specify possible efficiency of carotid endarterectomy in preventive maintenance against repeated apoplectic attack or strokes. Yet the criteria of usage and execution of the carotid endarterectomy are still to be discussed.

  11. Early repeated maternal separation induces alterations of ...

    Indian Academy of Sciences (India)

    The long-term effects of repeated maternal separation (MS) during early postnatal life on reelin expression in the hippocampus of developing rats were investigated in the present study. MS was carried out by separating Wistar rat pups singly from their mothers for 3 h a day during postnatal days (PND) 2–14. Reelin mRNA ...

  12. 47 CFR 22.1015 - Repeater operation. (United States)


    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... the time. Table I-2—Maximum ERP (Watts) Distance from the 4.8 km (3 mi) limit 30 meters (100 feet) 61...

  13. Repeated events and total time on test

    DEFF Research Database (Denmark)

    Kvist, Kajsa; Andersen, Per Kragh; Angst, Jules


    We adopt the total time on test procedure to investigate monotone time trends in the intensity in a repeated event setting. The correct model is assumed to be a proportional hazards model, with a random effect to account for dependence within subjects. The method offers a simple routine for testi...... and a long-term Swiss clinical study on recurrence in affective disorder....

  14. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir


    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  15. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)



    Dec 18, 2006 ... Simple sequence repeats (SSRs) or microsatellites are the repetitive sequence motifs of 1–6 bp (Schlotterer 2000). They are scattered throughout the genomes of all the known organisms ranging from viruses to eukaryotes (Heller et al. 1982; Ellegren 2004). The origin, evolution and ubiquitous occurrence ...

  16. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts


    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  17. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter


    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads to s...... method involving differences between orthogonal projections onto subspaces generated by within-subject models....

  18. Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats. (United States)

    Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A


    Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.

  19. Inhibition of breast cancer cell proliferation in repeated and non-repeated treatment with zoledronic acid

    Directory of Open Access Journals (Sweden)

    Ibrahim Toni


    Full Text Available Abstract Background Zoledronic acid is used to treat bone metastases and has been shown to reduce skeletal-related events and exert antitumor activity. The present in vitro study investigates the mechanism of action of Zoledronic Acid on breast cancer cell lines with different hormonal and HER2 patterns. Furthermore, we investigated the efficacy of repeated versus non-repeated treatments. Methods The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and MDA-MB-231. Non-repeated treatment (single exposure of 168 hrs’ duration with zoledronic acid was compared with repeated treatment (separate exposures, each of 48 hrs’ duration, for a total of 168 hrs at different dosages. A dose–response profile was generated using sulforhodamine B assay. Apoptosis was evaluated by TUNEL assay and biomolecular characteristics were analyzed by western blot. Results Zoledronic acid produced a dose-dependent inhibition of proliferation in all cell lines. Anti-proliferative activity was enhanced with the repeated treatment, proving to be statistically significant in the triple-negative lines. In these lines repeated treatment showed a cytocidal effect, with apoptotic cell death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK expression. Apoptosis was not observed in estrogen receptor-positive line: p21 overexpression suggested a slowing down of cell cycle. A decrease in RAS and pMAPK expression was seen in HER2-overexpressing line after treatment. Conclusions The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Repeated treatment has a killing effect on triple-negative lines due to apoptosis activation. Further research is warranted especially in the treatment of triple-negative breast cancer.


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


    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...

  2. Incidence of Repeat Breeding Syndrome in Cattle from Four Local ...

    African Journals Online (AJOL)

    The study investigated the incidence of repeat breeding syndrome in cattle and determined the progesterone profile of repeat breeders in four Local Government Areas of Adamawa State, Nigeria. One hundred herds were sampled during the study and fifty-seven repeat breeders were identified. The proportions of repeat ...

  3. 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


    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.

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

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


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

  5. Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

    Directory of Open Access Journals (Sweden)

    Yu Cong


    Full Text Available Nipah virus (NiV is a paramyxovirus (genus Henipavirus that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM model following intratracheal (IT and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT and magnetic resonance imaging (MRI to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human

  6. Repeated interactions in open quantum systems

    Energy Technology Data Exchange (ETDEWEB)

    Bruneau, Laurent, E-mail: [Laboratoire AGM, Université de Cergy-Pontoise, Site Saint-Martin, BP 222, 95302 Cergy-Pontoise (France); Joye, Alain, E-mail: [Institut Fourier, UMR 5582, CNRS-Université Grenoble I, BP 74, 38402 Saint-Martin d’Hères (France); Merkli, Marco, E-mail: [Department of Mathematics and Statistics Memorial University of Newfoundland, St. John' s, NL Canada A1C 5S7 (Canada)


    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  7. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.


    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

  8. Hypoglycaemic hemiplegia: a repeat SPECT study. (United States)

    Shintani, S; Tsuruoka, S; Shiigai, T


    During a hypoglycaemic right hemiplegia induced by a deliberate overdose of oral hypoglycaemics, brain CT and angiography revealed no abnormalities. SPECTs made one day and six days later showed relative hypoperfusion in the left hemisphere. Repeat SPECT study suggested that the left hemisphere was more vulnerable than the right in the cerebral blood perfusion. This vulnerability might provoke the right hemiplegia in a critical condition, such as severe hypoglycaemia. Images PMID:8509788

  9. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus


    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  10. 2D Metals by Repeated Size Reduction. (United States)

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui


    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe


    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  12. Repeated Measurement of Divers’ Word Fluency. (United States)


    side if necessary and identify by block number) WORD FLUENCY MEASUREMENT NEUROPSYCHOLOGY PSYCHOLOGY DIVING NAVSEA TASK NO. 86-54 SATURATION NEDU TEST...WORDS: <II Word Fluency--,, Neuropsychology’-" Diving Saturation Measurement Pyschology NAVSEA Task #86-54 NEDU Test Plan #86-10 v N. .,#7V REPEATED...function (Fillskov & Boll, -V 1981). One type of test with clinical significance reflects Word Fluency (Borkowski, Benton & Spreen, 1967; Lezak, 1983). Word

  13. Multiplexed Memory-Insensitive Quantum Repeaters


    Collins, O. A.; Jenkins, S. D.; Kuzmich, A.; Kennedy, T. A. B.


    Long-distance quantum communication via distant pairs of entangled quantum bits (qubits) is the first step towards more secure message transmission and distributed quantum computing. To date, the most promising proposals require quantum repeaters to mitigate the exponential decrease in communication rate due to optical fiber losses. However, these are exquisitely sensitive to the lifetimes of their memory elements. We propose a multiplexing of quantum nodes that should enable the construction...

  14. Security of Quantum Repeater Network Operation (United States)


    taxonomies for RFID tags, because both RFID tags and quantum links and nodes are sensitive to their local environment, and attacks at the physical level...vulnerable to being hacked . Thus, operation of the quantum repeater network is vulnerable to undetectable disruption of the network operation. This...Jogenfors, J., Elhassan, A. M., Ahrens, J., Bourennane, M., & Larsson, J. (2015). Hacking the Bell test using classical light in energy-time

  15. Multiplexing schemes for quantum repeater networks (United States)

    Aparicio, Luciano; Van Meter, Rodney


    When built, quantum repeaters will allow the distribution of entangled quantum states across large distances, playing a vital part in many proposed quantum technologies. Enabling multiple users to connect through the same network will be key to their real-world deployment. Previous work on repeater technologies has focussed only on simple entanglment production, without considering the issues of resource scarcity and competition that necessarily arise in a network setting. In this paper we simulated a thirteen-node network with up to five flows sharing different parts of the network, measuring the total throughput and fairness for each case. Our results suggest that the Internet-like approach of statistical multiplexing use of a congested link gives the highest aggregate throughput. Time division multiplexing and buffer space multiplexing were slightly less effective, but all three schemes allow the sum of multiple flows to substantially exceed that of any one flow, improving over circuit switching by taking advantage of resources that are forced to remain idle in circuit switching. All three schemes proved to have excellent fairness. The high performance, fairness and simplicity of implementation support a recommendation of statistical multiplexing for shared quantum repeater networks.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. Stalled DNA Replication Forks at the Endogenous GAA Repeats Drive Repeat Expansion in Friedreich's Ataxia Cells. (United States)

    Gerhardt, Jeannine; Bhalla, Angela D; Butler, Jill Sergesketter; Puckett, James W; Dervan, Peter B; Rosenwaks, Zev; Napierala, Marek


    Friedreich's ataxia (FRDA) is caused by the expansion of GAA repeats located in the Frataxin (FXN) gene. The GAA repeats continue to expand in FRDA patients, aggravating symptoms and contributing to disease progression. The mechanism leading to repeat expansion and decreased FXN transcription remains unclear. Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3'-5' progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases. Treatment of FRDA cells with GAA-specific polyamides rescues DNA replication fork stalling and alleviates expansion of the GAA repeats, implicating DNA triplexes as a replication impediment and suggesting that fork stalling might be a therapeutic target for FRDA. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Repeated buckling of composite shear panels (United States)

    Singer, Josef; Weller, Tanchum


    Failures in service of aerospace structures and research at the Technion Aircraft Structures Laboratory have revealed that repeatedly buckled stiffened shear panels might be susceptible to premature fatigue failures. Extensive experimental and analytical studies have been performed at Technion on repeated buckling, far in excess of initial buckling, for both metal and composite shear panels with focus on the influence of the surrounding structure. The core of the experimental investigation consisted of repeated buckling and postbuckling tests on Wagner beams in a three-point loading system under realistic test conditions. The effects of varying sizes of stiffeners, of the magnitude of initial buckling loads, of the panel aspect ratio and of the cyclic shearing force, V sub cyc, were studied. The cyclic to critical shear buckling ratios, (V sub cyc/V sub cr) were on the high side, as needed for efficient panel design, yet all within possible flight envelopes. The experiments were supplemented by analytical and numerical analyses. For the metal shear panels the test and numerical results were synthesized into prediction formulas, which relate the life of the metal shear panels to two cyclic load parameters. The composite shear panels studied were hybrid beams with graphite/epoxy webs bonded to aluminum alloy frames. The test results demonstrated that composite panels were less fatigue sensitive than comparable metal ones, and that repeated buckling, even when causing extensive damage, did not reduce the residual strength by more than 20 percent. All the composite panels sustained the specified fatigue life of 250,000 cycles. The effect of local unstiffened holes on the durability of repeatedly buckled shear panels was studied for one series of the metal panels. Tests on 2024 T3 aluminum panels with relatively small unstiffened holes in the center of the panels demonstrated premature fatigue failure, compared to panels without holes. Preliminary tests on two graphite

  19. Repeated-sprint ability and aerobic fitness. (United States)

    Thébault, Nicolas; Léger, Luc A; Passelergue, Philippe


    The purpose of this study was to reinvestigate the relationship between aerobic fitness and fatigue indices of repeated-sprint ability (RSA), with special attention to methodological normalization. Soldiers were divided into low (n = 10) and high (n = 9) fitness groups according to a preset maximal aerobic speed (MAS) of 17 km·h(-1) (∼60 ml O2·kg(-1)·min) measured with the University of Montreal Track Test (UMTT). Subjects' assessment included the RSA test (3 sets of 5 40-m sprints with 1-minute rest between sprints and 1.5 minutes between sets), a 40-m sprint (criterion test used in the computation of fatigue indices for the RSA test), strength and power measurement of the lower limbs, and the 20-m shuttle run test (20-m SRT) and the UMTT, which are measures of maximal aerobic power. The highest correlation with the RSA fatigue indices was obtained with the 20-m SRT (r = 0.90, p = 0.0001, n = 19), a test with 180° direction changes and accelerations and decelerations. The lower correlation (r = 0.66, p tests better disclose the importance of aerobic fitness for RSA and that aerobic power is not the sole determinant of RSA. However, neither strength nor vertical jumping power was correlated to the RSA fatigue indices. Subjects with greater MAS were able to maintain almost constant level of speed throughout series of repeated sprints and achieved better recovery between series. A MAS of at least 17 km·h(-1) favors constant and high speed level during repeated sprints. From a practical point of view, a high aerobic fitness is a precious asset in counteracting fatigue in sports with numerous sprint repetitions.

  20. Identifying uniformly mutated segments within repeats. (United States)

    Sahinalp, S Cenk; Eichler, Evan; Goldberg, Paul; Berenbrink, Petra; Friedetzky, Tom; Ergun, Funda


    Given a long string of characters from a constant size alphabet we present an algorithm to determine whether its characters have been generated by a single i.i.d. random source. More specifically, consider all possible n-coin models for generating a binary string S, where each bit of S is generated via an independent toss of one of the n coins in the model. The choice of which coin to toss is decided by a random walk on the set of coins where the probability of a coin change is much lower than the probability of using the same coin repeatedly. We present a procedure to evaluate the likelihood of a n-coin model for given S, subject a uniform prior distribution over the parameters of the model (that represent mutation rates and probabilities of copying events). In the absence of detailed prior knowledge of these parameters, the algorithm can be used to determine whether the a posteriori probability for n=1 is higher than for any other n>1. Our algorithm runs in time O(l4logl), where l is the length of S, through a dynamic programming approach which exploits the assumed convexity of the a posteriori probability for n. Our test can be used in the analysis of long alignments between pairs of genomic sequences in a number of ways. For example, functional regions in genome sequences exhibit much lower mutation rates than non-functional regions. Because our test provides means for determining variations in the mutation rate, it may be used to distinguish functional regions from non-functional ones. Another application is in determining whether two highly similar, thus evolutionarily related, genome segments are the result of a single copy event or of a complex series of copy events. This is particularly an issue in evolutionary studies of genome regions rich with repeat segments (especially tandemly repeated segments).

  1. Repeatability and Reproducibility of Virtual Subjective Refraction. (United States)

    Perches, Sara; Collados, M Victoria; Ares, Jorge


    To establish the repeatability and reproducibility of a virtual refraction process using simulated retinal images. With simulation software, aberrated images corresponding with each step of the refraction process were calculated following the typical protocol of conventional subjective refraction. Fifty external examiners judged simulated retinal images until the best sphero-cylindrical refraction and the best visual acuity were achieved starting from the aberrometry data of three patients. Data analyses were performed to assess repeatability and reproducibility of the virtual refraction as a function of pupil size and aberrometric profile of different patients. SD values achieved in three components of refraction (M, J0, and J45) are lower than 0.25D in repeatability analysis. Regarding reproducibility, we found SD values lower than 0.25D in the most cases. When the results of virtual refraction with different pupil diameters (4 and 6 mm) were compared, the mean of differences (MoD) obtained were not clinically significant (less than 0.25D). Only one of the aberrometry profiles with high uncorrected astigmatism shows poor results for the M component in reproducibility and pupil size dependence analysis. In all cases, vision achieved was better than 0 logMAR. A comparison between the compensation obtained with virtual and conventional subjective refraction was made as an example of this application, showing good quality retinal images in both processes. The present study shows that virtual refraction has similar levels of precision as conventional subjective refraction. Moreover, virtual refraction has also shown that when high low order astigmatism is present, the refraction result is less precise and highly dependent on pupil size.

  2. Mechanical processes with repeated attenuated impacts

    CERN Document Server

    Nagaev, R F


    This book is devoted to considering in the general case - using typical concrete examples - the motion of machines and mechanisms of impact and vibro-impact action accompanied by a peculiar phenomenon called "impact collapse". This phenomenon is that after the initial collision, a sequence of repeated gradually quickening collisions of decreasing-to-zero intensity occurs, with the final establishment of protracted contact between the interacting bodies. The initiation conditions of the impact collapse are determined and calculation techniques for the quantitative characteristics of the corresp

  3. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland


    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...... that for every level of renegotiation cost, there exists a discount factor such that any collusive profit can be supported as an equilibrium outcome. Hence, any arbitrary small renegotiation cost will suffice to facilitate collusive outcomes for sufficiently patient firms. This result stands in stark contrast...

  4. Repeat Sequence Proteins as Matrices for Nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Drummy, L.; Koerner, H; Phillips, D; McAuliffe, J; Kumar, M; Farmer, B; Vaia, R; Naik, R


    Recombinant protein-inorganic nanocomposites comprised of exfoliated Na+ montmorillonite (MMT) in a recombinant protein matrix based on silk-like and elastin-like amino acid motifs (silk elastin-like protein (SELP)) were formed via a solution blending process. Charged residues along the protein backbone are shown to dominate long-range interactions, whereas the SELP repeat sequence leads to local protein/MMT compatibility. Up to a 50% increase in room temperature modulus and a comparable decrease in high temperature coefficient of thermal expansion occur for cast films containing 2-10 wt.% MMT.

  5. The Perpetual Repeater: an Educative Musical Experience.

    Directory of Open Access Journals (Sweden)

    Svetlana Skriagina


    Full Text Available To commemorate the 40th anniversary of the Music Undergraduate Program of the Universidad Pedagógica Nacional (National Pedagogic University, two musical events were planned: an original work written for choir, soloists and symphonic band, and an opera for children. As a result, the cantata ‘The Perpetual Repeater” has been created as an adaptation of a work named “50 Milions de Segons” (50 Millions of Seconds, staged by the CATANIA project of the Barcelona Servei Educatiu de L’Auditori. This work tells the story of those school teachers who, paradoxically enough repeat the same course year after year. After visiting L’Auditori of Barcelona to participate in the pedagogic musical work carried out with school children, we considered the possibility of developing an analogous project, in a similar sociocultural and educational environment, within our Music Undergraduate Program. So, this article deals with two fundamental moments which are essential to understand the educational work implemented with the ISPA students of sixth degree, as well as with a group of the program’s students: The Purpose, which describes in detail the planning of the musical work for children, and The Experience, in which the way the process of The Perpetual Repeater Cantatawas carried out is described.

  6. Aggregating quantum repeaters for the quantum internet (United States)

    Azuma, Koji; Kato, Go


    The quantum internet holds promise for accomplishing quantum teleportation and unconditionally secure communication freely between arbitrary clients all over the globe, as well as the simulation of quantum many-body systems. For such a quantum internet protocol, a general fundamental upper bound on the obtainable entanglement or secret key has been derived [K. Azuma, A. Mizutani, and H.-K. Lo, Nat. Commun. 7, 13523 (2016), 10.1038/ncomms13523]. Here we consider its converse problem. In particular, we present a universal protocol constructible from any given quantum network, which is based on running quantum repeater schemes in parallel over the network. For arbitrary lossy optical channel networks, our protocol has no scaling gap with the upper bound, even based on existing quantum repeater schemes. In an asymptotic limit, our protocol works as an optimal entanglement or secret-key distribution over any quantum network composed of practical channels such as erasure channels, dephasing channels, bosonic quantum amplifier channels, and lossy optical channels.

  7. Extending Teach and Repeat to Pivoting Wheelchairs

    Directory of Open Access Journals (Sweden)

    Guillermo Del Castillo


    Full Text Available The paper extends the teach-and-repeat paradigm that has been successful for the control of holonomic robots to nonholonomic wheelchairs which may undergo pivoting action over the course of their taught movement. Due to the nonholonomic nature of the vehicle kinematics, estimation is required -- in the example given herein, based upon video detection of wall-mounted cues -- both in the teaching and the tracking events. In order to accommodate motion that approaches pivoting action as well as motion that approaches straight-line action, the estimation equations of the Extended Kalman Filter and the control equations are formulated using two different definitions of a nontemporal independent variable. The paper motivates the need for pivoting action in real-life settings by reporting extensively on the abilities and limitations of estimation-based teach-and-repeat action where pivoting and near-pivoting action is disallowed. Following formulation of the equations in the near-pivot mode, the paper reports upon experiments where taught trajectories which entail a seamless mix of near-straight and near-pivot action are tracked.

  8. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.


    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  9. Repeatable assessment protocol for electromagnetic trackers (United States)

    Haidegger, Tamas; Sirokai, Beáta; Fenyvesi, Gábor; Kovács, Levente; Benyó, Balázs; Benyó, Zoltán


    In the past decades, many new trends appeared in interventional medicine. One of the most groundbreaking ones is Image-Guided Surgery (IGS). The main benefit of IGS procedures is the reduction of the patient's pain and collateral damage through improved accuracy and targeting. Electromagnetic Tracking (EMT) has been introduced to medical applications as an effective tool for navigation. However, magnetic fields can be severely distorted by ferromagnetic materials and electronic equipment, which is a major barrier towards their wider application. The focus of the study is to determine and compensate the inherent errors of the different types of EMTs, in order to improve their accuracy. Our aim is to develop a standardized, simple and repeatable assessment protocol; to determine tracking errors with sub-millimeter accuracy, hence increasing the measurement precision and reliability. For initial experiments, the NDI Aurora and the Ascension medSAFE systems were used in a standard laboratory environment. We aim to advance to the state-of-the art by describing and disseminating an easily reproducible calibration method, publishing the CAD files of the accuracy phantom and the source of the evaluation data. This should allow the wider spread of the technique, and eventually lead to the repeatable and comparable assessment of EMT systems.

  10. TERRA: telomeric repeat-containing RNA. (United States)

    Luke, Brian; Lingner, Joachim


    Telomeres, the physical ends of eukaryotic chromosomes, consist of tandem arrays of short DNA repeats and a large set of specialized proteins. A recent analysis has identified telomeric repeat-containing RNA (TERRA), a large non-coding RNA in animals and fungi, which forms an integral component of telomeric heterochromatin. TERRA transcription occurs at most or all chromosome ends and it is regulated by RNA surveillance factors and in response to changes in telomere length. TERRA functions that are emerging suggest important roles in the regulation of telomerase and in orchestrating chromatin remodelling throughout development and cellular differentiation. The accumulation of TERRA at telomeres can also interfere with telomere replication, leading to a sudden loss of telomere tracts. Such a phenotype can be observed upon impairment of the RNA surveillance machinery or in cells from ICF (Immunodeficiency, Centromeric region instability, Facial anomalies) patients, in which TERRA is upregulated because of DNA methylation defects in the subtelomeric region. Thus, TERRA may mediate several crucial functions at the telomeres, a region of the genome that had been considered to be transcriptionally silent.

  11. Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

    Directory of Open Access Journals (Sweden)

    Ahmed Abdulkadhim Hamad


    Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

  12. The absolute number of repeat operations for complex intra ...

    African Journals Online (AJOL)

    abdominal sepsis, questions about futility of treatment frequently arise. This study focuses specifically on patients who required two or more repeat laparotomies and describes the spectrum of disease necessitating multiple repeat laparotomies ...

  13. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)


    of triplet repeats (Pearson and Sinden 1998a; Sinden. 1999). Expansions or deletions can occur by simple. Table 1. Trinucleotide repeats in human genetic disease. Repeat length. Disease. Gene. Locus. Repeata. Normal. Pre- mutation. Disease. Protein/possible biological effect of expansion. Fragile X syndrome. FMR1.

  14. Novel expressed sequence tag- simple sequence repeats (EST-SSR)

    African Journals Online (AJOL)

    Using different bioinformatic criteria, the SUCEST database was used to mine for simple sequence repeat (SSR) markers. Among 42,189 clusters, 1,425 expressed sequence tag- simple sequence repeats (EST-SSRs) were identified in silico. Trinucleotide repeats were the most abundant SSRs detected. Of 212 primer pairs ...

  15. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)

    Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA. Richard R Sinden Vladimir N ... Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, ...

  16. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed? (United States)

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.


    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  17. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated? (United States)

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal


    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  18. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2. (United States)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten; Skovby, Flemming; Hjermind, Lena E; Nielsen, Jørgen E; Nielsen, Troels Tolstrup


    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which - like CAG codons - code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.

  19. The hidden price of repeated traumatic exposure. (United States)

    Levy-Gigi, Einat; Richter-Levin, Gal


    Neuroimaging studies have demonstrated reduced hippocampal volume in trauma-exposed individuals without posttraumatic stress disorder (PTSD). However, the implications of such a deficit in this non-clinical population are still unclear. Animal and human models of PTSD suggest that hippocampal deficit may result in impaired learning and use of associations between contextual information and aversive events. Previous study has shown that individuals with PTSD have a selective impairment in reversing the negative outcome of context-related information. The aim of this study was to test whether non-PTSD individuals who are repeatedly exposed to traumatic events display similar impairment. To that end, we compared the performance of active-duty firefighters who are frequently exposed to traumatic events as part of their occupational routine and civilian matched-controls with no history of trauma-exposure. We used a novel cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context-related information. As predicted, we found that while both trauma-exposed firefighters and unexposed matched-controls were able to acquire and retain stimulus-outcome associations, firefighters struggled to learn that a previously negative context is later associated with a positive outcome. This impairment did not correlate with levels of PTSD, anxiety or depressive symptoms. The results suggest that similar to individuals with PTSD, highly exposed individuals fail to associate traumatic outcomes with their appropriate context. This impairment may reflect a possible hidden price of repeated traumatic exposure, which is not necessarily associated with PTSD diagnosis, and may affect the way highly exposed individuals interpret and react to their environment.

  20. Repeat spine imaging in transferred emergency department patients. (United States)

    Bible, Jesse E; Kadakia, Rishin J; Kay, Harrison F; Zhang, Chi E; Casimir, Geoffrey E; Devin, Clinton J


    Retrospective study. Assess frequency of repeat spine imaging in patients transferred with known spine injuries from outside hospital (OSH) to tertiary receiving institution (RI). Unnecessary repeat imaging after transfer has started to become a recognized problem with the obvious issues related to repeat imaging along with potential for iatrogenic injury with movement of patients with spine problems. Consecutive adult patients presenting to a single 1-level trauma center with spine injuries during a 51-month period were reviewed (n = 4500), resulting in 1427 patients transferred from OSH emergency department. All imaging and radiology reports from the OSH were reviewed, as well as studies performed at RI. A repeat was the same imaging modality used on the same spine region as OSH imaging. The overall rate of repeat spine imaging for both OSH imaging sent and not sent was 23%, and 6% if repeat spine imaging via traumagram (partial/full-body computed tomography [CT]) was excluded as a repeat. The overall rate of repeat CT was 29% (7% dedicated spine CT scans and 22% part of nondedicated spine CT scan).An observation of only those patients with OSH imaging that was sent and viewable revealed that 23% underwent repeat spine imaging with 23% undergoing repeat spine CT and 41% repeat magnetic resonance imaging.In those patients with sent and viewable OSH imaging, a lack of reconstructions prompted 14% of repeats, whereas inadequate visualization of injury site prompted 8%. In only 8% of the repeats did it change management or provide necessary surgical information. This study is the first to investigate the frequency of repeat spine imaging in transfers with known spine injuries and found a substantially high rate of repeat spine CT with minimal alteration in care. Potential solutions include only performing scans at the OSH necessary to establish a diagnosis requiring transfer and improving communication between OSH and RI physicians. 4.

  1. Role of DNA Polymerases in Repeat-Mediated Genome Instability

    Directory of Open Access Journals (Sweden)

    Kartik A. Shah


    Full Text Available Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich’s ataxia (GAAn repeats in a yeast experimental system. The elementary step of expansion corresponded to ∼160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, suggesting a link between the scale of expansions and Okazaki fragment size. Expandable repeats strongly elevated the rate of mutations at substantial distances around them, a phenomenon we call repeat-induced mutagenesis (RIM. Notably, defects in the replicative DNA polymerases δ and ∊ strongly increased rates for both repeat expansions and RIM. The increases in repeat-mediated instability observed in DNA polymerase δ mutants depended on translesion DNA polymerases. We conclude that repeat expansions and RIM are two sides of the same replicative mechanism.

  2. Structural and Energetic Characterization of the Ankyrin Repeat Protein Family.

    Directory of Open Access Journals (Sweden)

    R Gonzalo Parra


    Full Text Available Ankyrin repeat containing proteins are one of the most abundant solenoid folds. Usually implicated in specific protein-protein interactions, these proteins are readily amenable for design, with promising biotechnological and biomedical applications. Studying repeat protein families presents technical challenges due to the high sequence divergence among the repeating units. We developed and applied a systematic method to consistently identify and annotate the structural repetitions over the members of the complete Ankyrin Repeat Protein Family, with increased sensitivity over previous studies. We statistically characterized the number of repeats, the folding of the repeat-arrays, their structural variations, insertions and deletions. An energetic analysis of the local frustration patterns reveal the basic features underlying fold stability and its relation to the functional binding regions. We found a strong linear correlation between the conservation of the energetic features in the repeat arrays and their sequence variations, and discuss new insights into the organization and function of these ubiquitous proteins.

  3. 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)


    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.)

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

    DEFF Research Database (Denmark)

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


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

  5. Transdifferentiation of Small Cell Carcinoma of the Urinary Bladder from Urothelial Carcinoma after Transurethral Resection of a Bladder Tumor, Intravesical Bacillus Calmette-Guerin Instillation, and Chemotherapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Kento Morozumi


    Full Text Available A 73-year-old male underwent transurethral resection of a bladder tumor in August 2010 and April 2011. Pathological examination revealed urothelial carcinoma. After the surgery, chemotherapy and intravesical Bacillus Calmette-Guerin instillation were performed. In September 2014, he once again underwent transurethral resection of the bladder tumor for recurrence, and was again diagnosed with urothelial carcinoma, pT2, by pathological examination. After neoadjuvant chemotherapy, radical cystectomy for tumor recurrence was performed. Pathological examination at this time revealed small cell carcinoma, pT3N0. It is rare for urothelial carcinoma to change to small cell carcinoma, and the mechanism and cause of this change are still unknown. In this case report, we discuss what causes small cell carcinoma of the urinary bladder and review the literature regarding its origin.

  6. Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify Patients Who Will Be More Sensitive to Intravesical Instillations for the Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy.

    Directory of Open Access Journals (Sweden)

    Xingbo Long

    Full Text Available To date, prophylactic intravesical chemotherapy after radical nephroureterectomy is one of the few available treatments that effectively prevent secondary bladder cancer. However, treating all patients with prophylactic intravesical chemotherapy is excessive for patients who are at a low risk or insensitive to the treatment. Thus, to guide individualized clinical treatment, in addition to identifying patients who are at risk of bladder cancer recurrence, it is equally necessary to identify the patients who will benefit the most from prophylactic, postoperative intravesical instillation therapy.Epidermal growth factor receptor (EGFR and Ki-67 expression levels were measured using immunohistochemical staining samples from 320 patients with upper urinary tract urothelial carcinoma (UTUC from 2004 to 2012. Although no patients received intravesical chemotherapy after RNU before 2008, this method began to be used in 2008 to prevent bladder cancer recurrence. To identify the patients who would most benefit from intravesical chemotherapy, we assessed biological interactions between intravesical chemotherapy and clinicopathological factors or biomarkers.The incidence rates of bladder UTUC recurrence decreased after intravesical chemotherapy, and the decrease was greater in patients with low Ki-67 levels, negative EGFR staining and preoperative positive urine cytology. Biological interactions were observed between intravesical chemotherapy, low-level Ki-67 and EGFR negativity. The multivariate analysis showed that after balancing a variety of factors, intravesical chemotherapy is a protective factor for preventing intravesical recurrence in the negative EGFR, low-level Ki-67 and preoperative positive urine cytology sub-groups but not in their corresponding sub-groups. Additionally, the multivariate analysis revealed that preoperative positive urine cytology and Ki-67 were not but that EGFR positivity was an independent risk factor for recurrence after

  7. A Repeated Signal Difference for Recognising Patterns

    Directory of Open Access Journals (Sweden)

    Kieran Greer


    Full Text Available This paper describes a new mechanism that might help with defining pattern sequences, by the fact that it can produce an upper bound on the ensemble value that can persistently oscillate with the actual values produced from each pattern. With every firing event, a node also receives an on/off feedback switch. If the node fires then it sends a feedback result depending on the input signal strength. If the input signal is positive or larger, it can store an ‘on’ switch feedback for the next iteration. If the signal is negative or smaller it can store an ‘off’ switch feedback for the next iteration. If the node does not fire, then it does not affect the current feedback situation and receives the switch command produced by the last active pattern event for the same neuron. The upper bound therefore also represents the largest or most enclosing pattern set and the lower value is for the actual set of firing patterns. If the pattern sequence repeats, it will oscillate between the two values, allowing them to be recognised and measured more easily, over time. Tests show that changing the sequence ordering produces different value sets, which can also be measured.

  8. Hydrological Modeling and Repeatability with Brokering (United States)

    Easton, Z. M.; Collick, A.; Srinivasan, R.; Braeckel, A.; Nativi, S.; McAlister, C.; Wright, D. J.; Khalsa, S. J. S.; Fuka, D.


    Data brokering aims to provide those in the hydrological sciences with access to relevant data to represent physical, biological, and chemical characteristics researchers need to accelerate discovery in their domain. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these models requires many different data sources from different disciplines (e.g., atmospheric, geoscience, ecology). In hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, more suitable data products exist. An added complexity is that various science communities have differing data formats, storage protocols and manipulation methods, which makes use by a non domain scientist difficult and time consuming. We propose data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering increases the efficiency with which data are collected, models are initialized, and results are analyzed. As an added benefit, it appears brokering significantly increases the repeatability of a study.

  9. Multineuronal Spike Sequences Repeat with Millisecond Precision

    Directory of Open Access Journals (Sweden)

    Koki eMatsumoto


    Full Text Available Cortical microcircuits are nonrandomly wired by neurons. As a natural consequence, spikes emitted by microcircuits are also nonrandomly patterned in time and space. One of the prominent spike organizations is a repetition of fixed patterns of spike series across multiple neurons. However, several questions remain unsolved, including how precisely spike sequences repeat, how the sequences are spatially organized, how many neurons participate in sequences, and how different sequences are functionally linked. To address these questions, we monitored spontaneous spikes of hippocampal CA3 neurons ex vivo using a high-speed functional multineuron calcium imaging technique that allowed us to monitor spikes with millisecond resolution and to record the location of spiking and nonspiking neurons. Multineuronal spike sequences were overrepresented in spontaneous activity compared to the statistical chance level. Approximately 75% of neurons participated in at least one sequence during our observation period. The participants were sparsely dispersed and did not show specific spatial organization. The number of sequences relative to the chance level decreased when larger time frames were used to detect sequences. Thus, sequences were precise at the millisecond level. Sequences often shared common spikes with other sequences; parts of sequences were subsequently relayed by following sequences, generating complex chains of multiple sequences.

  10. The genomic landscape of rapid repeated evolutionary ... (United States)

    Atlantic killifish populations have rapidly adapted to normally lethal levels of pollution in four urban estuaries. Through analysis of 384 whole killifish genome sequences and comparative transcriptomics in four pairs of sensitive and tolerant populations, we identify the aryl hydrocarbon receptor–based signaling pathway as a shared target of selection. This suggests evolutionary constraint on adaptive solutions to complex toxicant mixtures at each site. However, distinct molecular variants apparently contribute to adaptive pathway modification among tolerant populations. Selection also targets other toxicity-mediatinggenes and genes of connected signaling pathways; this indicates complex tolerance phenotypes and potentially compensatory adaptations. Molecular changes are consistent with selection on standing genetic variation. In killifish, high nucleotide diversityhas likely been a crucial substrate for selective sweeps to propel rapid adaptation. This manuscript describes genomic evaluations that contribute to our understanding of the ecological and evolutionary risks associated with chronic contaminant exposures to wildlife populations. Here, we assessed genetic patterns associated with long-term response to an important class of highly toxic environmental pollutants. Specifically, chemical-specific tolerance has rapidly and repeatedly evolved in an estuarine fish species resident to estuaries of the Atlantic U.S. coast. We used laboratory studies to ch

  11. R loops stimulate genetic instability of CTG.CAG repeats. (United States)

    Lin, Yunfu; Dent, Sharon Y R; Wilson, John H; Wells, Robert D; Napierala, Marek


    Transcription stimulates the genetic instability of trinucleotide repeat sequences. However, the mechanisms leading to transcription-dependent repeat length variation are unclear. We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts. In vitro transcribed CG-rich repeating sequences, unlike AT-rich repeats and nonrepeating sequences, form stable, ribonuclease A-resistant structures. These RNA.DNA hybrids are eliminated by ribonuclease H treatment. Mutation in the rnhA1 gene that decreases the activity of ribonuclease HI stimulates the instability of CTG.CAG repeats in E. coli. Importantly, the effect of ribonuclease HI depletion on repeat instability requires active transcription. We also showed that transcription-dependent CTG.CAG repeat instability in human cells is stimulated by siRNA knockdown of RNase H1 and H2. In addition, we used bisulfite modification, which detects single-stranded DNA, to demonstrate that the nontemplate DNA strand at transcribed CTG.CAG repeats remains partially single-stranded in human genomic DNA, thus indicating that it is displaced by an RNA.DNA hybrid. These studies demonstrate that persistent hybrids between the nascent RNA transcript and the template DNA strand at CTG.CAG tracts promote instability of DNA trinucleotide repeats.

  12. ATXN2 trinucleotide repeat length correlates with risk of ALS. (United States)

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar


    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Improving repeated sprint ability in young elite soccer players: repeated shuttle sprints vs. explosive strength training. (United States)

    Buchheit, Martin; Mendez-Villanueva, Alberto; Delhomel, Gregory; Brughelli, Matt; Ahmaidi, Said


    To compare the effects of explosive strength (ExpS) vs. repeated shuttle sprint (RS) training on repeated sprint ability (RSA) in young elite soccer players, 15 elite male adolescents (14.5 ± 0.5 years) performed, in addition to their soccer training program, RS (n = 7) or ExpS (n = 8) training once a week for a total of 10 weeks. RS training consisted of 2-3 sets of 5-6 × 15- to 20-m repeated shuttle sprints interspersed with 14 seconds of passive or 23 seconds of active recovery (≈2 m·s⁻¹); ExpS training consisted of 4-6 series of 4-6 exercises (e.g., maximal unilateral countermovement jumps (CMJs), calf and squat plyometric jumps, and short sprints). Before and after training, performance was assessed by 10 and 30 m (10 and 30 m) sprint times, best (RSAbest) and mean (RSAmean) times on a repeated shuttle sprint ability test, a CMJ, and a hopping (Hop) test. After training, except for 10 m (p = 0.22), all performances were significantly improved in both groups (all p's < 0.05). Relative changes in 30 m (-2.1 ± 2.0%) were similar for both groups (p = 0.45). RS training induced greater improvement in RSAbest (-2.90 ± 2.1 vs. -0.08 ± 3.3%, p = 0.04) and tended to enhance RSAmean more (-2.61 ± 2.8 vs. -0.75 ± 2.5%, p = 0.10, effect size [ES] = 0.70) than ExpS. In contrast, ExpS tended to induce greater improvements in CMJ (14.8 ± 7.7 vs. 6.8 ± 3.7%, p = 0.02) and Hop height (27.5 ± 19.2 vs. 13.5 ± 13.2%, p = 0.08, ES = 0.9) compared with RS. Improvements in the repeated shuttle sprint test were only observed after RS training, whereas CMJ height was only increased after ExpS. Because RS and ExpS were equally efficient at enhancing maximal sprinting speed, RS training-induced improvements in RSA were likely more related to progresses in the ability to change direction.

  14. 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


    received a single intratracheal instillation of 18, 54 and 162 mu g of CNT or 54, 162 and 486 mu g of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore...... 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...

  15. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting*


    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F.; Ignatova, Zoya


    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the −1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded re...

  16. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis (United States)


    Award Number: W81XWH-13-1-0237 TITLE: IImpact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis PRINCIPAL INVESTIGATOR: David T...Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0237 5c. PROGRAM ELEMENT...repeat expression in pancreatic cancer metastatic potential. An inducible over-expression vector was created and was successfully used in cancer cell

  17. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex


    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  18. Predictors of repeat pregnancy in a program for pregnant teens. (United States)

    Pfitzner, Mark A; Hoff, Charles; McElligott, Kathleen


    To describe repeat pregnancy among adolescents and to compare those who experienced a repeat pregnancy to those who did not. Retrospective case control of all adolescents who entered and exited the Teen Mother & Child Program, a multidisciplinary clinic for pregnant and parenting teens and their children, between 1985 and 2000. Repeat pregnancy. Over the 16-yr study period, 1838 teens entered and exited the program with the mean time in the program of 1.9 yrs. 194 (10.6%) teens went on to have a second pregnancy, and 4 of those had a third pregnancy. Ninety-two percent (n=175) of these pregnancies resulted in a live birth. The mean interval between delivery of the initial child and delivery of the second child was 21.8 months (range 5.4-53.2). Teens repeating (R) were compared to those who did not repeat (NR). R were younger at entry and older at exit from the program (both Pteen pregnancy program experienced a repeat pregnancy while in the program. Compared to nonrepeaters, adolescents who experienced a repeat pregnancy were younger, were more frequently Hispanic, and were more likely to be in a stable relationship with the baby's father. Many of the program's clients have psychosocial factors reported in the literature to be associated with repeat pregnancy. A history of suicide gestures/attempts and a significant psychiatric history were more common in those who had a repeat pregnancy. Disappointingly, only about 25% of the adolescents completed high school by the time they exited the program whether they experienced a repeat pregnancy or not. Although directing interventions (e.g., mental health services, counseling those who miscarried) to teens who appear to be at highest risk for a repeat pregnancy may decrease their risk of repeating, all teens in our program would likely benefit from such services.

  19. Coexistence of 3G repeaters with LTE base stations. (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon


    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  20. A Comparison of First Time and Repeat Rural DUI Offenders. (United States)

    Dickson, Megan F; Wasarhaley, Nesa E; Webster, J Matthew

    The purpose of the current study was to examine whether the differences found between first time and repeat rural DUI offenders were the same as those found previously in urban samples. A total of 118 rural DUI offenders were interviewed, approximately half (51.7%) of which were repeat offenders. Although demographic and mental health characteristics were similar across the two groups, repeat offenders reported more extensive substance use and criminal histories. Results suggest that the pattern of differences between rural first time and repeat DUI offenders may be different from the pattern found in prior urban-based studies. Treatment implications are discussed.

  1. Should I repeat my 1:2s QC rejection? (United States)

    Parvin, Curtis A; Kuchipudi, Lakshmi; Yundt-Pacheco, John C


    Repeating a QC that is outside 2SD from the mean (1:2s rule) appears to be a common practice. Although this form of repeat sampling is frowned on by many, the comparative power of the approach has not been formally evaluated. We computed power functions mathematically and by computer simulation for 4 different 1:2s repeat-sampling strategies, as well as the 1:2s rule, the 1:3s rule, and 2 common QC multirules. The false-rejection rates for the repeat-sampling strategies were similarly low to those of the 1:3s QC rule. The error detection rates for the repeat-sampling strategies approached those of the 1:2s QC rule for moderate to large out-of-control error conditions. In most cases, the power of the repeat-sampling strategies was superior to the power of the QC multirules we evaluated. The increase in QC utilization rate ranged from 4% to 13% for the repeat-sampling strategies investigated. The repeat-sampling strategies provide an effective tactic to take advantage of the desirable properties of both the 1:2s and 1:3s QC rules. Additionally, the power of the repeat-sampling strategies compares favorably with the power of 2 common QC multirules. These improvements come with a modest increase in the average number of controls tested.

  2. Misleading Children: Causal Attributions of Inconsistency under Repeated Questioning. (United States)

    Siegal, Michael; And Others


    Four studies investigated whether inconsistency of children aged four to six on developmental tasks may reflect a misinterpretation of the experimenter's intent in communication under repeated questioning. (SKC)

  3. R-loops: targets for nuclease cleavage and repeat instability. (United States)

    Freudenreich, Catherine H


    R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

  4. The effectiveness of repeat lumbar transforaminal epidural steroid injections. (United States)

    Murthy, Naveen S; Geske, Jennifer R; Shelerud, Randy A; Wald, John T; Diehn, Felix E; Thielen, Kent R; Kaufmann, Timothy J; Morris, Jonathan M; Lehman, Vance T; Amrami, Kimberly K; Carter, Rickey E; Maus, Timothy P


    The aim of this study was to determine 1) if repeat lumbar transforaminal epidural steroid injections (TFESIs) resulted in recovery of pain relief, which has waned since an index injection, and 2) if cumulative benefit could be achieved by repeat injections within 3 months of the index injection. Retrospective observational study with statistical modeling of the response to repeat TFESI. Academic radiology practice. Two thousand eighty-seven single-level TFESIs were performed for radicular pain on 933 subjects. Subjects received repeat TFESIs >2 weeks and <1 year from the index injection. Hierarchical linear modeling was performed to evaluate changes in continuous and categorical pain relief outcomes after repeat TFESI. Subgroup analyses were performed on patients with <3 months duration of pain (acute pain), patients receiving repeat injections within 3 months (clustered injections), and in patients with both acute pain and clustered injections. Repeat TFESIs achieved pain relief in both continuous and categorical outcomes. Relative to the index injection, there was a minimal but statistically significant decrease in pain relief in modeled continuous outcome measures with subsequent injections. Acute pain patients recovered all prior benefit with a statistically significant cumulative benefit. Patients receiving clustered injections achieved statistically significant cumulative benefit, of greater magnitude in acute pain patients. Repeat TFESI may be performed for recurrence of radicular pain with the expectation of recovery of most or all previously achieved benefit; acute pain patients will likely recover all prior benefit. Repeat TFESIs within 3 months of the index injection can provide cumulative benefit. Wiley Periodicals, Inc.

  5. Rhythm facilitates the detection of repeating sound patterns

    Directory of Open Access Journals (Sweden)

    Vani G. Rajendran


    Full Text Available This study investigates the influence of temporal regularity on human listeners’ ability to detect a repeating noise pattern embedded in statistically identical non-repeating noise. Human listeners were presented with white noise stimuli that either contained a frozen segment of noise that repeated in a temporally regular or irregular manner, or did not contain any repetition at all. Subjects were instructed to respond as soon as they detected any repetition in the stimulus. Pattern detection performance was best when repeated targets occurred in a temporally regular manner, suggesting that temporal regularity plays a facilitative role in pattern detection. A modulation filterbank model could account for these results.

  6. Cardiorespiratory Coordination in Repeated Maximal Exercise

    Directory of Open Access Journals (Sweden)

    Sergi Garcia-Retortillo


    Full Text Available Increases in cardiorespiratory coordination (CRC after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1 were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax, maximal oxygen consumption (VO2 max, or ventilatory threshold (VT, an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08 was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43 in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC

  7. Differentiating Schistosoma haematobium from Related Animal Schistosomes by PCR Amplifying Inter-Repeat Sequences Flanking Newly Selected Repeated Sequences


    Abbasi, Ibrahim; HAMBURGER, JOSEPH; Kariuki, Curtis; Peter L Mungai; Muchiri, Eric M.; King, Charles H.


    In schistosomiasis elimination programs, successful discrimination of Schistosoma haematobium from the related animal Schistosoma parasites will be essential for accurate detection of human parasite transmission. Polymerase chain reaction assays employing primers from two newly selected repeated sequences, named Sh73 and Sh77, did not discriminate S. haematobium when amplifying Sh73-77 intra- or inter-repeats. However, amplification between Sh73 and the previously described DraI repeat exhibi...

  8. Repeatability study of replicate crash tests: A signal analysis approach. (United States)

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason


    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

  9. Development of simple sequence repeat markers in cymbopogon species. (United States)

    Kumar, Jitendra; Verma, Vijeshwar; Shahi, Ashok Kumar; Qazi, Gulam Nab; Balyan, Harindra Singh


    The genus Cymbopogon comprises about 140 species, which produce characteristic aromatic essential oils. However, the phenotypic identification of species of Cymbopogon has been difficult as a result of widespread occurrence of natural variants, which differ in ploidy levels and chemotaxonomic complexities. Therefore, we have developed a set of simple sequence repeat markers from a genomic library of Cymbopogon jwarancusa to help in the precise identification of the species (including accessions) of Cymbopogon. For this purpose, we isolated 16 simple sequence repeat containing genomic deoxyribonucleic acid clones of C. jwarancusa, which contained a total of 32 simple sequence repeats with a range of 1 to 3 simple sequence repeats per clone. The majority (68.8%) of the 32 simple sequence repeats comprised dinucleotide repeat motifs followed by simple sequence repeats with trinucleotide (21.8%) and other higher order repeat motifs. Eighteen (81.8%) of the 22 designed primers for the above simple sequence repeats amplified products of expected sizes, when tried with genomic DNA of C. jwarancusa, the source species. Thirteen (72.2%) of the 18 functional primers detected polymorphism among the three species of Cymbopogon (C. flexuosus, C. pendulus and C. jwarancusa) and amplified a total of 95 alleles (range 1-18 alleles) with a PIC value of 0.44 to 0.96 per simple sequence repeat. Thus, the higher allelic range and high level of polymorphism demonstrated by the newly developed simple sequence repeat markers are likely to have many applications such as in improvement of essential oil quality by authentication of Cymbopogon species and varieties and mapping or tagging the genes controlling agronomically important traits of essential oils, which can further be utilized in marker assisted breeding.

  10. Witness recall across repeated interviews in a case of repeated abuse. (United States)

    Brubacher, Sonja P; La Rooy, David


    In this illustrative case study we examine the three forensic interviews of a girl who experienced repeated sexual abuse from ages 7 to 11. She disclosed the abuse after watching a serialized television show that contained a storyline similar to her own experience. This triggered an investigation that ended in successful prosecution of the offender. Because this case involved abuse that was repeated on a weekly basis for 4 years we thus investigated the degree to which the child's narrative reflected specific episodes or generic accounts, and both the interviewer's and child's attempts to elicit and provide, respectively, specific details across the 3 interviews collected in a 1 month period. Across the 3 interviews, the child's account was largely generic, yet on a number of occasions she provided details specific to individual incidents (episodic leads) that could have been probed further. As predicted: earlier interviews were characterized more by episodic than generic prompts and the reverse was true for the third interview; the child often responded using the same style of language (episodic or generic) as the interviewer; and open questions yielded narrative information. We discuss the importance of adopting children's words to specify occurrences, and the potential benefits of permitting generic recall in investigative interviews on children's ability to provide episodic leads. Despite the fact that the testimony was characterized by generic information about what usually happened, rather than specific episodic details about individual occurrences, this case resulted in successful prosecution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Short-sequence DNA repeats in prokaryotic genomes

    NARCIS (Netherlands)

    A.F. van Belkum (Alex); S. Scherer; L. van Alphen (Loek); H.A. Verbrugh (Henri)


    textabstractShort-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or

  12. Chromosomal organization of simple sequence repeats in the ...

    Indian Academy of Sciences (India)

    ... to the oligonucleotide repeat. The intercalary, centromeric and telomeric bands were observed along the chromosomes, and for each particular repeat every chromosome pair presented a similar pattern, allowing karyotypic analysis with all the SSRs tested. Our study is the first in mollusks to show the application of SSR in ...

  13. Inter Simple Sequence Repeat (ISSR) analysis of wild and cultivated ...

    African Journals Online (AJOL)



    Aug 9, 2010 ... simple sequence repeat (ISSR) polymorphism in the genus Oryza. Theor. Appl. Genet. 100: 1311-1320. Kantety RV, Zeng X, Bennetzen JL, Zehr BE (1995). Assessment of genetic diversity in dent and popcorn (Zea mays L.) inbred lines using inter-simple sequence repeat (ISSR) amplification. Mol. Breed.

  14. Training repeated effort ability in national team male volleyball players. (United States)

    Sheppard, Jeremy M; Gabbett, Tim; Borgeaud, Russell


    This case study evaluated the effect of repeated lateral movement and jumping training on repeated effort ability in a group of national team male volleyball players. Twelve volleyball players were assessed on their volleyball-specific repeated movement and jumping abilities using a volleyball-specific repeated effort test (RET) before and after 12 weeks of training. The athletes performed between 8 and 9 volleyball training sessions per week, with 5 to 6 of these sessions including specific training aimed at improving repeated effort ability. Typically these training sessions involved 8 to 12 repetitions of 2 to 3 block jumps over a 9-m lateral distance (ie, the athletes had to perform jumps and lateral movements, typical of front court play in volleyball). Population-specific repeatability data were used to determine whether any changes that may have occurred in this study were beyond the minimal clinically important difference (MCID) for this testing procedure. Improvements in all variables of the RET were observed for each athlete involved in the study, with a small-to-moderate magnitude observed for the mean changes in each variable (Cohen's d, 0.21 to 0.59). All of the improvements in the results exceeded the MCID. These findings demonstrate that the RET is sensitive to training-induced changes. Lateral movement speed and repeated lateral movement speed, as well as jumping and repeated jumping ability are trainable qualities in high-performance volleyball players.

  15. Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

    NARCIS (Netherlands)

    Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.


    Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

  16. Characteristics of Reproductive Tracts of Repeat Breeders in Cattle ...

    African Journals Online (AJOL)

    The study observed the characteristics and assessed abnormalities in reproductive tracts of repeat breeders in cattle. Fourty (40) herds were sampled during the study and fifty seven (57) repeat breeders were identified. The animals had normal reproductive tracts with good body condition scores (BCS) ranging from 2.5- 4.5 ...

  17. Inter Simple Sequence Repeat (ISSR) analysis of wild and cultivated ...

    African Journals Online (AJOL)

    Inter Simple Sequence Repeat (ISSR) analysis of wild and cultivated rice species from Ethiopia. ... African Journal of Biotechnology ... The genetic diversity of three wild rice populations of Ethiopia along with three cultivated rice populations were studied using Inter simple sequence repeats (ISSRs) as a molecular marker.

  18. Cognitive behavioural therapy halves the risk of repeated suicide attempts

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Gøtzsche, Pernille K


    is excluded, the risk ratio becomes 0.61 (0.46-0.80) and the heterogeneity in the results disappears (I(2 )= 0%). Conclusions Cognitive behavioural therapy reduces not only repeated self-harm but also repeated suicide attempts. It should be the preferred treatment for all patients with depression....

  19. Repeat photography as a tool for detecting and monitoring historical ...

    African Journals Online (AJOL)

    Repeat photography was used to illustrate long-term changes occurring in coastal habitats in the Western Cape, South Africa. Hi storic images were sourced from books and theses, the public and subject specialists, and repeat photographs were then taken from the same perspectives. Visible changes could be categorised ...

  20. Analysis of CR1 Repeats in the Zebra Finch Genome

    Directory of Open Access Journals (Sweden)

    George E. Liu


    Full Text Available Most bird species have smaller genomes and fewer repeats than mammals. Chicken Repeat 1 (CR1 repeat is one of the most abundant families of repeats, ranging from ~133,000 to ~187,000 copies accounting for ~50 to ~80% of the interspersed repeats in the zebra finch and chicken genomes, respectively. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to multiple CR1 subfamilies in the chicken. In this study, we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the zebra finch genome. We identified and validated 34 CR1 subfamilies and further analyzed the correlation between these subfamilies. We also discovered 4 novel lineage-specific CR1 subfamilies in the zebra finch when compared to the chicken genome. We built various evolutionary trees of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.


    African Journals Online (AJOL)


    There was significant difference (p<0.05) between the two farms in the magnitude of .... eij = Random error. µ = common mean. Estimates of repeatability of common hatchability problems in Isa-Brown breeders flock were obtained using the formula below (Becker, 1992). .... Unrepeatable repeatabilities: a common mistake.

  2. Y-Chromosome short tandem repeat, typing technology, locus ...

    African Journals Online (AJOL)

    Y-Chromosome short tandem repeat, typing technology, locus information and allele frequency in different population: A review. ... This review will highlight the importance of the Y- Chromosome as a tool for tracing human evolution and describes some details of Y-chromosomal short tandem repeat (STR) analysis. Among ...

  3. Turkish population data on the short tandem repeat locus TPOX

    DEFF Research Database (Denmark)

    Vural, B; Poda, M; Atlioglu, E


    Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals.......Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals....

  4. Contraceptive Use among Women Seeking Repeat Abortion in ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Although still poorly understood, risk factors for repeat abortion likely vary in different countries9. Less is known about the women who require repeat abortion services in low-resource settings. Some of the available data from Africa is dated and/or of limited generalizability. In Vietnam,. Huong et al found that more than 70% ...

  5. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated

  6. Determination of allele frequencies in nine short tandem repeat loci ...

    African Journals Online (AJOL)



    Apr 17, 2008 ... DNA fraction. Analysis of STRs is the most widely used method of genotyping used in forensic identification of individuals and for testing paternity. This is because ... Each STR is distinguished by the number of times a sequence is repeated, ... number of copies of the repeat sequence contained within the ...

  7. Measurement Precision for Repeat Examinees on a Standardized Patient Examination (United States)

    Raymond, Mark R.; Swygert, Kimberly A.; Kahraman, Nilufer


    Examinees who initially fail and later repeat an SP-based clinical skills exam typically exhibit large score gains on their second attempt, suggesting the possibility that examinees were not well measured on one of those attempts. This study evaluates score precision for examinees who repeated an SP-based clinical skills test administered as part…

  8. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.


    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...... as hitherto unappreciated but complex genetic modifiers of depression.......Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...... depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons...

  9. Alu repeats: A source for the genesis of primate microsatellites

    Energy Technology Data Exchange (ETDEWEB)

    Arcot, S.S.; Batzer, M.A. [Lawrence Livermore National Lab., CA (United States); Wang, Zhenyuan [Marshfield Medical Research Foundation, WI (United States)] [and others


    As a result of their abundance, relatively uniform distribution, and high degree of polymorphism, microsatellites and minisatellites have become valuable tools in genetic mapping, forensic identity testing, and population studies. In recent years, a number of microsatellite repeats have been found to be associated with Alu interspersed repeated DNA elements. The association of an Alu element with a microsatellite repeat could result from the integration of an Alu element within a preexisting microsatellite repeat. Alternatively, Alu elements could have a direct role in the origin of microsatellite repeats. Errors introduced during reverse transcription of the primary transcript derived from an Alu {open_quotes}master{close_quote} gene or the accumulation of random mutations in the middle A-rich regions and oligo(dA)-rich tails of Alu elements after insertion and subsequent expansion and contraction of these sequences could result in the genesis of a microsatellite repeat. We have tested these hypotheses by a direct evolutionary comparison of the sequences of some recent Alu elements that are found only in humans and are absent from nonhuman primates, as well as some older Alu elements that are present at orthologous positions in a number of nonhuman primates. The origin of {open_quotes}young{close_quotes} Alu insertions, absence of sequences that resemble microsatellite repeats at the orthologous loci in chimpanzees, and the gradual expansion of microsatellite repeats in some old Alu repeats at orthologous positions within the genomes of a number of nonhuman primates suggest that Alu elements are a source for the genesis of primate microsatellite repeats. 48 refs., 5 figs., 3 tabs.

  10. Structural basis for triplet repeat disorders: a computational analysis. (United States)

    Baldi, P; Brunak, S; Chauvin, Y; Pedersen, A G


    Over a dozen major degenerative disorders, including myotonic distrophy, Huntington's disease and fragile X syndrome, result from unstable expansions of particular trinucleotides. Remarkably, only some of all the possible triplets, namely CAG/CTG, CGG/CCG and GAA/TTC, have been associated with the known pathological expansions. This raises some basic questions at the DNA level. Why do particular triplets seem to be singled out? What is the mechanism for their expansion and how does it depend on the triplet itself? Could other triplets or longer repeats be involved in other diseases? Using several different computational models of DNA structure, we show that the triplets involved in the pathological repeats generally fall into extreme classes. Thus, CAG/CTG repeats are particularly flexible, whereas GCC, CGG and GAA repeats appear to display both flexible and rigid (but curved) characteristics depending on the method of analysis. The fact that (1) trinucleotide repeats often become increasingly unstable when they exceed a length of approximately 50 repeats, and (2) repeated 12-mers display a similar increase in instability above 13 repeats, together suggest that approximately 150 bp is a general threshold length for repeat instability. Since this is about the length of DNA wrapped up in a single nucleosome core particle, we speculate that chromatin structure may play an important role in the expansion mechanism. We furthermore suggest that expansion of a dodecamer repeat, which we predict to have very high flexibility, may play a role in the pathogenesis of the neurodegenerative disorder multiple system atrophy (MSA).,,,

  11. Progressive GAA.TTC repeat expansion in human cell lines. (United States)

    Ditch, Scott; Sammarco, Mimi C; Banerjee, Ayan; Grabczyk, Ed


    Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders. Friedreich ataxia (FRDA) is a relentlessly progressive neurodegenerative disorder caused by GAA.TTC repeat expansion in the first intron of the FXN gene. The expanded repeat reduces FXN mRNA expression and the length of the repeat tract is proportional to disease severity. Somatic expansion of the GAA.TTC repeat sequence in disease-relevant tissues is thought to contribute to the progression of disease severity during patient aging. Previous models of GAA.TTC instability have not been able to produce substantial levels of expansion within an experimentally useful time frame, which has limited our understanding of the molecular basis for this expansion. Here, we present a novel model for studying GAA.TTC expansion in human cells. In our model system, uninterrupted GAA.TTC repeat sequences display high levels of genomic instability, with an overall tendency towards progressive expansion. Using this model, we characterize the relationship between repeat length and expansion. We identify the interval between 88 and 176 repeats as being an important length threshold where expansion rates dramatically increase. We show that expansion levels are affected by both the purity and orientation of the repeat tract within the genomic context. We further demonstrate that GAA.TTC expansion in our model is independent of cell division. Using unique reporter constructs, we identify transcription through the repeat tract as a major contributor to GAA.TTC expansion. Our findings provide novel insight into the mechanisms responsible for GAA.TTC expansion in human cells.

  12. Triplet-repeat microsatellites shared among hard and soft pines. (United States)

    Kutil, B L; Williams, C G


    Vascular plant species have shown a low level of microsatellite conservation compared to many animal species. Finding trans-specific microsatellites for plants may be improved by using a priori knowledge of genome organization. Fifteen triplet-repeat microsatellites from hard pine (Pinus taeda L.) were tested for trans-specific amplification across seven hard pines (P. palustris Mill., P. echinata Mill., P. radiata D. Don., P. patula Schiede et Deppe, P. halepensis Mill., P. kesiya Royle), a soft pine (P. strobus L.), and Picea rubens Sargent. Seven of 15 microsatellites had trans-specific amplification in both hard and soft pine subgenera. Two P. taeda microsatellites had conserved flanking regions and repeat motifs in all seven hard pines, soft pine P. strobus, and P. rubens. Perfect triplet-repeat P. taeda microsatellites appear to be better candidates for trans-specific polymorphism than compound microsatellites. Not all perfect triplet-repeat microsatellites were conserved, but all conserved microsatellites had perfect repeat motifs. Persistent microsatellites PtTX2123 and PtTX3020 had highly conserved flanking regions and a conserved repeat motif composition with variable repeat unit numbers. Using trinucleotide microsatellites improved trans-specific microsatellite recovery among hard and soft pine species.

  13. The repeatability of behaviour: a meta-analysis (United States)

    Bell, Alison M.; Hankison, Shala J.; Laskowski, Kate L.


    There is increasing interest in individual differences in animal behaviour. Recent research now suggests that an individual’s behaviour, once considered to be plastic, may be more predictable than previously thought. Here, we take advantage of the large number of studies that have estimated the repeatability of various behaviours to evaluate whether there is good evidence for consistent individual differences in behaviour and to answer some outstanding questions about possible factors that can influence repeatability. Specifically, we use meta-analysis to ask whether different types of behaviours were more repeatable than others, and if repeatability estimates depended on taxa, sex, age, field versus laboratory, the number of measures and the interval between measures. Some of the overall patterns that were revealed by this analysis were that repeatability estimates were higher in the field compared to the laboratory and repeatability was higher when the interval between observations was short. Mate preference behaviour was one of the best studied but least repeatable behaviours. Our findings prompt new insights into the relative flexibility of different types of behaviour and offer suggestions for the design and analysis of future research. PMID:24707058

  14. A De Novo Genome Assembly Algorithm for Repeats and Nonrepeats

    Directory of Open Access Journals (Sweden)

    Shuaibin Lian


    Full Text Available Background. Next generation sequencing platforms can generate shorter reads, deeper coverage, and higher throughput than those of the Sanger sequencing. These short reads may be assembled de novo before some specific genome analyses. Up to now, the performances of assembling repeats of these current assemblers are very poor. Results. To improve this problem, we proposed a new genome assembly algorithm, named SWA, which has four properties: (1 assembling repeats and nonrepeats; (2 adopting a new overlapping extension strategy to extend each seed; (3 adopting sliding window to filter out the sequencing bias; and (4 proposing a compensational mechanism for low coverage datasets. SWA was evaluated and validated in both simulations and real sequencing datasets. The accuracy of assembling repeats and estimating the copy numbers is up to 99% and 100%, respectively. Finally, the extensive comparisons with other eight leading assemblers show that SWA outperformed others in terms of completeness and correctness of assembling repeats and nonrepeats. Conclusions. This paper proposed a new de novo genome assembly method for resolving complex repeats. SWA not only can detect where repeats or nonrepeats are but also can assemble them completely from NGS data, especially for assembling repeats. This is the advantage over other assemblers.

  15. HINGE: long-read assembly achieves optimal repeat resolution. (United States)

    Kamath, Govinda M; Shomorony, Ilan; Xia, Fei; Courtade, Thomas A; Tse, David N


    Long-read sequencing technologies have the potential to produce gold-standard de novo genome assemblies, but fully exploiting error-prone reads to resolve repeats remains a challenge. Aggressive approaches to repeat resolution often produce misassemblies, and conservative approaches lead to unnecessary fragmentation. We present HINGE, an assembler that seeks to achieve optimal repeat resolution by distinguishing repeats that can be resolved given the data from those that cannot. This is accomplished by adding "hinges" to reads for constructing an overlap graph where only unresolvable repeats are merged. As a result, HINGE combines the error resilience of overlap-based assemblers with repeat-resolution capabilities of de Bruijn graph assemblers. HINGE was evaluated on the long-read bacterial data sets from the NCTC project. HINGE produces more finished assemblies than Miniasm and the manual pipeline of NCTC based on the HGAP assembler and Circlator. HINGE also allows us to identify 40 data sets where unresolvable repeats prevent the reliable construction of a unique finished assembly. In these cases, HINGE outputs a visually interpretable assembly graph that encodes all possible finished assemblies consistent with the reads, while other approaches such as the NCTC pipeline and FALCON either fragment the assembly or resolve the ambiguity arbitrarily. © 2017 Kamath et al.; Published by Cold Spring Harbor Laboratory Press.

  16. Environmental stress induces trinucleotide repeat mutagenesis in human cells (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.


    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

  17. The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor. (United States)

    Gazdhar, Amiq; Grad, Iwona; Tamò, Luca; Gugger, Mathias; Feki, Anis; Geiser, Thomas


    Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in respiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial microinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their secretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the potential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the alveolar epithelium in vitro and improve bleomycin induced lung injury in vivo. IPSC-cm was collected from cultured iPSC derived from human foreskin fibroblasts and its biological effects on alveolar epithelial wound repair was studied in an alveolar wound healing assay in vitro. Furthermore, iPSC-cm was intratracheally instilled 7 days after bleomycin induced injury in the rat lungs and histologically and biochemically assessed 7 days after instillation. iPSC-cm increased alveolar epithelial wound repair in vitro compared with medium control. Intratracheal instillation of iPSC-cm in bleomycin-injured lungs reduced the collagen content and improved lung fibrosis in the rat lung in vivo. Profibrotic TGFbeta1 and α-smooth muscle actin (α-sma) expression were markedly reduced in the iPSC-cm treated group compared with control. Antifibrotic hepatocyte growth factor (HGF) was detected in iPSC-cm in biologically relevant levels, and specific inhibition of HGF in iPSC-cm attenuated the antifibrotic effect of iPSC-cm, indicating a central role of HGF in iPSC-cm. iPSC-cm increased alveolar epithelial wound repair in vitro and attenuated bleomycin induced fibrosis in vivo, partially due to the presence of HGF and may represent a promising novel, cell free therapeutic option against lung injury and fibrosis.

  18. Sequence conservation of an avian centromeric repeated DNA component. (United States)

    Madsen, C S; Brooks, J E; de Kloet, E; de Kloet, S R


    The approximately 190-bp centromeric repeat monomers of the spur-winged lapwing (Vanellus spinosus, Charadriidae), the Chilean flamingo (Phoenicopterus chilensis, Phoenicopteridae), the sarus crane (Grus antigone, Gruidae), parrots (Psittacidae), waterfowl (Anatidae), and the merlin (Falco columbarius, Falconidae) contain elements that are interspecifically highly variable, as well as elements (trinucleotides and higher order oligonucleotides) that are highly conserved in sequence and relative location within the repeat. Such conservation suggests that the centromeric repeats of these avian species have evolved from a common ancestral sequence that may date from very early stages of avian radiation.

  19. Hybrid quantum repeater based on resonant qubit-field interactions (United States)

    Bernád, József Zsolt


    We propose a hybrid quantum repeater based on ancillary coherent field states and material qubits coupled to optical cavities. For this purpose, resonant qubit-field interactions and postselective field measurements are determined which are capable of realizing all necessary two-qubit operations for the actuation of the quantum repeater. We explore both theoretical and experimental possibilities of generating near-maximally-entangled qubit pairs (F >0.999 ) over long distances. It is shown that our scheme displays moderately low repeater rates, between 5 ×10-4 and 23 pairs per second, over distances up to 900 km, and it relies completely on current technology of cavity quantum electrodynamics.

  20. Autonomic dysreflexia and repeatability of cardiovascular changes during same session repeat urodynamic investigation in women with spinal cord injury. (United States)

    Walter, Matthias; Knüpfer, Stephanie C; Leitner, Lorenz; Mehnert, Ulrich; Schubert, Martin; Curt, Armin; Kessler, Thomas M


    To investigate autonomic dysreflexia (AD) and repeatability of cardiovascular changes during same session repeat urodynamic investigation (UDI) in women with spinal cord injury (SCI). Prospective investigation of 33 consecutive women with suprasacral SCI suffering from neurogenic lower urinary tract dysfunction (NLUTD) undergoing same session repeat UDI and synchronous continuous cardiovascular monitoring [systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)]. UDIs were performed according to the International Continence Society guidelines. AD was defined according to the International Standards to document remaining Autonomic Function after SCI. Neurological level of SCI was determined using the American Spinal Injury Association impairment scale. Mean age and duration since SCI of the 33 women were 58 ± 19 and 6 ± 11 years, respectively. Overall AD incidence was 73 % (24/33), and 19 of the 33 women (58 %) showed AD in both UDIs. The repeatability of detecting AD between the two same session UDIs was good (κ = 0.67, 95 % CI 0.4-0.94). When applying the Bland and Altman method, wide 95 % limits of agreement for differences in same session SBP, DBP and HR indicated poor repeatability. There was a significant increase in SBP (p UDI and repeat measurements considering the high incidence of AD, the relevant risks involved with sudden hypertension and the poor repeatability of cardiovascular monitoring.

  1. Awareness of Repeat Antenatal HIV Testing in Mothers Six Weeks ...

    African Journals Online (AJOL)

    PMTCT) recommend that all pregnant women and breastfeeding mothers must have HIV tests every 3 months. However, less than 10% of pregnant women in Lusaka District get retested. Repeat HIV testing identifies women who seroconvert ...

  2. Identifying Misconceptions of Nine Grade Students on Repeating Decimals

    Directory of Open Access Journals (Sweden)

    Adnan Baki


    Full Text Available The aim of this study is to identify misconceptions of nine grade students on the topic of repeating decimal numbers. Data were obtained from forty students through “Diagnostic Test of Repeating Decimal Numbers” including open-ended questions. Questions were prepared according to the classification of misconceptions as overgeneralization, overspecialization, mistranslation and limited conception. As a part of rational numbers unit the topic of “representation of repeating decimals” is introduced at 6, 7, 8 and 9 grades in our schools. In spite of this, findings of this study illustrate that even nine grade students still have some common misconceptions about this topic. Findings illustrated that most students’ misconceptions were based on overgeneralization. In addition to this students also shared the other categories of misconceptions as well.Key Words:    Decimals, repeating decimals, misconceptions

  3. Discriminant analysis for repeated measures data: a review

    Directory of Open Access Journals (Sweden)

    Lisa Lix


    Full Text Available Discriminant analysis (DA encompasses procedures for classifying observations into groups (i.e., predictive discriminative analysis and describing the relative importance of variables for distinguishing amongst groups (i.e., descriptive discriminative analysis. In recent years, a number of developments have occurred in DA procedures for the analysis of data from repeated measures designs. Specifically, DA procedures have been developed for repeated measures data characterized by missing observations and/or unbalanced measurement occasions, as well as high-dimensional data in which measurements are collected repeatedly on two or more variables. This paper reviews the literature on DA procedures for univariate and multivariate repeated measures data, focusing on covariance pattern and linear mixed-effects models. A numeric example illustrates their implementation using SAS software.

  4. Experimental nested purification for a linear optical quantum repeater (United States)

    Chen, Luo-Kan; Yong, Hai-Lin; Xu, Ping; Yao, Xing-Can; Xiang, Tong; Li, Zheng-Da; Liu, Chang; Lu, He; Liu, Nai-Le; Li, Li; Yang, Tao; Peng, Cheng-Zhi; Zhao, Bo; Chen, Yu-Ao; Pan, Jian-Wei


    Quantum repeaters1-4 are essential elements for demonstrating global-scale quantum communication. Over the past few decades, tremendous efforts have been dedicated to implementing a practical quantum repeater5-10. However, nested purification1, the backbone of a quantum repeater, remains a challenge because the capacity for successive entanglement manipulation is still absent. Here, we propose and demonstrate an architecture of nested purification using spontaneous parametric downconversion sources11. A heralded entangled photon pair with higher fidelity is successfully purified from two copies of low-fidelity pairs that experience entanglement swapping and noisy channels. By delicately designing the optical circuits, double-pair emission noise is eliminated automatically and the purified state can be used for scalable entanglement connections to extend the communication distance. Combined with a quantum memory, our approach can be applied immediately in the implemention of a practical quantum repeater.

  5. Versatile communication strategies among tandem WW domain repeats

    National Research Council Canada - National Science Library

    Dodson, Emma Joy; Fishbain-Yoskovitz, Vered; Rotem-Bamberger, Shahar; Schueler-Furman, Ora


    .... The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions...

  6. The repeatability of metabolic rate declines with time. (United States)

    White, Craig R; Schimpf, Natalie G; Cassey, Phillip


    The evolutionary causes of variation in metabolic rate within and among species are a topic of enduring interest. Variation between individuals is the raw material on which natural selection acts, and so recent years have seen an increase in the number of studies that examine the consequences of inter-individual differences in metabolic rate for organismal performance. A minimum requirement for a trait to evolve is that it must differ consistently between individuals, and these differences must be heritable. The time constancy of a trait is assessed by estimating its repeatability, which represents the ratio of the between-individual component of phenotypic variance to total phenotypic variance. A previous meta-analysis of repeatability concluded that metabolic rate is, on average, repeatable. Here, we expand on this earlier analysis by including extra data published in the intervening years and demonstrate that the repeatability of metabolic rate decreases as the interval between measurements increases.

  7. A Unique Intervention Program for Repeat Impaired Driving Offenders. (United States)

    Parsons, Martin; And Others


    Describes IMPACT (Insight, Motivation, Progress, Assessment, Counseling, Treatment), successful intervention approach for repeat impaired driving offenders. Explains intensive, residential, weekend experience in which program participants examine their alcohol- and drug-related behaviors. Notes that, through interaction with peers, participants…

  8. Effect of repeated earthquake on inelastic moment resisting concrete frame (United States)

    Tahara, R. M. K.; Majid, T. A.; Zaini, S. S.; Faisal, A.


    This paper investigates the response of inelastic moment resisting concrete building under repeated earthquakes. 2D models consist of 3-storey, 6-storey and 9-storey representing low to medium rise building frame were designed using seismic load and ductility class medium (DCM) according to the requirements set by Euro Code 8. Behaviour factor and stiffness degradation were also taken into consideration. Seven sets of real repeated earthquakes as opposed to artificial earthquakes data were used. The response of the frame was measured in terms of the inter-storey drift and maximum displacement. By adopting repeated earthquake, the recorded mean IDR increased in the range of 3% - 21%. Similarly, in the case of maximum displacement, the values also increased from 20 mm to 40 mm. The findings concluded that the effect of using repeated earthquake in seismic analysis considerably influenced the inter-storey drift and the maximum displacement.

  9. Folding landscapes of ankyrin repeat proteins: experiments meet theory. (United States)

    Barrick, Doug; Ferreiro, Diego U; Komives, Elizabeth A


    Nearly 6% of eukaryotic protein sequences contain ankyrin repeat (AR) domains, which consist of several repeats and often function in binding. AR proteins show highly cooperative folding despite a lack of long-range contacts. Both theory and experiment converge to explain that formation of the interface between elements is more favorable than formation of any individual repeat unit. IkappaBalpha and Notch both undergo partial folding upon binding perhaps influencing the binding free energy. The simple architecture, combined with identification of consensus residues that are important for stability, has enabled systematic perturbation of the energy landscape by single point mutations that affect stability or by addition of consensus repeats. The folding energy landscapes appear highly plastic, with small perturbations re-routing folding pathways.

  10. Repeatability and Reproducibility of Decisions by Latent Fingerprint Examiners (United States)

    Ulery, Bradford T.; Hicklin, R. Austin; Buscaglia, JoAnn; Roberts, Maria Antonia


    The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner) results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive) was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as “difficult” than for “easy” or “moderate” comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4); 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization). Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases. PMID:22427888

  11. Repeatability and reproducibility of decisions by latent fingerprint examiners.

    Directory of Open Access Journals (Sweden)

    Bradford T Ulery

    Full Text Available The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as "difficult" than for "easy" or "moderate" comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4; 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization. Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases.

  12. Repeated nondiagnostic result of thyroid fine-needle aspiration biopsy

    Directory of Open Access Journals (Sweden)

    Klaudia Ziemiańska


    Full Text Available Aim of the study: Fine-needle aspiration biopsy (FNAB is the most accurate and cost-effective method to evaluate the risk of malignancy of thyroid nodules, but approximately 1–24% of FNABs generate a nondiagnostic result (ND-FNAB. The aim of this study was to determine the predictive factors of a repeated nondiagnostic result of FNAB. Material and methods : A total of 4018 FNABs performed in a territorial referral centre were analysed, of which 288 (7.17% were nondiagnostic. Medical records were available for 245 biopsies performed in 228 patients. The retrospective analysis of factors that may influence a repeat ND-FNAB, including demographic, clinical and ultrasound characteristics, was performed. Results : A repeat FNAB was performed in 159 nodules giving a diagnostic result in 79.2% of cases. The time between the biopsies ranged from 1 to 611 days (mean 154.4, median 119. The timing of a repeat FNAB did not significantly alter the diagnostic output (p = 0.29. In the univariate analysis, significant predictors of a repeat ND-FNAB were older patient age (p = 0.02, L-thyroxine supplementation (p = 0.05, and a history of 131 I therapy (p < 0.0001. In the multivariate analysis, only a history of 131 I therapy was a statistically significant risk factor for a repeat ND-FNAB (p = 0.002. Conclusions : Patients with a history of 131 I therapy and ND-FNAB should undergo periodic ultrasonographic assessment rather than a repeat biopsy. The interval between repeated FNABs recommended by guidelines does not affect the diagnostic output.

  13. Evaluation of repeat Clostridium difficile enzyme immunoassay testing. (United States)

    Cardona, Diana M; Rand, Kenneth H


    Clostridium difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis, which have significant morbidity and mortality. Accurate and timely diagnosis is critical. Repeat enzyme immunoassay testing for C. difficile toxin has been recommended because of tests between 1 January 2006 and 31 December 2006 were retrospectively analyzed for results and testing patterns. The Wampole C. difficile Tox A/B II enzyme immunoassay kit was used. There were a total of 8,256 tests from 3,112 patients; 49% of tests were repeated. Of the 3,749 initially negative patient tests, 96 were positive upon repeat testing within 10 days of the first test. Of repeat tests, 0.9% repeated on day 0 (same day as the first test), 1.8% on day 1, 3.8% on day 2, 2.6% on day 3, 5.4% on days 4 to 6, and 10.6% on days 7 to 10 were positive. Thirty-eight patients had a positive test within 48 h of an initial negative test, and based on chart review, 18 patients were treated empirically while 16 were treated following the new result. None had evidence of medical complications. Of initially positive patients, 91% were positive upon repeat testing on day 0, 75% on day 1, and 58% on day 2, to a low of 14% on days 7 to 10. Depending on the clinical setting, these data support not repeating C. difficile tests within 2 days of a negative result and limiting repeat testing to >/=1 week of a positive result.

  14. Are major repeater patients addicted to suicidal behavior? (United States)

    Blasco-Fontecilla, Hilario; Artieda-Urrutia, Paula; Berenguer-Elias, Nuria; Garcia-Vega, Juan Manuel; Fernandez-Rodriguez, Monica; Rodriguez-Lomas, Cesar; Gonzalez-Villalobos, Isabel; Iruela-Cuadrado, Luis; de Leon, José


    The literature provides support for the hypothesis that some major repeaters (individuals with >=5 lifetime suicide attempts) are addicted to suicidal behavior (SB). This study explores whether major repeaters are addicted to SB or not using 7 criteria: tolerance (Criterion 1), withdrawal (Criterion 2), loss of control (Criterion 3), problems in quitting/cutting down (Criterion 4), much time spent using (Criterion 5), substantial reduction in activities (Criterion 6), and adverse physiological/physical consequences (Criterion 7). Total dependence on SB was indicated by the presence of 3 or more of the 7 criteria in the last 12 months. This cross-sectional study at Puerta de Hierro University Hospital (Madrid, Spain) recruited 118 suicide attempters including 8 major repeaters (7%, 8/118), who were all females. The association between each SB addiction criterion, physiological dependence and total dependence with major repeater status was tested for significance and for effect size with odds ratios (ORs) and their 95% confidence intervals. As hypothesized, major repeaters met significantly higher frequency of criteria for total dependence on SB, OR=62.9 (6.4-615). A backward stepwise logistic regression model was used to provide an OR between major repeater status and total dependence status corrected by confounding variables. Age, panic disorder without agoraphobia, borderline personality disorder, history of psychiatric inpatient admission, and total dependence on SB were introduced as independent variables with major repeater status as the dependent variable. The model selected total dependence and age as the remaining significant variables in the last step. Accordingly, major repeaters appear to be addicted to SB.

  15. Use of Health Information Exchange and Repeat Imaging Costs. (United States)

    Jung, Hye-Young; Vest, Joshua R; Unruh, Mark A; Kern, Lisa M; Kaushal, Rainu


    The aim of this study was to quantify the association between health information exchange (HIE) use and cost savings attributable to repeat imaging. Imaging procedures associated with HIE were compared with concurrent controls on the basis of propensity score matching over the period from 2009 to 2010 in a longitudinal cohort study. The study sample (n = 12,620) included patients ages 18 years and older enrolled in the two largest commercial health plans in a 13-county region of western New York State served by the Rochester Regional Health Information Organization. The primary outcome was a continuous measure of costs associated with repeat imaging. The determinant of interest, HIE use, was defined as system access after the initial imaging procedure and before repeat imaging. HIE use was associated with an overall estimated annual savings of $32,460 in avoided repeat imaging, or $2.57 per patient. Basic imaging (radiography, ultrasound, and mammography) accounted for 85% of the estimated avoided cases of repeat imaging. Advanced imaging (CT and MRI) accounted for 13% of avoided procedures but constituted half of the estimated savings (50%). HIE systems may reduce costs associated with repeat imaging. Although inexpensive imaging procedures constituted the largest proportion of avoided repeat imaging in our study, most of the estimated cost savings were due to small reductions in repeated advanced imaging procedures. HIE systems will need to be leveraged in ways that facilitate greater reductions in advanced imaging to achieve appreciable cost savings. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  16. Reputation without commitment in finitely-repeated games


    Yildiz, Muhamet; Weinstein, Jonathan


    In the reputation literature, players have \\emph{commitment types} which represent the possibility that they do not have standard payoffs but instead are constrained to follow a particular plan. In this paper, we show that arbitrary commitment types can emerge from incomplete information about the stage payoffs. In particular, any finitely repeated game with commitment types is strategically equivalent to a standard finitely repeated game with incomplete information about the stage payoffs. T...

  17. Towards highly multimode optical quantum memory for quantum repeaters


    Jobez, Pierre; Timoney, Nuala; Laplane, Cyril; Etesse, Jean; Ferrier, Alban; Goldner, Philippe; Gisin, Nicolas; Afzelius, Mikael


    Long-distance quantum communication through optical fibers is currently limited to a few hundreds of kilometres due to fiber losses. Quantum repeaters could extend this limit to continental distances. Most approaches to quantum repeaters require highly multimode quantum memories in order to reach high communication rates. The atomic frequency comb memory scheme can in principle achieve high temporal multimode storage, without sacrificing memory efficiency. However, previous demonstrations hav...

  18. A note on renegotiation in repeated Bertrand duopolies

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland


    Weak Renegotiation-Proofness (WRP) singles out marginal cost pricing as a unique pure-strategy equilibrium of the infinitely repeated Bertrand duopoly. We show that, with a discrete strategy space, WRP does not eliminate any relevant subgame perfect equilibrium outcome......Weak Renegotiation-Proofness (WRP) singles out marginal cost pricing as a unique pure-strategy equilibrium of the infinitely repeated Bertrand duopoly. We show that, with a discrete strategy space, WRP does not eliminate any relevant subgame perfect equilibrium outcome...

  19. Considerations on repeated repairing of weldments in Inconel 718 alloy (United States)

    Bayless, E. O.; Lovoy, C. V.; Mcilwain, M. C.; Munafo, P.


    The effects of repeated weld repairs on the metallurgical characteristics, high cycle fatigue (HCF), and tensile properties of Inconel 718 butt weld joints were determined. A 1/4 in thick plate and a 1/2 in thick plate were used as well as tungsten inert gas welding, and Inconel 718 filler wire. Weld panels were subjected to 2, 6, and 12 repeated repairs and were made in a highly restrained condition. Post weld heat treatments were also conducted with the welded panel in the highly restrained condition. Results indicate that no significant metallurgical anomaly is evident as a result of up to twelve repeated weld repairs. No degradation in fatigue life is noted for up to twelve repeated repairs. Tensile results from specimens which contained up to twelve repeated weld repairs revealed no significant degradation in UTS and YS. However, a significant decrease in elongation is evident with specimens (solution treated and age hardened after welding) which contained twelve repeated repairs. The elongation loss is attributed to the presence of a severe notch on each side (fusion line) of the repair weld bead reinforcement.

  20. Impact of Repeated Exposures on Information Spreading in Social Networks. (United States)

    Zhou, Cangqi; Zhao, Qianchuan; Lu, Wenbo


    Clustered structure of social networks provides the chances of repeated exposures to carriers with similar information. It is commonly believed that the impact of repeated exposures on the spreading of information is nontrivial. Does this effect increase the probability that an individual forwards a message in social networks? If so, to what extent does this effect influence people's decisions on whether or not to spread information? Based on a large-scale microblogging data set, which logs the message spreading processes and users' forwarding activities, we conduct a data-driven analysis to explore the answer to the above questions. The results show that an overwhelming majority of message samples are more probable to be forwarded under repeated exposures, compared to those under only a single exposure. For those message samples that cover various topics, we observe a relatively fixed, topic-independent multiplier of the willingness of spreading when repeated exposures occur, regardless of the differences in network structure. We believe that this finding reflects average people's intrinsic psychological gain under repeated stimuli. Hence, it makes sense that the gain is associated with personal response behavior, rather than network structure. Moreover, we find that the gain is robust against the change of message popularity. This finding supports that there exists a relatively fixed gain brought by repeated exposures. Based on the above findings, we propose a parsimonious model to predict the saturated numbers of forwarding activities of messages. Our work could contribute to better understandings of behavioral psychology and social media analytics.

  1. Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway. (United States)

    Millership, C; Phillips, J J; Main, E R G


    Repeat proteins are formed from units of 20-40 aa that stack together into quasi one-dimensional non-globular structures. This modular repetitive construction means that, unlike globular proteins, a repeat protein's equilibrium folding and thus thermodynamic stability can be analysed using linear Ising models. Typically, homozipper Ising models have been used. These treat the repeat protein as a series of identical interacting subunits (the repeated motifs) that couple together to form the folded protein. However, they cannot describe subunits of differing stabilities. Here we show that a more sophisticated heteropolymer Ising model can be constructed and fitted to two new helix deletion series of consensus tetratricopeptide repeat proteins (CTPRs). This analysis, showing an asymmetric spread of stability between helices within CTPR ensembles, coupled with the Ising model's predictive qualities was then used to guide reprogramming of the unfolding pathway of a variant CTPR protein. The designed behaviour was engineered by introducing destabilising mutations that increased the thermodynamic asymmetry within a CTPR ensemble. The asymmetry caused the terminal α-helix to thermodynamically uncouple from the rest of the protein and preferentially unfold. This produced a specific, highly populated stable intermediate with a putative dimerisation interface. As such it is the first step in designing repeat proteins with function regulated by a conformational switch. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Quantum key distribution with two-segment quantum repeaters

    Energy Technology Data Exchange (ETDEWEB)

    Kampermann, Hermann; Abruzzo, Silvestre; Bruss, Dagmar [Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf (Germany)


    Quantum repeaters represent one possible way to achieve long-distance quantum key distribution. One way of improving the repeater rate and decreasing the memory coherence time is the usage of multiplexing. Motivated by the experimental fact that long-range connections are practically demanding, we extend the analysis of the quantum repeater multiplexing protocol to the case of short-range connections. We derive formulas for the repeater rate and we show that short-range connections lead to most of the benefits of a full-range multiplexing protocol. A less demanding QKD-protocol without quantum memories was recently introduced by Lo et al. We generalize this measurement-device-independent quantum key Distribution protocol to the scenario where the repeater Station contains also heralded quantum memories. We assume either single-photon sources or weak coherent pulse sources plus decay states. We show that it is possible to significantly outperform the original proposal, even in presence of decoherence of the quantum memory. We give formulas in terms of device imperfections i.e., the quantum bit error rate and the repeater rate.

  3. Evolutionary dynamics of satellite DNA repeats from Phaseolus beans. (United States)

    Ribeiro, Tiago; Dos Santos, Karla G B; Richard, Manon M S; Sévignac, Mireille; Thareau, Vincent; Geffroy, Valérie; Pedrosa-Harand, Andrea


    Common bean (Phaseolus vulgaris) subtelomeres are highly enriched for khipu, the main satellite DNA identified so far in this genome. Here, we comparatively investigate khipu genomic organization in Phaseolus species from different clades. Additionally, we identified and characterized another satellite repeat, named jumper, associated to khipu. A mixture of P. vulgaris khipu clones hybridized in situ confirmed the presence of khipu-like sequences on subterminal chromosome regions in all Phaseolus species, with differences in the number and intensity of signals between species and when species-specific clones were used. Khipu is present as multimers of ∼500 bp and sequence analyses of cloned fragments revealed close relationship among khipu repeats. The new repeat, named jumper, is a 170-bp satellite sequence present in all Phaseolus species and inserted into the nontranscribed spacer (NTS) of the 5S rDNA in the P. vulgaris genome. Nevertheless, jumper was found as a high-copy repeat at subtelomeres and/or pericentromeres in the Phaseolus microcarpus lineage only. Our data argue for khipu as an important subtelomeric satellite DNA in the genus and for a complex satellite repeat composition of P. microcarpus subtelomeres, which also contain jumper. Furthermore, the differential amplification of these repeats in subtelomeres or pericentromeres reinforces the presence of a dynamic satellite DNA library in Phaseolus.

  4. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.


    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  5. GAA repeat polymorphism in Turkish Friedreich's ataxia patients. (United States)

    Yilmaz, M Bertan; Koç, A Filiz; Kasap, Halil; Güzel, A Irfan; Sarica, Yakup; Süleymanova, Dilara


    Friedreich's ataxia (FRDA), the most common subtype of early onset hereditary spinocerebellar ataxia (SCA), is an autosomal recessive neurodegenerative disorder caused by unstable GAA tri-nucleotide expansions in the first intron of FRDA gene located at 9q13-q21.1 position. Results of GAA repeat polymorphism in 80 Turkish SCA patients and 38 family members of 11 typical FRDA patients were reported. GAA triplet repeat size ranged from approximately 7 to 34 in normal alleles and from approximately 66 to 1300 in mutant alleles. Twenty six patients were homozygous for GAA expansion and size of expanded alleles differed from approximately 425 to 1300 repeats. Children 2 and 6 years old (showing no ataxia symptoms) of one family had homozygous GAA expansions reaching approximately 925 repeats. All 11 families studied had at least 1 afflicted child and 9 parents and 2 siblings were carrier (heterozygous) with mutant alleles ranging from 66 to 850 repeats. Family studies confirmed the meiotic instability and stronger effect of expansion in the smaller alleles on phenotype and a negative correlation between GAA repeat expansion size and onset-age of the disease.

  6. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao


    that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N...... terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also...... with a helix-turn-helix DNA-binding motif. Although this putative motif is shared by other archaeal proteins, orthologs of SSO454 were only detected in species within the Sulfolobus genus and in the closely related Acidianus genus. We infer that the genus-specific protein induces an opening of the structure...

  7. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten


    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective...

  8. Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues. (United States)

    Axford, Michelle M; López-Castel, Arturo; Nakamori, Masayuki; Thornton, Charles A; Pearson, Christopher E


    Recently, curious mutations have been reported to occur within the (CTG)n repeat tract of the myotonic dystrophy type 1 (DM1) locus. For example, the repeat, long presumed to be a pure repeat sequence, has now been revealed to often contain interruption motifs in a proportion of cases with expansions. Similarly, a few de novo somatic CTG expansions have been reported to arise from non-expanded DM1 alleles with 5-37 units, thought to be genetically stable. This study has characterised a novel mutation configuration at the DM1 CTG repeat that arose as somatic mosaicism in a juvenile onset DM1 patient with a non-expanded allele of (CTG)12 and tissue specific expansions ranging from (CTG)1100 to 6000. The mutation configuration replaced the CTG tract with a non-CTG repeat insertion of 43 or 60 nucleotides, precisely placed in the position of the CTG tract with proper flanking sequences. The inserts appeared to arise from a longer human sequence on chromosome 4q12, and may have arisen through DNA structure mediated somatic inter-gene recombination or replication/repair template switching errors. De novo insertions were detected in cerebral cortex and skeletal muscle, but not in heart or liver. Repeat tracts with -1 or -2 CTG units were also detected in cerebellum, which may have arisen by contractions of the short (CTG)12 allele. This non-CTG configuration expands current understanding of the sequence variations that can arise at this hypermutable site.

  9. Repeated high-intensity exercise in professional rugby union. (United States)

    Austin, Damien; Gabbett, Tim; Jenkins, David


    The aim of the present study was to describe the frequency, duration, and nature of repeated high-intensity exercise in Super 14 rugby union. Time-motion analysis was used during seven competition matches over the 2008 and 2009 Super 14 seasons; five players from each of four positional groups (front row forwards, back row forwards, inside backs, and outside backs) were assessed (20 players in total). A repeated high-intensity exercise bout was considered to involve three or more sprints, and/or tackles and/or scrum/ruck/maul activities within 21 s during the same passage of play. The range of repeated high-intensity exercise bouts for each group in a match was as follows: 11-18 for front row forwards, 11-21 for back row forwards, 13-18 for inside backs, and 2-11 for outside backs. The durations of the most intense repeated high-intensity exercise bouts for each position ranged from 53 s to 165 s and the minimum recovery periods between repeated high-intensity exercise bouts ranged from 25 s for the back row forwards to 64 s for the front row forwards. The present results show that repeated high-intensity exercise bouts vary in duration and activities relative to position but all players in a game will average at least 10 changes in activity in the most demanding bouts and complete at least one tackle and two sprints. The most intense periods of activity are likely to last as long as 120 s and as little as 25 s recovery may separate consecutive repeated high-intensity exercise bouts. The present findings can be used by coaches to prepare their players for the most demanding passages of play likely to be experienced in elite rugby union.

  10. Instability of repeated DNAs during transformation in Escherichia coli. (United States)

    Hashem, Vera I; Klysik, Elzbieta A; Rosche, William A; Sinden, Richard R


    Escherichia coli has provided an important model system for understanding the molecular basis for genetic instabilities associated with repeated DNA. Changes in triplet repeat length during growth following transformation in E. coli have been used as a measure of repeat instability. However, very little is known about the molecular and biological changes that may occur on transformation. Since only a small proportion of viable cells become competent, uncertainty exists regarding the nature of these transformed cells. To establish whether the process of transformation can be inherently mutagenic for certain DNA sequences, we used a genetic assay in E. coli to compare the frequency of genetic instabilities associated with transformation with those occurring in plasmid maintained in E. coli. Our results indicate that, for certain DNA sequences, bacterial transformation can be highly mutagenic. The deletion frequency of a 106 bp perfect inverted repeat is increased by as much as a factor of 2 x 10(5) following transformation. The high frequency of instability was not observed when cells stably harboring plasmid were rendered competent. Thus, the process of transformation was required to observe the instability. Instabilities of (CAG).(CTG) repeats are also dramatically elevated upon transformation. The magnitude of the instability is dependent on the nature and length of the repeat. Differences in the methylation status of plasmid used for transformation and the methylation and restriction/modification systems present in the bacterial strain used must also be considered in repeat instability measurements. Moreover, different E. coli genetic backgrounds show different levels of instability during transformation.

  11. RNA FISH for detecting expanded repeats in human diseases. (United States)

    Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J


    RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Lung apoptosis after intra-pulmonary instillation of Benzo(apyrene in Wistar rats Apoptose pulmonar após instilação intrapulmonar de Benzo(apireno em ratos Wistar

    Directory of Open Access Journals (Sweden)

    Baldomero Antonio Kato da Silva


    Full Text Available PURPOSE: To evaluate the influence of pulmonary instillation of Benzo[a]pyrene in lung apoptosis of Wistar rats. METHODS: Male Rattus norvegicus albinus, Wistar lineage was carried through an intra-pulmonary instillation of the Benzo[a]pyrene (B[a]P dilution in alcohol 70%. Three experimental groups had been formed with 08 animals each: Control Group (Alcohol 70%; B[a]P Group 40 mg/kg; e B[a]P Group 80mg/kg, submitted to euthanasia 16 and 18 weeks after the experimental procedure. The pulmonary sections had been processed by TUNEL method and submitted to the histomorphometric analysis to quantify the apoptotic cell number. RESULTS: After 16 weeks, mean of apoptotic cells number in control group (19,3±3,2 was greater than 40mg/Kg group (11,8±1,9; pOBJETIVO: Avaliar a influência da instilação intrapulmonar de Benzo[a]pireno na apoptose pulmonar de ratos Wistar. MÉTODOS: Rattus norvegicus albinus, linhagem Wistar machos foram submetidos à instilação intra-pulmonar da diluição em álcool 70% de Benzo[a]pireno (B[a]P. Foram formados três grupos experimentais com 08 animais cada: Grupo Controle (álcool 70%; Grupo B[a]P 40 mg/kg; e Grupo B[a]P 80mg/kg, submetidos a eutanásia 16 e 18 semanas após o procedimento experimental. As secções pulmonares foram processadas pelo método TUNEL e submetidas à análise histomorfométrica para quantificação do número de células apoptóticas. RESULTADOS: Após 16 semanas, a média do número de células apoptóticas do grupo controle (19,3±3,2 mostrou-se maior que o grupo 40mg/Kg (11,8±1,9; p<0,01 e 80mh/Kg (7,0±1,4; p<0,01. Diferença significante foi também observada entre os grupos 40mg/Kg e 80mg/Kg (p<0,05. Após 18 semanas, a média do número de células apoptóticas do grupo controle (18,0±2,2 mostrou-se maior que o grupo 40mg/Kg (8,8±1,7; p<0,01 e 80mh/Kg (5,5±1,3; p<0,01. Não foi observada diferença significante entre os grupos 40 e 80mg/Kg (ns. CONCLUSÃO: A instila

  13. Effect of repeated Kangaroo Mother Care on repeated procedural pain in preterm infants: A randomized controlled trial. (United States)

    Gao, Haixia; Xu, Guihua; Gao, Honglian; Dong, Rongzhi; Fu, Hongjie; Wang, Danwen; Zhang, Heng; Zhang, Hua


    Preterm infants' repeated exposure to painful procedures may lead to negative consequences. Thus, non-pharmacological pain management is essential due to medication side effects. Kangaroo Mother Care, which aims at offering human care to neonates, has been established for the treatment of a single painful procedure, but the effectiveness of Kangaroo Mother Care across repeated painful procedures is unknown. To test the effectiveness of repeated Kangaroo Mother Care on repeated heel-stick pain in preterm neonates. Randomized controlled trial. Level III Neonatal Intensive Care Unit at a large teaching hospital in northeast China. Preterm infants (gestational age less than 37 weeks) (n=80) were recruited and randomly assigned using a random table format to either an incubator group (n=40) or Kangaroo Mother Care group (n=40). Pain assessments were carried out during four routine heel stick procedures. For the first heel stick, preterm infants in each group received no intervention (routinely stayed in incubator). During the next three heel sticks, the infants in Kangaroo Mother Care group received heel sticks during Kangaroo Mother Care, while infants in the incubator group received heel sticks in incubator. The procedure of each heel stick included 3 phases: baseline, blood collection and recovery. Crying, grimacing and heart rate in response to pain were evaluated at each phase across four heel sticks by three trained independent observers who were blinded to the purpose of the study. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation phases of heel stick. 75 preterm infants completed the protocol. Between-group comparison revealed that preterm infants' heart rate was significantly lower, and the duration of crying and facial grimacing were both significantly shorter in the Kangaroo Mother Care group (n=38) than the incubator group (n=37) from the blood collection phase to recovery phase during repeated heel sticks. No

  14. Flanking Variation Influences Rates of Stutter in Simple Repeats

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    August E. Woerner


    Full Text Available It has been posited that the longest uninterrupted stretch (LUS of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL. While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.

  15. Computer Simulation Studies of CTG Triplet Repeat Sequences (United States)

    Rasaiah, Jayendran. C.; Lynch, Joshua


    Long segments of CTG trinucleotide repeats in human DNA are correlated with a class of neurological diseases (myotonic dystrophy, fragile-X syndrome, and Kenndy's disease). These diseases are characterized by genetic anticipation and are thought to arise from replication errors caused by unusual conformations of CTG repeat segments. We have studied the properties of a single short segment of double starnded DNA with CTG repeats in 0.5 M sodium chloride solution with molecular dynamics simulations. The simulations are carried out in the micro canonical ensemble using an all-atom force field with CHARMM parameters. The TIPS3 water model is used to simulate a molecular solvent. Electrostatic interactions are calculated by Ewald summation and the equations of motion integrated using a Verlet algorithm in conjunction with SHAKE constrained dynamics to maintain bond lengths. The simulation of CTG repeat sequence is compared with a control system containing CAG triplet repeats to determine possible differencesin the conformation and elasticity of the two sequences.


    Directory of Open Access Journals (Sweden)



    Full Text Available ABSTRACT Repeatability analysis has been used to study traits in several crops, assisting in the definition of the minimum number needed to evaluate genotypes more efficiently and with less time and resource consumption. So far, however, no repeatability studies on cactus pear have been found in the literature. The objective of this study was to determine the coefficient of repeatability for cactus pear fruits traits and the minimum number of evaluations (fruit that can provide acceptable accuracy for the prediction of the true value. The experiment was conducted at the Federal Institute of Bahia/Campus Guanambi, with 150 fruits collected from three municipalities in the state of Bahia. The coefficients of repeatability were estimated by the methods of analysis of variance, principal components based on the covariance (PCCV and correlation (PCC matrices, and structural analysis based on the correlation matrix (SA. The analysis of variance showed that, except for fruit diameter, the effect of the production site (municipality was significant for all traits evaluated. The PCCV method was proven the most suitable for studying the repeatability of quality traits of cactus pear fruits. Seven fruits were required to determine, with 90% confidence, the traits length, diameter, fruit firmness, skin thickness, number of seeds, fruit mass, bark mass, pulp mass, pH, titratable acidity, soluble solids, SS/AT ratio, and pulp yield.

  17. Occupational COPD and HMOX1 repeats in a Danish population

    DEFF Research Database (Denmark)

    Würtz, Else; Brasch-Andersen, Charlotte; Steffensen, Rudi


    Background: Dinucleotide repeats (GT)n in the 5’prime promoter region of the heme oxygenase 1 (HMOX1) gene modulate the gene expression. Long repeats might affect occurrence of COPD. We aimed to investigate associations of the HMOX1 polymorphism of (GT)n repeats to occurrence of COPD.......Methods: This population based cohort included 4703 Danes aged 45-84 of Northern European descents. COPD was defined by LLN: 2.5th FEV1/FVC and FEV1 centiles. The occupational exposures were defined as years with vapour, gas, dust or fume (VGDF) exposure. The HMOX1 repeat was genotyped by fragment analysis and capillary......, analyses are attempted replicated in a younger Danish cohort aged 20-44.Results: A HMOX1 (GT)n genotype was present in 4423 participants and distributed as S/S 12%, S/M 42%, M/M 35%, S/L 4%, M/L 7% and L/L 0.1%. The crude association between COPD and at least one long GT repeat (S/L, M/L, L/L) GT genotype...

  18. Physiological Consequences of Repeated Exposures to Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Robert S. Thompson


    Full Text Available Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days to a context that they were conditioned to fear (conditioned fear test, CFT. Repeated exposure to CFT produced body weight loss, adrenal hypertrophy, thymic involution, and basal corticosterone elevation. In vivo biotelemetry measures revealed that CFT evokes sympathetic nervous system driven increases in heart rate (HR, mean arterial pressure (MAP, and core body temperature. Extinction of behavioral (freezing and physiological responses to CFT was prevented using minimal reinstatement footshock. MAP responses to the CFT did not diminish across 20 days of exposure. In contrast, HR and cardiac contractility responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a pre-clinical marker of CV dysfunction. Flattened diurnal rhythms, common to stress-related mood/anxiety disorders, were found for most physiological measures. Thus, repeated CFT produces adaptations indicative of the health damaging effects of psychological/emotional stress.

  19. Time course of the attenuation effect of repeated antipsychotic treatment on prepulse inhibition disruption induced by repeated phencyclidine treatment (United States)

    Li, Ming; He, Erik; Volf, Nick


    Antagonism of prepulse inhibition (PPI) deficits produced by psychotomimetic drugs has been widely used as an effective tool for the study of the mechanisms of antipsychotic action and identifying potential antipsychotic drugs. Many studies have relied on the acute effect of a single administration of antipsychotics, whereas patients with schizophrenia are treated chronically with antipsychotic drugs. The clinical relevance of acute antipsychotic effect in this model is still an open question. In this study, we investigated the time course of repeated antipsychotic treatment on persistent PPI deficit induced by repeated phencyclidine (PCP) treatment. After a baseline test with saline, male Sprague-Dawley rats were repeatedly injected with either vehicle, haloperidol (0.05 mg/kg), clozapine (5.0 or 10.0 mg/kg), olanzapine (2.0 mg/kg), risperidone (1.0 mg/kg) or quetiapine (10 mg/kg), followed by PCP (1.5 mg/kg, sc) and tested for PPI once daily for 6 consecutive days. A single injection of PCP disrupted PPI and this effect was maintained with repeated PCP injections throughout the testing period. Acute clozapine, but not other antipsychotic drugs, attenuated acute PCP-induced PPI disruption at both tested doses. With repeated treatment, clozapine and quetiapine maintained their attenuation, while risperidone enhanced its effect with a significant reduction of PCP-induced disruption toward the end of treatment period. In contrast, repeated haloperidol and olanzapine treatments were ineffective. The PPI effects of these drugs were more conspicuous at a higher prepulse level (e.g. 82 dB) and were dissociable from their effects on startle response and general activity. Overall, the repeated PCP-PPI model appears to be a useful model for the study of the time-dependent antipsychotic effect, and may help identify potential treatments that have a quicker onset of action than current antipsychotics. PMID:21402097

  20. The effects of repeated thought suppression attempts on thought occurrence. (United States)

    Hooper, Nic; McHugh, Louise


    In the thought suppression literature the completion of one suppression and one expression phase is called an indulgence cycle. The current study aimed to determine the effects on thought frequency of entering multiple indulgence cycles. Participants were assigned to one of two groups. The repeated suppression group was required to complete 3 suppression and 3 think free phases in alternating fashion. The suppress think free group was required to complete 1 suppression phase before entering 5 think free phases. Participants pressed a spacebar to report each unwanted target thought occurrence. Participants in the repeated suppression group experienced maintenance of the number of unwanted thought intrusions in both suppression and think free phases, whereas those in the suppress think free group experienced a significant decline in target thought occurrence. The maintenance effect of engaging in repeated suppression attempts is discussed.

  1. Chronic adhesive arachnoiditis after repeat epidural blood patch. (United States)

    Carlswärd, C; Darvish, B; Tunelli, J; Irestedt, L


    Epidural blood patching is an effective treatment for postdural puncture headache but has potential risks. Arachnoiditis is a very rare disabling condition and few cases have been described following an epidural blood patch. We present a case of chronic adhesive arachnoiditis in a parturient treated with a repeat epidural blood patch. A healthy 29-year-old woman had an accidental dural puncture following epidural insertion during labour. Initial treatment of postdural puncture headache with an epidural blood patch was ineffective and was therefore repeated. She gradually developed severe neurological symptoms consistent with arachnoiditis confirmed with magnetic resonance imaging. Despite intensive multimodal treatment with analgesics and physiotherapy, her neurological condition remains unresolved two years later. This serious but rare complication should encourage caution when treating parturients with postdural puncture headache with a repeat epidural blood patch. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Identification of repeats in DNA sequences using nucleotide distribution uniformity. (United States)

    Yin, Changchuan


    Repetitive elements are important in genomic structures, functions and regulations, yet effective methods in precisely identifying repetitive elements in DNA sequences are not fully accessible, and the relationship between repetitive elements and periodicities of genomes is not clearly understood. We present an ab initio method to quantitatively detect repetitive elements and infer the consensus repeat pattern in repetitive elements. The method uses the measure of the distribution uniformity of nucleotides at periodic positions in DNA sequences or genomes. It can identify periodicities, consensus repeat patterns, copy numbers and perfect levels of repetitive elements. The results of using the method on different DNA sequences and genomes demonstrate efficacy and accuracy in identifying repeat patterns and periodicities. The complexity of the method is linear with respect to the lengths of the analyzed sequences. The Python programs in this study are freely available to the public upon request or at Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Absence of bacterial resistance following repeat exposure to photodynamic therapy (United States)

    Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.


    The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were PDT is effective in the eradication of pathogens including antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

  4. A dynamic trinucleotide repeat (TNR) expansion in the DMD gene. (United States)

    Kekou, Kyriaki; Sofocleous, Christalena; Papadimas, George; Petichakis, Dimitris; Svingou, Maria; Pons, Roser-Maria; Vorgia, Pelagia; Gika, Artemis; Kitsiou-Tzeli, Sophia; Kanavakis, Emmanuel


    Dystrophinopathies are allelic X-linked myopathies caused by large deletions/duplications or small lesions along the DMD gene. An unexpected dynamic trinucleotide (GAA) expansion, ranging from ∼59 to 82 pure GAA repeats, within the DMD intron 62, was revealed to segregate through three family generations. From the pedigree, two female patients were referred for DMD investigation due to chronic myopathy and a muscle biopsy compatible with dystrophinopathy. As the size of the GAA repeat is limited to 11-33 within the general population our findings may provide a novel insight towards a Trinucleotide Repeat Expansion. Whether this TNR has an impact on the reported phenotype remains to be resolved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Efficient Synthesis of the Lewis A Tandem Repeat

    Directory of Open Access Journals (Sweden)

    Daisuke Kobayashi


    Full Text Available The convergent synthesis of the Lewis A (Lea tandem repeat is described. The Lea tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Lea unit, {β-d-Gal-(1→3-[α-l-Fuc-(1→4]-β-d-GlcNAc}, was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyltrifluoroacetimidate. This common Lea unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Lea tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyltrifluoroacetimidate method.

  6. Attempted suicide in Denmark. III. Assessment of repeated suicidal behaviour

    DEFF Research Database (Denmark)

    Wang, A G; Nielsen, B; Bille-Brahe, U


    features for the repeaters were previous suicidal behaviour and suicidal behaviour among relatives. Many had a psychiatric record and expressed chronic somatic complaints. Around the time of the attempt, many expressed hopelessness, isolation and suicidal ideation. Pierce's Suicide Intent Scale performed......Ninety-nine patients, randomly chosen among hospital admitted suicide attempters, were initially interviewed at the Department of Psychiatry, Odense University Hospital, Denmark, and then followed up for a period of about 3 years. Half of the patients repeated the attempt in the follow-up period......, mostly in the first year. Ten patients committed suicide, half of them in the first 3 months after the interview, shortly after discharge from hospital. The majority of the repeaters were living alone, while those that committed suicide were mostly married women aged 50-60 years. Other characteristic...

  7. Instability of (CTGn•(CAGn trinucleotide repeats and DNA synthesis

    Directory of Open Access Journals (Sweden)

    Liu Guoqi


    Full Text Available Abstract Expansion of (CTGn•(CAGn trinucleotide repeat (TNR microsatellite sequences is the cause of more than a dozen human neurodegenerative diseases. (CTGn and (CAGn repeats form imperfectly base paired hairpins that tend to expand in vivo in a length-dependent manner. Yeast, mouse and human models confirm that (CTGn•(CAGn instability increases with repeat number, and implicate both DNA replication and DNA damage response mechanisms in (CTGn•(CAGn TNR expansion and contraction. Mutation and knockdown models that abrogate the expression of individual genes might also mask more subtle, cumulative effects of multiple additional pathways on (CTGn•(CAGn instability in whole animals. The identification of second site genetic modifiers may help to explain the variability of (CTGn•(CAGn TNR instability patterns between tissues and individuals, and offer opportunities for prognosis and treatment.

  8. Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation. (United States)

    Punga, Tanel; Bühler, Marc


    Friedreich ataxia is a degenerative disease caused by deficiency of the protein frataxin (FXN). An intronic expansion of GAA triplets in the FXN-encoding gene, FXN, causes gene silencing and thus reduced FXN protein levels. Although it is widely assumed that GAA repeats block transcription via the assembly of an inaccessible chromatin structure marked by methylated H3K9, direct proof for this is lacking. In this study, we analysed different histone modification patterns along the human FXN gene in FRDA patient-derived lymphoblastoid cell lines. We show that FXN mRNA synthesis, but not turnover rates are affected by an expanded GAA repeat tract. Importantly, rather than preventing transcription initiation, long GAA repeat tracts affect transcription at the elongation step and this can occur independently of H3K9 methylation. Our data demonstrate that finding novel strategies to overcome the transcription elongation problem may develop into promising new treatments for FRDA.

  9. Repeat prostate biopsy: who, how and when?. a review. (United States)

    Djavan, Bob; Remzi, Mesut; Schulman, Claude C; Marberger, Michael; Zlotta, Alexandre R


    Urologists are frequently faced with the dilemma of treating a patient with a high index of suspicion of prostate cancer (PCa), but an initial set of negative biopsies. In this review, we evaluated the current knowledge on repeat prostate biopsies, focusing on when to perform them and in which patients, how many samples to take, where to direct the biopsies and what morbidity should be expected. We focussed on the available literature and the multicenter European Prostate Cancer Detection (EPCD) study. The EPCD study included 1051 men with a total PSA from 4 to 10 ng/ml who underwent a transrectal ultrasound (TRUS) guided sextant biopsy and a repeat biopsy in case of a negative initial biopsy. Most studies support that increasing the number of biopsy cores as compared to the sextant technique and improving prostate peripheral zone (PZ) sampling result in a significant improvement in the detection of prostate cancer without increase in morbidity or effects on quality of life. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. At least 10% of patients with negative sextant prostatic biopsy results in the EPCD study were diagnosed with PCa on repeat biopsy, percent free PSA and PSA density of the transition zone being the most accurate predictors. Despite differences in location (more apico-dorsal) and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy were similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Indications and ideal number of biopsy cores to take when repeating biopsies in patients who already underwent extensive biopsy protocols on the first biopsy remains to be determined.

  10. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick


    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  11. Repeat-aware modeling and correction of short read errors. (United States)

    Yang, Xiao; Aluru, Srinivas; Dorman, Karin S


    High-throughput short read sequencing is revolutionizing genomics and systems biology research by enabling cost-effective deep coverage sequencing of genomes and transcriptomes. Error detection and correction are crucial to many short read sequencing applications including de novo genome sequencing, genome resequencing, and digital gene expression analysis. Short read error detection is typically carried out by counting the observed frequencies of kmers in reads and validating those with frequencies exceeding a threshold. In case of genomes with high repeat content, an erroneous kmer may be frequently observed if it has few nucleotide differences with valid kmers with multiple occurrences in the genome. Error detection and correction were mostly applied to genomes with low repeat content and this remains a challenging problem for genomes with high repeat content. We develop a statistical model and a computational method for error detection and correction in the presence of genomic repeats. We propose a method to infer genomic frequencies of kmers from their observed frequencies by analyzing the misread relationships among observed kmers. We also propose a method to estimate the threshold useful for validating kmers whose estimated genomic frequency exceeds the threshold. We demonstrate that superior error detection is achieved using these methods. Furthermore, we break away from the common assumption of uniformly distributed errors within a read, and provide a framework to model position-dependent error occurrence frequencies common to many short read platforms. Lastly, we achieve better error correction in genomes with high repeat content. The software is implemented in C++ and is freely available under GNU GPL3 license and Boost Software V1.0 license at " = redeem". We introduce a statistical framework to model sequencing errors in next-generation reads, which led to promising results in detecting and correcting errors

  12. Dog genetic polymorphism revealed by synthetic tandem repeats. (United States)

    Mariat, D; Robert, L


    We are studying the genetic polymorphism associated with Variable Number of Tandem Repeat (VNTR) loci in 13 breeds of dogs, namely: Alaskan Malamute, Barzoi, Beagle, Belgian Shepherd, Fox Terrier, Griffon, Labrador, Irish Setter, Spaniel, Dachshund, Irish Terrier, Shar Pei and Poodle. Our approach is based upon synthetic tandem repeats (STRs). Using a panel of these arbitrary unit polymers to detect minisatellites, we are attempting to develop paternity testing systems on pure bred dog pedigrees. We are evaluating the potential importance of STRs as a tool for the isolation of minisatellites in dogs, as well as for the characterization of dog genetic markers.

  13. Relationship between income and repeat criminal victimization in Brazil

    Directory of Open Access Journals (Sweden)

    Marcelo Justus


    Full Text Available This study analyzes the effect of income on repeat criminal victimization in Brazil using data from the 2009 National Household Sample Survey and its special supplement on victimization and access to justice. Two count-data models were estimated for four types of crime: theft, robbery, attempted theft/robbery, and physical assault. A positive nonlinear effect of income on repeat victimization for the three types of property crimes and a negative nonlinear effect of income on physical assault were observed.

  14. Layered Architectures for Quantum Computers and Quantum Repeaters (United States)

    Jones, Nathan C.

    This chapter examines how to organize quantum computers and repeaters using a systematic framework known as layered architecture, where machine control is organized in layers associated with specialized tasks. The framework is flexible and could be used for analysis and comparison of quantum information systems. To demonstrate the design principles in practice, we develop architectures for quantum computers and quantum repeaters based on optically controlled quantum dots, showing how a myriad of technologies must operate synchronously to achieve fault-tolerance. Optical control makes information processing in this system very fast, scalable to large problem sizes, and extendable to quantum communication.

  15. Practical repeaters for ultralong-distance quantum communication (United States)

    Vinay, Scott E.; Kok, Pieter


    Quantum repeaters enable long-range quantum communication in the presence of attenuation. Here we propose a method to construct a robust quantum repeater network using only existing technology. We combine the ideas of brokered graph-state construction with double-heralded entanglement generation to form a system that is able to perform all parts of the procedure in a way that is highly tolerant to photon loss and imperfections in detectors. We show that when used in quantum key distribution this leads to secure kilohertz bit rates over intercontinental distances.

  16. Positional repeatability measurements of stepper motors at cryogenic temperatures (United States)

    Pompea, S. M.; Hall, M. S.; Bartko, F.; Houck, J. R.


    For cryogenically-cooled infrared instruments and telescopes employed in space, reliable and predictable motor operations at 4 K in vacuum are in most cases necessary. For the Shuttle Infrared Telescope Facility (SIRTF), stepper motors may be employed in a number of applications. A test facility was designed and built for measuring stepper motor positional repeatability, in vacuum, over a temperature range from ambient to liquid helium temperature. Tests regarding positional repeatability were conducted at different motor speeds, directions of motor rotation, step sizes, and power conditions. In addition, tests were performed with respect to the ability of the motor to remain in a position with no power applied to the motor.

  17. Effect of repeated Ribavirin treatment on grapevine viruses. (United States)

    Komínek, P; Komínková, M; Jandová, B

    The effect of Ribavirin treatment for the chemotherapy of several grapevine viruses was evaluated. Four grapevine cultivars were repeatedly treated with Ribavirin in two different concentrations and with three different lengths of treatment. Repeating the Ribavirin treatment always had a significant effect on the number of healthy grapevine plants obtained. Ribavirin concentration and length of exposure showed a significant difference in sanitation of the Grapevine rupestris stem pitting-associated virus. During sanitation of the Grapevine Pinot gris virus and Grapevine fleck virus, those two factors did not show significant differences in the elimination of grapevine viruses.

  18. Instilling defect tolerance in new compounds (United States)

    Walsh, Aron; Zunger, Alex


    The properties of semiconducting solids are determined by the imperfections they contain. Established physical phenomena can be converted into practical design principles for optimizing defects and doping in a broad range of technology-enabling materials.

  19. Instilling a Love of Learning at Home (United States)

    Chasek, Arlene S.; Rosen, Michelle


    The programs of the Rutgers' Center for Family Involvement in Schools create a partnership for learning between families and schools that promotes and enhances academic success. They also create a powerful school climate that demonstrates respect, trust, and belonging. In addition to teacher-training programs, the center conducts summer leadership…

  20. Repeatability and reproducibility of individual abutment impression, assessed with a blue light scanner

    National Research Council Canada - National Science Library

    Jeon, Jin-Hun; Kim, Dong-Yeon; Lee, Jae-Jun; Kim, Ji-Hwan; Kim, Woong-Chul


    We assessed the repeatability and reproducibility of abutment teeth dental impressions, digitized with a blue light scanner, by comparing the discrepancies in repeatability and reproducibility values...

  1. USGS Southwest Repeat Photography Collection: Kanab Creek, southern Utah and northern Arizona, 1872-2010 (United States)

    Department of the Interior — The USGS Southwest Repeat Photography Collection (‘Collection’), formerly named the Desert Laboratory Repeat Photography Collection, is now housed by the Southwest...

  2. Prevalence of Repeat Pregnancy Including Pregnancy Outcome of Teenage Women

    Directory of Open Access Journals (Sweden)

    Pattarawalai Talungchit, M.D., Ph.D.


    Full Text Available Objective: To determine the prevalence and possible factors of repeat teenage pregnancy including their pregnancy outcomes compared to primi-gravida teenage pregnancy. Methods: 1,684 medical records of teenage pregnancy delivered or received termination of pregnancy at Siriraj hospital from July 2009 to June 2011 were reviewed. The characteristics and pregnancy outcomes of primi- and multi-gravida teenage pregnancies were studied and compared between groups. Results: The prevalence of repeat pregnancies among the study population was around 20% (338/1,684. Age of multi-gravida teenagers and their husbands were significantly higher than those of primi-gravida. Only 5% of primigravida and 25% of multi-gravida were documented as using contraception before getting pregnant (p < 0.001. Oral contraceptive was the most common method using in both groups. Multi-gravida teenagers were significantly diagnosed as anemia before delivery or termination of pregnancy (p = 0.03, although immediate pregnancy outcomes among the two groups were not significantly different. Before they were discharged from the hospital, less than half of them got immediate contraceptive methods especially long-acting reversible contraception. Conclusion: The prevalence of repeat pregnancy among teenagers at Siriraj Hospital was approximately 20%. Lack of proper contraception might be the factor related to repeat pregnancy. Although immediate pregnancy outcomes among primi-and multi-gravida teenagers were not significantly different, long term outcomes of both teenage mothers and their children were still limited.

  3. Large Torque Variations in Two Soft Gamma Repeaters

    NARCIS (Netherlands)

    Woods, P.M.; Kouveliotou, C.; Göğüş, E.; Finger, M.H.; Swank, J.; Markwardt, C.B.; Hurley, K.; van der Klis, M.


    We have monitored the pulse frequencies of the two soft gamma repeaters SGR 1806-20 and SGR 1900+14 through the beginning of year 2001 using primarily Rossi X-Ray Timing Explorer Proportional Counter Array observations. In both sources, we observe large changes in the spin-down torque up to a factor

  4. Development of specific simple sequence repeat (SSR) markers for ...

    African Journals Online (AJOL)

    The bulk segregant analysis (BSA) using simple sequence repeat (SSR) markers were deployed to identify the location and genetic effect of this gene. We have generated new set of SSR markers to identify progenies carrying TGMS gene in a cross TGMS/PTT1. The TGMS gene was located on chromosome 2 with 0.0 cM ...

  5. Inter-simple sequence repeats (ISSR) and morphological diversity in ...

    African Journals Online (AJOL)

    Morphological characteristics as well as inter-simple sequence repeats (ISSR) molecular markers were used to study the species relationship in Onosma species (Boraginaceae) in Iran. Principal component analysis (PCA) showed that morphological characters like caule leaf size and shape, bract shape, corolla shape, ...

  6. Inter simple sequence repeat (ISSR) markers as reproducible and ...

    African Journals Online (AJOL)

    Rose is one of the most important cultivated ornamental plants in the world. A molecular approach using inter-simple sequence repeat (ISSR) markers was applied to seven species of Rosa. To obtain clear and reproducible bands on 2% agarose gels, 9 ISSR primers and 5 parameters (annealing temperature, DNA ...

  7. Repeated Reading Intervention Effects in Kindergartners with Partial Letter Knowledge

    NARCIS (Netherlands)

    Gorp, K. van; Segers, P.C.J.; Verhoeven, L.T.W.


    The direct, transfer and retention effects of a repeated reading intervention study of single CVC (consonant in the onset and a vowel and consonant in the rime) words in kindergartners with partial letter knowledge were examined. A total of 26 second-year kindergartners participated in this study.

  8. Repeated Reading Intervention Effects in Kindergartners with Partial Letter Knowledge (United States)

    van Gorp, Karly; Segers, Eliane; Verhoeven, Ludo


    The direct, transfer and retention effects of a repeated reading intervention study of single CVC (consonant in the onset and a vowel and consonant in the rime) words in kindergartners with partial letter knowledge were examined. A total of 26 second-year kindergartners participated in this study. Participants were divided over two feedback…

  9. Repeated mild injury causes cumulative damage to hippocampal cells

    NARCIS (Netherlands)

    E.J. Matser (Amy); C.I. de Zeeuw (Chris); J.T. Weber (John)


    textabstractAn interesting hypothesis in the study of neurotrauma is that repeated traumatic brain injury may result in cumulative damage to cells of the brain. However, post-injury sequelae are difficult to address at the cellular level in vivo. Therefore, it is necessary to

  10. Pharmacokinetics of oestriol after repeated oral administration to dogs

    NARCIS (Netherlands)

    Hoeijmakers, M.; Janszen, B.; Coert, A.; Horspool, L.


    The aim of the present study was to investigate the pharmacokinetics of oestriol in plasma in the dog after repeated oral administration of oestriol tablets, a preparation intended for the treatment of urinary incontinence in the bitch. The study was performed in six healthy, entire, adult female

  11. Goat breeding structure and repeatability of litter size in smallholder ...

    African Journals Online (AJOL)

    One hundred and sixteen (116) does from 22 randomly selected smallholder herds in Kano and environs were surveyed to evaluate the goat breeding herd structure and to estimate the repeatability of litter size. The study revealed that the average herd size of smallholder goats in the study area is 15.5 goats. The average ...

  12. Repeatedly Reactivated Memories Become More Resistant to Hippocampal Damage (United States)

    Lehmann, Hugo; McNamara, Kathryn C.


    We examined whether repeated reactivations of a context memory would prevent the typical amnesic effects of post-training damage to the hippocampus (HPC). Rats were given a single contextual fear-conditioning session followed by 10 reactivations, involving a brief return to the conditioning context (no shock). Subsequently, the rats received sham…

  13. Automated detection of repeated structures in building facades

    Directory of Open Access Journals (Sweden)

    M. Previtali


    Full Text Available Automatic identification of high-level repeated structures in 3D point clouds of building façades is crucial for applications like digitalization and building modelling. Indeed, in many architectural styles building façades are governed by arrangements of objects into repeated patterns. In particular, façades are generally designed as the repetition of some few basic objects organized into interlaced and\\or concatenated grid structures. Starting from this key observation, this paper presents an algorithm for Repeated Structure Detection (RSD in 3D point clouds of building façades. The presented methodology consists of three main phases. First, in the point cloud segmentation stage (i the building façade is decomposed into planar patches which are classified by means of some weak prior knowledge of urban buildings formulated in a classification tree. Secondly (ii, in the element clustering phase detected patches are grouped together by means of a similarity function and pairwise transformations between patches are computed. Eventually (iii, in the structure regularity estimation step the parameters of repeated grid patterns are calculated by using a Least- Squares optimization. Workability of the presented approach is tested using some real data from urban scenes.

  14. Repeated oral administration of capsaicin increases anxiety-like ...

    Indian Academy of Sciences (India)


    Jul 22, 2013 ... This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of ...

  15. Repeated oral administration of capsaicin increases anxiety-like ...

    Indian Academy of Sciences (India)

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy ...

  16. Postoperative repeated respiratory insufficiency and thyrotoxicosis in molar pregnancy. (United States)

    Cekic, B; Geze, S; Ulusoy, H; Coskun, I; Erturk, E


    Following the removal of a hydatiform mole in a 34-year-old, 14-week pregnant patient, thyrotoxicosis and respiratory insufficiency attacks were twice unexpectedly repeated. The symptoms were resolved with the administration of plasmapheresis, antithyroid and β-blocker drugs and non-invasive mechanical ventilation; however, she was again operated due to prolonged elevated β-hCG.

  17. Maternal views and experiences regarding repeat Caesarean section

    African Journals Online (AJOL)


    Nov 28, 2014 ... countries continue to show strong aversion to cesarean section.[5] On the evidence of recent publications from sub‑Saharan Africa, the willingness of women to accept repeat caesarean delivery is low.[1,5]. A woman's refusal of cesarean section can create a challenging situation for obstetric care providers.

  18. Insertion device and method for accurate and repeatable target insertion (United States)

    Gubeli, III, Joseph F.; Shinn, Michelle D.; Bevins, Michael E.; Dillon-Townes, Lawrence; Neil, George R.


    The present invention discloses a device and a method for inserting and positioning a target within a free electron laser, particle accelerator, or other such device that generates or utilizes a beam of energy or particles. The system includes a three-point registration mechanism that insures angular and translational accuracy and repeatability of positioning upon multiple insertions within the same structure.

  19. Reproducibility and Reliability of Repeated Quantitative Fluorescence Angiography

    DEFF Research Database (Denmark)

    Nerup, Nikolaj; Knudsen, Kristine Bach Korsholm; Ambrus, Rikard


    that the camera can detect. As the emission of fluorescence is dependent of the excitatory light intensity, reduction of this may solve the problem. The aim of the present study was to investigate the reproducibility and reliability of repeated quantitative FA during a reduction of excitatory light....

  20. Association of placenta praevia with repeat cesarean section in ...

    African Journals Online (AJOL)

    Association of placenta praevia with repeat cesarean section in Omdurman Maternity Hospital, Sudan 2010- 2012. ... This association has been investigated long time ago, however in this hospital there is no documented evidence. This study was ... All women operated were followed till discharge from hospital. Results: ...

  1. A General Model for Repeated Audit Controls Using Monotone Subsampling

    NARCIS (Netherlands)

    Raats, V.M.; van der Genugten, B.B.; Moors, J.J.A.


    In categorical repeated audit controls, fallible auditors classify sample elements in order to estimate the population fraction of elements in certain categories.To take possible misclassifications into account, subsequent checks are performed with a decreasing number of observations.In this paper a

  2. Validating simple sequence repeat (SSR) markers for introgression ...

    African Journals Online (AJOL)

    Low hybridization efficiency (22.5%) was achieved using the anther dehiscence method. Such low hybridization efficiency requires use of molecular markers to easily identify plants harbouring the required genotypes. Key words: Stay-green, drought tolerance, quantitative trait loci (QTL), simple sequence repeat (SSR) ...

  3. Evaluation of genetic diversity in rice using simple sequence repeats ...

    African Journals Online (AJOL)

    The dendrogram revealed 8 major distinct clusters. Higher range of similarity values for related genotypes using simple sequence repeats (SSR) provides greater confidence for the assessment of genetic diversity and relationships. The polymorphism information content (PIC) value for the SSR loci ranged from 0.36 to 0.98.

  4. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis (United States)


    repeat expansions through RNA-derived DNA intermediates in cancer”. * Denotes co-corresponding authors Oral Presentations Ting DT. Diversity of... mycoplasma contamination giving negative results. For drug treatment, cells were cultured in the presence of either DMSO or 100 µM 2’,3’-dideoxycytidine

  5. Repfinder: Finding approximately repeated scene elements for image editing

    KAUST Repository

    Cheng, Ming-Ming


    Repeated elements are ubiquitous and abundant in both manmade and natural scenes. Editing such images while preserving the repetitions and their relations is nontrivial due to overlap, missing parts, deformation across instances, illumination variation, etc. Manually enforcing such relations is laborious and error-prone. We propose a novel framework where user scribbles are used to guide detection and extraction of such repeated elements. Our detection process, which is based on a novel boundary band method, robustly extracts the repetitions along with their deformations. The algorithm only considers the shape of the elements, and ignores similarity based on color, texture, etc. We then use topological sorting to establish a partial depth ordering of overlapping repeated instances. Missing parts on occluded instances are completed using information from other instances. The extracted repeated instances can then be seamlessly edited and manipulated for a variety of high level tasks that are otherwise difficult to perform. We demonstrate the versatility of our framework on a large set of inputs of varying complexity, showing applications to image rearrangement, edit transfer, deformation propagation, and instance replacement. © 2010 ACM.

  6. Development of simple sequence repeat (SSR) markers that are ...

    African Journals Online (AJOL)

    Simple sequence repeats (SSRs) markers were developed through data mining of 3,803 expressed sequence tags (ESTs) previously published. A total of 144 di- to penta-type SSRs were identified and they were screened for polymorphism between two turnip cultivars, 'Tsuda' and 'Yurugi Akamaru'. Out of 90 EST-SSRs for ...

  7. Analysis of B-genome derived simple sequence repeat (SSR ...

    African Journals Online (AJOL)

    A study was conducted to investigate the genetic variability between 40 Musa genotypes maintained at the Musa germplasm collection of the International Institute for Tropical Agriculture, Ibadan using nine B-genome derived simple sequence repeat (SSR) markers. The nine primers produced reproducible and discrete ...

  8. Repeated simple sedimentation technique and prevalence of bovine ...

    African Journals Online (AJOL)

    techniques in detection of Schistosoma eggs of cattle increases by repeated faecal examinations. As useful method ... simple faecal examination in detection of Schistosoma eggs in chronic form has not achieved a level of .... immunity was suppression of worm fecundity (Bushara et al., 1980). It was also reported that local ...

  9. The repeatability of reproduction rate in the Tygerboek Merino Dock ...

    African Journals Online (AJOL)

    The repeatability of reproduction rate at 2 years or up to 3 years of age was investigated by regression methods considering subsequent reproduction averaged over a number of lambing opportunities or within sUbsequent age groups. Results from the study suggested multiple birth rate at 2 years of age to be more ...

  10. Identifying repeat DUI crash factors using state crash records. (United States)

    Fu, Haoqiang


    The objective of this study is to identify high risk factors that are closely related to repeat DUI crashes using readily available information from the state crash records. Survival analysis was used and a Cox proportional hazards model was developed using the police-reported crash records in the state of Louisiana. A variety of variables were found to be significant in predicting repeat DUI crashes. The factors included the characteristics of the drivers (gender, race, and age), the types of the vehicle (light truck/pick up truck or other), the characteristics of the crash (hit-and-run, driver violations, and whether the driver is arrested), the type of location (residential area or other), and the characteristics of the roadway (highway type and roadway type). This study provides a comprehensive picture of the repeat DUI crashes. The model can quantitatively predict the relative hazards of repeat DUI crashes. It can be used to identify the characteristics of the crash-involved DUI drivers who are at greatest risk of being involved in a subsequent DUI crash, allowing to apply appropriate remedial measures to reduce the risk.

  11. Mixture Models for the Analysis of Repeated Count Data.

    NARCIS (Netherlands)

    van Duijn, M.A.J.; Böckenholt, U


    Repeated count data showing overdispersion are commonly analysed by using a Poisson model with varying intensity parameter. resulting in a mixed model. A mixed model with a gamma distribution for the Poisson parameter does not adequately fit a data set on 721 children's spelling errors. An

  12. The development of ingroup favoritism in repeated social dilemmas

    Directory of Open Access Journals (Sweden)

    Angela Rachael Dorrough


    Full Text Available In two comprehensive and fully incentivized studies, we investigate the development of ingroup favoritism as one of two aspects of parochial altruism in repeated social dilemmas. Specifically, we test whether ingroup favoritism is a fixed phenomenon that can be observed from the very beginning and remains stable over time, or whether it develops (increases vs. decreases during repeated contact. Ingroup favoritism is assessed through cooperation behavior in a repeated continuous prisoner’s dilemma where participants sequentially interact with ten members of the ingroup (own city and university and subsequently with ten members of the outgroup (other city and university, or vice versa. In none of the experiments do we observe initial differences in cooperation behavior for interaction partners from the ingroup, as compared to outgroup, and we only observe small differences in expectations regarding the interaction partners’ cooperation behavior. After repeated interaction, however, including a change of groups, clear ingroup favoritism can be observed. Instead of being due to gradual and potentially biased updating of expectations, we found that these emerging differences were mainly driven by the change of interaction partners’ group membership that occurred after round 10. This indicates that in social dilemma settings ingroup favoritism is to some degree dynamic in that it is enhanced and sometimes only observable if group membership is activated by thinking about both the interaction with the ingroup and the outgroup.


    African Journals Online (AJOL)


    Agrosearch (2013) Volume 13(2):51-58 HATCH-OUT ANALYSIS AND REPEATABILITY ESTIMATES OF COMMON. HATCHABILITY PROBLEMS IN ISA-BROWN BREEDER STOCK. *Fayeye T. R. and Olapade A. A.. Department of Animal Production, Faculty of Agriculture, University ...

  14. Monitoring selective logging in western Amazonia with repeat lidar flights (United States)

    H.E. Andersen; S.E. Reutebuch; R.J. McGaughey; M.V.N. d' Oliveira; M. Keller


    The objective of this study was to test the use of repeat flight, airborne laser scanning data (lidar) for estimating changes associated with low-impact selective logging (approx. 10-15 m3 ha−1 = 5-7% of total standing volume harvested) in natural tropical forests in the Western Brazilian Amazon. Specifically, we investigated change in area...

  15. Large cryptic internal sequence repeats in protein structures from ...

    Indian Academy of Sciences (India)


    [Sarani R, Udayaprakash N A, Subashini R, Mridula P, Yamane T and Sekar K 2009 Large cryptic internal sequence repeats in protein structures from Homo sapiens; J. Biosci. 34 103–112]. Keywords. Propensity; structure–function correlation; human genome; structural plasticity; three-dimensional structure; identical and.

  16. Intrarater repeatability of shade selections with two shade guides. (United States)

    Hammad, Ihab A


    Color research has shown that shade guides do not always represent the color of natural teeth. Moreover, visual evaluation has been found to be unreliable and inconsistent. This investigation evaluated the effects of 2 shade guides on the intrarater repeatability (reliability) of prosthodontists and general practitioners with regard to shade selection. Ten prosthodontists and ten general practitioners (all men, 35-45 years old) with an average practice experience of 14 years participated in this study. Examiners were tested to eliminate color blindness. Each clinician used Vita Lumin Vacuum and Vitapan 3D-Master shade guides to determine the shades of the maxillary right canines of 20 patients following a standard protocol. The identification codes of the shade tabs were masked to prevent shade memory. All teeth were polished before each shade selection, and the selection process was standardized for controlled lighting and procedures. Shade selections were randomly repeated 1 month later by the same practitioners on the same group of patients in accordance with the same shade-selection protocol. Analysis of variance and t tests for individual comparisons among means were performed (P3D-Master shade guide significantly improved the intrarater repeatability of general practitioners compared with the Vita Lumin Vacuum shade guide (P3D-Master shade guide notably improved intrarater repeatability among the general practitioners.

  17. Reduction in gesture during the production of repeated references

    NARCIS (Netherlands)

    Hoetjes, M.W.; Koolen, R.M.F.; Goudbeek, M.B.; Krahmer, E.J.; Swerts, M.G.J.


    In dialogue, repeated references contain fewer words (which are also acoustically reduced) and fewer gestures than initial ones. In this paper, we describe three experiments studying to what extent gesture reduction is comparable to other forms of linguistic reduction. Since previous studies showed

  18. Intersession repeatability of acoustic rhinometry measurements in healthy volunteers. (United States)

    Al Ahmari, Mohammed Dhafer; Wedzicha, Jadwiga Anna; Hurst, John Robert


    Acoustic rhinometry is a rapid, reliable and non-invasive technique for the evaluation of conditions associated with impaired nasal patency. This study aimed to examine the intersession repeatability of acoustic rhinometry measurements of unilateral and combined nasal parameters in a group of healthy volunteers. Twenty healthy volunteers were studied. In each subject, acoustic rhinometry measurements were performed on five consecutive days, with multiple recordings. Five clinically relevant parameters were measured in each session and the intersession repeatability of these measurements was expressed in terms of mean coefficient of variation, intraclass correlation coefficient and inter-item correlations. Intraclass correlation coefficients showed a high, and greater repeatability over time for all the combined (mean) values compared to the unilateral values. All intraclass correlations for combined values were ≥0.80 confirming almost perfect agreement. All intraclass correlations and inter-item correlations were associated with Pmeasurements. Acoustic rhinometry provides highly repeatable measurements of nasal patency, which is best for combined (mean) nasal parameters. This property makes it suitable for use in the diagnosis and follow-up of conditions associated with nasal obstruction, either structural or functional.

  19. Conservative Sample Size Determination for Repeated Measures Analysis of Covariance


    Timothy M Morgan; Case, L. Douglas


    In the design of a randomized clinical trial with one pre and multiple post randomized assessments of the outcome variable, one needs to account for the repeated measures in determining the appropriate sample size. Unfortunately, one seldom has a good estimate of the variance of the outcome measure, let alone the correlations among the measurements over time.

  20. Modeling and Dynamic Analysis on Animals’ Repeated Learning Process


    Lin, Mu; Yang, Jinqiao; Xu, Bin


    Part 5: Learning and Novel Algorithms; International audience; Dynamical modeling is used to describe the process of animals’ repeated learning. Theoretical analysis is done to explore the dynamic property of this process, such as the limit sets and their stability. The scope of variables is provided for different practical purpose, cooperated with necessary numerical simulation.