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Sample records for mice underwent intratracheal

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

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

    2011-01-01

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

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

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    Shi Z

    2017-03-01

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

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

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    Kyung-Hwa Jung

    2016-09-01

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

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

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    Nemmar A

    2017-04-01

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

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

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rhea Bhargava

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

  7. Intratracheal injection of adenovirus containing the human MNSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis

    International Nuclear Information System (INIS)

    Epperly, Michael W.; Bray, Jenifer A.; Krager, Stephen; Berry, Luann M.; Gooding, William; Engelhardt, John F.; Zwacka, Ralf; Travis, Elizabeth L.; Greenberger, Joel S.

    1999-01-01

    Purpose: A dose and volume limiting factor in radiation treatment of thoracic cancer is the development of fibrosis in normal lung. The goal of the present study was to determine whether expression prior to irradiation of a transgene for human manganese superoxide dismutase (MnSOD) or human copper/zinc superoxide dismutase (Cu/ZnSOD) protects against irradiation-induced lung damage in mice. Methods and Materials: Athymic Nude (Nu/J) mice were intratracheally injected with 10 9 plaque-forming units (PFU) of a replication-incompetent mutant adenovirus construct containing the gene for either human MnSOD, human copper/zinc superoxide dismutase (Cu/ZnSOD) or LacZ. Four days later the mice were irradiated to the pulmonary cavity to doses of 850, 900, or 950 cGy. To demonstrate adenoviral infection, nested reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out with primers specific for either human MnSOD or Cu/ZnSOD transgene on freshly explanted lung, trachea, or alveolar type II cells, and immunohistochemistry was used to measure LacZ expression. RNA was extracted on day 0, 1, 4, or 7 after 850 cGy of irradiation from lungs of mice that had previously received adenovirus or had no treatment. Slot blot analysis was performed to quantitate RNA expression for IL-1, tumor necrosis factor (TNF)-α, TGF-β, MnSOD, or Cu/ZnSOD. Lung tissue was explanted and tested for biochemical activity of MnSOD or Cu/ZnSOD after adenovirus injection. Other mice were sacrificed 132 days after irradiation, lungs excised, frozen in OCT, (polyvinyl alcohol, polyethylene glycol mixture) sectioned, H and E stained, and evaluated for percent of the lung demonstrating organizing alveolitis. Results: Mice injected intratracheally with adenovirus containing the gene for human MnSOD had significantly reduced chronic lung irradiation damage following 950 cGy, compared to control mice or mice injected with adenovirus containing the gene for human Cu/ZnSOD or LacZ. Immunohistochemistry

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

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

    2014-01-01

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

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

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

    2017-11-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

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

    2015-01-01

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

  13. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    Science.gov (United States)

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

    2014-06-01

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

  17. Enhanced bioavailability of opiates after intratracheal administration

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

    Basmadzhieva, K; Kolev, K; Balabaeva, L

    1981-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Waheed Rahman

    2018-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-30

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Science.gov (United States)

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

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

  8. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Science.gov (United States)

    Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

    2014-01-01

    Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  9. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Directory of Open Access Journals (Sweden)

    Zhe Liang

    Full Text Available Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis.Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival.In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice.Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  10. Cecal ligation and puncture followed by MRSA pneumonia increases mortality in mice and blunts production of local and systemic cytokines

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E.; Liang, Zhe; Breed, Elise R.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Burd, Eileen M.; Farris, Alton B.; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2011-01-01

    Mortality in the ICU frequently results from the synergistic effect of two temporally-distinct infections. This study examined the pathophysiology of a new model of intraabdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed three days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival while animals with CLP followed by MRSA pneumonia had 67% seven-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage (BAL) concentrations of MRSA compared to sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased BAL levels of IL-6, TNF-α, and G-CSF compared to those given intratracheal saline while CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared to those subjected to sham laparotomy while this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count or lymphocyte apoptosis was identified in CLP/MRSA mice compared to animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection. PMID:21937950

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chia-Feng Yang

    2010-08-01

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

  14. Cecal ligation and puncture followed by methicillin-resistant Staphylococcus aureus pneumonia increases mortality in mice and blunts production of local and systemic cytokines.

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E; Liang, Zhe; Breed, Elise R; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Hotchkiss, Richard S; Coopersmith, Craig M

    2012-01-01

    Mortality in the intensive care unit frequently results from the synergistic effect of two temporally distinct infections. This study examined the pathophysiology of a new model of intra-abdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed 3 days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival, whereas animals with CLP followed by MRSA pneumonia had 67% 7-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage concentrations of MRSA compared with sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased bronchoalveolar lavage levels of interleukin 6 (IL-6), tumor necrosis factor α, and granulocyte colony-stimulating factor compared with those given intratracheal saline, whereas CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared with those subjected to sham laparotomy, whereas this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count, or lymphocyte apoptosis was identified in CLP/MRSA mice compared with animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection.

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

    NARCIS (Netherlands)

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

    1983-01-01

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

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

    International Nuclear Information System (INIS)

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

    1975-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yamamoto Kazuhiro

    2010-03-01

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

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

    Science.gov (United States)

    Lorenzoni, A G; Wideman, R F

    2008-04-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Angela Maria Rizzo

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Pylev, L N

    1963-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  7. Megarectumsigma underwent surgery for chronic faecal impact action

    International Nuclear Information System (INIS)

    Canessa, C.; Gomez del Valle, M.; Caraballo, M.

    2002-01-01

    Seven patients with megarectumsigma underwent surgery for chronic faecal impaction,reviewing clinical diagnosis, aetiology and medical and surgical management.It is suggested medical management of chronic faecal impaction trying to achieve elective surgery.The curative surgery should include the resection of all pathologic bowel, but in Duhamel procedure and its modifications distal rectal tran section should be at the peritoneal reflection.Habr-Gama modification has shown to be technically easier and it has been communicated good functional results.Local unfavourable conditions may be resolve by staged surgery,which allows outline definitive bowel reconstruction after functional assessment

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-05-02

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

  13. ALGORITHM FOR MANAGEMENT OF HYPERTENSIVE PATIENTS UNDERWENT UROLOGY INTERVENTIONS

    Directory of Open Access Journals (Sweden)

    S. S. Davydova

    2013-01-01

    Full Text Available Aim. To study the efficacy of cardiovascular non-invasive complex assessment and pre-operative preparation in hypertensive patients needed in surgical treatment of urology dis- eases.Material and methods. Males (n=883, aged 40 to 80 years were included into the study. The main group consisted of patients that underwent laparotomic nephrectomy (LTN group; n=96 and patients who underwent laparoscopic nephrectomy (LSN group; n=53. Dynamics of ambulatory blood pressure monitoring (ABPM data was analyzed in these groups in the immediate postoperative period. The efficacy of a package of non-invasive methods for cardiovascular system assessment was studied. ABPM was performed after nephrectomy (2-nd and 10-th days after surgery in patients with complaints of vertigo episodes or intense general weakness to correct treatment.Results. In LTN group hypotension episodes or blood pressure (BP elevations were observed in 20 (20.8% and 22 (22.9% patients, respectively, on the 2-nd day after the operation. These complications required antihypertensive treatment correction. Patients with hypotension episodes were significantly older than patients with BP elevation and had significantly lower levels of 24-hour systolic BP, night diastolic BP and minimal night systolic BP. Re-adjustment of antihypertensive treatment on the 10-th postoperative day was required to 2 (10% patients with hypotension episodes and to 1 (4.5% patient with BP elevation. Correction of antihypertensive therapy was required to all patients in LSN group on the day 2, and to 32 (60.4% patients on the 10-th day after the operation. Reduction in the incidence of complications (from 1.2% in 2009 to 0.3% in 2011, p<0.001 was observed during the application of cardiovascular non-invasive complex assessment and preoperative preparation in hypertensive patients.Conclusion. The elaborated management algorithm for patients with concomitant hypertension is recommended to reduce the cardiovascular

  14. ALGORITHM FOR MANAGEMENT OF HYPERTENSIVE PATIENTS UNDERWENT UROLOGY INTERVENTIONS

    Directory of Open Access Journals (Sweden)

    S. S. Davydova

    2015-09-01

    Full Text Available Aim. To study the efficacy of cardiovascular non-invasive complex assessment and pre-operative preparation in hypertensive patients needed in surgical treatment of urology dis- eases.Material and methods. Males (n=883, aged 40 to 80 years were included into the study. The main group consisted of patients that underwent laparotomic nephrectomy (LTN group; n=96 and patients who underwent laparoscopic nephrectomy (LSN group; n=53. Dynamics of ambulatory blood pressure monitoring (ABPM data was analyzed in these groups in the immediate postoperative period. The efficacy of a package of non-invasive methods for cardiovascular system assessment was studied. ABPM was performed after nephrectomy (2-nd and 10-th days after surgery in patients with complaints of vertigo episodes or intense general weakness to correct treatment.Results. In LTN group hypotension episodes or blood pressure (BP elevations were observed in 20 (20.8% and 22 (22.9% patients, respectively, on the 2-nd day after the operation. These complications required antihypertensive treatment correction. Patients with hypotension episodes were significantly older than patients with BP elevation and had significantly lower levels of 24-hour systolic BP, night diastolic BP and minimal night systolic BP. Re-adjustment of antihypertensive treatment on the 10-th postoperative day was required to 2 (10% patients with hypotension episodes and to 1 (4.5% patient with BP elevation. Correction of antihypertensive therapy was required to all patients in LSN group on the day 2, and to 32 (60.4% patients on the 10-th day after the operation. Reduction in the incidence of complications (from 1.2% in 2009 to 0.3% in 2011, p<0.001 was observed during the application of cardiovascular non-invasive complex assessment and preoperative preparation in hypertensive patients.Conclusion. The elaborated management algorithm for patients with concomitant hypertension is recommended to reduce the cardiovascular

  15. Quantification of lung fibrosis and emphysema in mice using automated micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Ellen De Langhe

    Full Text Available BACKGROUND: In vivo high-resolution micro-computed tomography allows for longitudinal image-based measurements in animal models of lung disease. The combination of repetitive high resolution imaging with fully automated quantitative image analysis in mouse models of lung fibrosis lung benefits preclinical research. This study aimed to develop and validate such an automated micro-computed tomography analysis algorithm for quantification of aerated lung volume in mice; an indicator of pulmonary fibrosis and emphysema severity. METHODOLOGY: Mice received an intratracheal instillation of bleomycin (n = 8, elastase (0.25 U elastase n = 9, 0.5 U elastase n = 8 or saline control (n = 6 for fibrosis, n = 5 for emphysema. A subset of mice was scanned without intervention, to evaluate potential radiation-induced toxicity (n = 4. Some bleomycin-instilled mice were treated with imatinib for proof of concept (n = 8. Mice were scanned weekly, until four weeks after induction, when they underwent pulmonary function testing, lung histology and collagen quantification. Aerated lung volumes were calculated with our automated algorithm. PRINCIPAL FINDINGS: Our automated image-based aerated lung volume quantification method is reproducible with low intra-subject variability. Bleomycin-treated mice had significantly lower scan-derived aerated lung volumes, compared to controls. Aerated lung volume correlated with the histopathological fibrosis score and total lung collagen content. Inversely, a dose-dependent increase in lung volume was observed in elastase-treated mice. Serial scanning of individual mice is feasible and visualized dynamic disease progression. No radiation-induced toxicity was observed. Three-dimensional images provided critical topographical information. CONCLUSIONS: We report on a high resolution in vivo micro-computed tomography image analysis algorithm that runs fully automated and allows quantification of aerated lung volume in mice. This

  16. Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

    Science.gov (United States)

    Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

    2016-11-25

    Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nalabotu SK

    2011-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Alex J Mann

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-06

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

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

    Directory of Open Access Journals (Sweden)

    Ümit Aydogmus

    2014-08-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Jenny R. Roberts

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Giri, S.N.

    1987-01-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xia Xiao

    2016-09-01

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

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

    Science.gov (United States)

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

    2012-08-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-15

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

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

    Science.gov (United States)

    Yoshimura, M; Tsugawa, C; Tsubota, N

    1994-11-01

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

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

    Science.gov (United States)

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

    1999-05-14

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Konrad Urbanek

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  9. Serum Zn levels in dysphagic patients who underwent endoscopic gastrostomy for long term enteral nutrition

    OpenAIRE

    Adriana Santos, Carla; Fonseca, Jorge; Brito, José; Fernandes, Tânia; Gonçalves, Luísa; Sousa Guerreiro, António

    2014-01-01

    Background and aims: Dysphagic patients who underwent endoscopic gastrostomy (PEG) usually present protein-energy malnutrition, but little is known about micronutrient malnutrition. The aim of the present study was the evaluation of serum zinc in patients who underwent endoscopic gastrostomy and its relationship with serum proteins, whole blood zinc, and the nature of underlying disorder. Methods: From patients that underwent gastrostomy a blood sample was obtained minutes before the procedur...

  10. 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

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    Masanori Horie

    2016-01-01

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

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

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    Alexandre Robbe

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  15. Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

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    Gil Sucheol

    2012-10-01

    Full Text Available Abstract Background Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS. The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice. Methods C57BL/6 (B6 and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP of 3 cm of water. Results Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC, and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice. Conclusions We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.

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

    OpenAIRE

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  18. [A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

    Science.gov (United States)

    Komiyama, Sosuke; Izumiya, Yasuhito; Kimura, Yu; Nakashima, Shingo; Kin, Syuichi; Kawakami, Sadao

    2018-03-01

    A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

  19. Dysphagia among Adult Patients who Underwent Surgery for Esophageal Atresia at Birth

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    Valérie Huynh-Trudeau

    2015-01-01

    Full Text Available BACKGROUND: Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and/or anatomical anomalies.

  20. Effect of using pump on postoperative pleural effusion in the patients that underwent CABG

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    Mehmet Özülkü

    2015-08-01

    Full Text Available Abstract Objective: The present study investigated effect of using pump on postoperative pleural effusion in patients who underwent coronary artery bypass grafting. Methods: A total of 256 patients who underwent isolated coronary artery bypass grafting surgery in the Cardiovascular Surgery clinic were enrolled in the study. Jostra-Cobe (Model 043213 105, VLC 865, Sweden heart-lung machine was used in on-pump coronary artery bypass grafting. Off-pump coronary artery bypass grafting was performed using Octopus and Starfish. Proximal anastomoses to the aorta in both on-pump and off-pump techniques were performed by side clamps. The patients were discharged from the hospital between postoperative day 6 and day 11. Results: The incidence of postoperative right pleural effusion and bilateral pleural effusion was found to be higher as a count in Group 1 (on-pump as compared to Group 2 (off-pump. But the difference was not statistically significant [P>0.05 for right pleural effusion (P=0.893, P>0.05 for bilateral pleural effusion (P=0.780]. Left pleural effusion was encountered to be lower in Group 2 (off-pump. The difference was found to be statistically significant (P<0.05, P=0.006. Conclusion: Under the light of these results, it can be said that left pleural effusion is less prevalent in the patients that underwent off-pump coronary artery bypass grafting when compared to the patients that underwent on-pump coronary artery bypass grafting.

  1. Incidence of Bradycardia and Outcomes of Patients Who Underwent Orbital Atherectomy Without a Temporary Pacemaker.

    Science.gov (United States)

    Lee, Michael S; Nguyen, Heajung; Shlofmitz, Richard

    2017-02-01

    We analyzed the incidence of bradycardia and the safety of patients with severely calcified coronary lesions who underwent orbital atherectomy without the insertion of a temporary pacemaker. The presence of severely calcified coronary lesions can increase the complexity of percutaneous coronary intervention due to the difficulty in advancing and optimally expanding the stent. High-pressure inflations to predilate calcified lesions may cause angiographic complications like perforation and dissection. Suboptimal stent expansion is associated with stent thrombosis and restenosis. Orbital atherectomy safely and effectively modifies calcified plaque to facilitate optimal stent expansion. The incidence of bradycardia in orbital atherectomy is unknown. Fifty consecutive patients underwent orbital atherectomy from February 2014 to September 2016 at our institution, none of whom underwent insertion of a temporary pacemaker. The final analysis included 47 patients in this retrospective study as 3 patients were excluded because of permanent pacemaker implantation. The primary endpoint was significant bradycardia, defined as bradycardia requiring emergent pacemaker placement or a heart rate pacemaker appears to be safe.

  2. Comparison of Voice Quality Between Patients Who Underwent Inferior Turbinoplasty or Radiofrequency Cauterization.

    Science.gov (United States)

    Göker, Ayşe Enise; Aydoğdu, İmran; Saltürk, Ziya; Berkiten, Güler; Atar, Yavuz; Kumral, Tolgar Lütfi; Uyar, Yavuz

    2017-01-01

    The aim of this study was to analyze and compare the vocal quality in patients who underwent either submucosal turbinectomy or radiofrequency cauterization. In this study, we enrolled 60 patients diagnosed with inferior concha hypertrophy. These patients were divided into two groups by using computer program "Research Randomizer." Of the 60 patients, 30 underwent submucosal inferior turbinoplasty and 30 underwent radiofrequency cauterization. The control group was composed of 30 healthy adults with no nasal or upper aerodigestive system pathology. The patients were checked at weeks 1, 2, and 4. Voice records were taken before the procedure and at week 4 postprocedure. The mean age of patients in the inferior turbinoplasty group was 29.4 years (range: 19-42 years); in the radiofrequency group, it was 30.30 years (range: 18-50 years). There was no statistical difference in age between groups. In the inferior turbinoplasty group, there were 16 male and 14 female patients, and in the radiofrequency group, there were 13 male and 17 female patients. There was no significant difference in the number of males and females between groups. Voice professionals, especially singers, actors, and actresses, should be informed about possible voice changes before undergoing endonasal surgery because these individuals are more sensitive to changes in resonance organs. We believe that voice quality should be regarded as a highly important parameter when measuring the success of endonasal surgery. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  3. Evolution of elderly patients who underwent cardiac surgery with cardiopulmonary bypass

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    Alain Moré Duarte

    2016-01-01

    Full Text Available Introduction: There is a steady increase in the number of elderly patients with severe cardiovascular diseases who require a surgical procedure to recover some quality of life that allows them a socially meaningful existence, despite the risks.Objectives: To analyze the behavior of elderly patients who underwent cardiac surgery with cardiopulmonary bypass.Method: A descriptive, retrospective, cross-sectional study was conducted with patients over 65 years of age who underwent surgery at the Cardiocentro Ernesto Che Guevara, in Santa Clara, from January 2013 to March 2014.Results: In the study, 73.1% of patients were men; and there was a predominance of subjects between 65 and 70 years of age, accounting for 67.3%. Coronary artery bypass graft was the most prevalent type of surgery and had the longest cardiopulmonary bypass times. Hypertension was present in 98.1% of patients. The most frequent postoperative complications were renal dysfunction and severe low cardiac output, with 44.2% and 34.6% respectively.Conclusions: There was a predominance of men, the age group of 65 to 70 years, hypertension, and patients who underwent coronary artery bypass graft with prolonged cardiopulmonary bypass. Renal dysfunction was the most frequent complication.

  4. Acute myocardial infarctation in patients with critical ischemia underwent lower limb revascularization

    Directory of Open Access Journals (Sweden)

    Esdras Marques Lins

    2013-12-01

    Full Text Available BACKGROUND: Atherosclerosis is the main cause of peripheral artery occlusive disease (PAOD of the lower limbs. Patients with PAOD often also have obstructive atherosclerosis in other arterial sites, mainly the coronary arteries. This means that patients who undergo infrainguinal bypass to treat critical ischemia have a higher risk of AMI. There are, however, few reports in the literature that have assessed this risk properly. OBJECTIVE: The aim of this study was to determine the incidence of acute myocardial infarction in patients who underwent infrainguinal bypass to treat critical ischemia of the lower limbs caused by PAOD. MATERIAL AND METHODS: A total of 64 patients who underwent 82 infrainguinal bypass operations, from February 2011 to July 2012 were studied. All patients had electrocardiograms and troponin I blood assays during the postoperative period (within 72 hours. RESULTS: There were abnormal ECG findings and elevated blood troponin I levels suggestive of AMI in five (6% of the 82 operations performed. All five had conventional surgery. The incidence of AMI as a proportion of the 52 conventional surgery cases was 9.6%. Two patients died. CONCLUSION: There was a 6% AMI incidence among patients who underwent infrainguinal bypass due to PAOD. Considering only cases operated using conventional surgery, the incidence of AMI was 9.6%.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peters Annette

    2010-09-01

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

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

    1992-01-01

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

  9. Factors related to postoperative pain among patients who underwent radiofrequency ablation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hsieh, Y.-C.; Yap, Y.-S.; Hung, C.-H.; Chen, C.-H.; Lu, S.-N.; Wang, J.-H.

    2013-01-01

    Aim: To evaluate the incidence and associated factors of postoperative intense pain and haemodynamic changes during radiofrequency ablation of hepatocellular carcinoma. Materials and methods: A total of 123 consecutive hepatocellular carcinoma patients who underwent radiofrequency ablation were prospectively recruited. Patient factors, tumour characteristics, procedural factors, intraoperative haemodynamic changes, complications, postoperative events, laboratory values before and after ablation, and postoperative pain were evaluated. Postoperative pain was scored using a visual analogue scale after the procedure. Results: The mean age of the patients was 65.6 ± 9.6 years. In multiple logistic regression analysis, patients who underwent general anaesthesia [odds ratio (95% CI): 2.68 (1.23–5.81); p = 0.013] and had more postoperative nausea and vomiting episodes [3.10 (1.11–8.63); p = 0.036] were associated with intense pain. These findings remain robust after propensity score matching. For mean difference values between before and after RFA, higher in change in aspartate transaminase (p = 0.026), alanine transaminase (p = 0.016) and white blood cell count (p = 0.015), and lower in change in haemoglobin (p = 0.009) were also correlated with intense pain. There was no significant difference in haemodynamic changes between the general anaesthesia and local anaesthesia group during ablation. Conclusion: General anaesthesia, postoperative nausea and vomiting, and laboratory factors were associated with postoperative intense pain in patients who underwent radiofrequency ablation. Counselling and modification of analgesics should be considered in patients with related factors for intense pain

  10. Safety and Tolerability of Transitioning from Cangrelor to Ticagrelor in Patients Who Underwent Percutaneous Coronary Intervention.

    Science.gov (United States)

    Badreldin, Hisham A; Carter, Danielle; Cook, Bryan M; Qamar, Arman; Vaduganathan, Muthiah; Bhatt, Deepak L

    2017-08-01

    The 3 phase 3 CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively demonstrated the safety of transitioning from cangrelor, a potent, parenteral rapidly-acting P2Y 12 inhibitor, to clopidogrel in patients who underwent percutaneous coronary intervention (PCI). However, variation in timing of therapy, site-specific binding, and drug half-lives may theoretically complicate switching to other oral P2Y 12 inhibitors. Since regulatory approval, limited data are available regarding the "real-world" safety and tolerability of transitioning to these more potent oral P2Y 12 antagonists. From November 2015 to January 2017, we evaluated the clinical profiles and efficacy and safety outcomes in cangrelor-treated patients who underwent PCI transitioned to clopidogrel (n = 42) or ticagrelor (n = 82) at a large, tertiary care center. Most patients receiving cangrelor underwent PCI with a drug-eluting stent for acute coronary syndrome via a radial approach in the background of unfractionated heparin. Stent thrombosis within 48 hours was rare and occurred in 1 patient treated with ticagrelor. Global Use of Strategies to Open Occluded Coronary Arteries-defined bleeding occurred in 20% of patients switched to ticagrelor and 29% of patients switched to clopidogrel, but none were severe or life-threatening. In conclusion, rates of stent thrombosis and severe/life-threatening bleeding were low and comparable with those identified in the CHAMPION program, despite use of more potent oral P2Y 12 inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Surrogate pregnancy in a patient who underwent radical hysterectomy and bilateral transposition of ovaries.

    Science.gov (United States)

    Azem, Foad; Yovel, Israel; Wagman, Israel; Kapostiansky, Rita; Lessing, Joseph B; Amit, Ami

    2003-05-01

    To evaluate IVF-surrogate pregnancy in a patient with ovarian transposition after radical hysterectomy for carcinoma of the cervix. Case report. A maternity hospital in Tel Aviv that is a major tertiary care and referral center. A 29-year-old woman who underwent Wertheim's hysterectomy for carcinoma of the uterine cervix and ovarian transposition before total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to surrogate mother. Outcome of IVF cycle. A twin pregnancy in the first cycle. This is the second reported case of controlled ovarian stimulation and oocyte retrieval performed on a transposed ovary.

  12. [A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

    Science.gov (United States)

    Takase, Koki; Murata, Kohei; Kagawa, Yoshinori; Nose, Yohei; Kawai, Kenji; Sakamoto, Takuya; Naito, Atsushi; Murakami, Kohei; Katsura, Yoshiteru; Omura, Yoshiaki; Takeno, Atsushi; Nakatsuka, Shinichi; Takeda, Yutaka; Kato, Takeshi; Tamura, Shigeyuki

    2018-01-01

    Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

  13. HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment.

    Science.gov (United States)

    Costa, Cynthia Hernandes; Gelmini, Georgia Fernanda; Wowk, Pryscilla Fanini; Mattar, Sibelle Botogosque; Vargas, Rafael Gustavo; Roxo, Valéria Maria Munhoz Sperandio; Schuffner, Alessandro; Bicalho, Maria da Graça

    2012-09-01

    The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART. Copyright © 2012. Published by Elsevier Inc.

  14. Sarcopenia: a new predictor of postoperative complications for elderly gastric cancer patients who underwent radical gastrectomy.

    Science.gov (United States)

    Zhou, Chong-Jun; Zhang, Feng-Min; Zhang, Fei-Yu; Yu, Zhen; Chen, Xiao-Lei; Shen, Xian; Zhuang, Cheng-Le; Chen, Xiao-Xi

    2017-05-01

    A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy. We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography-assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia. Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Effect of different pneumoperitoneum pressure on stress state in patients underwent gynecological laparoscopy

    Directory of Open Access Journals (Sweden)

    Ai-Yun Shen

    2016-10-01

    Full Text Available Objective: To observe the effect of different CO2 pneumoperitoneum pressure on the stress state in patients underwent gynecological laparoscopy. Methods: A total of 90 patients who were admitted in our hospital from February, 2015 to October, 2015 for gynecological laparoscopy were included in the study and divided into groups A, B, and C according to different CO2 pneumoperitoneum pressure. The changes of HR, BP, and PetCO2 during the operation process in the three groups were recorded. The changes of stress indicators before operation (T0, 30 min during operation (T1, and 12 h after operation (T2 were compared. Results: The difference of HR, BP, and PetCO2 levels before operation among the three groups was not statistically significant (P>0.05. HR, BP, and PetCO2 levels 30 min after pneumoperitoneum were significantly elevated when compared with before operation (P0.05. PetCO2 level 30 min after pneumoperitoneum in group B was significantly higher than that in group A (P0.05. Conclusions: Low pneumoperitoneum pressure has a small effect on the stress state in patients underwent gynecological laparoscopy, will not affect the surgical operation, and can obtain a preferable muscular relaxation and vision field; therefore, it can be selected in preference.

  16. Circulating S100B and Adiponectin in Children Who Underwent Open Heart Surgery and Cardiopulmonary Bypass

    Directory of Open Access Journals (Sweden)

    Alessandro Varrica

    2015-01-01

    Full Text Available Background. S100B protein, previously proposed as a consolidated marker of brain damage in congenital heart disease (CHD newborns who underwent cardiac surgery and cardiopulmonary bypass (CPB, has been progressively abandoned due to S100B CNS extra-source such as adipose tissue. The present study investigated CHD newborns, if adipose tissue contributes significantly to S100B serum levels. Methods. We conducted a prospective study in 26 CHD infants, without preexisting neurological disorders, who underwent cardiac surgery and CPB in whom blood samples for S100B and adiponectin (ADN measurement were drawn at five perioperative time-points. Results. S100B showed a significant increase from hospital admission up to 24 h after procedure reaching its maximum peak (P0.05 have been found all along perioperative monitoring. ADN/S100B ratio pattern was identical to S100B alone with the higher peak at the end of CPB and remained higher up to 24 h from surgery. Conclusions. The present study provides evidence that, in CHD infants, S100B protein is not affected by an extra-source adipose tissue release as suggested by no changes in circulating ADN concentrations.

  17. Outcome of Patients Underwent Emergency Department Thoracotomy and Its Predictive Factors

    Directory of Open Access Journals (Sweden)

    Shahram Paydar

    2014-08-01

    Full Text Available Introduction: Emergency department thoracotomy (EDT may serve as the last survival chance for patients who arrive at hospital in extremis. It is considered as an effective tool for improvement of traumatic patients’ outcome. The present study was done with the goal of assessing the outcome of patients who underwent EDT and its predictive factors. Methods: In the present study, medical charts of 50 retrospective and 8 prospective cases underwent emergency department thoracotomy (EDT were reviewed during November 2011 to June 2013. Comparisons between survived and died patients were performed by Mann-Whitney U test and the predictive factors of EDT outcome were measured using multivariate logistic regression analysis. P < 0.05 considered statistically significant. Results: Fifty eight cases of EDT were enrolled (86.2% male. The mean age of patients was 43.27±19.85 years with the range of 18-85. The mean time duration of CPR was recorded as 37.12±12.49 minutes. Eleven cases (19% were alive to be transported to OR (defined as ED survived. The mean time of survival in ED survived patients was 223.5±450.8 hours. More than 24 hours survival rate (late survived was 6.9% (4 cases. Only one case (1.7% survived to discharge from hospital (mortality rate=98.3%. There were only a significant relation between ED survival and SBP, GCS, CPR duration, and chest trauma (p=0.04. The results demonstrated that initial SBP lower than 80 mmHg (OR=1.03, 95% CI: 1.001-1.05, p=0.04 and presence of chest trauma (OR=2.6, 95% CI: 1.75-3.16, p=0.02 were independent predictive factors of EDT mortality. Conclusion: The findings of the present study showed that the survival rate of trauma patients underwent EDT was 1.7%. In addition, it was defined that falling systolic blood pressure below 80 mmHg and blunt trauma of chest are independent factors that along with poor outcome.

  18. Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

    Science.gov (United States)

    Yoon, Aera; Lee, Yoo-Young; Park, Won; Huh, Seung Jae; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2015-05-01

    The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (β = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (β = 71.08, P = 0.006), and BMI before treatment (underweight: β = -59.93, P = 0.05; overweight: β = -40.62, P = 0.041). Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

  19. Clinical outcomes for 14 consecutive patients with solid pseudopapillary neoplasms who underwent laparoscopic distal pancreatectomy.

    Science.gov (United States)

    Nakamura, Yoshiharu; Matsushita, Akira; Katsuno, Akira; Yamahatsu, Kazuya; Sumiyoshi, Hiroki; Mizuguchi, Yoshiaki; Uchida, Eiji

    2016-02-01

    The postoperative results of laparoscopic distal pancreatectomy for solid pseudopapillary neoplasm of the pancreas (SPN), including the effects of spleen-preserving resection, are still to be elucidated. Of the 139 patients who underwent laparoscopic pancreatectomy for non-cancerous tumors, 14 consecutive patients (average age, 29.6 years; 1 man, 13 women) with solitary SPN who underwent laparoscopic distal pancreatectomy between March 2004 and June 2015 were enrolled. The tumors had a mean diameter of 4.8 cm. Laparoscopic spleen-preserving distal pancreatectomy was performed in eight patients (spleen-preserving group), including two cases involving pancreatic tail preservation, and laparoscopic spleno-distal pancreatectomy was performed in six patients (standard resection group). The median operating time was 317 min, and the median blood loss was 50 mL. Postoperatively, grade B pancreatic fistulas appeared in two patients (14.3%) but resolved with conservative treatment. No patients had postoperative complications, other than pancreatic fistulas, or required reoperation. The median postoperative hospital stay was 11 days, and the postoperative mortality was zero.None of the patients had positive surgical margins or lymph nodes with metastasis. The median follow-up period did not significantly differ between the two groups (20 vs 39 months, P = 0.1368). All of the patients are alive and free from recurrent tumors without major late-phase complications. Laparoscopic distal pancreatectomy might be a suitable treatment for patients with SPN. A spleen-preserving operation is preferable for younger patients with SPN, and this study demonstrated the non-inferiority of the procedure compared to spleno-distal pancreatectomy. © 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  20. Beneficial Effect of the Nutritional Support in Children Who Underwent Hematopoietic Stem Cell Transplant.

    Science.gov (United States)

    Koç, Nevra; Gündüz, Mehmet; Tavil, Betül; Azik, M Fatih; Coşkun, Zeynep; Yardımcı, Hülya; Uçkan, Duygu; Tunç, Bahattin

    2017-08-01

    The aim of this study was to evaluate nutritional status in children who underwent hematopoietic stem cell transplant compared with a healthy control group. A secondary aim was to utilize mid-upper arm circumference as a measure of nutritional status in these groups of children. Our study group included 40 children (18 girls, 22 boys) with mean age of 9.2 ± 4.6 years (range, 2-17 y) who underwent hematopoietic stem cell transplant. Our control group consisted of 20 healthy children (9 girls, 11 boys). The children were evaluated at admission to the hospital and followed regularly 3, 6, 9, and 12 months after discharge from the hospital. In the study group, 27 of 40 patients (67.5%) received nutritional support during hematopoietic stem cell transplant, with 15 patients (56%) receiving enteral nutrition, 6 (22%) receiving total parenteral nutrition, and 6 (22%) receiving enteral and total parenteral nutrition. Chronic malnutrition rate in the study group was 47.5% on admission to the hospital, with the control group having a rate of 20%. One year after transplant, the rate decreased to 20% in the study group and 5% in the control group. The mid-upper arm circumference was lower in children in the study group versus the control group at the beginning of the study (P groups at follow-up examinations (P > .05). During follow-up, all anthropometric measurements increased significantly in both groups. Monitoring nutritional status and initiating appropriate nutritional support improved the success of hematopoietic stem cell transplant and provided a more comfortable process during the transplant period. Furthermore, mid-upper arm circumference is a more sensitive, useful, and safer parameter that can be used to measure nutritional status of children who undergo hematopoietic stem cell transplant.

  1. Size effects of latex nanomaterials on lung inflammation in mice

    International Nuclear Information System (INIS)

    Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie; Koike, Eiko; Shimada, Akinori

    2009-01-01

    Effects of nano-sized materials (nanomaterials) on sensitive population have not been well elucidated. This study examined the effects of pulmonary exposure to (latex) nanomaterials on lung inflammation related to lipopolysaccharide (LPS) or allergen in mice, especially in terms of their size-dependency. In protocol 1, ICR male mice were divided into 8 experimental groups that intratracheally received a single exposure to vehicle, latex nanomaterials (250 μg/animal) with three sizes (25, 50, and 100 nm), LPS (75 μg/animal), or LPS plus latex nanomaterials. In protocol 2, ICR male mice were divided into 8 experimental groups that intratracheally received repeated exposure to vehicle, latex nanomaterials (100 μg/animal), allergen (ovalbumin: OVA; 1 μg/animal), or allergen plus latex nanomaterials. In protocol 1, latex nanomaterials with all sizes exacerbated lung inflammation elicited by LPS, showing an overall trend of amplified lung expressions of proinflammatory cytokines. Furthermore, LPS plus nanomaterials, especially with size less than 50 nm, significantly elevated circulatory levels of fibrinogen, macrophage chemoattractant protein-1, and keratinocyte-derived chemoattractant, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. In protocol 2, latex nanomaterials with all sizes did not significantly enhance the pathophysiology of allergic asthma, characterized by eosinophilic lung inflammation and Igs production, although latex nanomaterials with less than 50 nm significantly induced/enhanced neutrophilic lung inflammation. These results suggest that latex nanomaterials differentially affect two types of (innate and adaptive immunity-dominant) lung inflammation

  2. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    DEFF Research Database (Denmark)

    Bengtson, Stefan; Knudsen, Kristina Bram; Kyjovska, Zdenka O.

    2017-01-01

    assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

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

    Science.gov (United States)

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

    2011-02-28

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

  4. Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Åsa, E-mail: asa.gustafsson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bergström, Ulrika [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Organismal Biology, Uppsala University, SE-751 Uppsala (Sweden); Ågren, Lina [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Österlund, Lars [Dept of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 Uppsala (Sweden); Sandström, Thomas [Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden)

    2015-10-01

    The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. - Highlights: • Hematite NPs induce differential responses in airways of healthy and allergic mice. • Hematite induced an airway inflammation in healthy mice. • Hematite induced cellular reduction in the alveolus and lymph nodes of allergic mice. • Cell death is possible due to extensive pro-oxidative environment in allergic mice. • It is important to include sensitive individuals when valuing health effects of NPs.

  5. Study of the seroma volume changes in the patients who underwent Accelerated Partial Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Ho; Son, Sang Jun; Mun, Jun Ki; Seo, Seok Jin; Lee, Je Hee [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-06-15

    By analyzing seroma volume changes in the patients who underwent Partial breast radiation therapy after breast conserving surgery, we try to contribute to the improvement of radiotherapy effect. Enrolled 20 patients who underwent partial breast radiation therapy by ViewRay MRIdian System were subject. After seeking for the size of the removed sample in the patients during surgery and obtained seroma volume changes on a weekly basis. On the Basis of acquired volume, it was compared with age, term from start of the first treatment after surgery, BMI (body mass index) and the extracted sample size during surgery. And using the ViewRay MRIdian RTP System, the figure was analyzed by PTV(=seroma volume + margin) to obtain a specific volume of the Partial breast radiation therapy. The changes of seroma volume from MR simulation to the first treatment (a week) is 0~5% in 8, 5~10% in 3, 10 to 15% in 2, and 20% or more in 5 people. Two patients(A, B patient) among subjects showed the biggest change. The A patient's 100% of the prescribed dose volume is 213.08 cc, PTV is 181.93 cc, seroma volume is 15.3 cc in initial plan. However, while seroma volume decreased 65.36% to 5.3 cc, 100% of the prescribed dose volume was reduced to 3.4% to 102.43 cc and PTV also did 43.6% to 102.54 cc. In the case of the B patient, seroma volume decreased 42.57% from 20.2 cc to 11.6 cc. Because of that, 100% of the prescribed dose volume decreased 8.1% and PTV also did to 40%. As the period between the first therapy and surgery is shorter, the patient is elder and the size of sample is smaller than 100 cc, the change grow bigger. It is desirable to establish an adaptive plan according to each patient's changes of seroma volume through continuous observation. Because partial breast patients is more sensitive than WBRT patients about dose conformity in accordance with the volume change.

  6. Dysphagia among adult patients who underwent surgery for esophageal atresia at birth.

    Science.gov (United States)

    Huynh Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickeal

    2015-03-01

    Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and⁄or anatomical anomalies. To determine the motor and anatomical causes of dysphagia. A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, nonpropagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14%, diverticula in 14% and stenosis in 7

  7. Study of the seroma volume changes in the patients who underwent Accelerated Partial Breast Irradiation

    International Nuclear Information System (INIS)

    Kim, Dae Ho; Son, Sang Jun; Mun, Jun Ki; Seo, Seok Jin; Lee, Je Hee

    2016-01-01

    By analyzing seroma volume changes in the patients who underwent Partial breast radiation therapy after breast conserving surgery, we try to contribute to the improvement of radiotherapy effect. Enrolled 20 patients who underwent partial breast radiation therapy by ViewRay MRIdian System were subject. After seeking for the size of the removed sample in the patients during surgery and obtained seroma volume changes on a weekly basis. On the Basis of acquired volume, it was compared with age, term from start of the first treatment after surgery, BMI (body mass index) and the extracted sample size during surgery. And using the ViewRay MRIdian RTP System, the figure was analyzed by PTV(=seroma volume + margin) to obtain a specific volume of the Partial breast radiation therapy. The changes of seroma volume from MR simulation to the first treatment (a week) is 0~5% in 8, 5~10% in 3, 10 to 15% in 2, and 20% or more in 5 people. Two patients(A, B patient) among subjects showed the biggest change. The A patient's 100% of the prescribed dose volume is 213.08 cc, PTV is 181.93 cc, seroma volume is 15.3 cc in initial plan. However, while seroma volume decreased 65.36% to 5.3 cc, 100% of the prescribed dose volume was reduced to 3.4% to 102.43 cc and PTV also did 43.6% to 102.54 cc. In the case of the B patient, seroma volume decreased 42.57% from 20.2 cc to 11.6 cc. Because of that, 100% of the prescribed dose volume decreased 8.1% and PTV also did to 40%. As the period between the first therapy and surgery is shorter, the patient is elder and the size of sample is smaller than 100 cc, the change grow bigger. It is desirable to establish an adaptive plan according to each patient's changes of seroma volume through continuous observation. Because partial breast patients is more sensitive than WBRT patients about dose conformity in accordance with the volume change

  8. Comparative analysis of pain in patients who underwent total knee replacement regarding the tourniquet pressure

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    Marcos George de Souza Leão

    Full Text Available ABSTRACT OBJECTIVES: To evaluate through the visual analog scale (VAS the pain in patients undergoing total knee replacement (TKR with different pressures of the pneumatic tourniquet. METHODS: An observational, randomized, descriptive study on an analytical basis, with 60 patients who underwent TKR, divided into two groups, which were matched: a group where TKR was performed with tourniquet pressures of 350 mmHg (standard and the other with systolic blood pressure plus 100 mmHg (P + 100. These patients had their pain assessed by VAS at 48 h, and at the 5th and 15th days after procedure. Secondarily, the following were also measured: range of motion (ROM, complications, and blood drainage volume in each group; the data were subjected to statistical analysis. RESULTS: After data analysis, there was no statistical difference regarding the incidence of complications (p = 0.612, ROM (p = 0.202, bleeding after 24 and 48 h (p = 0.432 and p = 0.254 or in relation to VAS. No correlation was observed between time of ischemia compared to VAS and bleeding. CONCLUSIONS: The use of the pneumatic tourniquet pressure at 350 mmHg or systolic blood pressure plus 100 mmHg did not influence the pain, blood loss, ROM, and complications. Therefore the pressures at these levels are safe and do not change the surgery outcomes; the time of ischemia must be closely observed to avoid major complications.

  9. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Rivera Franco, Monica M; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR ( P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens ( P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  10. Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2016-01-01

    Full Text Available PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR. Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5% and overexpression (≥5%. Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2. However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02. Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  11. [A survey of perioperative asthmatic attack among patients with bronchial asthma underwent general anesthesia].

    Science.gov (United States)

    Ie, Kenya; Yoshizawa, Atsuto; Hirano, Satoru; Izumi, Sinyuu; Hojo, Masaaki; Sugiyama, Haruhito; Kobayasi, Nobuyuki; Kudou, Kouichirou; Maehara, Yasuhiro; Kawachi, Masaharu; Miyakoshi, Kouichi

    2010-07-01

    We investigated the risk factor of perioperative asthmatic attack and effectiveness of preventing treatment for asthmatic attack before operation. We performed retrospective chart review of one hundred eleven patients with asthma underwent general anesthesia and surgical intervention from January 2006 to October 2007 in our hospital. The rate of perioperative asthmatic attack were as follows; 10.2% (5 in 49 cases) in no pretreatment group, 7.5% (3 in 40 cases) in any pretreatments except for systemic steroid, and 4.5% (1 in 22 cases) in systemic steroid pretreatment group. Neither preoperative asthma severity nor duration from the last attack had significant relevancy to perioperative attack rate. The otolaryngological surgery, especially those have nasal polyp and oral surgery had high perioperative asthma attack rate, although there was no significant difference. We recommend the systemic steroid pretreatment for asthmatic patients, especially when they have known risk factor such as administration of the systemic steroid within 6 months, or possibly new risk factor such as nasal polyp, otolaryngological and oral surgery.

  12. Stress and Quality of Life for Taiwanese Women Who Underwent Infertility Treatment.

    Science.gov (United States)

    Cheng, Ching-Yu; Stevenson, Eleanor Lowndes; Yang, Cheng-Ta; Liou, Shwu-Ru

    2018-04-28

    To describe the psychological stress and quality of life experienced by women who underwent fertility treatment in Taiwan. Cross-sectional, correlational study. Recruitment was conducted and questionnaires administered at a reproductive medicine center in Chiayi City, Taiwan. Informed consent to participate was obtained from 126 women who sought fertility treatment at the center. The Chinese Fertility Problem Inventory and Fertility Quality of Life scale were used to measure participants' levels of fertility-related stress and fertility-related quality of life. Descriptive statistics, correlation, and regression analysis were used. Overall, participants reported low levels of fertility-related stress and fertility-related quality of life; however, they had relatively high levels of stress related to need for parenthood. Women who were older, had greater body mass indexes, and consumed coffee regularly had lower fertility-related quality of life. Social and relationship concerns and stress related to need for parenthood were significant predictors of low fertility-related quality of life. In a culture in which childbearing is generally an expectation and an important part of family life, women who experience infertility are at risk to experience fertility-related stress. Social support and family consultation might be offered to improve women's fertility-related quality of life. Copyright © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  13. Association between ambient air pollution and pregnancy rate in women who underwent IVF.

    Science.gov (United States)

    Choe, S A; Jun, Y B; Lee, W S; Yoon, T K; Kim, S Y

    2018-04-05

    Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI

  14. Predictors of weight regain in patients who underwent Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Shantavasinkul, Prapimporn Chattranukulchai; Omotosho, Philip; Corsino, Leonor; Portenier, Dana; Torquati, Alfonso

    2016-11-01

    Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for obesity and results in long-term weight loss and resolution of co-morbidities. However, weight regain may occur as soon as 1-2 years after surgery. This retrospective study aimed to investigate the prevalence of weight regain and possible preoperative predictors of this phenomenon after RYGB. An academic medical center in the United States. A total of 1426 obese patients (15.8% male) who underwent RYGB during January 2000 to 2012 and had at least a 2-year follow-up were reviewed. We included only patients who were initially successful, having achieved at least 50% excess weight loss at 1 year postoperatively. Patients were then categorized into either the weight regain group (WR) or sustained weight loss (SWL) group based upon whether they gained≥15% of their 1-year postoperative weight. Weight regain was observed in 244 patients (17.1%). Preoperative body mass index was similar between groups. Body mass index was significantly higher and percent excess weight loss was significantly lower in the WR group (Pweight regain was 19.5±9.3 kg and-.8±8.5 in the WR and SWL groups, respectively (Pweight loss. Moreover, a longer duration after RYGB was associated with weight regain. Multivariate analysis revealed that younger age was a significant predictor of weight regain even after adjusting for time since RYGB. The present study confirmed that a longer interval after RYGB was associated with weight regain. Younger age was a significant predictor of weight regain even after adjusting for time since RYGB. The findings of this study underscore the complexity of the mechanisms underlying weight loss and regain after RYGB. Future prospective studies are needed to further explore the prevalence, predictors, and mechanisms of weight regain after RYGB. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  15. Quality of life in locally advanced prostate cancer patients who underwent hormonal treatment combined with radiotherapy

    International Nuclear Information System (INIS)

    Koga, Hirofumi; Naito, Seiji; Fukui, Iwao; Tsukamoto, Taiji; Matsuoka, Naoki; Fujimoto, Hiroyuki

    2004-01-01

    The aim of this study is to estimate the feasibility of quality of life (QOL) research and to evaluate the QOL prospectively in locally advanced prostate cancer patients treated with hormonal treatment combined with radiotherapy. The treatment schedule was that patients with decreasing prostatic specific antigen (PSA) levels below 10 ng/ml after receiving 6 months of neoadjuvant hormonal treatment were randomly divided into two groups; one group was the continuous hormonal treatment group and the other was the intermittent hormonal treatment group. Both groups received a total dose of 72 Gy external beam radiotherapy with concomitant hormonal treatment followed by 6 months of adjuvant hormonal treatment following radiotherapy. At 14 months, patients either underwent continuous or intermittent hormonal treatment according to the random allocation. QOL was assessed at baseline, and at 6, 8, 14, and 20 months after treatment using functional assessment of cancer treatment-general (FACT-G), P with the other 3 items comprising bother of urination, bother of bowel movement, and bother of sexual activity. Between January 2000 and June 2003, a total of 188 patients were enrolled in this study. The rate of collection of baseline QOL sheets was 98.0%. The rate of answer to questions of QOL sheets was 99.0%. At baseline, the average score of FACT-G, P was 120.7 and the maximum score was more than twice the minimum score. Dysfunction of urination and bowel movement was correlated with the bother of urination and bowel movement, respectively. On the other hand, dysfunction of sexual activity was not correlated with the bother of sexual activity. In June 2003, all of the QOL sheets at baseline, and at 6, 8, and 14 months were completely collected from a total of 72 patients. Although QOL at 8 months was significantly affected compared with QOL at baseline and at 6 months, QOL at 14 months was significantly improved compared with that at 8 months and there was no significant

  16. Effect of anti-podoplanin antibody administration during lipopolysaccharide-induced lung injury in mice.

    Science.gov (United States)

    Lax, Sian; Rayes, Julie; Thickett, David R; Watson, Steve P

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a devastating pulmonary condition in the critically ill patient. A therapeutic intervention is yet to be found that can prevent progression to ARDS. We recently demonstrated that the interaction between podoplanin expressed on inflammatory alveolar macrophages (iAMs) and its endogenous ligand, platelet C-type lectin-like 2 (CLEC-2), protects against exaggerated lung inflammation during a mouse model of ARDS. In this study, we aim to investigate the therapeutic use of a crosslinking/activating anti-podoplanin antibody (α-PDPN, clone 8.1.1) during lipopolysaccharide (LPS)-induced lung inflammation in mice. Intravenous administration of α-PDPN was performed 6 hours after intratracheal LPS in wildtype, C57Bl/6 mice. Lung function decline was measured by pulse oximetry as well as markers of local inflammation including bronchoalveolar lavage neutrophilia and cytokine/chemokine expression. In parallel, alveolar macrophages were isolated and cultured in vitro from haematopoietic-specific podoplanin-deficient mice (Pdpn fl/fl VAV1cre + ) and floxed-only controls treated with or without LPS in the presence or absence of α-PDPN. Lung function decline as well as alveolar neutrophil recruitment was significantly decreased in mice treated with the crosslinking/activating α-PDPN in vivo. Furthermore, we demonstrate that, in vitro, activation of podoplanin on iAMs regulates their secretion of proinflammatory cytokines and chemokines. These data confirm the importance of the CLEC-2-podoplanin pathway during intratracheal (IT)-LPS and demonstrate the beneficial effect of targeting podoplanin during IT-LPS in mice possibly via modulation of local cytokine/chemokine expression. Moreover, these data suggest that podoplanin-targeted therapies may have a beneficial effect in patients at risk of developing ARDS.

  17. Oleic Acid Induces Lung Injury in Mice through Activation of the ERK Pathway

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves-de-Albuquerque

    2012-01-01

    Full Text Available Oleic acid (OA can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1β production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation.

  18. [Findings from Total Colonoscopy in Obstructive Colorectal Cancer Patients Who Underwent Stent Placement as a Bridge to Surgery(BTS)].

    Science.gov (United States)

    Maruo, Hirotoshi; Tsuyuki, Hajime; Kojima, Tadahiro; Koreyasu, Ryohei; Nakamura, Koichi; Higashi, Yukihiro; Shoji, Tsuyoshi; Yamazaki, Masanori; Nishiyama, Raisuke; Ito, Tatsuhiro; Koike, Kota; Ikeda, Takashi; Takayanagi, Yasuhiro; Kubota, Hiroyuki

    2017-11-01

    We clinically investigated 34 patients with obstructive colorectal cancer who underwent placement of a colonic stent as a bridge to surgery(BTS), focusing on endoscopic findings after stent placement.Twenty -nine patients(85.3%)underwent colonoscopy after stent placement, and the entire large intestine could be observed in 28(96.6%).Coexisting lesions were observed in 22(78.6%)of these 28 patients.The lesions comprised adenomatous polyps in 17 patients(60.7%), synchronous colon cancers in 5 patients(17.9%), and obstructive colitis in 3 patients(10.7%), with some overlapping cases.All patients with multiple cancers underwent one-stage surgery, and all lesions were excised at the same time.Colonoscopy after colonic stent placement is important for preoperative diagnosis of coexisting lesions and planning the extent of resection. These considerations support the utility of colonic stenting for BTS.

  19. Prevention of lymphocyte apoptosis in septic mice with cancer increases mortality.

    Science.gov (United States)

    Fox, Amy C; Breed, Elise R; Liang, Zhe; Clark, Andrew T; Zee-Cheng, Brendan R; Chang, Katherine C; Dominguez, Jessica A; Jung, Enjae; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Linehan, David C; Coopersmith, Craig M

    2011-08-15

    Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.

  20. Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

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    Thomas Gille

    2018-01-01

    Full Text Available Background. Severe obstructive sleep apnea (OSA with chronic intermittent hypoxia (IH is common in idiopathic pulmonary fibrosis (IPF. Here, we evaluated the impact of IH on bleomycin- (BLM- induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day or intermittent air (IA. In the four experimental groups, we evaluated (i survival; (ii alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii lung cell apoptosis; and (iv pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05. Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02 and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001. Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group. At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

  1. Impact of Polypharmacy on Adherence to Evidence-Based Medication in Patients who Underwent Percutaneous Coronary Intervention.

    Science.gov (United States)

    Mohammed, Shaban; Arabi, Abdulrahaman; El-Menyar, Ayman; Abdulkarim, Sabir; AlJundi, Amer; Alqahtani, Awad; Arafa, Salah; Al Suwaidi, Jassim

    2016-01-01

    The primary objective of this study was to evaluate the impact of polypharmacy on primary and secondary adherence to evidence-based medication (EBM) and to measure factors associated with non-adherence among patients who underwent percutaneous coronary intervention (PCI). We conducted a retrospective analysis for patients who underwent PCI at a tertiary cardiac care hospital in Qatar. Patients who had polypharmacy (defined as ≥6 medications) were compared with those who had no polypharmacy at hospital discharge in terms of primary and secondary adherence to dual antiplatelet therapy (DAPT), beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEIs) and statins. A total of 557 patients (mean age: 53±10 years; 85%; males) who underwent PCI were included. The majority of patients (84.6%) received ≥6 medications (polypharmacy group) while only 15.4% patients received ≥5 medications (nonpolypharmacy group). The two groups were comparable in term of gender, nationality, socioeconomic status and medical insurance. The non-polypharmacy patients had significantly higher adherence to first refill of DAPT compared with patients in the polypharmacy group (100 vs. 76.9%; p=0.001). Similarly, the non-polypharmacy patients were significantly more adherent to secondary preventive medications (BB, ACEI and statins) than the polypharmacy group. In patients who underwent PCI, polypharmacy at discharge could play a negative role in the adherence to the first refill of EBM. Further studies should investigate other parameters that contribute to long term non-adherence.

  2. Open-lung protective ventilation with pressure control ventilation, high-frequency oscillation, and intratracheal pulmonary ventilation results in similar gas exchange, hemodynamics, and lung mechanics.

    Science.gov (United States)

    Sedeek, Khaled A; Takeuchi, Muneyuki; Suchodolski, Klaudiusz; Vargas, Sara O; Shimaoka, Motomu; Schnitzer, Jay J; Kacmarek, Robert M

    2003-11-01

    Pressure control ventilation (PCV), high-frequency oscillation (HFO), and intratracheal pulmonary ventilation (ITPV) may all be used to provide lung protective ventilation in acute respiratory distress syndrome, but the specific approach that is optimal remains controversial. Saline lavage was used to produce acute respiratory distress syndrome in 21 sheep randomly assigned to receive PCV, HFO, or ITPV as follows: positive end-expiratory pressure (PCV and ITPV) and mean airway pressure (HFO) were set in a pressure-decreasing manner after lung recruitment that achieved a ratio of Pao2/Fio2 > 400 mmHg. Respiratory rates were 30 breaths/min, 120 breaths/min, and 8 Hz, respectively, for PCV, ITPV, and HFO. Eucapnia was targeted with peak carinal pressure of no more than 35 cm H2O. Animals were then ventilated for 4 h. There were no differences among groups in gas exchange, lung mechanics, or hemodynamics. Tidal volume (PCV, 8.9 +/- 2.1 ml/kg; ITPV, 2.7 +/- 0.8 ml/kg; HFO, approximately 2.0 ml/kg) and peak carinal pressure (PCV, 30.6 +/- 2.6 cm H2O; ITPV, 22.3 +/- 4.8 cm H2O; HFO, approximately 24.3 cm H2O) were higher in PCV. Pilot histologic data showed greater interstitial hemorrhage and alveolar septal expansion in PCV than in HFO or ITPV. These data indicate that HFO, ITPV, and PCV when applied with an open-lung protective ventilatory strategy results in the same gas exchange, lung mechanics, and hemodynamic response, but pilot data indicate that lung injury may be greater with PCV.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  5. APACHE II SCORING SYSTEM AND ITS MODIFICATION FOR THE ASSESSMENT OF DISEASE SEVERITY IN CHILDREN WHO UNDERWENT POLYCHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    А. V. Sotnikov

    2014-01-01

    Full Text Available Short-term disease prognosis should be considered for the appropriate treatment policy based on the assessment of disease severity in patients with acute disease. The adequate assessment of disease severity and prognosis allows the indications for transferring patients to the resuscitation and intensive care department to be defined more precisely. Disease severity of patients who underwent polychemotherapy was assessed using APACHE II scoring system.

  6. The Demographics of Patients with Skin Cancer who Underwent Surgery in Diyarbakır and Performed Surgical Techniques

    Directory of Open Access Journals (Sweden)

    Burhan Özalp

    2018-06-01

    Full Text Available Objective: The major factor for developing malignant skin cancers is sunlight exposure. This study aimed to evaluate the demographics of patients with skin cancers who underwent surgery in Diyarbakır where the population is exposed to more sunlight than most other Turkish cities. Methods: The medical records of patients who underwent surgery for malignant skin cancer excision between 2011 and 2016 were searched using University Hospital’s patient database program. Data about patients’ demographics, cancer features, and the surgical techniques performed were collected. Results: Over a 5-year period, 190 patients underwent surgical excision. The male to female ratio was 1.56, and the mean age was 65.8 ± 15.7 (range, 20-94 years. The most common skin cancer was basal cell carcinoma (n=138, 72.7%, followed by squamous cell carcinoma (n=45, 23.7% and malignant melanoma (n=5, 2.6%. The most common surgery was primary excision, which was performed in 90 of 190 patients (47.36%; tissue reconstruction with a skin graft or flap surgery was required for the remaining 100 (52.63%, showing a significant difference (p<0.001. Conclusion: Basal cell carcinoma is the most common skin cancer, and less than half of the patients sought treatment immediately after they recognized the lesion. The public should be educated about skin cancers to increase early diagnosis and encourage timely treatment, thereby decreasing morbidity and mortality from skin cancer.

  7. Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI.

    Science.gov (United States)

    Esinler, I

    2014-01-01

    To compare the performance of microdose flare-up (MF) and flexible-multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-15

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  10. Clinical Outcomes of patients with coronary artery disease who underwent FFR evaluation of intermediate coronary lesionS– COFFRS study

    Directory of Open Access Journals (Sweden)

    Srinivasa Prasad

    2017-07-01

    Conclusion: In our experience, MACE events were not higher in patients with FFR > 0.8 and kept under medical therapy and were similarly lower in patients with FFR ≤0.8 and underwent revascularisation (p = 0.73. Also MACE events were higher in patients with FFR ≤ 0.8 and did not undergo revascularisation compared to other two appropriately treated groups (p = 0.03. FFR based revascularization decision appears to be a safe strategy in Indian patients.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-02

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

  12. Assessment of carvacrol for control of avian aspergillosis in intratracheally challenged chickens in comparison to voriconazole with a reference on economic impact.

    Science.gov (United States)

    Tartor, Y H; Hassan, F A M

    2017-11-01

    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

  13. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Damlund, Dina S. M.; Christophersen, Lars; Jensen, Peter Østrup

    2016-01-01

    , the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system...... with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected...... using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs...

  14. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability

    Directory of Open Access Journals (Sweden)

    Lirong Zhang

    2018-01-01

    Full Text Available Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS. Three main components (naringin, naringenin, and hesperetin were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n=47 and control group (CG, received 20 mg placebo daily, n=48. After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P>0.01. The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  15. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability.

    Science.gov (United States)

    Zhang, Lirong; Xu, Xiaohua; Jiang, Tiechao; Wu, Kunzhe; Ding, Chuanbo; Liu, Zhen; Zhang, Xuanhe; Yu, Tianhua; Song, Changlong

    2018-01-01

    Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium . Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47) and control group (CG, received 20 mg placebo daily, n = 48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group ( P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.

  16. Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

    Science.gov (United States)

    Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

    2000-01-01

    The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-11-01

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

  19. Tumor deposit is a poor prognostic indicator in patients who underwent simultaneous resection for synchronous colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Lin Q

    2015-01-01

    Full Text Available Qi Lin,# Ye Wei,# Li Ren,# Yunshi Zhong,# Chunzhi Qin, Peng Zheng, Pingping Xu, Dexiang Zhu, Meiling Ji, Jianmin XuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China#These authors contributed equally to this workBackground: Tumor deposits are one of the important influencing factors among the different editions of Tumor, Node, Metastasis classification. Incidence and prognosis of tumor deposits in stage I, II, and III colorectal cancer patients has been explored. The aim of this study was to determine the prognostic value of tumor deposits in stage IV colorectal cancer patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLM.Methods: Clinicopathological and outcome data of 146 consecutive SCRLM patients who underwent simultaneous R0 resection between July 2003 and July 2013 were collected from our prospectively established SCRLM database. The prognostic value of tumor deposits was evaluated by Kaplan–Meier and Cox regression analysis.Results: Tumor deposits were detected in 41.8% (61/146 of these SCRLM patients. Tumor deposits were significantly correlated with lymph node metastasis and nerve invasion of the primary tumors (P=0.002, P=0.041; respectively. The Kaplan–Meier survival analysis revealed that the overall survival (OS and disease-free survival (DFS of SCRLM patients with tumor deposits were significantly poorer than those with no tumor deposits (P=0.039, P=0.001; respectively. And with multivariate analysis, we found that positive tumor deposits were significantly associated with shorter DFS independent of lymph node status (P=0.002. Subgroup analysis found that of the 57 SCRLM patients with negative lymph node status, the OS and DFS of patients with positive tumor deposits were significantly shorter than those with negative tumor deposits (P=0.002 and P=0.031, respectively. Of the 89 patients with positive lymph node status, the OS of

  20. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes.

    Science.gov (United States)

    Pardi, Norbert; Tuyishime, Steven; Muramatsu, Hiromi; Kariko, Katalin; Mui, Barbara L; Tam, Ying K; Madden, Thomas D; Hope, Michael J; Weissman, Drew

    2015-11-10

    In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clinical trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-containing mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. Subcutaneous, intramuscular and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10days. For several days, high levels of protein production could be achieved in the lung from the intratracheal administration of mRNA. Intravenous and intraperitoneal and to a lesser extent intramuscular and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Papain-induced experimental pulmonary emphysema in male and female mice.

    Science.gov (United States)

    Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

    2014-08-15

    In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. [Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis].

    Science.gov (United States)

    Aceves-Velázquez, Eduardo; Vieyra-Herrera, Gerardo; Rodríguez-Chávez, Laura; Herrera-Alarcón, Valentín

    2017-07-16

    According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Autotransplantation of spleen tissue in children with mansonic schistosomiasis who underwent splenectomy: Evaluation of splenic residual functions

    Directory of Open Access Journals (Sweden)

    Brandt Carlos Teixeira

    1998-01-01

    Full Text Available Autotransplantation of spleen tissue is an attempt for maintenance of splenic functions when splenectomy is indicated in children. It minimizes the risks of overwhelming postsplenectomy infection and it has been done in children with severe portal hypertension due to hepatosplenic mansonic schistosomiasis that underwent splenectomy. The purposes of this investigation were to study the morphology of the residual splenic tissue; to evaluate the residual filtration function of this splenosis; and to assess the immune response to polyvalent pneumococcal vaccine of these patients. Twenty-three children with portal hypertension from mansonic schistosomiasis who underwent splenectomy, ligature of the left gastric vein, autotransplantation of spleen tissue into an omental pouch were evaluated for residual splenic parenchyma and functions. Tc-99m sulfur colloid liver-spleen scans were used for detection of splenic nodules. The search for Howell Jolly bodies were used for assessing the filtration function and Enzyme-linked immunosorbent assay was used for measuring the relative rise in titter of specific pneumococcal antibodies. Splenosis was evident in all children; however, in two there were less than five splenic nodules in the greater omentum, which was considered insufficient. Howell-Jolly bodies were found in the peripheral blood only in these two patients with less evident splenosis. The immune response was adequate in 15 patients; it was intermediate in 4 patients and inadequate in 4 patients. Autotransplantation of spleen tissue into an omental pouch is efficient in maintaining the filtration splenic function in more than 90% of the cases and the immune response to pneumococcal vaccination in approximately 65% of the children.

  4. The association between orthostatic hypotension and cognitive state among adults 65 years and older who underwent a comprehensive geriatric assessment

    Science.gov (United States)

    Punchick, Boris; Freud, Tamar; Press, Yan

    2016-01-01

    Abstract The prevalence of cognitive impairment and orthostatic hypotension (OH) increases with age, but the results of studies that assessed possible associations between them are inconsistent. The aim of this study is to assess possible associations between cognitive impairment and OH in patients ≥65 years of age who underwent a comprehensive geriatric assessment. A retrospective analysis was conducted of the computerized medical records of the study population from 2005 to 2013. Data collected included blood pressure measurements that enabled the calculation of OH, results of the mini-mental state examination (MMSE), results of the Montreal cognitive assessment (MoCA) test, and cognitive diagnoses that were determined over the course of the assessment. The rate of OH in the study population of 571 adults was 32.1%. The mean MMSE score was 22.5 ± 5.2 among participants with OH and 21.6 ± 5.8 among those without OH (P = 0.09). The absence of a significant association between OH and MMSE remained after adjusting the MMSE score for age and education level. The mean MoCA score was 16.4 ± 5.0 among participants with OH and 16.4 ± 4.8 among those without (P = 0.33). The prevalence of OH was 39% among participants without cognitive impairment, 28.9% among those with mild cognitive impairment (MCI), and 30.6% among those with dementia (P = 0.13). There was no association between OH and cognitive impairment in adults who underwent a comprehensive geriatric assessment. PMID:27442658

  5. Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer.

    Science.gov (United States)

    Elsayegh, Nisreen; Webster, Rachel D; Gutierrez Barrera, Angelica M; Lin, Heather; Kuerer, Henry M; Litton, Jennifer K; Bedrosian, Isabelle; Arun, Banu K

    2018-05-07

    Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non-BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non-BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non-BRCA carriers and BRCA carriers (P = 0.6205). Among non-BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non-BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non-BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non-BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non-BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. MDMA reinstates cocaine-seeking behaviour in mice.

    Science.gov (United States)

    Trigo, José Manuel; Orejarena, Maria Juliana; Maldonado, Rafael; Robledo, Patricia

    2009-06-01

    MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and tested for reinstatement. Acute MDMA, but not d-amphetamine or saline reinstated cocaine-seeking behaviour in mice in which cocaine self-administration and contingent cues were previously extinguished. Acute MDMA can reinstate cocaine-seeking behaviour in mice.

  7. 65. Impact of focused echocardiography in clinical decision of patients presented with STMI, underwent primary percutenouse angioplasty

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    M. Qasem

    2016-07-01

    Full Text Available Echocardiography in coronary artery diseases is an essential, routine echocardiography prior to primary percutaneous angioplasty is not clear. In our clinical practice in primary angioplasty we faced lots of complications either before or during or after the procedure. Moreover, lots of incidental findings that discovered after the procedure which if known will affect the plan of management. One-hundred-nineteen consecutive underwent primary angioplasty. All patients underwent FE prior to the procedure in catheterization lab while the patient was preparing for the procedure. FE with 2DE of LV at base, mid and apex, and apical stander views. Diastology grading, E/E′ and color doppler of mitral and aortic valve were performed. (N = 119 case of STMI were enrolled, mean age 51 ± 12 year. Eleven cases (9.2% had normal coronary and normal LV function. Twenty cases (17% of MI complication detected before the procedures: RV infarction 8.4% (5.1% asymptomatic and 3.3% symptomatic, ischemic MR (8.4%, LV apical aneurysm (0.8%, significant pericardial effusion (0.80%. Acute pulmonary edema in 17 cases (14.3%: six cases (5.1% developed acute pulmonary edema on the cath lab with grade 3 diastolic dysfunction and E/E ′  >20, 9 cases (7.6% develop acute pulmonary edema in CCU with grade 2–3 diastolic dysfunction and E/E′ 15–20. 2 cases (2.7% develop acute pulmonary in CCU with grade 1–2 diastolic dysfunction and E/E′ 9–14. One case (0.8% presented cardiac tamponade 2 h post PCI. Incidental finding not related to STMI were as follow: 2 cases (1.7% with severe fibro degenerative MR, 2 cases (1.7% with mild to moderate AR and 2 cases (1.7% with mild to moderate AS. Isoled CABG 5/4.2% and CABG and MVR 2/1.7%. FE play an important role in guiding the management, early detection the incidental findings and complication post PCI.

  8. Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

    Science.gov (United States)

    Mabuchi, Yasushi; Yahata, Tamaki; Kobayashi, Aya; Tanizaki, Yuko; Minami, Sawako; Ino, Kazuhiko

    2015-06-01

    Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  9. Prosthetic reconstruction with an obturator using swing-lock attachment for a patient underwent maxillectomy: A clinical report

    Science.gov (United States)

    2016-01-01

    Patients who underwent resection of maxilla due to benign or malignant tumor, or accident will have defect in palatal area. They get retention, support and stability from remaining tissues which are hardly optimal. The advantage of swing-lock attachment design is having multiple contacts on labial and lingual side of the abutment teeth by retentive strut and palatal bracing component. Because the force is distributed equally to abutment teeth, abutment teeth of poor prognosis can be benefited from it. It is also more advantageous to cover soft tissue defects which are hard to reach with conventional prosthesis. A 56-year-old female patient who had undergone a maxillectomy due to malignant melanoma complaining of loose and unstable surgical obturator. Surveyed crowns were placed on #12, 26, and 27. Teeth #11, 21, 22, and 23 had lingual rest seat and #24 had mesial rest seat to improve stability and support of the obturator. This clinical report presents the prosthetic management of a patient treated with obturator on the maxilla using swing-lock attachment to the remaining teeth. PMID:27826392

  10. Anatomical location of metastatic lymph nodes: an indispensable prognostic factor for gastric cancer patients who underwent curative resection.

    Science.gov (United States)

    Zhao, Bochao; Zhang, Jingting; Zhang, Jiale; Chen, Xiuxiu; Chen, Junqing; Wang, Zhenning; Xu, Huimian; Huang, Baojun

    2018-02-01

    Although the numeric-based lymph node (LN) staging was widely used in the worldwide, it did not represent the anatomical location of metastatic lymph nodes (MLNs) and not reflect extent of LN dissection. Therefore, in the present study, we investigated whether the anatomical location of MLNs was still necessary to evaluate the prognosis of node-positive gastric cancer (GC) patients. We reviewed 1451 GC patients who underwent radical gastrectomy in our institution between January 1986 and January 2008. All patients were reclassified into several groups according to the anatomical location of MLNs and the number of MLNs. The prognostic differences between different patient groups were compared and clinicopathologic features were analyzed. In the present study, both anatomical location of MLNs and the number of MLNs were identified as the independent prognostic factors (p location of MLNs was considered (p location of MLNs had no significant effect on the prognosis of these patients, the higher number of MLNs in the extraperigastric area was correlated with the unfavorable prognosis (p location of MLNs was an important factor influencing the prognostic outcome of GC patients. To provide more accurate prognostic information for GC patients, the anatomical location of MLNs should not be ignored.

  11. Transcranial doppler sonography in two patients who underwent decompressive craniectomy for traumatic brain swelling: report of two cases

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    Bor-Seng-Shu Edson

    2004-01-01

    Full Text Available The role of decompressive craniectomy in the treatment of severe posttraumatic cerebral swelling remains quite a controversial issue. To the best of our knowledge, there is no study demonstrating the effect of decompressive craniectomy on cerebral blood flow (CBF velocity by means of transcranial Doppler sonography (TCD. We present two patients who developed traumatic brain swelling and uncontrollable intracranial hypertension with coma and signs of transtentorial herniation. One patient underwent bifrontal, while the second, unilateral, frontotemporoparietal decompressive craniectomy with dural expansion. In both patients, TCD examinations were performed immediately before and after surgery to study the cerebral hemodynamic changes related to the operations. Pre and postoperative TCD examinations demonstrated a significant increase in blood flow velocity in the intracranial arteries in both subjects. In conclusion, our cases suggest that decompressive craniectomy with dural expansion may result in elevation of CBF velocity in patients with massive brain swelling. The increase in CBF velocity appears to occur not only in the decompressed hemisphere, but also on the opposite side.

  12. Assessment of quality of life of patients who underwent anterior cruciate ligament reconstruction and a rehabilitation program

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    Moises Cohen

    2004-12-01

    Full Text Available Introduction: Quality of life can be defined as the expression of aconceptual model that tries to represent patient’s perspectivesand his/her level of satisfaction expressed by numbers. Theobjective of this study is to evaluate the parameters of quality oflife of 23 patients who underwent surgery for anterior cruciateligament reconstruction. Methods: We adopted SF-36, a generichealth-related evaluation questionnaire, to obtain informationregarding several aspects of patients’ health conditions, and theLysholm questionnaire, specific to evaluate the symptoms andfunction of the knee. The questionnaires were applied at two stagesof the treatment: pre- and postoperatively (after the rehabilitationprogram. Results: Before surgery, the Lysholm questionnairepresented the following results: excellent in 4% of the cases, goodin 22%, fair in 22%, and poor in 52%. After surgery (Lysholm e SF-36 the correlation level was approximately 44% (p = 0.041.Discussion: The correlation between the Lysholm and the SF-36questionnaires showed the following: the lower the level of pain,the higher the Lysholm score. The high scores presented by theLysholm questionnaire are directly proportional to physical andemotional aspects, and to functional capacity. Conclusion:Analysis of both questionnaires, as well as of their correlation,showed some improvement in patients´ quality of life. We werealso able to demonstrate the importance and usefulness of applyingthe two questionnaires at three different moments: before, duringand after physiotherapeutic intervention.

  13. The Characteristics of Cervical Cancer Patients Who Underwent a Radical Hysterectomy at Sanglah Hospital Denpasar in 2015

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    I Nyoman Bayu Mahendra

    2016-05-01

    Full Text Available Background: Cervical cancer is the most common gynecologic cancer in women. It is the main cause of cancer-related death in women in developing countries. Cervical cancer in Indonesia is the second most cancer affecting Indonesian women and the prevalence is relatively stable in the last 30 years. Cervical cancer was closely related to the histologic type of itself. A squamous cell carcinoma has a specific route of local spreading and a lymphatic route. The sample of this study are cervical cancer patients who underwent a radical hysterectomy from January 1 to December 31, 2015 in Sanglah Hospital Denpasar, Bali. The aim of this study is to discover the characteristics of the patients by age, parity, education level, marital status, sexual activity, the first symptoms and the early screening done, and the clinical staging. Methods: This descriptive study involved 20 patients in Sanglah Hospital Denpasar who had a radical hysterectomy from January 1 until December 31, 2015. The characteristics are gathered from the patients’ medical record. Results: The most cases done radical hysterectomy between 41-45 years old which proportion was 40%, the most parity was parity 2 (60%, elementary school was the most education level (35%, all of the samples only married once and sexually active, the most first symptom was vaginal bleeding (55%, only 10% had pap smear as early detection, and the most clinical stage was stage IIB (50%.

  14. A systematic review of methods for quantifying serum testosterone in patients with prostate cancer who underwent castration.

    Science.gov (United States)

    Comas, I; Ferrer, R; Planas, J; Celma, A; Regis, L; Morote, J

    2018-03-01

    The clinical practice guidelines recommend measuring serum testosterone in patients with prostate cancer (PC) who undergo castration. The serum testosterone concentration should be IA) has become widespread, although their metrological characteristics do not seem appropriate for quantifying low testosterone concentrations. The objective of this review is to analyse the methods for quantifying testosterone and to establish whether there is scientific evidence that justifies measuring it in patients with PC who undergo castration, through liquid chromatography attached to a mass spectrometry in tandem (LC-MSMS). We performed a search in PubMed with the following MeSH terms: measurement, testosterone, androgen suppression and prostate cancer. We selected 12 studies that compared the metrological characteristics of various methods for quantifying serum testosterone compared with MS detection methods. IAs are standard tools for measuring testosterone levels; however, there is evidence that IAs lack accuracy and precision for quantifying low concentrations. Most chemiluminescent IAs overestimate their concentration, especially below 100ng/dL. The procedures that use LC-MSMS have an adequate lower quantification limit and proper accuracy and precision. We found no specific evidence in patients with PC who underwent castration. LC-MSMS is the appropriate method for quantifying low serum testosterone concentrations. We need to define the level of castration with this method and the optimal level related to better progression of the disease. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Studies on the clinical course of chronic hepatitis in the patients who underwent serial needle liver biopsies

    International Nuclear Information System (INIS)

    Hirata, Tetsuro

    1984-01-01

    In order to evaluate the changes in biochemical liver function tests and hepatic scintigraphic findings of chronic hepatitis, the author analyzed 35 patients who underwent serial liver biopsies. The results were summerized as follows: 1. Histological deteriorations in chronic hepatitis more inclined to be presented in the scintigraphic abnormalities such as the increased uptake of radioisotope in the spleen and bone marrow than the deteriorations in biochemical liver function tests. Moreover, the increased radioisotope uptake by spleen and bone marrow in hepatic scintigram highly correlated with histological deteriorations. On the other hand, in the cases with histological improvement no scintigraphic improvement was ovserved. 2. Comparing the changes in the result of liver function tests with histological features, biochemical deteriorations significantly correlated with histological deteriorations, although biochemical improvements were not reliable indicators of histological improvements. 3. Changes in biochemical parameters such as serum GOT, GPT, albumin, γ-globulin, TTT and ALP were analyzed by means of Hayashi's second method of quantification and predictive values for histological feactures were calculated. As a result, histological deteriorations were predicted in 89.5% of the cases, but histological improvements were predicted only in 66.7%. In the various biochemical parameters, γ-globulin was considered as most important in predicting histological features and ALP was ranked the second. (J.P.N.)

  16. The Effect of Prazosin and Oxybutynin on the Symptoms Due to Using Double J Catheter in Patients Underwent TUL

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    K. Tavakkoli Tabassi

    2014-01-01

    Full Text Available Background & Aims: Double J catheter has been used for years as an independent practice or a part of other urological practices. Although these catheters have solved many patients’ problems but those can cause symptoms and problems for patients. The aim of this study was the investigation the effect of prazosin and oxybutynin on the degree of symptoms due to using Double J catheter. Methods: In this interventional study, patients who underwent TUL from July 2008 to march 2008 in the lithotripsy ward of Imam Reza hospital were entered to the study and randomly divided in 3 groups randomly. In the first group, placebo, in the second group, oxybutynin, in the third group prazosin were prescribed. Three weeks later standard questionnaire Ureteric Stent Symptom Questionnaire (USSQ was completed. After collecting data, was analyzed using SPSS software. Results: A total of 113 patients (70 men 43 women were included to the study. The mean age was 39 years. There were no significance difference among urinary symptoms score pain of body and physical activity problems in three groups (P>0.05, but there was a significant difference in general health and work problems among them (P<0.05. Conclusion: Oxybutynin caused a low effect on improvement of general health and work problems in patients who were studied. It might Prazosin does not has a sufficient time to affect on urinary symptoms, because of shortness of usage.

  17. Enhancement of antigen-induced eosinophilic inflammation in the airways of mast-cell deficient mice by diesel exhaust particles

    International Nuclear Information System (INIS)

    Ichinose, Takamichi; Takano, Hirohisa; Miyabara, Yuichi; Sadakaneo, Kaori; Sagai, Masaru; Shibamoto, Takayuki

    2002-01-01

    The present study was conducted to clarify the involvement of mast cells in the exacerbating effect of diesel exhaust particles (DEP) toward allergic airway inflammation and airway hyperresponsiveness (AHR). Airway inflammation by the infiltration of cosinophils with goblet cell proliferation and AHR, as well as by the production of antigen-specific IgG1 and IgE, in plasma were examined using mast cell-deficient mice (W/W v ) and normal mice (W/W + ). Both groups of mice received ovalbumin (OVA) or OVA+DEP intratracheally. The eosinophilic airway inflammation and goblet cell proliferation promoted by OVA were significantly greater in W/W + than in W/W v . A similar result was observed in AHR, but was not significant among both groups of mice. DEP enhanced OVA induced-allergic airway inflammation, goblet cell proliferation, and development of AHR in W/W v , but not in W/W + . DEP decreased production of antigen-specific IgG1 and IgE in both groups of mice. Mast cells were observed in the submucosal layer of the main bronchus in W/W v . The number of mast cells was significantly decreased by OVA treatment. The results indicate that mast cells are not necessary to enhance airway damage and development of AHR in W/W v by DEP. However, mast cells may be required for the OVA-induced cosinophilic inflammation, airway damage with goblet cell proliferation, and AHR in W/W +

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-18

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  20. Cloning Mice.

    Science.gov (United States)

    Ogura, Atsuo

    2017-08-01

    Viable and fertile mice can be generated by somatic nuclear transfer into enucleated oocytes, presumably because the transplanted somatic cell genome becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring of mice were obtained by directly injecting donor nuclei into recipient enucleated oocytes. When this method is used (the so-called Honolulu method of somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely condense within the enucleated metaphase II-arrested oocytes, which contain high levels of M-phase-promoting factor (MPF). It is believed that the condensation of the donor chromosomes promotes complete reprogramming of the donor genome within the mouse oocytes. Another key to the success of mouse cloning is the use of blunt micropipettes attached to a piezo impact-driving micromanipulation device. This system saves a significant amount of time during the micromanipulation of oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a group of 20 oocytes can be enucleated within 10 min by an experienced operator. This protocol is composed of seven parts: (1) preparing micropipettes, (2) setting up the enucleation and injection micropipettes, (3) collecting and enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor nuclei, (6) activating embryos and culturing, and (7) transferring cloned embryos. © 2017 Cold Spring Harbor Laboratory Press.

  1. Periodical assessment of genitourinary and gastrointestinal toxicity in patients who underwent prostate low-dose-rate brachytherapy

    International Nuclear Information System (INIS)

    Tanaka, Nobumichi; Asakawa, Isao; Anai, Satoshi; Hirayama, Akihide; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2013-01-01

    To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)). A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out. Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity. The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity

  2. Clinical and echocardiographic findings of patients with suspected acute pulmonary thromboembolism who underwent computed tomography pulmonary angiography

    Directory of Open Access Journals (Sweden)

    Atoosa Adibi

    2016-01-01

    Full Text Available Background: The aim of the study was to determine the correlation between clinical and echocardiographic findings and risk factors of patients with suspected acute pulmonary thromboembolism (PTE who underwent computed tomography pulmonary angiography (CTPA. Materials and Methods: In this cross-sectional study, 310 hospitalized patients aged >18 years with high clinical suspicion of PTE referred to imaging center of our hospital from different wards for CTPA were enrolled. The frequency of different clinical presentations, risk factors, items of Wells' criteria, and echocardiographic findings was compared in patients with and without PTE, which have been diagnosed according to the CTPA results. Results: PTE was diagnosed in 53 (17.1% of patients with suspected PTE. From clinical manifestations, tachypnea, pleuritic chest pain, and edema of lower extremities were significantly more frequent among patients with PTE (P < 0.05. Major surgery was the risk factor which was significantly more prevalent among patients with PTE (P < 0.05. Frequency of all criteria of Wells' criteria, except hemoptysis, was significantly higher in patients with PTE (P < 0.05. The frequency of all studied echocardiographic variables was significantly higher in patients with PTE (P < 0.05. Conclusion: It is suggested that we could use the results of this study for utilizing the diagnostic process of PTE in patients with highly clinical suspicion of PTE and providing more validated decision. Using the results of this study, we could identify high-risk patients and made appropriate risk assessment for better management of patients with suspected PTE as well as reduce the rate of unnecessary CTPA and its related adverse consequences.

  3. The effects of transfusion of irradiated blood upon cellular immune response in patients underwent open heart surgery

    International Nuclear Information System (INIS)

    Togashi, Ken-ichi; Nakazawa, Satoshi; Moro, Hisanaga; Yazawa, Masatomo; Kanazawa, Hiroshi; Hayashi, Jun-ichi; Yamazaki, Yoshihiko; Eguchi, Shoji

    1989-01-01

    The purpose of this paper is to demonstrate the effect of the transfusion of blood received 1500 rad exposure upon the immune response in 14 patients underwent various type of cardiac surgery. 13 patients received known amounts banked blood and irradiated fresh blood, while one patient received a lot of amounts of banked and irradiated and non-irradiated fresh blood. The authors studied the numbers of lymphocytes as well as lymphocyte subsets such as pan-T cells, B cells, helper/inducer T cells (T H/I ), cytotoxic/supressor T cells (T C/S ), active T cells, natural killer (NK) cells and NK cell activity during two weeks after surgeries. In all 14 patients, pan-T lymphocytes decreased markedly in a few days after surgeries, but increased to higher levels on the eight postoperative day than the levels preoperatively. T H/I and T C/S lymphocytes changed on the similar pattern as pan-T lymphocytes. Active T and B cells did not change significantly in two weeks. The number and activity of NK cells gave the lowest levels on the second postoperative day and did not recovery to the preoperative levels in two weeks. One patient received non-irradiated fresh blood showed the similar immune response as other 13 patients, while he gave the lower levels than others did. This patient died of graft-versus-host disease (GVHD)-like syndrome on the 36th postoperative day. It may be thought that the transfusion of irradiated blood would prevent the host from GVHD and gave the better effects on the immune response than that of non-irradiated blood following open-heart surgeries. (author)

  4. Early prediction of treatment response by serum CRP levels in patients with advanced esophageal cancer who underwent definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Yoneda, Masayuki; Fujiwara, Hitoshi; Okamura, Shinichi

    2010-01-01

    Serum C reactive protein (CRP) has been shown to be associated with the progression of esophageal cancer. The purpose of this study was to examine the relationship between treatment response and serum CRP levels in time course during definitive chemoradiotherapy (CRT) in terms of early prediction of CRT response by serum CRP. The subjects of this study were 36 patients with cT3/cT4 esophageal squamous cell carcinoma who underwent definitive CRT in our hospital. Serum CRP levels during definitive CRT (pretreatment, 1W, 2W and 3W after CRT initiation) were compared between CR and non-CR group. In addition, partition model was constructed to discriminate CR with non-CR and the prediction accuracy was evaluated. The patients were consisted of 28 males and 8 females. At pretreatment diagnosis, tumors were categorized as T3 (n=21) and T4 (n=15). Thirty four patients received FP-based chemotherapy and 2 patients received docetaxel-based chemotherapy. Treatment responses were categorized as CR (n=8), partial response (PR) (n=14), no change (NC) (n=2) and progressive disease (PD) (n=12). Serum CRP levels at the time of 2W after CRT initiation (CRT2W) in CR group were low compared to those in non-CR group (p=0.071). The partition model was constructed based on CRP levels at CRT2W. The prediction accuracies to discriminate CR from non-CR by CRP ≤0.1 were 50%, 82%, and 75% in sensitivity, specificity and accuracy, respectively. Serum CRP is a useful biomarker for an early prediction of CRT response. (author)

  5. CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2013-02-01

    Full Text Available Abstract Background There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS. Methods We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration. Results The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p  1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively. The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p = 0.02 and 0.04 respectively. Conclusions The increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.

  6. Comparison of quality of life between men and women who underwent Transforaminal Percutaneous Endoscopic Discectomy for lumbar disc herniation.

    Science.gov (United States)

    Kapetanakis, Stylianos; Gkasdaris, Grigorios; Thomaidis, Tryfon; Charitoudis, Georgios; Kazakos, Konstantinos

    2017-01-01

    Studies describing the efficacy of TPED on shortness of recovery and improvement of postoperative quality of life are limited, especially regarding gender something that has never been reported before in the literature. The purpose of this study is to evaluate possible differences of the health-related quality of life in patients who underwent TPED for LDH in accordance with sex. Seventy-six patients diagnosed and treated with TPED for LDH with 1 year follow-up were selected and divided into two groups of equal number depending on sex. Their quality of life was evaluated by using the SF-36 before the operation, six weeks, three, six and twelve months postoperatively. A statistical analysis was conducted, in order to compare the 8 scaled scores of the SF-36 combining each time two chronological phases in the total of patients, in each group and between groups. Fifty-two (68.4%) patients were ≤63 years old, while the rest 24 (31,4%) were >63 years old (mean ±SD = 56,5 ±12,1 years). Apart from the PF domain, the scores were higher in every visit for the two groups, but the change between groups was not significant. Women had a significantly higher increase of PF score in 3 months after TPED and in the interval 6 weeks-3 months comparing with men. However, in the intervals 3 months-6 months and 3 months-12 months men presented significantly higher increase compared to women. Statistically significant improvement of the quality of life for both men and women was observed. Generally, there was no significant difference between the two groups. As regards to the physical functioning, it appears to be a significant difference which is counterpoised over time. 2. TPED for LDH does not present major differences in the improvement of quality of life regarding gender.

  7. Preoperative evaluation of myocardial viability by thallium-201 imaging in patients with old myocardial infarction who underwent coronary revascularization

    International Nuclear Information System (INIS)

    Naruse, Hitoshi; Ohyanagi, Mitsumasa; Iwasaki, Tadaaki; Miyamoto, Takashi; Fukuchi, Minoru

    1992-01-01

    The myocardial uptake and redistribution in thallium scintigraphy and the regional wall motion by echocardiography were evaluated by a semi-quantitative method in 42 patients who previously had myocardial infarction (50 target vessels) and underwent coronary revascularization. The aim of this study was to elucidate the significance of the initial image, delayed image and redistribution on thallium-201 scintigraphy for clinical diagnosis of the myocardial viability. As a semi-quantitative analysis, we used a bull's-eye display for thallium image and centerline method for echocardiographic wall motion, and compared the results before and after revascularization. As a result, the thallium grade improved postoperatively in all 17 areas which preoperatively had showed redistribution, and also in 11 of the 32 areas without preoperative redistribution. The sensitivity, specificity and accuracy of preoperative thallium redistribution for predicting myocardial viability were 61%, 100% and 78%, respectively, when the postoperative improvement in the thallium grade was used as the standard. The postoperative probability of improvement in the thallium grade increased in proportion to the preoperative grade (delayed image)(p<0.01). There was no correlation between the preoperative thallium delayed image and postoperative improvement in wall motion. Postoperative improvement in thallium image and wall motion could not be predicted from the preoperative wall motion. Thus, postoperative improvement in thallium images can be anticipated if redistribution is present on the preoperative thallium image, and the preoperative thallium delayed image is useful for predicting myocardial viability. Improvement in wall motion could not be predicted preoperatively by these methods. (author)

  8. Accuracy of bone SPECT/CT for identifying hardware loosening in patients who underwent lumbar fusion with pedicle screws

    Energy Technology Data Exchange (ETDEWEB)

    Hudyana, Hendrah; Maes, Alex [AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); University Hospital Leuven, Department of Morphology and Medical Imaging, Leuven (Belgium); Vandenberghe, Thierry; Fidlers, Luc [AZ Groeninge, Department of Neurosurgery, Kortrijk (Belgium); Sathekge, Mike [University of Pretoria, Department of Nuclear Medicine, Pretoria (South Africa); Nicolai, Daniel [AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); Wiele, Christophe van de [AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); University Ghent, Department of Radiology and Nuclear Medicine, Ghent (Belgium)

    2016-02-15

    The aim of this retrospective study was to evaluate the accuracy of bone SPECT (single photon emission computed tomography)/CT (computed tomography) in diagnosing loosening of fixation material in patients with recurrent or persistent back pain that underwent lumbar arthrodesis with pedicle screws using surgery and clinical follow-up as gold standard A total of 48 patients (median age 49 years, range 21-81 years; 17 men) who had undergone lumbar spinal arthrodesis were included in this retrospective analysis. SPECT/CT results were compared to the gold standard of surgical evaluation or clinical follow-up. Positive SPECT/CT results were considered true positives if findings were confirmed by surgery or if clinical and other examinations were completely consistent with the positive SPECT/CT finding. They were considered false positives if surgical evaluation did not find any loose pedicle screws or if symptoms subsided with non-surgical therapy. Negative SPECT/CT scans were considered true negatives if symptoms either improved without surgical intervention or remained stable over a minimum follow-up period of 6 months. Negative SPECT/CT scans were determined to be false negatives if surgery was still required and loosening of material was found. The median length of time from primary surgery to bone SPECT/CT referral was 29.5 months (range 12-192 months). Median follow-up was 18 months (range 6-57) for subjects who did not undergo surgery. Thirteen of the 48 patients were found to be positive for loosening on bone SPECT/CT. Surgical evaluation (8 patients) and clinical follow-up (5 patients) showed that bone SPECT/CT correctly predicted loosening in 9 of 13 patients, while it falsely diagnosed loosening in 4 patients. Of 35 negative bone SPECT/CT scans, 12 were surgically confirmed. In 18 patients, bone SPECT/CT revealed lesions that could provide an alternative explanation for the symptoms of pain (active facet degeneration in 14 patients, and disc and sacroiliac

  9. Changes in expression of cytokines in polyhexamethylene guanidine-induced lung fibrosis in mice: Comparison of bleomycin-induced lung fibrosis.

    Science.gov (United States)

    Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Lee, Kyuhong

    2018-01-15

    Inhalation of polyhexamethylene guanidine (PHMG) causes irreversible pulmonary injury, such as pulmonary fibrosis. However, the mechanism underlying PHMG-induced lung injury is unclear. In this study, we compared the difference in time-dependent lung injury between PHMG- and bleomycin (BLM)-treated mice and determined cytokines involved in inducing lung injury by performing cytokine antibody array analysis. Mice were treated once with 1.8mg/kg BLM or 1.2mg/kg PHMG through intratracheal instillation and were sacrificed on days 7 and 28. Bronchoalveolar lavage fluid (BALF) analysis showed that the number of neutrophils was significantly higher in PHMG-treated mice than in BLM-treated mice on day 7. Histopathological analysis showed inflammatory cell infiltration and fibrosis mainly in the terminal bronchioles and alveoli in the lungs of PHMG- and BLM-treated mice. However, continuous macrophage infiltration in the alveolar space and bronchioloalveolar epithelial hyperplasia (BEH) were only observed in PHMG-treated mice. Cytokine antibody array analysis showed that 15 and eight cytokines were upregulated in PHMG- and BLM-treated mice, respectively, on day 7. On day 28, 13 and five cytokines were upregulated in PHMG and BLM-treated mice, respectively. In addition, the expressed cytokines between days 7 and 28 in BLM-treated mice were clearly different, but were similar in PHMG-treated mice. Consequently, between PHMG- and BLM-treated mice, we observed differences in the expression patterns and types of cytokines. These differences are considered to be a result of the inflammatory processes induced by both substances, which may mainly involve macrophage infiltration. Therefore, continuous induction of the inflammatory response by PHMG may play an important role in the development of pulmonary fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Chilakapati, Shanmuga Reddy; Serasanambati, Mamatha; Manikonda, Pavan Kumar; Chilakapati, Damodar Reddy; Watson, Ronald Ross

    2014-08-01

    Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized by excessive collagen deposition, with no effective treatments. We investigated the efficacy of natural products with high anti-inflammatory activity, such as passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal instillation of bleomycin to induce PF. Daily PFPE treatment significantly reduced loss of body mass and mortality rate in mice compared with those treated with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid on both days 7 and 21, PFPE administration significantly attenuated these phenomena compared with bleomycin group. On day 7, the decreased superoxide dismutase and myeloperoxidase activities observed in the bleomycin group were significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline deposition in the bleomycin group was also suppressed by PFPE administration. PFPE treatment significantly attenuated extensive inflammatory cell infiltration and accumulation of collagen in lung tissue sections of bleomycin-induced mice on days 7 and 21, respectively. Our results indicate that administration of PFPE decreased bleomycin-induced PF because of anti-inflammatory and antioxidant activities.

  11. Dendritic Cells Primed with Paracoccidioides brasiliensis Peptide P10 Are Therapeutic in Immunosuppressed Mice with Paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Leandro B. R. Silva

    2017-06-01

    Full Text Available Paracoccidioidomycosis (PCM is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P. brasiliensis Pb18 to establish the therapeutic efficacy of P10-pulsed DCs. Immunosuppressed and infected animals that received DCs had a reduction in their fungal burden, and this result was most pronounced in mice receiving DCs primed with P10. The efficacy of therapeutic DCs was significantly augmented by concomitant treatment with trimethoprim-sulfamethoxazole. Additionally, primed-DCs with or without the antifungal drug induced a beneficial Th1-biased immune response and significantly reduced tissue damage. In conclusion, these studies with immunocompromised mice demonstrate that P10-pulsed DCs with or without concomitant antifungal drugs are potently effective in combating invasive PCM. These findings support further translational studies to validate the use of P10-primed DCs for PCM in immunocompetent and immunosuppressed hosts.

  12. Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice

    DEFF Research Database (Denmark)

    Li, Fan; Jørgensen, Jesper Tranekjær; Madsen, Jacob

    2015-01-01

    The aim of this study was to evaluate the feasibility to perform voxel-wise kinetic modeling on datasets obtained from tumor-bearing mice that underwent dynamic PET scans with 64Cu-ATSM and extract useful physiological parameters.METHODS: Tumor-bearing mice underwent 90-min dynamic PET scans...... relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of 64Cu-ATSM as a hypoxia-specific PET tracer....

  13. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    International Nuclear Information System (INIS)

    Zebedeo, Christian Nash; Davis, Chad; Peña, Cecelia; Ng, Kok Wei; Pfau, Jean C.

    2014-01-01

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T H 17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were distinct

  16. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Zebedeo, Christian Nash; Davis, Chad [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Peña, Cecelia [Northwest Nazarene University, Nampa, ID (United States); Ng, Kok Wei [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Pfau, Jean C., E-mail: pfaujean@isu.edu [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States)

    2014-03-15

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were

  17. Pulmonary hypertension and vascular remodeling in mice exposed to crystalline silica.

    Science.gov (United States)

    Zelko, Igor N; Zhu, Jianxin; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-11-28

    Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces survival in affected subjects. An animal model of silicosis has been described previously however, the magnitude of vascular remodeling and hemodynamic effects of inhaled silica are largely unknown. Considering the importance of such information, this study investigated whether mice exposed to silica develop pulmonary hypertension and vascular remodeling. C57BL6 mice were intratracheally injected with either saline or crystalline silica at doses 0.2 g/kg, 0.3 g/kg and 0.4 g/kg and then studied at day 28 post-exposure. Pulmonary hypertension was characterized by changes in right ventricular systolic pressure and lung histopathology. Mice exposed to saline showed normal lung histology and hemodynamic parameters while mice exposed to silica showed increased right ventricular systolic pressure and marked lung pathology characterized by a granulomatous inflammatory reaction and increased collagen deposition. Silica-exposed mice also showed signs of vascular remodeling with pulmonary artery muscularization, vascular occlusion, and medial thickening. The expression of pro-inflammatory genes such as TNF-α and MCP-1 was significantly upregulated as well as the expression of the pro-remodeling genes collagen type I, fibronectin and the metalloproteinases MMP-2 and TIMP-1. On the other hand, the expression of several vasculature specific genes involved in the regulation of endothelial function was significantly attenuated. We characterized a new animal model of pulmonary hypertension secondary to pulmonary fibrosis induced by crystalline silica. Our data suggest that silica promotes the damage of the

  18. Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

    International Nuclear Information System (INIS)

    Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

    1976-01-01

    Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

  19. Radiation enhances silica translocation to the pulmonary interstitium and increases fibrosis in mice

    International Nuclear Information System (INIS)

    Adamson, I.Y.R.

    1992-01-01

    The effects of whole body irradiation (WBR) on particle clearance and the development of pulmonary fibrosis have been investigated. Using carbon, clearance is accomplished by polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM), and only a few particles reach the interstitum. However, in preirradiated mice, the usual eflux of inflammatory cells is much delayed so that more free carbon remains in the alveoli, and by 1 week, many particles cross the epithelium to be phagocytized by interstitial macrophages. Carbon is found in the peribronchiolar interstitium 6 months later with no evidence of fibrosis. In the present study, mice received 1 mg silica intratracheally 2 days after 6.5 Gy WBR when the white blood cell count was low. A much-reduced Am and PMN response was found in the following 2 weeks compared to the reaction to silica alone, and many silica particles reached interstitial macrophages. In this case, macrophage activation by silica was associated with fibroblast proliferation, and by 16 weeks, much more pulmonary fibrosis was produced than after silica or irradiation only. This was measured biochemically and correlated with a large increase in retained silica in the irradiation-silica group. The results indicate that radiation inhibits the inflammatory response to particle instillation, resulting in greater translocation of free particles to the pulmonary interstitium. In the case of silica, the greater, prolonged interaction with interstitial macrophages leads to a much exaggerated fibrotic reaction. 17 refs., 11 figs

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

    Science.gov (United States)

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

    2010-01-01

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

  1. Toxicological studies on palytoxin and ostreocin-D administered to mice by three different routes.

    Science.gov (United States)

    Ito, Emiko; Yasumoto, Takeshi

    2009-09-01

    Palytoxin (PLT) first isolated from zoanthids is extremely lethal to animals by intraperitoneal or intravenous administration but shows little toxicity by gavage dosing in contradiction to the occurrence of fatal poisoning due to PLT-containing seafood. In order to fully elucidate its potential risks to human we evaluated the toxicological effects via three ways of dosing: gavage, intra-tracheal administration (IT) and sublingual administration. A new analog, 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin isolated from the dinoflagellate Ostreopsis siamensis and named ostreocin-D (OSD), was also used for comparison, additionally conducted by i.p. By gavage dosing, both toxins did not produce death in mice at the maximum dosage of 200 microg/kg of PLT and 300 microg/kg of OSD. Addition of dietary lipid components to PLT solutions for gavage or use of ulcerated mice did not alter the results, indicating no enhancement of PLT absorption. The two toxins were most toxic by the IT route, causing bleeding and alveolar destruction in the lung and resultant death at 2 microg/kg of PLT, and 11 microg/kg of OSD. Both toxins also induced organ injuries after 24h when dosed by sublingual administration at about 200 microg/kg. The injuries became fatal when PLT was dosed 2 or 3 times. The results pointed to the necessity of taking multiple approaches to assess the potential health risks due to PLT and its analogs in food and environments.

  2. Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

    Science.gov (United States)

    Kawai, Kazushige; Ishihara, Soichiro; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

    2017-04-01

    Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. This was a retrospective comparative study. This study was conducted at a single referral hospital. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. Although endoscopic assessment after chemoradiotherapy correlated with pathological response

  3. In vivo fluorescence imaging of bacteriogenic cyanide in the lungs of live mice infected with cystic fibrosis pathogens.

    Directory of Open Access Journals (Sweden)

    Seong-Won Nam

    Full Text Available BACKGROUND: Pseudomonas aeruginosa (PA and Burkholderia cepacia complex (Bcc, commonly found in the lungs of cystic fibrosis (CF patients, often produce cyanide (CN, which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown. METHODS AND FINDINGS: This work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4',5'-fluorescein dicarboxaldehyde with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs. CONCLUSIONS: The in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.

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

    Science.gov (United States)

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

    2010-08-01

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

  5. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Via, Laura E. [Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Kumar, Mia R.; Cornish, Joseph P. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD (United States); Johnson, Joshua C. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Pickel, James [Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD (United States); Hensley, Lisa E. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States)

    2015-11-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

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

    International Nuclear Information System (INIS)

    Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

    2015-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

  9. Long-term psychological distress, and styles of coping, in parents of children and adolescents who underwent invasive treatment for congenital cardiac disease

    NARCIS (Netherlands)

    Spijkerboer, Alinda W.; Helbing, Willem A.; Bogers, Ad J. J. C.; van Domburg, Ron T.; Verhulst, Frank C.; Utens, Elisabeth M. W. J.

    2007-01-01

    To assess the level of psychological distress and styles of coping in both mothers and fathers of children who underwent invasive treatment for congenital cardiac disease at least 7 years and 6 months ago. The General Health Questionnaire and the Utrecht Coping List were completed by parents of

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

    Directory of Open Access Journals (Sweden)

    Barfod Kenneth K

    2010-09-01

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

  11. Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice

    DEFF Research Database (Denmark)

    Johansson, Maria E.; Wickman, Anna; Skøtt, Ole

    2006-01-01

    OBJECTIVE: Using an aortic constriction model in mice, we studied whether the increase in pressure or the activation of the renin-angiotensin system (RAS) and its main receptors is the main driving force for plaque progression. METHODS: Male ApoE mice underwent sham surgery or placement of a supr...

  12. Epidural Hematoma and Abscess Related to Thoracic Epidural Analgesia: A Single-Center Study of 2,907 Patients Who Underwent Lung Surgery.

    Science.gov (United States)

    Kupersztych-Hagege, Elisa; Dubuisson, Etienne; Szekely, Barbara; Michel-Cherqui, Mireille; François Dreyfus, Jean; Fischler, Marc; Le Guen, Morgan

    2017-04-01

    To report the major complications (epidural hematoma and abscess) of postoperative thoracic epidural analgesia in patients who underwent lung surgery. Prospective, monocentric study. A university hospital. All lung surgical patients who received postoperative thoracic epidural analgesia between November 2007 and November 2015. Thoracic epidural analgesia for patients who underwent lung surgery. During the study period, data for 2,907 patients were recorded. The following 3 major complications were encountered: 1 case of epidural hematoma (0.34 case/1,000; 95% confidence interval 0.061-1.946), for which surgery was performed, and 2 cases of epidural abscesses (0.68 case/1,000; 95% confidence interval 0.189-2.505), which were treated medically. The risk range of serious complications was moderate; only the patient who experienced an epidural hematoma also experienced permanent sequelae. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Comparative study of short-term cardiovascular autonomic control in cardiac surgery patients who underwent coronary artery bypass grafting or correction of valvular heart disease.

    Science.gov (United States)

    Shvartz, Vladimir A; Kiselev, Anton R; Karavaev, Anatoly S; Vulf, Kristina A; Borovkova, Ekaterina I; Prokhorov, Mikhail D; Petrosyan, Andrey D; Bockeria, Olga L

    2018-01-01

    Introduction: Our aim was to perform a comparative study of short-term cardiovascular autonomic control in cardiac surgery patients who underwent coronary artery bypass grafting (CABG) or surgical correction of valvular heart disease (SCVHD ). Methods: The synchronous 15 minutes records of heart rate variability (HRV) and finger's photoplethysmographic waveform variability (PPGV) were performed in 42 cardiac surgery patients (12 women) aged 61.8 ± 8.6 years (mean ± standard deviation), who underwent CABG, and 36 patients (16 women) aged 54.2 ± 14.9 years, who underwent SCVHD , before surgery and in 5-7 days after surgery. Conventional time and frequency domain measures of HRV and index S of synchronization between the slow oscillations in PPGV and HRV were analyzed. We also calculated personal dynamics of these indices after surgery. Results: We found no differences ( Р > 0.05) in all studied autonomic indices (preoperative and post-surgery) between studied patients' groups, except for the preoperative heart rate, which was higher in patients who underwent SCVHD ( P = 0.013). We have shown a pronounced preoperative and post-surgery variability (magnitude of inter-quartile ranges) of all autonomic indices in studied patients. In the cluster analysis based on cardiovascular autonomic indices (preoperative and post-surgery), we divided all patients into two clusters (38 and 40 subjects) which did not differ in all clinical characteristics (except for the preoperative hematocrit, P = 0.038), index S, and all post-surgery HRV indices. First cluster (38 patients) had higher preoperative values of the HR, TP, HF, and HF%, and lower preoperative values of the LF% and LF/HF. Conclusion: The variability of cardiovascular autonomic indices in on-pump cardiac surgery patients (two characteristic clusters were identified based on preoperative indices) was not associated with their clinical characteristics and features of surgical procedure (including cardioplegia).

  14. Gender-linked impact of epicardial adipose tissue volume in patients who underwent coronary artery bypass graft surgery or non-coronary valve surgery

    OpenAIRE

    Maimaituxun, Gulinu; Shimabukuro, Michio; Salim, Hotimah Masdan; Tabata, Minoru; Yuji, Daisuke; Morimoto, Yoshihisa; Akasaka, Takeshi; Matsuura, Tomomi; Yagi, Shusuke; Fukuda, Daiju; Yamada, Hirotsugu; Soeki, Takeshi; Sugimoto, Takaki; Tanaka, Masashi; Takanashi, Shuichiro

    2017-01-01

    Background Traditional and non-traditional risk factors for atherosclerotic cardiovascular disease (ASCVD) are different between men and women. Gender-linked impact of epicardial adipose tissue volume (EATV) in patients undergoing coronary artery bypass grafting (CABG) remains unknown. Methods Gender-linked impact of EATV, abdominal fat distribution and other traditional ASCVD risk factors were compared in 172 patients (men: 115; women: 57) who underwent CABG or non-coronary valvular surgery ...

  15. The effect of size-segregated ambient particulate matter on Th1/Th2-like immune responses in mice.

    Directory of Open Access Journals (Sweden)

    Kuo-Liang Huang

    Full Text Available Particulate matter (PM has been associated with increased pulmonary and cardiovascular mortality and morbidity. Additionally, PM is known to exacerbate asthma. However, whether ambient PM exposure contributes to the onset of asthma, especially in non-atopic children and adults, is less conclusive. The current study aimed to evaluate the effects of size-fractioned PM on lung immune responses in healthy BALB/c mice.We collected PM10, PM2.5, PM1 and PM0.1 samples from October 2012 to August 2013 in the Taipei Basin. These PM samples were representative of urban traffic pollution. The samples were extracted and sonicated in phosphate-buffered saline (PBS. Female BALB/c mice were exposed to the samples via intratracheal instillation at three different doses: 1.75 mg/kg (35 μg/per mouse, 5 mg/kg (100 μg/per mouse, and 12.5 mg/kg (250 μg/per mouse. The mice were exposed on days 0 and 7, and PBS alone was used as a control. Following the exposures, the expression profiles of inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF were assessed. Exposure to PM10 resulted in inflammatory responses, including the recruitment of neutrophils and the induction of T helper 1 (Th1 cell-related cytokine release, such as TNF-α and IFN-γ. Furthermore, an allergic immune response, including the recruitment of eosinophils and the up-regulation of T helper 2 (Th2 cell-related cytokine release, such as IL-5 and IL-13, was also observed in the BALF of mice exposed to PM10.Our study showed that exposure to PM alone caused mixed Th1/Th2 inflammatory responses in healthy mice. These findings support the hypothesis that PM may contribute to the onset of asthma.

  16. Comparison of PSA value at last follow-up of patients who underwent low-dose rate brachytherapy and intensity-modulated radiation therapy for prostate cancer.

    Science.gov (United States)

    Tanaka, Nobumichi; Asakawa, Isao; Nakai, Yasushi; Miyake, Makito; Anai, Satoshi; Fujii, Tomomi; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2017-08-25

    To compare the PSA value at the last follow-up of patients who underwent prostate low-dose rate brachytherapy (LDR-BT) with that of patients who underwent intensity-modulated radiation therapy (IMRT). A total of 610 prostate cancer patients (cT1c-3bN0M0) were enrolled, and 445 of them underwent LDR-BT, while 165 received IMRT (74-76 Gy). The median follow-up period of these two groups was 75 months (LDR-BT) and 78 months (IMRT), respectively. We also evaluated the biochemical recurrence (BCR)-free rate using two definitions (Phoenix definition and PSA ≥ 0.2 ng/mL). The percentage of patients who achieved PSA LDR-BT group and 49.7% in the IMRT group (p LDR-BT group and 32.1% in the IMRT group (p LDR-BT groups was 89.5 and 95.0% (p LDR-BT groups, respectively (p LDR-BT was significantly lower than that of IMRT, and this result was particularly marked in patients with a normal testosterone level at the last follow-up.

  17. 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

    2017-04-01

    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

  18. 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.

    Science.gov (United States)

    Cong, Yu; Lentz, Margaret R; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent; Holbrook, Michael R

    2017-04-01

    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 condition.

  19. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    Science.gov (United States)

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

  20. Compound edaravone alleviates lipopolysaccharide (LPS)-induced acute lung injury in mice.

    Science.gov (United States)

    Zhang, Zhengping; Luo, Zhaowen; Bi, Aijing; Yang, Weidong; An, Wenji; Dong, Xiaoliang; Chen, Rong; Yang, Shibao; Tang, Huifang; Han, Xiaodong; Luo, Lan

    2017-09-15

    Acute lung injury (ALI) represents an unmet medical need with an urgency to develop effective pharmacotherapies. Compound edaravone, a combination of edaravone and borneol, has been developed for treatment of ischemia stroke in clinical phase III study. The purpose of the present study is to investigate the anti-inflammatory effect of compound edaravone on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and the therapeutic efficacy on LPS-induced ALI in mice. Edaravone and compound edaravone concentration-dependently decreased LPS-induced interleukin-6 (IL-6) production and cyclooxygenase-2 (COX-2) expression in RAW264.7 cells. The efficiency of compound edaravone was stronger than edaravone alone. In the animal study, compound edaravone was injected intravenously to mice after intratracheal instillation of LPS. It remarkably alleviated LPS-induced lung injury including pulmonary histological abnormalities, polymorphonuclear leukocyte (PMN) infiltration and extravasation. Further study demonstrated that compound edaravone suppressed LPS-induced TNF-α and IL-6 increase in mouse serum and bronchoalveolar lavage (BAL) fluid, and inhibited LPS-induced nuclear factor-κB (NF-κB) activation and COX-2 expression in mice lung tissues. Importantly, our findings demonstrated that the compound edaravone showed a stronger protective effect against mouse ALI than edaravone alone, which suggested the synergies between edaravone and borneol. In conclusion, compound edaravone could be a potential novel therapeutic drug for ALI treatment and borneol might produce a synergism with edaravone. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Aerosol azacytidine inhibits orthotopic lung cancers in mice through Its DNA demethylation and gene reactivation effects.

    Directory of Open Access Journals (Sweden)

    Xuan Qiu

    Full Text Available We devised an aerosol based demethylation therapy to achieve therapeutic efficacy in premalignant or in situ lesions of lung cancer, without systemic toxicity. Optimum regimens of aerosolized azacytidine (Aza were designed and used in orthotopic human non-small cell lung cancer xenograft models. The therapeutic efficacy and toxicity of aerosol Aza were compared with intravenously administered Aza. We observed that 80% of the droplets of the aerosol Aza measured ∼0.1-5 microns, which resulted in deposition in the lower bronchial airways. An animal model that phenocopies field carcinogeneisis in humans was developed by intratracheal inoculation of the human lung cancer cells in mice, thus resulting in their distribution throughout the entire airway space. Aerosolized Aza significantly prolonged the survival of mice bearing endo-bronchial lung tumors. The aerosol treatment did not cause any detectable lung toxicity or systemic toxicity. A pre-pharmacokinetic study in mice demonstrated that lung deposition of aerosolized Aza was significantly higher than the intravenous route. Lung tumors were resected after aerosol treatment and the methylation levels of 24 promoters of tumor-suppresser genes related to lung cancer were analyzed. Aerosol Aza significantly reduced the methylation level in 9 of these promoters and reexpressed several genes tested. In conclusion, aerosol Aza at non-cytotoxic doses appears to be effective and results in DNA demethylation and tumor suppressor gene re-expression. The therapeutic index of aerosol Aza is >100-fold higher than that of intravenous Aza. These results provide a preclinical rationale for a phase I clinical trial of aerosol Aza to be initiated at our Institution.

  2. Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

    Science.gov (United States)

    Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

    2004-06-01

    A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

  3. Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Qingqing; Tan, Danning; Ze, Yuguan; Sang, Xuezi [Medical College of Soochow University, Suzhou 215123 (China); Liu, Xiaorun [Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009 (China); Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009 (China); Gui, Suxin; Cheng, Zhe; Cheng, Jie; Hu, Renping; Gao, Guodong; Liu, Gan; Zhu, Min; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling [Medical College of Soochow University, Suzhou 215123 (China); Tang, Meng, E-mail: tm@seu.edu.cn [Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009 (China); Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009 (China); Hong, Fashui, E-mail: Hongfsh_cn@sina.com [Medical College of Soochow University, Suzhou 215123 (China)

    2012-10-15

    Highlights: Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NPs could be significantly accumulated in the lung. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NPs caused pulmonary injury in mice. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NP promoted the expression of inflammatory cytokines in the lung. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NP caused ROS overproduction in the lung. - Abstract: Exposure to titanium dioxide nanoparticles (TiO{sub 2} NPs) has been demonstrated to result in pulmonary inflammation in animals; however, very little is known about the molecular mechanisms of pulmonary injury due to TiO{sub 2} NPs exposure. The aim of this study was to evaluate the oxidative stress and molecular mechanism associated with pulmonary inflammation in chronic lung toxicity caused by the intratracheal instillation of TiO{sub 2} NPs for 90 consecutive days in mice. Our findings suggest that TiO{sub 2} NPs are significantly accumulated in the lung, leading to an obvious increase in lung indices, inflammation and bleeding in the lung. Exposure to TiO{sub 2} NPs significantly increased the accumulation of reactive oxygen species and the level of lipid peroxidation, and decreased antioxidant capacity in the lung. Furthermore, TiO{sub 2} NPs exposure activated nuclear factor-{kappa}B, increased the levels of tumor necrosis factor-{alpha}, cyclooxygenase-2, heme oxygenase-1, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1{beta}, and CYP1A1 expression. However, TiO{sub 2} NPs exposure decreased NF-{kappa}B-inhibiting factor and heat shock protein 70 expression. Our results suggest that the generation of pulmonary inflammation caused by TiO{sub 2} NPs in mice is closely related to oxidative stress and the expression of inflammatory cytokines.

  4. Chronic social stress leads to altered sleep homeostasis in mice.

    Science.gov (United States)

    Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

    2017-06-01

    Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention.

    Science.gov (United States)

    Harada, Kazuhiro; Kikuchi, Ryosuke; Suzuki, Susumu; Tanaka, Akihito; Aoki, Toshijiro; Iwakawa, Naoki; Kojima, Hiroki; Hirayama, Kenshi; Mitsuda, Takayuki; Sumi, Takuya; Negishi, Yosuke; Ishii, Hideki; Murohara, Toyoaki

    2018-02-02

    Periprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI. We enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI. HDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74-0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020). HDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.

  6. Effect of preinfarction angina pectoris on long-term survival in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

    Science.gov (United States)

    Taniguchi, Tomohiko; Shiomi, Hiroki; Toyota, Toshiaki; Morimoto, Takeshi; Akao, Masaharu; Nakatsuma, Kenji; Ono, Koh; Makiyama, Takeru; Shizuta, Satoshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Ando, Kenji; Kadota, Kazushige; Horie, Minoru; Kimura, Takeshi

    2014-10-15

    The influence of preinfarction angina pectoris (AP) on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) remains controversial. In 5,429 patients with acute myocardial infarction (AMI) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto AMI Registry, the present study population consisted of 3,476 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and in whom the data on preinfarction AP were available. Preinfarction AP defined as AP occurring within 48 hours of hospital arrival was present in 675 patients (19.4%). Patients with preinfarction AP was younger and more often had anterior AMI and longer total ischemic time, whereas they less often had history of heart failure, atrial fibrillation, and shock presentation. The infarct size estimated by peak creatinine phosphokinase was significantly smaller in patients with than in patients without preinfarction AP (median [interquartile range] 2,141 [965 to 3,867] IU/L vs 2,462 [1,257 to 4,495] IU/L, p <0.001). The cumulative 5-year incidence of death was significantly lower in patients with preinfarction AP (12.4% vs 20.7%, p <0.001) with median follow-up interval of 1,845 days. After adjusting for confounders, preinfarction AP was independently associated with a lower risk for death (hazard ratio 0.69, 95% confidence interval 0.54 to 0.86, p = 0.001). The lower risk for 5-year mortality in patients with preinfarction AP was consistently observed across subgroups stratified by total ischemic time, initial Thrombolysis In Myocardial Infarction flow grade, hemodynamic status, infarct location, and diabetes mellitus. In conclusion, preinfarction AP was independently associated with lower 5-year mortality in patients with STEMI who underwent primary PCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

    Energy Technology Data Exchange (ETDEWEB)

    Dhakal, Sughosh; Bates, James E. [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Casulo, Carla; Friedberg, Jonathan W.; Becker, Michael W.; Liesveld, Jane L. [Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States)

    2016-10-01

    Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

  8. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  9. The MICE Online Systems

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

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

    Directory of Open Access Journals (Sweden)

    Carsten Købler

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  12. Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

    Science.gov (United States)

    Ma, Hongge; Qiao, Shupei; Wang, Zeli; Geng, Shuai; Zhao, Yufang; Hou, Xiaolu; Tian, Weiming; Chen, Xiongbiao; Yao, Lifen

    2017-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses. Copyright © 2017 the American Physiological Society.

  13. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls

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

    Directory of Open Access Journals (Sweden)

    Ladefoged Ole

    2009-01-01

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

  15. Retrospective, Demographic, and Clinical Investigation of the Causes of Postoperative Infection in Patients With Lumbar Spinal Stenosis Who Underwent Posterior Stabilization.

    Science.gov (United States)

    Yaldiz, Can; Yaldiz, Mahizer; Ceylan, Nehir; Kacira, Ozlem Kitiki; Ceylan, Davut; Kacira, Tibet; Kizilcay, Gokhan; Tanriverdi, Taner

    2015-07-01

    Owing to the increasing population of elderly patients, a large number of patients with degenerative spondylosis are currently being surgically treated. Although basic measures for decreasing postoperative surgical infections (PSIs) are considered, it still remains among the leading causes of morbidity and mortality. The aim of this retrospective analysis is to present possible causes leading to PSI in patients who underwent surgery for lumbar degenerative spondylosis and highlight how it can be avoided to decrease morbidity and mortality. The study included 540 patients who underwent posterior stabilization due to degenerative lumbar stenosis between January 2013 and January 2014. The data before and after surgery was retrieved from the hospital charts. Patients with degenerative lumbar stenosis who were operated upon in this study had >2 levels of laminectomy and facetectomy. For this reason, posterior stabilization was performed for all the patients included in this study. Determining the causes of postoperative infection (PI) following spinal surgeries performed with instrumentation is a struggle. Seventeen different parameters that may be related to PI were evaluated in this study. The presence of systemic diseases, unknown glove perforations, and perioperative blood transfusions were among the parameters that increased the prevalence of PI. Alternatively, prolene sutures, double-layered gloves, and the use of rifampicin Sv (RIS) decreased the incidence of PI. Although the presence of systemic diseases, unnoticed glove perforations, and perioperative blood transfusions increased PIs, prolene suture material, double-layered gloves, and the use of RIS decreased PIs.

  16. A New Risk Factor Profile for Contrast-Induced Acute Kidney Injury in Patients Who Underwent an Emergency Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yuan, Ying; Qiu, Hong; Song, Lei; Hu, Xiaoying; Luo, Tong; Zhao, Xueyan; Zhang, Jun; Wu, Yuan; Qiao, Shubin; Yang, Yuejin; Gao, Runlin

    2018-07-01

    We developed a new risk factor profile for contrast-induced acute kidney injury (CI-AKI) under a new definition in patients who underwent an emergency percutaneous coronary intervention (PCI). Consecutive patients (n = 1061) who underwent an emergency PCI were divided into a derivation group (n = 761) and a validation group (n = 300). The rates of CI-AKI were 23.5% (definition 1: serum creatinine [SCr] increase ≥25% in 72 hours), 4.3% (definition 2: SCr increase ≥44.2 μmol/L in 72 hours), and 7.0% (definition 3: SCr increase ≥44.2 μmol/L in 7 days). Due to the high sensitivity of definition 1 and the high rate of missed cases for late diagnosis of CI-AKI under definition 2, definition 3 was used in the study. The risk factor profile included body surface area 15.00 × 10 9 /L ( P = .047), estimated glomerular filtration rate 133 μmol/L ( P = .007), intra-aortic balloon pump application ( P = .006), and diuretics administration ( P risk factor profile of CI-AKI under a new CI-AKI definition in emergency PCI patients is easily applicable with a useful predictive value.

  17. The importance of superficial basal cell carcinoma in a retrospective study of 139 patients who underwent Mohs micrographic surgery in a Brazilian university hospital

    Directory of Open Access Journals (Sweden)

    Luciana Takata Pontes

    2015-11-01

    Full Text Available OBJECTIVE: Mohs micrographic surgery is a specialized surgical procedure used to treat skin cancer. The purpose of this study was to better understand the profile of the patients who underwent the procedure and to determine how histology might be related to complications and the number of stages required for complete removal. METHODS: The records of patients who underwent Mohs micrographic surgery from October 2008 to November 2013 at the Dermatology Division of the Hospital of the Campinas University were assessed. The variables included were gender, age, anatomical location, histology, number of stages required and complications. RESULTS: Contingency tables were used to compare the number of stages with the histological diagnosis. The analysis showed that patients with superficial basal cell carcinoma were 9.03 times more likely to require more than one stage. A comparison between complications and histological diagnosis showed that patients with superficial basal cell carcinoma were 6.5 times more likely to experience complications. CONCLUSION: Although superficial basal cell carcinoma is typically thought to represent a less-aggressive variant of these tumors, its propensity for demonstrating “skip areas” and clinically indistinct borders make it a challenge to treat. Its particular nature may result in the higher number of surgery stages required, which may, as a consequence, result in more complications, including recurrence. Recurrence likely occurs due to the inadequate excision of the tumors despite their clear margins. Further research on this subtype of basal cell carcinoma is needed to optimize treatments and decrease morbidity.

  18. Vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert: a retrospective study of 1656 women in China.

    Science.gov (United States)

    Zhao, Lei; Lin, Ying; Jiang, Ting-Ting; Wang, Ling; Li, Min; Wang, Ying; Sun, Guo-Qiang; Xiao, Mei

    2017-12-21

    This study aimed to qualify relevant factors for vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert in a Chinese tertiary maternity hospital. A retrospective study was conducted in Hubei Maternal and Child Health Hospital. A total of 1656 pregnancies that underwent labor induction with vaginal dinoprostone insert between January and August 2016 were finally included in this study. Data were analyzed using univariate and multivariable regression modeling. Of 1656 women with PGE2-induced labor at term, 396 (23.91%) gave birth by cesarean section, 1260 (76.09%) had a vaginal delivery among which 921 (55.61%) delivered vaginally within 24 h. Multivariable regression analysis showed that maternal age (p labor induction, which was markedly higher than the overall annual vaginal delivery rate of 65.1% in China during 2014. Maternal age, parity, baseline fetal heart rate, and birth weight were significant factors for vaginal delivery. This study enables us to better understand the efficiency of dinoprostone and the potential predictors of vaginal delivery in dinoprostone-induced labor, which may be helpful to guide the clinical use of dinoprostone and therefore provide better service clinically.

  19. Association of Blood Fatty Acid Composition and Dietary Pattern with the Risk of Non-Alcoholic Fatty Liver Disease in Patients Who Underwent Cholecystectomy.

    Science.gov (United States)

    Shim, Poyoung; Choi, Dongho; Park, Yongsoon

    2017-01-01

    The relationship between diet and non-alcoholic fatty liver disease (NAFLD) in patients with gallstone disease and in those who have a high risk for NAFLD has not been investigated. This study was conducted to investigate the association between the risk of NAFLD and dietary pattern in patients who underwent cholecystectomy. Additionally, we assessed the association between erythrocyte fatty acid composition, a marker for diet, and the risk of NAFLD. Patients (n = 139) underwent liver ultrasonography to determine the presence of NAFLD before laparoscopic cholecystectomy, reported dietary intake using food frequency questionnaire, and were assessed for blood fatty acid composition. Fifty-eight patients were diagnosed with NAFLD. The risk of NAFLD was negatively associated with 2 dietary patterns: consuming whole grain and legumes and consuming fish, vegetables, and fruit. NAFLD was positively associated with the consumption of refined grain, meat, processed meat, and fried foods. Additionally, the risk of NAFLD was positively associated with erythrocyte levels of 16:0 and 18:2t, while it was negatively associated with 20:5n3, 22:5n3, and Omega-3 Index. The risk of NAFLD was negatively associated with a healthy dietary pattern of consuming whole grains, legumes, vegetables, fish, and fruit and with an erythrocyte level of n-3 polyunsaturated fatty acids rich in fish. © 2017 S. Karger AG, Basel.

  20. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  1. Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice

    OpenAIRE

    He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2013-01-01

    Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral te...

  2. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

    DEFF Research Database (Denmark)

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin

    2016-01-01

    /BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21...

  3. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice

    Science.gov (United States)

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B.; Carter, A. Brent; Rowe, Steven M.; Matalon, Sadis; Thannickal, Victor J.; Agarwal, Anupam

    2015-01-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1+/+, HO-1−/−, and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1−/− mice exhibited more severe emphysema compared with HO-1+/+ or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1+/+, HO-1−/−, and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1−/− PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1+/+ PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. PMID:26071551

  4. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice.

    Science.gov (United States)

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B; Carter, A Brent; Rowe, Steven M; Matalon, Sadis; Thannickal, Victor J; Agarwal, Anupam; Antony, Veena B

    2015-08-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1(+/+), HO-1(-/-), and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1(-/-) mice exhibited more severe emphysema compared with HO-1(+/+) or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1(+/+), HO-1(-/-), and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1(-/-) PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1(+/+) PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. Copyright © 2015 the American Physiological Society.

  5. Prognostic significance of nuclear factor of activated T-cells 5 expression in non-small cell lung cancer patients who underwent surgical resection.

    Science.gov (United States)

    Cho, Hyun Jin; Yun, Hwan-Jung; Yang, Hee Chul; Kim, Soo Jin; Kang, Shin Kwang; Che, Chengri; Lee, Sang Do; Kang, Min-Woong

    2018-06-01

    Nuclear factor of activated T-cells 5 (NFAT5) is known to be correlated with migration or invasion of tumor cells based on previous in vitro studies. The aim of this study was to analyze the relationship between NFAT5 expression and clinical prognosis in non-small cell lung cancer (NSCLC) patients who underwent surgical resection. A total of 92 NSCLC patients who underwent surgical resection were enrolled. The tissue microarray core was obtained from surgically resected tumor specimens. NFAT5 expression was evaluated by immunohistochemistry. Relationships of NFAT5 expression with disease recurrence, overall survival, and disease-free survival (DFS) were analyzed. The mean age of 92 patients was 63.7 y. The median follow-up duration was 63.3 mo. Fifty-one (55%) patients exhibited positive expression of NFAT5. Disease recurrence in the NFAT5-positive group was significantly (P = 0.022) higher than that in the NFAT5-negative group. NFAT5-positive expression (odds ratio: 2.632, 95% confidence interval: 1.071-6.465, P = 0.035) and pathologic N stage (N1-2 versus N0; odds ratio: 3.174, 95% confidence interval: 1.241-8.123, P = 0.016) were independent and significant risk factors for disease recurrence. DFS of the NFAT5-positive group was significantly worse than that of the NFAT5-negative group (89.7 versus 48.7 mo, P = 0.011). A multivariate analysis identified NFAT5 expression (P < 0.029) as a significant independent risk factor for DFS of patients with postoperative pathologic T and N stages (P < 0.001 and P = 0.017, respectively). NFAT5 expression is a useful prognostic biomarker for NSCLC patients who underwent surgical resection. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent Combined Argon-Helium Cryotherapy and IL-12 Treatment.

    Science.gov (United States)

    Li, Ming; Cui, Yao; Li, Xiqing; Guo, Yanwu; Wang, Bin; Zhang, Jiadong; Xu, Jian; Han, Shuangyin; Shi, Xiwen

    2016-08-01

    The aim of this study was to explore changes in tumor tissues of glioma-bearing rats that underwent argon-helium cryoablation as well as changes in antitumor immunity before and after combined interleukin 12 treatment. Two hundred sixty Wistar rats were randomly divided into a blank control group, intravenous injection interleukin-12 group, cryotherapy group, and cryotherapy + intravenous injection group. C6 glioma cells proliferated in vitro were implanted subcutaneously on the backs of rats to establish C6 glioma-bearing animal models. Each group underwent the corresponding treatments, and morphological changes in tumor tissues were examined using hematoxylin-eosin staining. CD11c staining was examined using immunohistochemistry, and differences in dendritic cells and T-cell subsets before and after treatment were analyzed using flow cytometry. The control group showed no statistical changes in terms of tumor tissue morphology and cellular immunity, cryotherapy group, and cryotherapy + intravenous injection group, among which the count for the cryotherapy + intravenous injection group was significantly higher than those of all other groups. In the argon-helium cryotherapy group, tumor cells were damaged and dendritic cell markers were positive. The number of CD11c+ and CD86+ cells increased significantly after the operation as did the cytokine interferon-γ level (P < .01), suggesting a shift toward Th1-type immunity. Combined treatment of argon-helium cryoablation and interleukin 12 for gliomas not only effectively injured tumor tissues but also boosted immune function and increased antitumor ability. Therefore, this approach is a promising treatment measure for brain gliomas. © The Author(s) 2015.

  7. HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study.

    Science.gov (United States)

    Jiang, Yibo; Chen, Lijuan; Tang, Yaoliang; Ma, Genshan; Shen, Chengxing; Qi, Chunmei; Zhu, Qi; Yao, Yuyu; Liu, Naifeng

    2010-05-01

    To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.

  8. Improved predictive value of GRACE risk score combined with platelet reactivity for 1-year cardiovascular risk in patients with acute coronary syndrome who underwent coronary stent implantation.

    Science.gov (United States)

    Li, Shan; Liu, Hongbin; Liu, Jianfeng; Wang, Haijun

    2016-11-01

    Both high platelet reactivity (HPR) and Global Registry of Acute Coronary Events (GRACE) risk score have moderate predictive value for major adverse cardiovascular disease (CVD) events in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI), whereas the prognostic significance of GRACE risk score combined with platelet function testing remains unclear. A total of 596 patients with non-ST elevation ACS who underwent PCI were enrolled. The P2Y 12 reaction unit (PRU) value was measured by VerifyNow P2Y 12 assay and GRACE score was calculated by GRACE risk 2.0 calculator. Patients were stratified by a pre-specified cutoff value of PRU 230 and GRACE score 140 to assess 1-year risk of cardiovascular death, non-fatal myocardial infarction (MI), and stent thrombosis. Seventy-two (12.1%) patients developed CVD events during 1-year follow-up. Patients with CVD events had a higher PRU value (244.6 ± 50.9 vs. 203.7 ± 52.0, p risk independently. Compared to patients with normal platelet reactivity (NPR) and GRACE score risk (HR: 5.048; 95% CI: 2.268-11.237; p risk score yielded superior risk predictive capacity beyond GRACE score alone, which is shown by improved c-statistic value (0.871, p = 0.002) as well as net reclassification improvement (NRI 0.263, p risk of adverse CVD events. The combination of platelet function testing and GRACE score predicted 1-year CVD risk better.

  9. Differential allergy responses to Metarhizium anisopliae fungal component extracts in BALB/c mice

    Science.gov (United States)

    Intratracheal aspiration (IA) exposure to Metarhizium anisopliae crude antigen (MACA), which is composed of equal protein amounts of mycelium (MYC), conidia (CON) and inducible proteases/chitinases (IND) extracts/filtrates, has resulted in responses characteristic of human allerg...

  10. Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available Traumatic brain injury (TBI has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain.

  11. Estimation of absorbed dose of radiosensitive organs and effective sose in patients underwent abdominopelvic spiral CT scan using impact CT patient dosimetry

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    Ayoub Amirnia

    2017-05-01

    Full Text Available Background: Due to the presence of radiosensitive organs in the abdominopelvic region and increasing the number of requests for CT scan examinations, concerns about increasing radiation doses in patients has been greatly elevated. Therefore, the goal of this study was to determine the absorbed dose of radiosensitive organs and the effective dose in patients underwent abdominopelvic CT scan using ImPACT CT patient dosimetry Calculator (version 1.0.4, Imaging Performance Assessment on Computed Tomography, www.impactscan.org. Methods: This prospective cross-sectional study was conducted in Imam Reza Hospital from November to February 2015 February 2015 in the Imam Reza Hospital, in Urmia, Iran. The demographic and dosimetric information of 100 patients who underwent abdominopelvic CT scan in a 6-slice CT scanner were obtained through the data collection forms. The demographic data of the patients included age, weight, gender, and BMI. The dosimetric parameters included pitch value, CT dose volume index (CTDIvol, dose-length product (DLP, tube voltage, tube current, exposure time, collimation size, scan length, and scan time. To determine the absorbed dose of radiosensitive organs and also the effective dose in patients, ImPACT CT patient dosimetry calculator was used. Results: The results of this study demonstrated that the mean and standard deviation (SD of patients' effective dose in abdominopelvic CT scan was 4.927±0.164 mSv. The bladder in both genders had the greatest mean organ dose, which was 64.71±17.15 mGy for men and 77.56±18.48 mGy for women (P<0.001. Conclusion: The effective dose values of this examination are in the same range as previous studies, as well as International Commission on Radiological Protection (ICRP recommendations. However, the radiation dose from CT scan has the largest contribution to the medical imaging. According to the ALARA principle, it is recommended that the scan parameters, especially mAs, should be

  12. A controlled clinical study of serosa-invasive gastric carcinoma patients who underwent surgery plus intraperitoneal hyperthermo-chemo-perfusion (IHCP).

    Science.gov (United States)

    Kim, J Y; Bae, H S

    2001-01-01

    Despite recent advances in the treatment of advanced gastric carcinomas, no satisfactory outcomes are available because of micrometastases and free-floating carcinoma cells already existing in the peritoneal cavity. From 1990, we started using intraperitoneal hyperthermo-chemo-perfusion (IHCP) to prevent and to treat peritoneal metastasis after surgical resection of stomach cancer. We analyzed 103 serosa-invasive gastric carcinoma patients who underwent surgical resection between 1990 and 1995. Fifty-two patients who received surgery plus IHCP were compared with 51 patients who underwent surgery only, as controls. IHCP was administered for 2 h with an automatic IHCP device (closed-circuit system) just after surgical resection, with the patient under hypothermic general anesthesia (32.4 degrees C-34.0 degrees C). As perfusate, we used 1.5% peritoneal dialysis solution mixed with 10 micrograms/ml of mitomycin-C (MMC), warmed at an inflow temperature of over 44 degrees C. The overall 5-year survival rate (5-YSR) of the 103 patients was 29.97%. The 5-YSR was higher in the IHCP group than in the control group, at 32.7% and 27.1%, respectively, but this difference was not significant. However, in the 65 serosa-invasive gastric carcinoma patients (excluding those in stage IV) the 5-YSR was significantly higher (P = 0.0379) in the IHCP group than in the control group, at 58.6% and 44.4%, respectively. On multivariate analysis of all 103 patients, depth of tumor invasion and lymph node metastasis were significant factors for survival, whereas significant factors on univariate analysis, such as combined operation, distant metastasis, and peritoneal metastasis, were not significant. The most common recurrence patterns were loco-regional in the IHCP group and peritoneal in the control group. Complete cytoreductive surgery plus IHCP is effective to prevent and to treat peritoneal metastasis, and it should lead to long-term survival for serosa-invasive gastric carcinoma patients

  13. Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1

    Directory of Open Access Journals (Sweden)

    Gauldie Jack

    2010-12-01

    Full Text Available Abstract Background Micro-computed tomography (micro-CT is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. Methods Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1. Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. Results We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. Conclusions Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

  14. Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Mazzei, Maria Antonietta; Khader, Leila; Cirigliano, Alfredo; Cioffi Squitieri, Nevada; Guerrini, Susanna; Forzoni, Beatrice; Marrelli, Daniele; Roviello, Franco; Mazzei, Francesco Giuseppe; Volterrani, Luca

    2013-12-01

    To evaluate the accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent a peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction surgery. Pre-HIPEC CT examinations of 43 patients with advanced ovarian cancer after neoadjuvant chemotherapy were analyzed by two radiologists. The PCI was scored according to the Sugarbaker classification, based on lesion size and distribution. The results were compared with macroscopic and histologic data after peritonectomy and HIPEC. To evaluate the accuracy of MDCT to detect and localize peritoneal carcinomatosis, both patient-level and regional-level analyses were conducted. A correlation between PCI CT and histologic values for each patient was searched according to the PCI grading. Considering the patient-level analysis, CT shows a sensitivity, specificity, PPV, NPV, and an accuracy in detecting the peritoneal carcinomatosis of 100 %, 40 %, 93 % 100 %, and 93 %, respectively. Considering the regional level analysis, a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 72 %, 80 %, 66 %, 84 %, and 77 %, respectively were obtained for the correlation between CT and histology. Our results encourage the use of MDCT as the only technique sufficient to select patients with peritoneal carcinomatosis for cytoreductive surgery and HIPEC on the condition that a CT examination will be performed using a dedicated protocol optimized to detect minimal peritoneal disease and CT images will be analyzed by an experienced reader.

  15. Improved image quality in abdominal CT in patients who underwent treatment for hepatocellular carcinoma with small metal implants using a raw data-based metal artifact reduction algorithm.

    Science.gov (United States)

    Sofue, Keitaro; Yoshikawa, Takeshi; Ohno, Yoshiharu; Negi, Noriyuki; Inokawa, Hiroyasu; Sugihara, Naoki; Sugimura, Kazuro

    2017-07-01

    To determine the value of a raw data-based metal artifact reduction (SEMAR) algorithm for image quality improvement in abdominal CT for patients with small metal implants. Fifty-eight patients with small metal implants (3-15 mm in size) who underwent treatment for hepatocellular carcinoma were imaged with CT. CT data were reconstructed by filtered back projection with and without SEMAR algorithm in axial and coronal planes. To evaluate metal artefact reduction, mean CT number (HU and SD) and artefact index (AI) values within the liver were calculated. Two readers independently evaluated image quality of the liver and pancreas and visualization of vasculature using a 5-point visual score. HU and AI values and image quality on images with and without SEMAR were compared using the paired Student's t-test and Wilcoxon signed rank test. Interobserver agreement was evaluated using linear-weighted κ test. Mean HU and AI on images with SEMAR was significantly lower than those without SEMAR (P small metal implants by reducing metallic artefacts. • SEMAR algorithm significantly reduces metallic artefacts from small implants in abdominal CT. • SEMAR can improve image quality of the liver in dynamic CECT. • Confidence visualization of hepatic vascular anatomies can also be improved by SEMAR.

  16. In vitro fertilization surrogate pregnancy in a patient who underwent radical hysterectomy followed by ovarian transposition, lower abdominal wall radiotherapy, and chemotherapy.

    Science.gov (United States)

    Steigrad, Stephen; Hacker, Neville F; Kolb, Bradford

    2005-05-01

    To describe an IVF surrogate pregnancy from a patient who had a radical hysterectomy followed by excision of a laparoscopic port site implantation with ovarian transposition followed by abdominal wall irradiation and chemotherapy, which resulted in premature ovarian failure from which there was partial recovery. Case report. Tertiary referral university women's hospital in Sydney, Australia and private reproductive medicine clinic in California. A 34-year-old woman who underwent laparoscopy for pelvic pain, shortly afterward followed by radical hysterectomy and pelvic lymph node dissection, who subsequently developed a laparoscopic port site recurrence, which was excised in association with ovarian transposition before abdominal wall irradiation and chemotherapy. Modified IVF treatment, transabdominal oocyte retrieval, embryo cryopreservation in Australia, and transfer to a surrogate mother in the United States. Pregnancy. Miscarriage in the second cycle and a twin pregnancy in the fourth cycle. This is the first case report of ovarian stimulation and oocyte retrieval performed on transposed ovaries after a patient developed premature ovarian failure after radiotherapy and chemotherapy with subsequent partial ovarian recovery.

  17. Diagnosis of accessory conduction pathway using ECG-gated emission CT analysis. Studies in patients with WPW syndrome who underwent surgery

    Energy Technology Data Exchange (ETDEWEB)

    Misaki, Takuro; Mukai, Keiichi; Tsubota, Makoto; Iwa, Takashi; Nakajima, Ken-ichi; Hisada, Kin-ichi

    1987-09-01

    Pinpointing the location of accessory conduction pathway (ACP) is of great importance in the surgical treatment for Wolff-Parkinson-White (WPW) syndrome. For this purpose, this study explored the usefulness of ECG-gated emission computed tomography (Gated-ECT) in 30 patients who preoperatively underwent Gated-ECT. The site of earliest contraction at level of atrioventicular valves, obtained on tomographic phase analysis, was compared with the site of earliest activation, obtained on epicardial mapping during surgery. The concordance rate of the two methods was 94 % (28/30). Among them, one patient was found to have the association of corrected transposition of great arteries on Gated-ECT. Gated-ECT was, however, of limited value in differentiating right posterior ACP from right postseptal ACP. The discordance between the sites of earliest contraction and activation, which was observed in the two others, was likely due to decreased wall motion resulting from myocardial disturbance. Gated-ECT may have a diagnostic potential for the location of ACP, especially in view of providing images that corresponded to the surgical anatomy. (Namekawa, K.).

  18. Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration.

    Science.gov (United States)

    Chang, Jee Suk; Kim, Kyung Hwan; Keum, Ki Chang; Noh, Sung Hoon; Lim, Joon Seok; Kim, Hyo Song; Rha, Sun Young; Lee, Yong Chan; Hyung, Woo Jin; Koom, Woong Sub

    2016-12-01

    To classify patients with nonmetastatic advanced gastric cancer who underwent D2-gastrectomy into prognostic groups based on peritoneal and systemic recurrence risks. Between 2004 and 2007, 1,090 patients with T3-4 or N+ gastric cancer were identified from our registry. Recurrence rates were estimated using a competing-risk analysis. Different prognostic groups were defined using recursive partitioning analysis (RPA). Median follow-up was 7 years. In the RPA-model for peritoneal recurrence risk, the initial node was split by T stage, indicating that differences between patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were 34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact on high-risk patients. The RPA model for systemic relapse incorporated N stage alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year cumulative incidences were 7.7% and 24.5%, respectively. We proposed risk stratification models of peritoneal and systemic recurrence in patients undergoing D2-gastrectomy. This classification could be used for stratification protocols in future studies evaluating adjuvant therapies such as preoperative chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Improved image quality in abdominal CT in patients who underwent treatment for hepatocellular carcinoma with small metal implants using a raw data-based metal artifact reduction algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Sofue, Keitaro; Sugimura, Kazuro [Kobe University Graduate School of Medicine, Department of Radiology, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Ohno, Yoshiharu [Kobe University Graduate School of Medicine, Advanced Biomedical Imaging Research Center, Kobe, Hyogo (Japan); Kobe University Graduate School of Medicine, Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe, Hyogo (Japan); Negi, Noriyuki [Kobe University Hospital, Division of Radiology, Kobe, Hyogo (Japan); Inokawa, Hiroyasu; Sugihara, Naoki [Toshiba Medical Systems Corporation, Otawara, Tochigi (Japan)

    2017-07-15

    To determine the value of a raw data-based metal artifact reduction (SEMAR) algorithm for image quality improvement in abdominal CT for patients with small metal implants. Fifty-eight patients with small metal implants (3-15 mm in size) who underwent treatment for hepatocellular carcinoma were imaged with CT. CT data were reconstructed by filtered back projection with and without SEMAR algorithm in axial and coronal planes. To evaluate metal artefact reduction, mean CT number (HU and SD) and artefact index (AI) values within the liver were calculated. Two readers independently evaluated image quality of the liver and pancreas and visualization of vasculature using a 5-point visual score. HU and AI values and image quality on images with and without SEMAR were compared using the paired Student's t-test and Wilcoxon signed rank test. Interobserver agreement was evaluated using linear-weighted κ test. Mean HU and AI on images with SEMAR was significantly lower than those without SEMAR (P < 0.0001). Liver and pancreas image qualities and visualizations of vasculature were significantly improved on CT with SEMAR (P < 0.0001) with substantial or almost perfect agreement (0.62 ≤ κ ≤ 0.83). SEMAR can improve image quality in abdominal CT in patients with small metal implants by reducing metallic artefacts. (orig.)

  20. The Biological Activity of Propolis-Containing Toothpaste on Oral Health Environment in Patients Who Underwent Implant-Supported Prosthodontic Rehabilitation

    Directory of Open Access Journals (Sweden)

    Tadeusz Morawiec

    2013-01-01

    Full Text Available The soft and periodontal tissues surrounding dental implants are particularly susceptible to bacteria invasion and inflammatory reactions due to complex histological structures. This study was carried out to investigate the influence of a propolis-containing hygienic agent on selected oral health parameters, oral microflora, and the condition of periodontal health. Sixteen subjects who underwent an oral rehabilitation with dental implants were selected and randomly assigned into two groups, which received a newly formulated propolis-containing toothpaste (3% (CA or a negative control without an active ingredient (CC. Approximal plaque index (API, oral hygiene index (OHI, debris component, and sulcus bleeding index (SBI were assessed in three subsequent stages. During the first and last examinations, the swabs were employed for microbiological inoculation. Propolis-containing toothpaste was found to be distinctively effective in improving oral health and the occurrence of gingivitis triggered by dental plaque. The qualitative and quantitative changes in oral bacteria spectrum were observed. Antibacterial measures containing propolis might be used as a natural adjuvant to other active substances in individuals with a high risk of periodontal problems against pathogenic oral microflora.

  1. The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

    Science.gov (United States)

    Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

    2015-12-01

    Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Improved image quality in abdominal CT in patients who underwent treatment for hepatocellular carcinoma with small metal implants using a raw data-based metal artifact reduction algorithm

    International Nuclear Information System (INIS)

    Sofue, Keitaro; Sugimura, Kazuro; Yoshikawa, Takeshi; Ohno, Yoshiharu; Negi, Noriyuki; Inokawa, Hiroyasu; Sugihara, Naoki

    2017-01-01

    To determine the value of a raw data-based metal artifact reduction (SEMAR) algorithm for image quality improvement in abdominal CT for patients with small metal implants. Fifty-eight patients with small metal implants (3-15 mm in size) who underwent treatment for hepatocellular carcinoma were imaged with CT. CT data were reconstructed by filtered back projection with and without SEMAR algorithm in axial and coronal planes. To evaluate metal artefact reduction, mean CT number (HU and SD) and artefact index (AI) values within the liver were calculated. Two readers independently evaluated image quality of the liver and pancreas and visualization of vasculature using a 5-point visual score. HU and AI values and image quality on images with and without SEMAR were compared using the paired Student's t-test and Wilcoxon signed rank test. Interobserver agreement was evaluated using linear-weighted κ test. Mean HU and AI on images with SEMAR was significantly lower than those without SEMAR (P < 0.0001). Liver and pancreas image qualities and visualizations of vasculature were significantly improved on CT with SEMAR (P < 0.0001) with substantial or almost perfect agreement (0.62 ≤ κ ≤ 0.83). SEMAR can improve image quality in abdominal CT in patients with small metal implants by reducing metallic artefacts. (orig.)

  3. Changes in neurotic personality profile associated with reduction of suicidal ideation in patients who underwent psychotherapy in the day hospital for the treatment of neurotic and behavioral disorders.

    Science.gov (United States)

    Rodziński, Paweł; Rutkowski, Krzysztof; Sobański, Jerzy A; Mielimąka, Michał; Murzyn, Agnieszka; Cyranka, Katarzyna; Dembińska, Edyta; Grządziel, Karolina; Klasa, Katarzyna; Müldner-Nieckowski, Łukasz; Smiatek-Mazgaj, Bogna

    2015-01-01

    Analysis of associations between changes in neurotic personality profile and reductionof suicidal ideation (SI) - or lack of such reduction - defined as its elimination or reduction of its intensity in patients who underwent a course of intensive psychotherapy conducted in integrative approach with predominance of psychodynamic approach. Symptom Checklist KO"O", Neurotic Personality Questionnaire KON-2006 and Life Inventory completed by 461 women and 219 men treated due to neurotic, behavioral or personality disorders in a day hospital between 2005-2013. During the qualification for the therapy 134 women and 80 men reported SI, of whom 84.3% and 77.5% respectively improved. Patients who improved in terms of SI obtained significantly greater reduction of global neurotic personality disintegration (neuroticism) than others (ppsychotherapy as a treatment method that leads to comprehensive improvement encompassing reduction of neurotic personality disorders (neuroticism) and of majority of neurotic personality traits, as well as SI reduction. The revealed associations weigh in favor of hypothesis on neuroticism as SI predisposing factor in patients with neurotic, behavioral and personality disorders.

  4. Dwarf Mice and Aging.

    Science.gov (United States)

    Masternak, Michal M; Darcy, Justin; Victoria, Berta; Bartke, Andrzej

    2018-01-01

    Dwarf mice have been studied for many decades, however, the focus of these studies shifted in 1996 when it was shown by Brown-Borg and her coworkers that Ames dwarf (Prop1 df ) mice are exceptionally long-lived. Since then, Snell dwarf (Pit1 dw ) and growth hormone receptor knockout (GHR-KO, a.k.a. Laron dwarf) mice were also shown to be exceptionally long-lived, presumably due to their growth hormone (GH)-deficiency or -resistance, respectively. What is of equal importance in these dwarf mice is their extended health span, that is, these animals have a longer period of life lived free of frailty and age-related diseases. This review article focuses on recent studies conducted in these dwarf mice, which concerned brown and white adipose tissue biology, microRNA (miRNA) profiling, as well as early-life dietary and hormonal interventions. Results of these studies identify novel mechanisms linking reduced GH action with extensions of both life span and health span. Copyright © 2017. Published by Elsevier Inc.

  5. Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

    Science.gov (United States)

    Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

    2017-07-01

    Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  6. Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS.

    Science.gov (United States)

    Finkin-Groner, E; Moradov, D; Shifrin, H; Bejar, C; Nudelman, A; Weinstock, M

    2015-02-01

    In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. AN917 and AN680 (1-10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 μmol · kg(-1)) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression. © 2014 The British Pharmacological Society.

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

    Science.gov (United States)

    Nalabotu, Siva Krishna

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

  8. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    International Nuclear Information System (INIS)

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-01-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  9. The Effect of Two Different Hand Exercises on Grip Strength, Forearm Circumference, and Vascular Maturation in Patients Who Underwent Arteriovenous Fistula Surgery

    Science.gov (United States)

    Kong, Sangwon; Lee, Kyung Soo; Kim, Junho

    2014-01-01

    Objective To compare the effect of two different hand exercises on hand strength and vascular maturation in patients who underwent arteriovenous fistula surgery. Methods We recruited 18 patients who had chronic kidney disease and had undergone arteriovenous fistula surgery for hemodialysis. After the surgery, 10 subjects performed hand-squeezing exercise with GD Grip, and other 8 subjects used Soft Ball. The subjects continued the exercises for 4 weeks. The hand grip strength, pinch strength (tip, palmar and lateral pinch), and forearm circumference of the subjects were assessed before and after the hand-squeezing exercise. The cephalic vein size, blood flow velocity and volume were also measured by ultrasonography in the operated limb. Results All of the 3 types of pinch strengths, grip strength, and forearm circumference were significantly increased in the group using GD Grip. Cephalic vein size and blood flow volume were also significantly increased. However, blood flow velocity showed no difference after the exercise. The group using Soft Ball showed a significant increase in the tip and lateral pinch strength and forearm circumference. The cephalic vein size and blood flow volume were also significantly increased. On comparing the effect of the two different hand exercises, hand-squeezing exercise with GD Grip had a significantly better effect on the tip and palmar pinch strength than hand-squeezing exercise with Soft Ball. The effect on cephalic vein size was not significantly different between the two groups. Conclusion The results showed that hand squeezing exercise with GD Grip was more effective in increasing the tip and palmar pinch strength compared to hand squeezing exercise with soft ball. PMID:25379494

  10. Evaluation of long-term results and quality of life in patients who underwent rib fixation with titanium devices after trauma.

    Science.gov (United States)

    Billè, Andrea; Okiror, Lawrence; Campbell, Aideen; Simons, Jason; Routledge, Tom

    2013-06-01

    To describe the long-term results, quality of life and chronic pain after chest wall fixation for traumatic rib fracture using a quality of life (QOL) score and a numeric pain score. Retrospective analysis of 10 consecutive patients who underwent surgery for rib fractures after trauma and reconstruction between October 2010 and March 2012. Chest rib fractures were fixed with titanium clips and bars or titanium plates and screws through a posterolateral thoracotomy. Pain was assessed with a numeric pain scale 0-10 and quality of life (QOL) with the EORTC questionnaire QLQ-C30. There were 5 males and 5 females. The median age was 58 years (range 21-80). There were no postoperative deaths. The only postoperative complication observed was a contralateral pleural effusion requiring drainage. Median length of stay of the drain and median length of hospital stay were 2 days (range 0-8) and 4 days (range 1-42 days), respectively. The average follow-up period of operatively managed patients was 14 months (range 8-23.5 months). Seven patients scored the pain as 0, one as 1 (mild), one as 4 (moderate) and one as 8 (severe). Only two patients are taking occasionally pain killers. Only one patient presents severe limitation in his life scoring his QOL as poor. Titanium devices (clips and bars; screws and plates) are effective and safe for repair of rib fractures and showed good long-term results in terms of pain and quality of life after the operation.

  11. Evaluation of late redislocation in patients who underwent open reduction and pelvic osteotomy as treament for developmental dysplasia of the hip.

    Science.gov (United States)

    Tuhanioğlu, Ümit; Cicek, Hakan; Ogur, Hasan U; Seyfettinoglu, Firat; Kapukaya, Ahmet

    2017-10-16

    The goal in the treatment of developmental dysplasia of the hip (DDH) is to achieve a stable and concentric reduction and to create a congruent relationship between the femoral head and the acetabulum. This study discusses the causes of loss of reduction in DDH patients who had a concentrically reduced hip at the time of removal of the hip spica cast and cessation of brace use and who later appeared with hip redislocation after mobilisation and ambulation. In addition, the possible interventions in such cases are also discussed. A retrospective evaluation was made of 13 patients diagnosed with DDH who developed redislocation following primary surgery. 6 of them had undergone the 1st surgery in our department between 2008 and 2016 and 7 had udergone surgery in another centre. For comparison reasons a 2nd group was formed of 13 demographically and clinically matched patients who had no loss of reduction. The groups were compared in terms of acetabular index, pelvic length, pelvic width, abduction degree of plaster, ossifying nucleus diameter, acetabular depth, and acetabular volume parameters. The average age of the patients was 23 months at initial surgery and 29 months at the time of revision surgery. No significant difference was found between the groups in terms of acetabular inclination angle, ossifying nucleus diameter, pelvic size, pelvic width, centre edge angle, acetabular volume, and depth. Contracted inferomedial capsule was found in 1 patient who underwent revision surgery and intact transverse acetabular ligament was seen in 1 patient. The loss of reduction in the remaining 11 patients was associated with high total anteversion of the femoral head and acetabulum. Correction of increased combined anteversion by femoral osteotomy can create a safe zone in terms of redislocation and can significantly contribute to the stability provided by capsulorrhaphy and pelvic osteotomy.

  12. A Case Series of Patients Who Underwent Laparoscopic Extraperitoneal Radical Prostatectomy with the Simultaneous Implant of a Penile Prosthesis: Focus on Penile Length Preservation

    Science.gov (United States)

    2018-01-01

    Purpose There are many grey areas in the field of penile rehabilitation after radical prostatectomy (RP). The preservation of the full dimensions of the penis is an important consideration for improving patients' compliance for the treatment. We present the first case series of patients treated by laparoscopic extraperitoneal RP and simultaneous penile prosthesis implantation (PPI) in order to preserve the full length of the penis and to improve patients' satisfaction. Materials and Methods From June 2013 to June 2014, 10 patients underwent simultaneous PPI (with an AMS InhibiZone prosthesis) and RP. Patients were evaluated by means of urological visits, questionnaires, and objective measurements before surgery, at discharge from the hospital, on postoperative days 21 to 28, each 3 months for the first year, and each 6 months thereafter. The main outcome measures were biochemical recurrence-free rate, penile length, and quality of life. Results Ten patients (mean age of 61 years; completed the study follow-up period (median, 32.2 months). No difference was found between the time of surgery and the 2-year follow-up evaluation in terms of penile length. The pre-surgery 36-Item Short Form Health Survey (SF-36) median score was 97. Patients were satisfied with their penile implants, and couples' level of sexual satisfaction was rated median 8. The median postoperative SF-36 score was 99 at 3 months follow-up. Conclusions Laparoscopic extraperitoneal RP surgery with simultaneous PPI placement seems to be an interesting possibility to propose to motivated patients for preserving the length of the penis and improving their satisfaction. PMID:29623695

  13. Changes in blood glucose level during and after light sedations using propofol-fentanyl and midazolam-fentanyl in diabetic patients who underwent cataract surgery.

    Science.gov (United States)

    Khalighinejad, Pooyan; Rahimi, Mojtaba; Naghibi, Khosro; Niknam, Negar

    2015-01-01

    Surgeries may trigger the stress response which leads to changes in blood glucose level, and studies suggest that different sedation and anesthesia methods have different effects on blood glucose level. The aim of this study was to investigate changes of blood glucose levels in diabetic patients and compare them in two sedation methods of propofol + fentanyl and midazolam + fentanyl. Totally, 80 diabetic candidates for cataract surgery who had all the inclusion criteria, underwent cataract surgery using two methods of propofol (1 mg/kg/h) + fentanyl (2 μg/kg) (Group P) and midazolam (0.03 mg/kg) + fentanyl (2 μg/kg) (Group M) for light sedation. In the end, 70 patients (Group P n = 35 and Group M n = 35) remained in the study. Patients' blood glucose levels, vital signs, and hemodynamic data were assessed 30 min prior to the surgery, each 15 min during surgery and at the end of surgery. Hemodynamic parameters did not have a statistically significant difference between the two groups mean blood glucose level in Group M was 149.15 mg/dl and in Group P was 149.2 mg/dl, and based on repeated measures analysis of variance test, significant differences were not observed between the two groups (P = 0.99). T-test showed no significant differences in the blood glucose level at any time of the study between the two groups. Light sedation methods of propofol + fentanyl and midazolam + fentanyl did not have any differences in alteration of blood glucose level.

  14. Gender-linked impact of epicardial adipose tissue volume in patients who underwent coronary artery bypass graft surgery or non-coronary valve surgery.

    Directory of Open Access Journals (Sweden)

    Gulinu Maimaituxun

    Full Text Available Traditional and non-traditional risk factors for atherosclerotic cardiovascular disease (ASCVD are different between men and women. Gender-linked impact of epicardial adipose tissue volume (EATV in patients undergoing coronary artery bypass grafting (CABG remains unknown.Gender-linked impact of EATV, abdominal fat distribution and other traditional ASCVD risk factors were compared in 172 patients (men: 115; women: 57 who underwent CABG or non-coronary valvular surgery (non-CABG.In men, EATV, EATV index (EATV/body surface area and the markers of adiposity such as body mass index, waist circumference and visceral fat area were higher in the CABG group than in the non-CABG group. Traditional ASCVD risk factors were also prevalent in the CABG group. In women, EATV and EATV index were higher in the CABG group, but other adiposity markers were comparable between CABG and non-CABG groups. Multivariate logistic regression analysis showed that in men, CABG was determined by EATV Index and other ASCVD risk factors including hypertension, dyslipidemia, adiponectin, high sensitive C-reactive protein (hsCRP and type 2 diabetes mellitus (Corrected R2 = 0.262, p < 0.0001, while in women, type 2 diabetes mellitus is a single strong predictor for CABG, excluding EATV Index (Corrected R2 = 0.266, p = 0.005.Our study found that multiple risk factors, including epicardial adipose tissue volume and traditional ASCVD factors are determinants for CABG in men, but type 2 diabetes mellitus was the sole determinant in women. Gender-specific disparities in risk factors of CABG prompt us to evaluate new diagnostic and treatment strategies and to seek underlying mechanisms.

  15. Gender-linked impact of epicardial adipose tissue volume in patients who underwent coronary artery bypass graft surgery or non-coronary valve surgery.

    Science.gov (United States)

    Maimaituxun, Gulinu; Shimabukuro, Michio; Salim, Hotimah Masdan; Tabata, Minoru; Yuji, Daisuke; Morimoto, Yoshihisa; Akasaka, Takeshi; Matsuura, Tomomi; Yagi, Shusuke; Fukuda, Daiju; Yamada, Hirotsugu; Soeki, Takeshi; Sugimoto, Takaki; Tanaka, Masashi; Takanashi, Shuichiro; Sata, Masataka

    2017-01-01

    Traditional and non-traditional risk factors for atherosclerotic cardiovascular disease (ASCVD) are different between men and women. Gender-linked impact of epicardial adipose tissue volume (EATV) in patients undergoing coronary artery bypass grafting (CABG) remains unknown. Gender-linked impact of EATV, abdominal fat distribution and other traditional ASCVD risk factors were compared in 172 patients (men: 115; women: 57) who underwent CABG or non-coronary valvular surgery (non-CABG). In men, EATV, EATV index (EATV/body surface area) and the markers of adiposity such as body mass index, waist circumference and visceral fat area were higher in the CABG group than in the non-CABG group. Traditional ASCVD risk factors were also prevalent in the CABG group. In women, EATV and EATV index were higher in the CABG group, but other adiposity markers were comparable between CABG and non-CABG groups. Multivariate logistic regression analysis showed that in men, CABG was determined by EATV Index and other ASCVD risk factors including hypertension, dyslipidemia, adiponectin, high sensitive C-reactive protein (hsCRP) and type 2 diabetes mellitus (Corrected R2 = 0.262, p EATV Index (Corrected R2 = 0.266, p = 0.005). Our study found that multiple risk factors, including epicardial adipose tissue volume and traditional ASCVD factors are determinants for CABG in men, but type 2 diabetes mellitus was the sole determinant in women. Gender-specific disparities in risk factors of CABG prompt us to evaluate new diagnostic and treatment strategies and to seek underlying mechanisms.

  16. Effect of right ventricular electrode location (outflow tract vs. apex) on mechanical Ventricular synchrony in patients that underwent pacemaker implant therapy

    International Nuclear Information System (INIS)

    Rincon, Oscar S; Saenz, Luis C; Salazar, Gabriel; Hernandez, Edgar

    2008-01-01

    Objective: to assess in depth the effect of ventricular stimulation from the right ventricular outflow tract and the apex on mechanical ventricular synchrony. Materials And Methods: cohort analytical study. 20 patients with indication of definitive pacemaker indication underwent trans thoracic echocardiogram before and after pacemaker implant with electrode implantation in the right ventricular outflow tract and in the apex (10 patients in each group). There was no structural cardiopathy, ejection fraction was ? 50%, QRS and AV conduction were normal. Mechanical ventricular asynchrony (M mode and tissue doppler) and implant and device parameters were evaluated. Statistical Analysis: results are given as mean values, standard deviation or percentages.Continuous variables were compared using Chi-square test and ANOVA. A p <0.05 value was considered statistically significant. Results: in five patients (25%) a pre-implant ventricular asynchrony was found; in seven (70%) ventricular asynchrony post-implant in the right ventricle outflow tract and in 5 (50%) in the apex. Mean interventricular pot-implant delay was 21,6 ms in the right ventricular outflow tract and 11,5 ms in the apex (p = 0,8); mean septal to lateral wall delay was 73 ms in the right ventricular outflow tract and 26 ms in the apex (p = 0,8). QRS post-implant delay was 134 ms in the right ventricular outflow tract and 140 ms in the apex (p = 0,1). No differences between implant parameters and device programming were found. Conclusions: presence of ventricular asynchrony was evidenced in patients with normal QRS and structurally healthy heart. Ventricular stimulation with pacemaker from the apex or the right ventricular outflow tract suggests acute ventricular asynchrony at least in 60% of the cases, without statistically significant difference between both groups.

  17. Phytophthora megakarya and Phytophthora palmivora, Closely Related Causal Agents of Cacao Black Pod Rot, Underwent Increases in Genome Sizes and Gene Numbers by Different Mechanisms

    Science.gov (United States)

    Ali, Shahin S.; Shao, Jonathan; Lary, David J.; Kronmiller, Brent A.; Shen, Danyu; Strem, Mary D.; Amoako-Attah, Ishmael; Akrofi, Andrew Yaw; Begoude, B.A. Didier; ten Hoopen, G. Martijn; Coulibaly, Klotioloma; Kebe, Boubacar Ismaël; Melnick, Rachel L.; Guiltinan, Mark J.; Tyler, Brett M.; Meinhardt, Lyndel W.

    2017-01-01

    Phytophthora megakarya (Pmeg) and Phytophthora palmivora (Ppal) are closely related species causing cacao black pod rot. Although Ppal is a cosmopolitan pathogen, cacao is the only known host of economic importance for Pmeg. Pmeg is more virulent on cacao than Ppal. We sequenced and compared the Pmeg and Ppal genomes and identified virulence-related putative gene models (PGeneM) that may be responsible for their differences in host specificities and virulence. Pmeg and Ppal have estimated genome sizes of 126.88 and 151.23 Mb and PGeneM numbers of 42,036 and 44,327, respectively. The evolutionary histories of Pmeg and Ppal appear quite different. Postspeciation, Ppal underwent whole-genome duplication whereas Pmeg has undergone selective increases in PGeneM numbers, likely through accelerated transposable element-driven duplications. Many PGeneMs in both species failed to match transcripts and may represent pseudogenes or cryptic genetic reservoirs. Pmeg appears to have amplified specific gene families, some of which are virulence-related. Analysis of mycelium, zoospore, and in planta transcriptome expression profiles using neural network self-organizing map analysis generated 24 multivariate and nonlinear self-organizing map classes. Many members of the RxLR, necrosis-inducing phytophthora protein, and pectinase genes families were specifically induced in planta. Pmeg displays a diverse virulence-related gene complement similar in size to and potentially of greater diversity than Ppal but it remains likely that the specific functions of the genes determine each species’ unique characteristics as pathogens. PMID:28186564

  18. Role of radiation in chemical leukemogenesis in mice

    International Nuclear Information System (INIS)

    Kajitani, Takashi; Hamada, Katsutomo; Ito, Takaaki; Yokoro, Kenjiro

    1980-01-01

    Leukemia was induced in adult mice 6 to 8 months of age by the combined use of x-rays and N-nitrosoethylurea (NEU). Changes in thymocytes due to irradiation with x-rays were studied in order to determine the mechanism of leukemogenesis. The incidence of leukemia was 61.3% in mice given sucessive doses of NEU immediately after whole-body irradiation with x-rays and 18.8% in mice given successive doses of NEU 3 months after whole-body irradiation with x-rays. The thymus weight, the thymocyte count, the mitotic index in thymocytes, and the rate of DNA-synthesizing cells in the thymus decreased rapidly in both adult and young adult mice that underwent whole-body irradiation (400 R). The lowest values were observed 3 days after irradiation. The thymus weight and thymocyte count in the irradiated mice returned to within normal range 7 to 8 days after irradiation (the values were almost the same as those before irradiation). Rapid rebound phenomena were observed in the rate of DNA-synthesizing cells and mitotic index in the thymus 5 days after irradiation. The results suggest that there is a close relationship between the incidence of leukemia and thymocyte activity after irradiation with x-rays; that is, there is a large percentage of juvenile cells with energetic proliferation capacity. (Tsunoda, M.)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  20. [Effects of chrysalis oil on learning, memory and oxidative stress in D-galactose-induced ageing model of mice].

    Science.gov (United States)

    Chen, Weiping; Yang, Qiongjie; Wei, Xing

    2013-11-01

    To investigate the effects of chrysalis oil on learning, memory and oxidative stress in D-galactose-induced ageing model of mice. Mice were injected intraperitoneally with D-galactose daily and received chrysalis oil intragastrically simultaneously for 30 d. Then mice underwent space navigation test and spatial probe test, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) contents in mouse brain were measured. Compared to model group, escape latency in mice treated with 6 ml/kg*d chrysalis oil was significantly shorter (Pchrysalis oil were significantly increased (PChrysalis oil treatment (12ml/kg*d) significantly increased SOD and GSH-PX activity and reduced MDA contents in brain of D-galactose-induced aging mice. Chrysalis oil can improve the ability of learning and memory in D-galactose-induced aging mice, and inhibit peroxidation in brain tissue.

  1. The Disability Impact and Associated Cost per Disability in Women Who Underwent Surgical Revision of Transvaginal Mesh Kits for Prolapse Repair.

    Science.gov (United States)

    Javadian, Pouya; Shobeiri, S Abbas

    2017-09-13

    The aim of this study was to investigate disability impact in patients and cost to the families of patients who have had complications of transvaginal prolapse mesh kits and underwent surgical revision. Patients who developed complications of transvaginal mesh kits for prolapse and who had undergone vaginal prolapse mesh surgical revision/removal in 2009 to 2014 at a single institution were identified by Current Procedural Terminology codes. The group was invited to complete a phone survey pertaining to the initial vaginal mesh used for prolapse surgery utilizing Sheehan Disability Scale (scale 0-10) and Years of life Lived with Disability (YLDs) questionnaires. The data collected were used to estimate the disability and cost analysis. We used our data to estimate the economic and quality-of-life impact of vaginal mesh complications on patients in the United States RESULTS: Sixty-two patients (62/198 [31.2%]) were consented to participate and completed the questionnaires by phone. Extremely disabled patients were 18 (29%) of 62 of whole cases, and 5 (8%) of 62 reported that they had no disability after vaginal mesh surgery. The median for overall disability score after vaginal mesh procedure was 8 (which reflects marked disability on a scale of 0-10). The majority of patients missed a median of 12 months of their school or work because of their mesh complications. Thirty-seven (59.6%) of 62 did not improve after mesh removal. Twenty-one (33.9%) of 62 stated that their family income dropped because of productivity loss related to mesh complications. The mean time between vaginal mesh surgery and mesh removal procedure was 4.7 years. Sheehan Disability Scale scores are significantly correlated with YLDs outcomes. Patients' overall disability score showed a significant correlation with YLDs scores (P mesh for prolapse reduction complications had a sustained disability impact that continued despite mesh removal. Likewise, the complications were associated with

  2. KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer.

    Science.gov (United States)

    Sideris, Michail; Moorhead, Jane; Diaz-Cano, Salvador; Bjarnason, Ingvar; Haji, Amyn; Papagrigoriadis, Savvas

    2016-10-01

    Transanal endoscopic microsurgery (TEMS) is emerging as an alternative treatment for rectal cancer Stage I. There remains a risk of local recurrence. The Aim of the study was to study the effect of biomarkers in local recurrence for Stage I rectal cancer following TEMS plus or minus radiotherapy. This is a case control study where we compared 10 early rectal cancers that had recurred, against 19 cases with no recurrence, total 29 patients (age=28.25-86.87, mean age=67.92 years, SD=14.91, Male, N=18, Female, N=11). All patients underwent TEMS for radiological Stage I rectal cancer (yT1N0M0 or yT2N0M0) established with combination of magnetic resonance imaging (MRI) and endorectal ultrasound. We prospectively collected all data on tumour histology, morphological features, as well as follow-up parameters. Molecular analysis was performed to identify their status on BRAF, KRAS, p16 O 6 -methylguanine-DNA methyltransferase (MGMT) and β-catenin. Out of 29 specimens analyzed, 19 were KRAS wild type (65.9%) and 10 mutant (34.5%). Recurrence of the tumour was noted in 10 cases (34.5%) from which 60% were pT1 (N=6) and 40% pT2 (N=4). There was a statistically significant association between KRAS mutant status and local recurrence (N=6, p=0.037). P16 expression greater than 5% (mean=10.8%, min=0, max=95) is linked with earlier recurrence within 11.70 months (N=7, p=0.004). Membranous β-catenin expression (N=12, 48%) was also related with KRAS mutant status (p=0.006) but not with survival (p>0.05). BRAF gene was found to be wild type in all cases tested (N=23). KRAS/p16/β-catenin could be used as a combined biomarker for prediction of local recurrence and stratification of the risk for further surgery. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

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    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets.

    Science.gov (United States)

    Götz, Alexander A; Rozman, Jan; Rödel, Heiko G; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Klingenspor, Martin; Stoeger, Tobias

    2011-09-27

    Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants. Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors

  6. Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets

    Directory of Open Access Journals (Sweden)

    Hrabě de Angelis Martin

    2011-09-01

    Full Text Available Abstract Background Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested. In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP, as a surrogate for ambient/urban particulate air pollutants. Methods Mice were fed a high caloric carbohydrate-rich (CA or a fat-rich (HF diet for six weeks and were compared to mice kept on a purified low fat (LF diet, respectively. Bronchoalveolar lavage (BAL and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. Results and discussion The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. Conclusion The increase in BAL pro-inflammatory factors in high caloric

  7. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage.

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P; Morales-Nebreda, Luisa; Cheng, Yuan; Hogan, Erin; Yeldandi, Anjana; Chi, Monica; Piseaux, Raul; Ridge, Karen; Michael Hart, C; Chandel, Navdeep; Scott Budinger, G R; Kamp, David W

    2016-12-01

    Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Crocidolite asbestos (100µg/50µL), TiO 2 (negative control), bleomycin (0.025 units/50µL), or PBS was instilled intratracheally in 8-10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role

  8. A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

    Science.gov (United States)

    Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

    2013-08-01

    Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

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

    Directory of Open Access Journals (Sweden)

    Chu-Wen Li

    2015-01-01

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

  10. Of mice and men

    DEFF Research Database (Denmark)

    Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan

    2014-01-01

    CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes...

  11. Evaluation of oxidative stress in mice subjected to aerobic exercise.

    Science.gov (United States)

    Lima, Mônica Cruvinel de; Marks, Guido; Silva, Iandara Schettert; Silva, Baldomero Antonio Kato da; Cônsolo, Lourdes Zélia Zanoni; Nogueira, Gabriel Bogalho

    2012-08-01

    To evaluate the influence of aerobic exercise on oxidative stress in mice. The study included twenty female mice Mus musculus-Swiss divided into two groups: sedentary control (GA) and exercise (GB), each containing ten animals. All animals underwent an adaptation period of seven days isolated in individual boxes. After this period, the animals in the exercise group (GB) were trained in angled running wheel with circumference of 25 cm assembled on an articulated axle during five minutes for three consecutive days. On the fourth day, they underwent an exercise program of one session lasting 45 minutes. The evaluation of oxidative stress was performed by determining the levels of malondialhyde derived of lipid peroxidation by the TBA method. The samples were read in a spectrophotometer at 535 nm. No significant difference was observed in the intergroup comparison of MDA levels in the tissues evaluated. A significant difference was observed in the intragroup comparison of MDA levels in the control group (p = 0.0201).The Tukeys' post hoc test indicated significantly lower values of MDA in the smooth muscle in relation to plasma. In the analysis of variance in the exercise group, a significant difference between tissues (p = 0.0009), with significantly lower values in the smooth muscle in relation to plasma (pstress in mice which were undergone a single session of aerobic exercise.

  12. Docetaxel chronopharmacology in mice.

    Science.gov (United States)

    Tampellini, M; Filipski, E; Liu, X H; Lemaigre, G; Li, X M; Vrignaud, P; François, E; Bissery, M C; Lévi, F

    1998-09-01

    Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms

  13. [Facilitation of the retention and acceleration of operant conditioning extinction after cingulate cortex lesions in BALB/c mice].

    Science.gov (United States)

    Destrade, C; Gauthier, M

    1981-12-21

    One week after receiving bilateral electrolytic lesions of the cingulate cortex, BALB/c Mice underwent acquisition, retention and extinction of an appetitive operant-conditioning task in a Skinner box. There was no significant difference between lesioned and control animals in acquisition; however, lesioned mice exhibited improved retention and faster extinction. These results suggest a possible involvement of the cingulate cortex in memory processes.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-15

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

  15. Mice take calculated risks.

    Science.gov (United States)

    Kheifets, Aaron; Gallistel, C R

    2012-05-29

    Animals successfully navigate the world despite having only incomplete information about behaviorally important contingencies. It is an open question to what degree this behavior is driven by estimates of stochastic parameters (brain-constructed models of the experienced world) and to what degree it is directed by reinforcement-driven processes that optimize behavior in the limit without estimating stochastic parameters (model-free adaptation processes, such as associative learning). We find that mice adjust their behavior in response to a change in probability more quickly and abruptly than can be explained by differential reinforcement. Our results imply that mice represent probabilities and perform calculations over them to optimize their behavior, even when the optimization produces negligible material gain.

  16. Milano summer particulate matter (PM10 triggers lung inflammation and extra pulmonary adverse events in mice.

    Directory of Open Access Journals (Sweden)

    Francesca Farina

    Full Text Available Recent studies have suggested a link between particulate matter (PM exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS, cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17 for a putative pro-carcinogenic marker (Cyp1B1 and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1 and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO. Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity

  17. Effect of bite-raised condition on the hippocampal cholinergic system of aged SAMP8 mice.

    Science.gov (United States)

    Katayama, Tasuku; Mori, Daisuke; Miyake, Hidekazu; Fujiwara, Shuu; Ono, Yumie; Takahashi, Toru; Onozuka, Minoru; Kubo, Kin-Ya

    2012-06-27

    Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Epidermal growth factor receptor restoration rescues the fatty liver regeneration in mice.

    Science.gov (United States)

    Zimmers, Teresa A; Jin, Xiaoling; Zhang, Zongxiu; Jiang, Yanlin; Koniaris, Leonidas G

    2017-10-01

    Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. Lean mice and mice made obese through feeding of a high-fat, hypercaloric diet underwent 70 or 80% hepatectomy. After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis, and delayed recovery of liver mass. Increasing liver resection to 80% was associated with mortality of 40% in lean and 80% in obese mice ( P steatosis might promote liver regeneration and survival following hepatic resection or transplantation. Copyright © 2017 the American Physiological Society.

  19. Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

    Science.gov (United States)

    Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

    2018-04-15

    Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

  20. Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

    International Nuclear Information System (INIS)

    Hiyoshi, Kyoko; Ichinose, Takamichi; Sadakane, Kaori; Takano, Hirohisa; Nishikawa, Masataka; Mori, Ikuko; Yanagisawa, Rie; Yoshida, Seiichi; Kumagai, Yoshito; Tomura, Shigeo; Shibamoto, Takayuki

    2005-01-01

    Asian sand dust (ASD) containing sulfate (SO 4 2- ) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO 4 2- toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO 4 2- (ASD-SO 4 ); OVA+ASD; OVA+ASD-SO 4 . ASD or ASD-SO 4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO 4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO 4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO 4 2- was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO 4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils

  1. Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Michael R Wilson

    2010-07-01

    Full Text Available Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO using a mouse model of lipopolysaccharide (LPS-induced pulmonary inflammation.Mice were exposed to 0-500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow.When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40-50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space.Overall, these data confirm some protective role for inhaled CO during pulmonary inflammation, although this required a dose that produced carboxyhemoglobin values close to potentially toxic levels for humans, and increased lung permeability.

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

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    Rafael Almeida-Reis

    2017-01-01

    Full Text Available Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL/6 mice received intratracheal elastase (ELA group or saline (SAL group. One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group. Controls received saline and BbCI (SALBC group. After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

  3. Cardiac autonomic modulation by estrogen in female mice undergoing ambulatory monitoring and in vivo electrophysiologic testing.

    Science.gov (United States)

    Saba, Samir; Shusterman, Vladimir; Usiene, Irmute; London, Barry

    2004-04-01

    Estrogen is an important modulator of cardiovascular risk, but its mechanism of action is not fully understood. We investigated the effect of ovariectomy and its timing on the cardiac electrophysiology in mice. Thirty female mice (age 18.8 +/- 3.1 weeks) underwent in vivo electrophysiologic testing before and after autonomic blockade. Fifteen mice were ovariectomized prepuberty (PRE) and ten postpuberty (POST), 2 weeks prior to electrophysiologic testing. Five age-matched sham-operated female mice (Control) served as controls. A subset of 13 mice (5 PRE, 3 POST, and 5 Controls) underwent 24-hour ambulatory monitoring. With ambulatory monitoring, the average (668 +/- 28 vs 769 +/- 52 b/min, P = 0.008) and minimum (485 +/- 47 vs 587 +/- 53 b/min, P = 0.02) heart rates were significantly slower in the ovariectomized mice (PRE and POST groups) compared to the Control group. At baseline electrophysiologic testing, there were no significant differences among the ovariectomized and intact mice in any of the measured parameters. With autonomic blockade, the Control group had a significantly larger change (delta) in the atrioventricular (AV) nodal Wenckebach (AVW) periodicity (deltaAVW = 11.3 +/- 2.9 vs 2.1 +/- 7.3 ms, P = 0.05) and functional refractory period (deltaFRP = 11.3 +/- 2.1 vs 1.25 +/- 6.8 ms, P = 0.02) compared to the ovariectomized mice. These results were not altered by the time of ovariectomy (PRE vs POST groups). Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.

  4. Experimental study of 99Tcm-HL91 and 99Tcm-MIBI in mice bearing Lewis lung cancer

    International Nuclear Information System (INIS)

    Han Chunqi; Li Yaming; Ren Yangang; Yi Lijie

    2000-01-01

    Objective: To evaluate the ability of detecting lung cancer by 99 Tc m -HL91 and 99 Tc m -MIBI in mice bearing Lewis lung cancer. Methods: Four model mice underwent whole body planar imaging at 2 h, 4 h after injection of 99 Tc m -MIBI; four mice underwent whole body planar imaging at 2 h and 4 h after injection of 99 Tc m -HL91, and the mice of the 99 Tc m -HL91 group were then killed, the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around the tumor, head and chest in whole body planar images, and radioactivity ratios of tumor to head (T/H), chest (T/C) and contralateral limbs (T/L) were calculated. Results: No significant tumor radioactivity in 2 h and 4 h images of 99 Tc m -MIBI mice (T/C: 0.20 +- 0.08 and 0.14 +- 0.07) was found; increased tumor radioactivity was identified in images of 99 Tc m -HL91 mice (T/C: 3.25 +- 1.25 and 2.44 +- 1.07), and there was significant difference (t = 4.8 - 7.5, P 99 Tc m -HL91 in tumor tissue of mice is higher and clearance rate is slower. 99 Tc m -HL91 is a valuable tumor imaging agent for clinical diagnosis for the cancer

  5. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

  6. Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

    Energy Technology Data Exchange (ETDEWEB)

    Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

    2002-04-15

    Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

  7. The Protective Effects of the Supercritical-Carbon Dioxide Fluid Extract of Chrysanthemum indicum against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Modulating Toll-Like Receptor 4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiao-Li Wu

    2014-01-01

    Full Text Available The supercritical-carbon dioxide fluid extract of Chrysanthemum indicum Linné. (CFE has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI induced by lipopolysaccharide (LPS in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1β, and IL-6, inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx. Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.

  8. Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice

    Directory of Open Access Journals (Sweden)

    Yoon-Young Sung

    2017-01-01

    Full Text Available Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET, on airway inflammation in ovalbumin- (OVA- induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3 expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p<0.01, pulmonary eosinophilic infiltration (p<0.05, mucus hypersecretion (p<0.01, and IL-4, IL-5, IL-13, and CCR3 production (p<0.05, as well as IgE levels (p<0.01. IVE and AET increased Foxp3 expression in lungs (p<0.05. IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p<0.05. Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p<0.01. These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

  9. Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.

    Science.gov (United States)

    Rakov, Helena; Engels, Kathrin; Hönes, Georg Sebastian; Strucksberg, Karl-Heinz; Moeller, Lars Christian; Köhrle, Josef; Zwanziger, Denise; Führer, Dagmar

    2016-01-01

    Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver. Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue

  10. Postsurgical food and water consumption, fecal corticosterone metabolites, and behavior assessment as noninvasive measures of pain in vasectomized BALB/c mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Kalliokoski, Otto; Teilmann, Anne C

    2012-01-01

    Recognition of pain and stress is a common challenge when working with laboratory mice. The aim of the current study was to identify noninvasive parameters to assess the severity and duration of possible pain and stress after vasectomy in BALB/c mice. Mice underwent isoflurane anesthesia......-related behaviors, but not FCM, may be useful as noninvasive parameters to assess postoperative pain and stress in vasectomized mice....... group compared with mice given anesthesia only. FCM were elevated the first day after anesthesia in the control mice but not in the vasectomized group. Vasectomy resulted in behavioral changes that were not seen in the group that was anesthetized only. In conclusion, food and water consumption and pain...

  11. Hydrogen-rich saline attenuates anxiety-like behaviors in morphine-withdrawn mice.

    Science.gov (United States)

    Wen, Di; Zhao, Peng; Hui, Rongji; Wang, Jian; Shen, Qianchao; Gong, Miao; Guo, Hongyan; Cong, Bin; Ma, Chunling

    2017-05-15

    Hydrogen therapy is a new medical approach for a wide range of diseases. The effects of hydrogen on central nervous system-related diseases have recently become increasingly appreciated, but little is known about whether hydrogen affects the morphine withdrawal process. This study aims to investigate the potential effects of hydrogen-rich saline (HRS) administration on naloxone-precipitated withdrawal symptoms and morphine withdrawal-induced anxiety-like behaviors. Mice received gradually increasing doses (25-100 mg/kg, i.p.) of morphine over 3 days. In the naloxone-precipitated withdrawal procedure, the mice were treated with three HRS (20 μg/kg, i.p.) injections, and naloxone (1 mg/kg, i.p.) was given 30 min after HRS administration. Body weight, jumping behavior and wet-dog shakes were immediately assessed. In the spontaneous withdrawal procedure, the mice were treated with HRS (20 μg/kg, i.p.) every 8-h. Mice underwent naloxone-precipitated or spontaneous withdrawal were tested for anxiety-like behaviors in the elevated plus-maze (EPM) and light/dark box (L/D box) paradigm, respectively. In addition, the levels of plasma corticosterone were measured. We found that HRS administration significantly reduced body weight loss, jumping behavior and wet-dog shakes in mice underwent naloxone-precipitated withdrawal, and attenuated anxiety-like behaviors in the EPM and L/D box tests after naloxone-precipitated withdrawal or a 2-day spontaneous withdrawal period. Hypo-activity or motor impairment after HRS administration was not observed in the locomotion tests. Furthermore, HRS administration significantly decreased the levels of corticosterone in morphine-withdrawn mice. These are the first findings to indicate that hydrogen might ameliorate withdrawal symptoms and exert an anxiolytic-like effect in morphine-withdrawal mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity.

    Science.gov (United States)

    Dailey, Lea Ann; Hernández-Prieto, Raquel; Casas-Ferreira, Ana Maria; Jones, Marie-Christine; Riffo-Vasquez, Yanira; Rodríguez-Gonzalo, Encarnación; Spina, Domenico; Jones, Stuart A; Smith, Norman W; Forbes, Ben; Page, Clive; Legido-Quigley, Cristina

    2015-02-01

    Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p < 0.05), as well as between nanoparticles of different surface hydrophobicity (p < 0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p < 0.01), CXCL1 levels (p < 0.05) and nanoparticle surface hydrophobicity (p < 0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

  13. Inborn anemias in mice

    International Nuclear Information System (INIS)

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an α-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes

  14. Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice.

    Science.gov (United States)

    Crawford, Robert S; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A; Abularrage, Christopher J; Yoo, Hyung-Jin; Lamuraglia, Glenn M; Watkins, Michael T

    2013-08-01

    We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice

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    Vasquez Elisardo C

    2010-05-01

    Full Text Available Abstract Background The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57 and hypercholesterolemic (ApoE female mice in both normal and ovariectomized conditions. Methods Twenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10-9 to 2 × 10-3 mol/L, acetylcholine (ACh and sodium nitroprusside (SNP (10-10 to 10-3 mol/L were evaluated in the isolated mesenteric arteriolar bed through dose-response curves. Results ACh-induced relaxation was significantly reduced (P 50 (-5.67 ± 0.18 vs. -6.23 ± 0.09 mol/L. Ovariectomy caused a significant impairment in ACh-induced relaxation in the C57 group (maximal response: 61 ± 4% but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 ± 5%. SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice. Conclusion These data show an impairment of endothelial function in the resistance vessels of spontaneously atherosclerotic (ApoE-deficient female mice compared with normal (C57 female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.

  16. Effect of Lowering Asymmetric Dimethylarginine (ADMA on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass

    Directory of Open Access Journals (Sweden)

    Johannes Jacobi

    2014-03-01

    Full Text Available The purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS inhibitor asymmetric dimethylarginine (ADMA and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1, on atherosclerosis in subtotally nephrectomized (SNX ApoE-deficient mice. Male DDAH1 transgenic mice (TG, n = 39 and C57Bl/6J wild-type littermates (WT, n = 27 with or without the deletion of the ApoE gene underwent SNX at the age of eight weeks. Animals were sacrificed at 12 months of age, and blood chemistry, as well as the extent of atherosclerosis within the entire aorta were analyzed. Sham treated (no renal mass reduction ApoE-competent DDAH1 transgenic and wild-type littermates (n = 11 served as a control group. Overexpression of DDAH1 was associated with significantly lower ADMA levels in all treatment groups. Surprisingly, SNX mice did not exhibit higher ADMA levels compared to sham treated control mice. Furthermore, the degree of atherosclerosis in ApoE-deficient mice with SNX was similar in mice with or without overexpression of DDAH1. Overexpression of the ADMA degrading enzyme, DDAH1, did not ameliorate atherosclerosis in ApoE-deficient SNX mice. Furthermore, SNX in mice had no impact on ADMA levels, suggesting a minor role of this molecule in chronic kidney disease (CKD in this mouse model.

  17. Resilience in Aging Mice.

    Science.gov (United States)

    Kirkland, James L; Stout, Michael B; Sierra, Felipe

    2016-11-01

    Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context

  18. Proteomic analysis of skeletal muscle in insulin-resistant mice: response to 6-week aerobic exercise.

    Directory of Open Access Journals (Sweden)

    Hairui Yuan

    Full Text Available Aerobic exercise has beneficial effects on both weight control and skeletal muscle insulin sensitivity through a number of specific signaling proteins. To investigate the targets by which exercise exerts its effects on insulin resistance, an approach of proteomic screen was applied to detect the potential different protein expressions from skeletal muscle of insulin-resistant mice after prolonged aerobic exercise training and their sedentary controls. Eighteen C57BL/6 mice were divided into two groups: 6 mice were fed normal chow (NC and 12 mice were fed high-fat diet (HFD for 10 weeks to produce an IR model. The model group was then subdivided into HFD sedentary control (HC, n = 6 and HFD exercise groups (HE, n = 6. Mice in HE group underwent 6 weeks of treadmill running. After 6 weeks, mice were sacrificed and skeletal muscle was dissected. Total protein (n = 6, each group was extracted and followed by citrate synthase, 2D proteome profile analysis and immunoblot. Fifteen protein spots were altered between the NC and HC groups and 23 protein spots were changed between the HC and HE groups significantly. The results provided an array of changes in protein abundance in exercise-trained skeletal muscle and also provided the basis for a new hypothesis regarding the mechanism of exercise ameliorating insulin resistance.

  19. The carcinogenic effects of fetal and postnatal radiation in female mice

    International Nuclear Information System (INIS)

    Kusama, Tomoko; Yoshizawa, Yasuo

    1982-01-01

    The present study was designed to investigate the carcinogenic effects of fetal and postnatal irradiation in female mice. The C57BL/6J mice were subjected to whole-body exposure to 1-Gy or 4-Gy 137 Cs γ-ray irradiation on the 15th fetal day or the 30th postnatal day. Following this, all mice were observed throughout their respective life spans under conventional rearing conditions. The tumor incidence rate, average latent period and distributions of various tumors were used as the quantitative parameters of radiation-induced carcinogenesis. The following conclusions can be draw: (1) The mean life span of mice that underwent 4-Gy irradiation at the age of 30 days was shorter than that of non-irradiated control mice. (2) In control mice, the tumor incidence was 75.7%. (3) In order to estimate the mean age and tumor incidence, an adjustment for competing death is necessary. (4) The adjusted tumor incidences of thymic lymphoma and breast tumor of the irradiated groups were not different from those of control group. On the other hand, there was a significant difference between the two in the adjusted incidence of reticular tissue neoplasm. (author)

  20. Mice, men and MHC supertypes

    DEFF Research Database (Denmark)

    Lundegaard, Claus

    2010-01-01

    vaccine formulations. Toxoplasma gondii, an intracellular parasite, causes severe neurologic and ocular disease in congenitally infected and immunocompromised individuals. No protective vaccine exists against human toxoplasmosis. However, studies with mice have revealed immunodominant cytotoxic T...

  1. Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

    Science.gov (United States)

    Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

    2017-06-01

    Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

  2. Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

    Science.gov (United States)

    Ibrahim, Osama M. A.; Dogru, Murat; Matsumoto, Yukihiro; Igarashi, Ayako; Kojima, Takashi; Wakamatsu, Tais Hitomi; Inaba, Takaaki; Shimizu, Takahiko; Shimazaki, Jun; Tsubota, Kazuo

    2014-01-01

    Purpose The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse. Methods Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results Corneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice. Conclusions Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations. PMID:25036096

  3. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    International Nuclear Information System (INIS)

    Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

    2013-01-01

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  4. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

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    Linlin Wang

    Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

  5. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Turowska, Agnieszka [sterna biologicals GmbH and Co. KG, Marburg (Germany); Librizzi, Damiano [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Baumgartl, Nadja [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Kuhlmann, Jens; Dicke, Tanja [sterna biologicals GmbH and Co. KG, Marburg (Germany); Merkel, Olivia [Department of Pharmaceutical Sciences, Wayne State University, Detroit (United States); Homburg, Ursula [sterna biologicals GmbH and Co. KG, Marburg (Germany); Höffken, Helmut [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Renz, Harald [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Garn, Holger, E-mail: garn@staff.uni-marburg.de [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany)

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  6. Comportamiento de los pacientesancianosoperados de cirugíacardíaca con circulaciónextracorpórea/ Evolution of elderly patients who underwent cardiac surgery with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Alain Moré Duarte

    2015-10-01

    Full Text Available Introduction: There is a steady increase in the number of elderly patients with severe cardiovascular diseases who require a surgical procedure to recover some quality of life that allows them a socially meaningful existence, despite the risks. Objectives: To analyze the behavior of elderly patients who underwent cardiac surgery with cardiopulmonary bypass. Method: A descriptive, retrospective, cross-sectional study was conducted with patients over 65 years of age who underwent surgery at the Cardiocentro Ernesto Che Guevara, in Santa Clara, from January 2013 to March 2014. Results: In the study, 73.1% of patients were men; and there was a predominance of subjects between 65 and 70 years of age, accounting for 67.3%. Coronary artery bypass graft was the most prevalent type of surgery and had the longest cardiopulmonary bypass times. Hypertension was present in 98.1% of patients. The most frequent postoperative complications were renal dysfunction and severe low cardiac output, with 44.2% and 34.6% respectively. Conclusions: There was a predominance of men, the age group of 65 to 70 years, hypertension, and patients who underwent coronary artery bypass graft with prolonged cardiopulmonary bypass. Renal dysfunction was the most frequent complication.

  7. Anxiolytic effects of orcinol glucoside and orcinol monohydrate in mice.

    Science.gov (United States)

    Wang, Xiaohong; Li, Guiyun; Li, Peng; Huang, Linyuan; Huang, Jianmei; Zhai, Haifeng

    2015-06-01

    Anxiety is a common psychological disorder, often occurring in combination with depression, but therapeutic drugs with high efficacy and safety are lacking. Orcinol glucoside (OG) was recently found to have an antidepressive action. To study the therapeutic potential of OG and orcinol monohydrate (OM) as anxiolytic agents. Anxiolytic effects in mice were measured using the elevated plus-maze, hole-board, and open-field tests. Eight groups of mice were included in each test. Thirty minutes before each test, mice in each group received one oral administration of OG (5, 10, or 20 mg/kg), OM (2.5, 5, or 10 mg/kg), the positive control diazepam (1 or 5 mg/kg), or control vehicle. Each mouse underwent only one test. Uptake of orcinol (5 mg/kg) in the brain was qualitatively detected using the HPLC-MS method. OG (5, 10, and 20 mg/kg) and OM (2.5 and 5 mg/kg) increased the time spent in open arms and the number of entries into open arms in the elevated plus-maze test. OG (5 and 10 mg/kg) and OM (2.5 and 5 mg/kg) increased the number of head-dips in the hole-board test. At all tested doses, OG and OM did not significantly affect the locomotion of mice in the open-field test. Orcinol could be detected in the mouse brain homogenates 30 min after oral OM administration, having confirmed that OM is centrally active. The results demonstrated that OG and OM are anxiolytic agents without sedative effects, indicating their therapeutic potential for anxiety.

  8. Linkage disequilibrium in wild mice.

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    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  9. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

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    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  10. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Science.gov (United States)

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  11. Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

    International Nuclear Information System (INIS)

    Saito-Fujita, Tomoko; Iwakawa, Mayumi; Nakamura, Etsuko; Nakawatari, Miyako; Fujita, Hidetoshi; Moritake, Takashi; Imai, Takashi

    2011-01-01

    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

  12. Voluntary Wheel Running in Mice.

    Science.gov (United States)

    Goh, Jorming; Ladiges, Warren

    2015-12-02

    Voluntary wheel running in the mouse is used to assess physical performance and endurance and to model exercise training as a way to enhance health. Wheel running is a voluntary activity in contrast to other experimental exercise models in mice, which rely on aversive stimuli to force active movement. This protocol consists of allowing mice to run freely on the open surface of a slanted, plastic saucer-shaped wheel placed inside a standard mouse cage. Rotations are electronically transmitted to a USB hub so that frequency and rate of running can be captured via a software program for data storage and analysis for variable time periods. Mice are individually housed so that accurate recordings can be made for each animal. Factors such as mouse strain, gender, age, and individual motivation, which affect running activity, must be considered in the design of experiments using voluntary wheel running. Copyright © 2015 John Wiley & Sons, Inc.

  13. Radiation carcinogenesis in scid mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

    1999-06-01

    Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

  14. Effect of aerobic exercise and fish oil supplements on plasma levels of inflammatory indexes in mice.

    Science.gov (United States)

    Alizadeh, Hamid; Bazgir, Behzad; Daryanoosh, Farhad; Koushki, Maryam; Sobhani, Vahid

    2014-01-01

    Exercise has positive and negative effects on immune system. Herein, we would like to investigate the effects of incremental aerobic training and fish oil supplementation on the plasma levels of CRP, CPK and IL-17 in trained mice. One of the major roles of immune system is to produce soluble or cellular components that provide the immunity against inflammatory agent. The purpose of this study is to investigate distinct and combine effects of incremental aerobic training and fish oil supplement on plasma levels of IL-17, CPK and CRP in trained male mice. Totally, 54 healthy male mice (2 months old, weight= 34±1 grams) were selected. At first 10 mice were killed to determine base line values, the rest of them were randomly divided into four groups, control group (C, n=11), supplement group (S, n=11), training group (T, n=11) and supplement-training group (ST, n=11).The supplement and supplement-training groups were fed with 0.2cc/day fish oil for 8 weeks. Training and supplement-training groups underwent exercise for 5 sessions per week for a period of 8 weeks on animal treadmill. SPSS 16.0 software and multivariate analysis of variance were used for statistical analysis of data Exercise and fish oil supplement lead to a decrease in CRP levels and subsequently causing a reduction in plasma levels of IL-17 and CK in mice (poil can reduce regulate inflammatory response caused by incremental exercise.

  15. Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays

    International Nuclear Information System (INIS)

    Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

    2014-01-01

    The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage. (author)

  16. Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

    Energy Technology Data Exchange (ETDEWEB)

    Groezinger, Gerd, E-mail: gerd.groezinger@med.uni-tuebingen.de; Schmehl, Joerg, E-mail: joerg.schmehl@med.uni-tuebingen.de; Bantleon, Ruediger, E-mail: ruediger.bantleon@med.uni-tuebingen.de; Kehlbach, Rainer, E-mail: rainer.kehlbach@uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Mehra, Tarun, E-mail: tarun.mehra@med.uni-tuebingen.de [University of Tuebingen, Department of Dermatology (Germany); Claussen, Claus, E-mail: gerd.groezinger@med.uni-tuebingen.de; Wiesinger, Benjamin, E-mail: benjamin.wiesinger@med.uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany)

    2012-12-15

    Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, {alpha}-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant. Results: Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 {mu}m{sup 2} [n = 15) in the WT group compared with only 8.4 (*1000 {mu}m{sup 2} [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

  17. Regulatory effects of adenosine A2A receptors on psychomotor ability and mood behavior of mice

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    Li JIANG

    2011-07-01

    Full Text Available Objective To explore the effects of gene knock-out,agonist or inhibitor of adenosine A2A receptor on the locomotor activity,and anxiety-or depression-like behavior of mice.Methods Male C57BL/6 mice,comprising those underwent gene knock-out of adenosine A2A receptor(A2AKO and their wild-type(WT littermates,were assigned into A2AKO group and WT group.Another batch of male C57BL/6,specific-pathogen-free(SPF mice,were assigned into SCH58261 group,CGS21680 group and control group.Mice of aforesaid 3 groups were transperitoneally administered with SCH58261,a specific inhibitor of adenosine A2A receptor at a dose of 2mg/kg,CGS21680,a specific agonist of adenosine A2A receptor at a dose of 0.5mg/kg,and vehicle(0.25ml,comprising DMSO and saline,respectively.Ten minutes after injection,mice of the 3 groups underwent open-field test,elevated plus-maze test and forced swimming test to detect their locomotor activity,anxiety-and depression-like behavior.Results a Compared with WT group,the total movement distance decreased(P 0.05.b Compared with control group,the total movement distance decreased and the stay time in the peripheral area increased significantly in the open field test(P 0.05.Conclusions The agonist of adenosine A2A receptor may depress the spontaneous motility and exploratory behavior,and exacerbate the anxiety and depression,and it simulates the effect induced by knock-out of A2A receptor gene,but it is opposite to the effect induced by A2A receptor inhibitor.

  18. Modified Protein Improves Vitiligo Symptoms in Mice

    Science.gov (United States)

    ... Vitiligo Symptoms in Mice Spotlight on Research Modified Protein Improves Vitiligo Symptoms in Mice By Colleen Labbe, ... D., Ph.D., Rush University. Altering a key protein involved in the development of vitiligo may protect ...

  19. Immunobiology of congenitally athymic-asplenic mice

    International Nuclear Information System (INIS)

    Gershwin, M.E.; Ahmed, A.; Ikeda, R.M.; Shifrine, M.; Wilson, F.

    1978-01-01

    A study has been made of congenitally athymic-asplenic mice obtained by the mating of nude by hereditarily asplenic (Dh/+) mice. The mice survived for up to 9 months, under specific pathogen-free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice were similar to those of their nude and asplenic littermates, there were a number of major immunologic differences. The athymic-asplenic mice appeared more immunologically compromised than nude mice. There was an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. There was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired. (author)

  20. Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis

    Directory of Open Access Journals (Sweden)

    Suassuna José HR

    2011-08-01

    Full Text Available Abstract Background ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1. Methods Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection. Results In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively. Conclusion ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in

  1. Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

    Science.gov (United States)

    DeMambro, Victoria E; Le, Phuong T; Guntur, Anyonya R; Maridas, David E; Canalis, Ernesto; Nagano, Kenichi; Baron, Roland; Clemmons, David R; Rosen, Clifford J

    2015-11-01

    Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21.

  2. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Science.gov (United States)

    Beery, Annaliese K.; Christensen, Jennifer D; Lee, Nicole S.; Blandino, Katrina L.

    2018-01-01

    Social behavior is often described as a unified concept, but highly social (group-living) species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex) during extended choice tests, although short-term preferences are not known. Mice (Mus musculus) are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT) typically used in mice (short, no direct contact), and the partner preference test (PPT) used in voles (long, direct contact). A subset of voles also underwent a PPT using barriers (long, no direct contact). In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of selective social

  3. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Directory of Open Access Journals (Sweden)

    Annaliese K. Beery

    2018-03-01

    Full Text Available Social behavior is often described as a unified concept, but highly social (group-living species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex during extended choice tests, although short-term preferences are not known. Mice (Mus musculus are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT typically used in mice (short, no direct contact, and the partner preference test (PPT used in voles (long, direct contact. A subset of voles also underwent a PPT using barriers (long, no direct contact. In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of

  4. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

    Directory of Open Access Journals (Sweden)

    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  5. Cassava is not a goitrogen in mice

    International Nuclear Information System (INIS)

    Hershman, J.M.; Pekary, A.E.; Sugawara, M.; Adler, M.; Turner, L.; Demetriou, J.A.; Hershman, J.D.

    1985-01-01

    To examine the effect of cassava on the thyroid function of mice, the authors fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [ 125 I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5'-monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5'-monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man

  6. Compensatory eye movements in mice

    NARCIS (Netherlands)

    A.M. van Alphen (Arjan)

    2002-01-01

    textabstractThis thesis will address the generation of compensatory eye movements in naturally mutated or genetically modified mice. The reason for generating compensatory eye movements is solely related to the requirements for good vision. In a subject moving through its environment the projection

  7. Transplacental arsenic carcinogenesis in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

  8. A novel platelet activating factor receptor antagonist reduces cell infiltration and expression of inflammatory mediators in mice exposed to desiccating conditions after PRK.

    Science.gov (United States)

    Esquenazi, Salomon; He, Jiucheng; Li, Na; Bazan, Nicolas G; Esquenazi, Isi; Bazan, Haydee E P

    2009-01-01

    To study the contribution of a novel PAF receptor antagonist LAU-0901 in the modulation of the increased inflammatory response in mice exposed to dessicating conditions (DE) after PRK. Eighty 13-14 week old female Balb/C mice were used. They were divided into two groups: One group was treated with LAU-0901 topical drops. The other group was treated with vehicle. In each group ten mice served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided in two additional groups: ten mice remained under normal conditions (NC) and the other ten were exposed to DE. After 1 week all animals underwent in vivo confocal microscopy, immunostaining and western blotting analysis. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-090). Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.

  9. Cardiac dysfunction in pneumovirus-induced lung injury in mice

    NARCIS (Netherlands)

    Bem, Reinout A.; van den Berg, Elske; Suidgeest, Ernst; van der Weerd, Louise; van Woensel, Job B. M.; Grotenhuis, Heynric B.

    2013-01-01

    To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice. Experimental animal study. Animal laboratory. C57Bl/6 mice. Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice. Pneumonia virus of mice-infected mice were

  10. Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

    Science.gov (United States)

    Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

    2012-09-01

    Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

  11. Low-Level Laser and Light-Emitting Diode Therapy for Pain Control in Hyperglycemic and Normoglycemic Patients Who Underwent Coronary Bypass Surgery with Internal Mammary Artery Grafts: A Randomized, Double-Blind Study with Follow-Up.

    Science.gov (United States)

    Lima, Andréa Conceição Gomes; Fernandes, Gilderlene Alves; Gonzaga, Isabel Clarisse; de Barros Araújo, Raimundo; de Oliveira, Rauirys Alencar; Nicolau, Renata Amadei

    2016-06-01

    This study aimed to evaluate the efficacy of low-level laser therapy (LLLT) and light-emitting diodes (LEDs) for reducing pain in hyperglycemic and normoglycemic patients who underwent coronary artery bypass surgery with internal mammary artery grafts. This study was conducted on 120 volunteers who underwent elective coronary artery bypass graft (CABG) surgery. The volunteers were randomly allocated to four different groups of equal size (n = 30): control, placebo, LLLT [λ = 640 nm and spatial average energy fluence (SAEF) = 1.06 J/cm(2)], and LED (λ = 660 ± 20 nm and SAEF = 0.24 J/cm(2)). Participants were also divided into hyperglycemic and normoglycemic subgroups, according to their fasting blood glucose test result before surgery. The outcome assessed was pain during coughing by a visual analog scale (VAS) and the McGill Pain Questionnaire. The patients were followed for 1 month after the surgery. The LLLT and LED groups showed a greater decrease in pain, with similar results, as indicated by both the VAS and the McGill questionnaire (p ≤ 0.05), on the 6th and 8th postoperative day compared with the placebo and control groups. The outcomes were also similar between hyperglycemic and normoglycemic patients. One month after the surgery, almost no individual reported pain during coughing. LLLT and LED had similar analgesic effects in hyperglycemic and normoglycemic patients, better than placebo and control groups.

  12. Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.

    Science.gov (United States)

    Tanaka, Nobumichi; Asakawa, Isao; Fujimoto, Kiyohide; Anai, Satoshi; Hirayama, Akihide; Hasegawa, Masatoshi; Konishi, Noboru; Hirao, Yoshihiko

    2012-09-14

    To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer. We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone. Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce. Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

  13. MAUS: MICE Analysis User Software

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) has developed the MICE Analysis User Software (MAUS) to simulate and analyse experimental data. It serves as the primary codebase for the experiment, providing for online data quality checks and offline batch simulation and reconstruction. The code is structured in a Map-Reduce framework to allow parallelization whether on a personal machine or in the control room. Various software engineering practices from industry are also used to ensure correct and maintainable physics code, which include unit, functional and integration tests, continuous integration and load testing, code reviews, and distributed version control systems. Lastly, there are various small design decisions like using JSON as the data structure, using SWIG to allow developers to write components in either Python or C++, or using the SCons python-based build system that may be of interest to other experiments.

  14. Progress of MICE RFCC Module

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A. B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

    2012-05-20

    Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

  15. Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

    Science.gov (United States)

    Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

    2018-02-20

    Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of

  16. The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

    Science.gov (United States)

    Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

    2016-08-01

    Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Standardization of a spinal cord lesion model and neurologic evaluation using mice

    Science.gov (United States)

    Borges, Paulo Alvim; Cristante, Alexandre Fogaça; de Barros-Filho, Tarcísio Eloy Pessoa; Natalino, Renato Jose Mendonça; dos Santos, Gustavo Bispo; Marcon, Raphael Marcus

    2018-01-01

    OBJECTIVE: To standardize a spinal cord lesion mouse model. METHODS: Thirty BALB/c mice were divided into five groups: four experimental groups and one control group (sham). The experimental groups were subjected to spinal cord lesion by a weight drop from different heights after laminectomy whereas the sham group only underwent laminectomy. Mice were observed for six weeks, and functional behavior scales were applied. The mice were then euthanized, and histological investigations were performed to confirm and score spinal cord lesion. The findings were evaluated to prove whether the method of administering spinal cord lesion was effective and different among the groups. Additionally, we correlated the results of the functional scales with the results from the histology evaluations to identify which scale is more reliable. RESULTS: One mouse presented autophagia, and six mice died during the experiment. Because four of the mice that died were in Group 5, Group 5 was excluded from the study. All the functional scales assessed proved to be significantly different from each other, and mice presented functional evolution during the experiment. Spinal cord lesion was confirmed by histology, and the results showed a high correlation between the Basso, Beattie, Bresnahan Locomotor Rating Scale and the Basso Mouse Scale. The mouse function scale showed a moderate to high correlation with the histological findings, and the horizontal ladder test had a high correlation with neurologic degeneration but no correlation with the other histological parameters evaluated. CONCLUSION: This spinal cord lesion mouse model proved to be effective and reliable with exception of lesions caused by a 10-g drop from 50 mm, which resulted in unacceptable mortality. The Basso, Beattie, Bresnahan Locomotor Rating Scale and Basso Mouse Scale are the most reliable functional assessments, and but the horizontal ladder test is not recommended. PMID:29561931

  18. Histone Acetylation in Microglia Contributes to Exercise-Induced Hypoalgesia in Neuropathic Pain Model Mice.

    Science.gov (United States)

    Kami, Katsuya; Taguchi, Satoru; Tajima, Fumihiro; Senba, Emiko

    2016-05-01

    Physical exercise can attenuate neuropathic pain (NPP), but the exact mechanism underlying exercise-induced hypoalgesia (EIH) remains unclear. Recent studies have shown that histone hyperacetylation via pharmacological inhibition of histone deacetylases in the spinal cord attenuates NPP, and that histone acetylation may lead to the production of analgesic factors including interleukin 10. We intended to clarify whether histone acetylation in microglia in the spinal dorsal horn contributes to EIH in NPP model mice. C57BL/6J mice underwent partial sciatic nerve ligation (PSL) and PSL- and sham-runner mice ran on a treadmill at a speed of 7 m/min for 60 min/d, 5 days per week, from 2 days after the surgery. PSL-sedentary mice developed mechanical allodynia and heat hyperalgesia, but such behaviors were significantly attenuated in PSL-runner mice. In immunofluorescence analysis, PSL surgery markedly increased the number of histone deacetylase 1-positive/CD11b-positive microglia in the ipsilateral superficial dorsal horn, and they were significantly decreased by treadmill-running. Moreover, the number of microglia with nuclear expression of acetylated H3K9 in the ipsilateral superficial dorsal horn was maintained at low levels in PSL-sedentary mice, but running exercise significantly increased them. Therefore, we conclude that the epigenetic modification that causes hyperacetylation of H3K9 in activated microglia may play a role in producing EIH. This article presents the importance of epigenetic modification in microglia in producing EIH. The current research is not only helpful for developing novel nonpharmacological therapy for NPP, but will also enhance our understanding of the mechanisms and availability of exercise in our daily life. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  19. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

    Science.gov (United States)

    Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

    2018-05-03

    Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

  20. TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling.

    Science.gov (United States)

    Ishizuka, Y; Shibukawa, Y; Nagayama, M; Decker, R; Kinumatsu, T; Saito, A; Pacifici, M; Koyama, E

    2014-03-01

    The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by--and possibly attributable to--altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.

  1. EFFECTS OF RUN TRAINING ON BONE DEVELOPMENT AND BONE MINERALIZATION IN GROWING MICE

    Directory of Open Access Journals (Sweden)

    B Gönül

    2011-06-01

    Full Text Available We planned to study the body weights, bone sizes and bone mineral (Ca, Mg, Zn contents of growing mice subjected to treadmill training. Twelve 4-week-old male Swiss Albino mice were divided into sedentary and exercise groups. The mice were trained by running exercise on a flat bed treadmill with 15 m/min, 30 min/day motion, throughout 5 days per week, for 12 weeks. The body weight of animals, and length, fat-free dry weight and Ca, Mg, and Zn contents of bones were measured in both groups. Body weights of animals, and lengths and wet and dry weights of the femur and the tibia were significantly higher in the exercised group. Also, the Zn, Mg and Ca mineral contents of bones in the group that underwent exercise were higher than in the other group. Running exercise with a flat bed treadmill performed by the growing mice is an effective exercise mode, especially for bone morphology.

  2. Effects of pre-natal X-ray exposure on learning behaviour of mice

    International Nuclear Information System (INIS)

    Frank, P.; Faber, U.; Budny, T.

    1983-01-01

    The authors investigated whether prenatal X-raying affects the learning behaviour of mice. For this purpose they irradiated mice of strain C57BL/6Ffm with 130 r at different points of the fetal phase. Unirradiated mice served as controls. The animals underwent two learning test series of 14 days each teaching them optical signs. The results of the test series show a distinctly inferior learning ability in the animals exposed to pre-natal irradiation as compared to unirradiated controls. The extent of the reduction of the learning ability depends on the stage of the pregnancy at the time of X-ray exposure. The greatest difference as compared to non-irradiated mice occurred in the animals irradiated at the earliest stage (13th/14th day of pregnancy). The results of the other test groups (15th/16th and 17th/18th day of pregnancy) exhibited less distinct, but still significant differences to the controls. Exposure at the latest period (17th/18th day) coincided with the smallest difference. (orig./MG) [de

  3. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Radhika V Seimon

    Full Text Available Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change ÷ [(total energy intake of mice on CD or ID-(total average energy intake of controls]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05. There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01. Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative

  4. Transgenic Expression of Dspp Partially Rescued the Long Bone Defects of Dmp1-null Mice

    Science.gov (United States)

    Jani, Priyam H.; Gibson, Monica P.; Liu, Chao; Zhang, Hua; Wang, Xiaofang; Lu, Yongbo; Qin, Chunlin

    2016-01-01

    Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that

  5. Resolvin D1 promotes corneal epithelial wound healing and restoration of mechanical sensation in diabetic mice.

    Science.gov (United States)

    Zhang, Zhenzhen; Hu, Xiaoli; Qi, Xia; Di, Guohu; Zhang, Yangyang; Wang, Qian; Zhou, Qingjun

    2018-01-01

    To investigate the effect and mechanism of proresolving lipid mediator resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical sensation in diabetic mice. Type 1 diabetes was induced in mice with intraperitoneal streptozocin injections. The healthy and diabetic mice underwent removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice. Regeneration of the corneal epithelium and nerves was observed with sodium fluorescein staining and whole-mount anti-β3-tubulin fluorescence staining. The inflammatory response level was measured with hematoxylin and eosin staining (inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity, and fluorescence staining (macrophage content). The reactive oxygen species (ROS) and glutathione (GSH) levels were examined with incubation with fluorescent probes, and oxidative stress-related protein expression levels were evaluated with fluorescence staining and western blotting. Topical application of RvD1 promoted regeneration of the corneal epithelium in diabetic mice, accompanied by the reactivation of signaling and inflammation resolution related to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4 expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE signaling pathway that was impaired in the corneal epithelium in the diabetic mice. More interestingly, topical application of RvD1 promoted regeneration of corneal nerves and completely restored impaired mechanical sensitivity of the cornea in diabetic mice. In addition, the promotion of corneal epithelial wound healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4. Topical application of RvD1 promotes corneal epithelial wound

  6. Clinical observation of the adverse drug reactions caused by non-ionic iodinated contrast media: results from 109,255 cases who underwent enhanced CT examination in Chongqing, China.

    Science.gov (United States)

    Li, X; Chen, J; Zhang, L; Liu, H; Wang, S; Chen, X; Fang, J; Wang, S; Zhang, W

    2015-03-01

    To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40-49 years (204 cases, 0.43%; p contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably.

  7. Changes in intensity of neurotic symptoms associated with reduction of suicidal ideation in patients who underwent psychotherapy in the day hospital for the treatment of neurotic and behavioral disorders.

    Science.gov (United States)

    Rodziński, Paweł; Rutkowski, Krzysztof; Murzyn, Agnieszka; Sobański, Jerzy A; Cyranka, Katarzyna; Dembińska, Edyta; Grządziel, Karolina; Klasa, Katarzyna; Mielimąka, Michał; Müldner-Nieckowski, Łukasz; Smiatek-Mazgaj, Bogna

    2017-06-18

    Analysis of associations between changes in the intensity of neurotic symptoms and reduction of suicidal ideation (SI) or lack of SI reduction, in patients who underwent a course of intensive psychotherapy conducted in integrative approach with predominance of psychodynamic approach in a day hospital. Symptom Checklist KO"O" and Life Inventory completed by 461 women and 219 men treated in the psychotherapeutic day hospital due to neurotic, behavioral or personality disorders between 2005-2013. During the qualification for the therapy 134 women and 80 men reported SI, of whom 84.3% and 77.5% respectively improved. The reduction of neurotic symptoms intensity was greater in patients of both genders who improved in terms of SI than in those who did not. This referred to global intensity of neurotic symptoms (OWK coefficient) in both genders (ppsychotherapy as a treatment method that leads to improvement in terms of both SI and neurotic symptoms. This suggests that the applied therapy may be effective in preventing suicidality in this group of patients. The observed associations also point in favor of hypothesis on similarities in etiopathogenesis of and partly identical personality-related factors predisposing to SI and neurotic disorders.

  8. [The Effects of Smart Program for Patients Who Underwent Percutaneous Coronary Intervention (SP-PCI) on Disease-Related Knowledge, Health Behavior, and Quality of Life: A Non-Randomized Controlled Trial].

    Science.gov (United States)

    Lee, Jueun; Lee, Haejung

    2017-12-01

    To identify the effects of a smart program for the patients who underwent percutaneous coronary intervention (SP-PCI) on coronary disease-related knowledge, health behaviors, and quality of life. A nonequivalent control group with a non-synchronized design was utilized and 48 participants (experimental=22, control=26) were recruited from a university hospital in Gyeongsang area from May to December, 2016. The 12-week SP-PCI consisted of self-study of health information using smart phone applications (1/week), walking exercise (>5/week) using smart band, feedback using Kakao talk (2/week), and telephone counseling (1/week). Patients in the control group received usual care from their primary health care providers and a brief health education with basic self-management brochure after the PCI. Data were analyzed using the SPSS 21.0 program through descriptive statistics, χ² test, and t-test. After the 12-week SP-PCI, the experimental group showed higher levels of coronary disease-related knowledge (t=2.43, p=.019), heart-related health behaviors (t=5.96, pPCI provided easy access and cost-effective intervention for patients after PCI and improved their knowledge of the disease, performance of health behaviors, and quality of life. Further study with a wider population is needed to evaluate the effects of SP-PCI on disease recurrence and quality of life for patients after PCI. © 2017 Korean Society of Nursing Science

  9. Management of difficult airway in intratracheal tumor surgery

    Directory of Open Access Journals (Sweden)

    Agarwal Surendra K

    2005-06-01

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

  10. 239Pu metabolism in the blood after its intratracheal administration

    International Nuclear Information System (INIS)

    Buldakov, L.A.; Khalturin, G.V.; Demina, G.A.

    1979-01-01

    The kinetics of the resorbed from the lungs plutonium metabolism and the forms of its presence in the blood as well as the dynamics of its deposit in the organs of secondary deposition (liver, skeleton) were studied in experiment with female rats. It was shown (gel-filtration method) that plutonium is present in blood serum in various physico-chemical forms: bound with macroglobulin, γ-globulin and albumin-transferrin fractions of proteins and not bound with proteins; this or that form of plutonium may dominate in time (4 min-64 days)

  11. Impaired Leptomeningeal Collateral Flow Contributes to the Poor Outcome following Experimental Stroke in the Type 2 Diabetic Mice

    Science.gov (United States)

    Akamatsu, Yosuke; Nishijima, Yasuo; Lee, Chih Cheng; Yang, Shih Yen; Shi, Lei; An, Lin; Wang, Ruikang K.; Tominaga, Teiji

    2015-01-01

    Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects. PMID:25740515

  12. Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice.

    Science.gov (United States)

    Groves, Natalie J; Zhou, Mei; Jhaveri, Dhanisha J; McGrath, John J; Burne, Thomas H J

    2017-12-01

    Vitamin D deficiency is prevalent in adults throughout the world. Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality; they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The main aim of this study was to determine if AVD deficiency would exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6 mice. Ten-week old male BALB/c and C57BL/6 mice were fed a control or vitamin D deficient diet for 10 weeks, and the mice were further separated into one of two groups for social treatment, either Separated (SEP) or Social Defeat (DEF). SEP mice were placed two per cage with a perforated Plexiglas divider, whereas the DEF mice underwent 10days of social defeat prior to behavioural testing. We found that AVD-deficient mice were more vulnerable to the effects of social stress using a social avoidance test, and this was dependent on strain. These results support the hypothesis that vitamin D deficiency may exacerbate behavioural outcomes in mice vulnerable to stress, a finding that can help guide future studies. Importantly, these discoveries support the epidemiological link between vitamin D deficiency and neuropsychiatric and neurodegenerative disorders; and has provided clues that can guide future studies related to unravelling the mechanisms of action linking adult vitamin D deficiency and adverse brain related outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  13. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

    Science.gov (United States)

    Fritz, Brandon M; Boehm, Stephen L

    2014-12-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Dim light at night increases depressive-like responses in male C3H/HeNHsd mice.

    Science.gov (United States)

    Fonken, Laura K; Nelson, Randy J

    2013-04-15

    Daily patterns of light exposure have become increasingly variable since the widespread adoption of electrical lighting during the 20th century. Seasonal fluctuations in light exposure, shift-work, and transmeridian travel are all associated with alterations in mood. These studies implicate fluctuations in environmental lighting in the development of depressive disorders. Here we argue that exposure to light at night (LAN) may be causally linked to depression. Male C3H/HeNHsd mice, which produce nocturnal melatonin, were housed in either a standard light/dark (LD) cycle or exposed to nightly dim (5 lux) LAN (dLAN). After four weeks in lighting conditions mice underwent behavioral testing and hippocampal tissue was collected at the termination of the study for qPCR. Here were report that mice exposed to dLAN increase depressive-like responses in both a sucrose anhedonia and forced swim test. In contrast to findings in diurnal grass rats, dLAN mice perform comparably to mice housed under dark nights in a hippocampus-dependent learning and memory task. TNFα and IL1β gene expression do not differ between groups, demonstrating that changes in these pro-inflammatory cytokines do not mediate dLAN induced depressive-like responses in mice. BDNF expression is reduced in the hippocampus of mice exposed to dLAN. These results indicate that low levels of LAN can alter mood in mice. This study along with previous work implicates LAN as a potential factor contributing to depression. Further understanding of the mechanisms through which LAN contributes to changes in mood is important for characterizing and treating depressive disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Therapeutic cloning in individual parkinsonian mice

    Science.gov (United States)

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2009-01-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  16. Transplantation of canine osteosarcoma into nude mice

    International Nuclear Information System (INIS)

    Shifrine, M.; Taylor, N.; Holloway, G.; Arnstein, P.R.; Chrisp, C.; Pool, R.; Whaley, C.

    1975-01-01

    Osteosarcomas from dogs were inoculated subcutaneously into mice. Sixty days later six mice had tumors that gradually increased in size. All tumors were undifferentiated sarcomas. Karyotypes of osteosarcomas grown in tissue culture and of tumors from mice inoculated with the culture were similar with two marker chromosomes. It was thus shown that radioinduced osteosarcomas can be cultivated in tissue culture while retaining their marker chromosomes and malignancy

  17. Zinc metabolism in genetically obese mice

    International Nuclear Information System (INIS)

    Kennedy, M.L.; Failla, M.L.

    1986-01-01

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65 Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65 Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65 Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65 Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

  18. Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

    Science.gov (United States)

    Benice, Ted S.; Raber, Jacob

    2009-01-01

    Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to…

  19. Incidence of postoperative implant-related bacterial endocarditis in dogs that underwent trans-catheter embolization of a patent ductus arteriosus without intra- and post-procedural prophylactic antibiotics.

    Science.gov (United States)

    Szatmári, Viktor

    2017-08-01

    Intra- and post-procedural prophylactic antibiotics are routinely administered by veterinary cardiologists to dogs that undergo trans-catheter embolization of a patent ductus arteriosus for prevention of implant-related infective endocarditis. The hypothesis of our study was that primary antibiotic prophylaxis is not necessary to prevent bacterial endocarditis. In this retrospective case series 54 client-owned dogs that underwent trans-catheter occlusion of a patent ductus arteriosus in a single tertiary veterinary referral center between 2004 and 2016 were evaluated. Follow-up information was gained by telephone interviews with the owners or the referring veterinarians, or from the digital archives of the authors' clinic. Inclusion criteria were that at least one metal implant (a coil or an Amplatz duct occluder) had to be delivered in the ductal ampulla, no local or systemic antibiotics were given on the day of the intervention or the week thereafter, at least 3 months of postoperative follow-up information was available, and the author was performing the procedure either as the primary or as the supervising cardiology specialist. None of the 54 dogs developed infective endocarditis in the postoperative 3 months. A study describing a similar population reports 2 of the included 47 dogs having developed infective endocarditis in the postoperative period despite the administration of intra- and post-procedural prophylactic antibiotics. We conclude that intra- and post-procedural antibiotic prophylaxis is not justified in dogs that undergo trans-catheter closure of a patent ductus arteriosus. Proper surgical technique and the use of new sterile catheters and implants are sufficient to prevent infective endocarditis in these dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Assessment of peri- and postoperative complications and Karnofsky-performance status in head and neck cancer patients after radiation or chemoradiation that underwent surgery with regional or free-flap reconstruction for salvage, palliation, or to improve function

    Directory of Open Access Journals (Sweden)

    Sertel Serkan

    2011-09-01

    Full Text Available Abstract Background Surgery after (chemoradiation (RCTX/RTX is felt to be plagued with a high incidence of wound healing complications reported to be as high as 70%. The additional use of vascularized flaps may help to decrease this high rate of complications. Therefore, we examined within a retrospective single-institutional study the peri--and postoperative complications in patients who underwent surgery for salvage, palliation or functional rehabilitation after (chemoradiation with regional and free flaps. As a second study end point the Karnofsky performance status (KPS was determined preoperatively and 3 months postoperatively to assess the impact of such extensive procedures on the overall performance status of this heavily pretreated patient population. Findings 21 patients were treated between 2005 and 2010 in a single institution (17 male, 4 female for salvage (10/21, palliation (4/21, or functional rehabilitation (7/21. Overall 23 flaps were performed of which 8 were free flaps. Major recipient site complications were observed in only 4 pts. (19% (1 postoperative haemorrhage, 1 partial flap loss, 2 fistulas and major donor site complications in 1 pt (wound dehiscence. Also 2 minor donor site complications were observed. The overall complication rate was 33%. There was no free flap loss. Assessment of pre- and postoperative KPS revealed improvement in 13 out of 21 patients (62%. A decline of KPS was noted in only one patient. Conclusions We conclude that within this (chemoradiated patient population surgical interventions for salvage, palliation or improve function can be safely performed once vascularised grafts are used.

  1. Diagnostic Accuracy of Detecting Hashimoto's Thyroiditis in Thyroid Cancer Patients Who Underwent Thyroid Surgery: Comparison of Ultrasonography, Positron Emission Tomography/CT, Contrast Enhanced CT, and Anti-Thyroid Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Gyun; Lee, Tae Hyun; Park, Dong Hee; Nam, Sang Been [Dept. of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2012-11-15

    To compare the diagnostic accuracy of ultrasonography (US), F18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), contrast enhanced CT (CECT), serum anti-thyroid antibody for detecting Hashimoto's thyroiditis in thyroid cancer patients who underwent neck surgery. A total of 150 patients with suspicious for thyroid cancer, who had previously undergone US guided needle aspiration of thyroid, were evaluated with the use of US, PET/CT, CECT and serum anti-thyroid antibody. The four studies were performed within two months before neck surgery. Hashimoto's thyroiditis was confirmed by histopathological results. The diagnostic accuracy of US, PET/CT, CECT and serum anti-thyroid antibody were calculated statistically. Hashimoto's thyroiditis was diagnosed in 51 out of the 150 patients, following neck surgery. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US were 76.5%, 92.9%, 84.8%, 88.5%, and 87.3%, respectively. The corresponding values of PET/CT were 37.3%, 96.0%, 82.6%, 74.8%, and 76.0%, and CECT were 62.7%, 89.9%, 76.2%, 82.4%, and 80.7%, and serum anti-thyroid antibody level were 90.2%, 93.9%, 88.5%, 94.9%, and 92.7%, respectively. McNemar test revealed significant difference among PET/CT and others, but no significant differences among US, CECT and serum anti-thyroid antibody. Overall, serum anti-thyroid antibody showed most accurate diagnostic performance. In detecting Hashimoto's thyroiditis, serum anti-thyroid antibody showed higher diagnostic accuracy than others. US also showed relatively high diagnostic accuracy.

  2. Diagnostic Accuracy of Detecting Hashimoto's Thyroiditis in Thyroid Cancer Patients Who Underwent Thyroid Surgery: Comparison of Ultrasonography, Positron Emission Tomography/CT, Contrast Enhanced CT, and Anti-Thyroid Antibody

    International Nuclear Information System (INIS)

    Kim, Young Gyun; Lee, Tae Hyun; Park, Dong Hee; Nam, Sang Been

    2012-01-01

    To compare the diagnostic accuracy of ultrasonography (US), F18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), contrast enhanced CT (CECT), serum anti-thyroid antibody for detecting Hashimoto's thyroiditis in thyroid cancer patients who underwent neck surgery. A total of 150 patients with suspicious for thyroid cancer, who had previously undergone US guided needle aspiration of thyroid, were evaluated with the use of US, PET/CT, CECT and serum anti-thyroid antibody. The four studies were performed within two months before neck surgery. Hashimoto's thyroiditis was confirmed by histopathological results. The diagnostic accuracy of US, PET/CT, CECT and serum anti-thyroid antibody were calculated statistically. Hashimoto's thyroiditis was diagnosed in 51 out of the 150 patients, following neck surgery. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US were 76.5%, 92.9%, 84.8%, 88.5%, and 87.3%, respectively. The corresponding values of PET/CT were 37.3%, 96.0%, 82.6%, 74.8%, and 76.0%, and CECT were 62.7%, 89.9%, 76.2%, 82.4%, and 80.7%, and serum anti-thyroid antibody level were 90.2%, 93.9%, 88.5%, 94.9%, and 92.7%, respectively. McNemar test revealed significant difference among PET/CT and others, but no significant differences among US, CECT and serum anti-thyroid antibody. Overall, serum anti-thyroid antibody showed most accurate diagnostic performance. In detecting Hashimoto's thyroiditis, serum anti-thyroid antibody showed higher diagnostic accuracy than others. US also showed relatively high diagnostic accuracy.

  3. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss

    2016-01-01

    , a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface...

  4. Dietary fish oil, and to a lesser extent the fat-1 transgene, increases astrocyte activation in response to intracerebroventricular amyloid-β 1-40 in mice.

    Science.gov (United States)

    Hopperton, Kathryn E; James, Nicholas C E; Mohammad, Dana; Irfan, Maha; Bazinet, Richard P

    2017-11-07

    Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer's disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear. Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques. GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals. Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.

  5. Probabilistic numerical discrimination in mice.

    Science.gov (United States)

    Berkay, Dilara; Çavdaroğlu, Bilgehan; Balcı, Fuat

    2016-03-01

    Previous studies showed that both human and non-human animals can discriminate between different quantities (i.e., time intervals, numerosities) with a limited level of precision due to their endogenous/representational uncertainty. In addition, other studies have shown that subjects can modulate their temporal categorization responses adaptively by incorporating information gathered regarding probabilistic contingencies into their time-based decisions. Despite the psychophysical similarities between the interval timing and nonverbal counting functions, the sensitivity of count-based decisions to probabilistic information remains an unanswered question. In the current study, we investigated whether exogenous probabilistic information can be integrated into numerosity-based judgments by mice. In the task employed in this study, reward was presented either after few (i.e., 10) or many (i.e., 20) lever presses, the last of which had to be emitted on the lever associated with the corresponding trial type. In order to investigate the effect of probabilistic information on performance in this task, we manipulated the relative frequency of different trial types across different experimental conditions. We evaluated the behavioral performance of the animals under models that differed in terms of their assumptions regarding the cost of responding (e.g., logarithmically increasing vs. no response cost). Our results showed for the first time that mice could adaptively modulate their count-based decisions based on the experienced probabilistic contingencies in directions predicted by optimality.

  6. AGONISTIC BEHAVIOR OF LABORATORY MICE

    Directory of Open Access Journals (Sweden)

    D. Cinghiţă

    2005-01-01

    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  7. Mice embryology: a microscopic overview.

    Science.gov (United States)

    Salvadori, Maria Letícia Baptista; Lessa, Thais Borges; Russo, Fabiele Baldino; Fernandes, Renata Avancini; Kfoury, José Roberto; Braga, Patricia Cristina Baleeiro Beltrão; Miglino, Maria Angélica

    2012-10-01

    In this work, we studied the embryology of mice of 12, 14, and 18 days of gestation by gross observation, light microscopy, and scanning electron microscopy. Grossly, the embryos of 12 days were observed in C-shaped region of the brain, eye pigmentation of the retina, first, second, and third pharyngeal arches gill pit nasal region on the fourth ventricle brain, cervical curvature, heart, liver, limb bud thoracic, spinal cord, tail, umbilical cord, and place of the mesonephric ridge. Microscopically, the liver, cardiovascular system and spinal cord were observed. In the embryo of 14 days, we observed structures that make up the liver and heart. At 18 days of gestation fetuses, it was noted the presence of eyes, mouth, and nose in the cephalic region, chest and pelvic region with the presence of well-developed limbs, umbilical cord, and placenta. Scanning electron microscopy in 18 days of gestation fetuses evidenced head, eyes closed eyelids, nose, vibrissae, forelimb, heart, lung, kidney, liver, small bowel, diaphragm, and part of the spine. The results obtained in this work describe the internal and external morphology of mice, provided by an integration of techniques and review of the morphological knowledge of the embryonic development of this species, as this animal is of great importance to scientific studies. Copyright © 2012 Wiley Periodicals, Inc.

  8. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

    Science.gov (United States)

    Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

    2016-10-15

    Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    Directory of Open Access Journals (Sweden)

    Ullrich Stephen E

    2011-01-01

    Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal

  10. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    International Nuclear Information System (INIS)

    Puebla-Osorio, Nahum; Miyahara, Yasuko; Coimbatore, Sreevidya; Limón-Flores, Alberto Y; Kazimi, Nasser; Ullrich, Stephen E; Zhu, Chengming

    2011-01-01

    The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. UVB-irradiated p53 +/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19 + , CD5 + , B220 + , IgM + and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. UV-irradiated p53 +/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The

  11. Euthanasia of neonatal mice with carbon dioxide

    Science.gov (United States)

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

    2005-01-01

    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  12. Reduced alcohol consumption in mice lacking preprodynorphin.

    Science.gov (United States)

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  13. Collagen-induced arthritis in mice

    NARCIS (Netherlands)

    Bevaart, Lisette; Vervoordeldonk, Margriet J.; Tak, Paul P.

    2010-01-01

    Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new

  14. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Madsen, Jens; Kejling, Karin

    2006-01-01

    Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd......-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared...... with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF...

  15. Pion contamination in the MICE muon beam

    International Nuclear Information System (INIS)

    Adams, D.; Barclay, P.; Bayliss, V.; Brashaw, T.W.; Alekou, A.; Apollonio, M.; Barber, G.; Asfandiyarov, R.; Blondel, A.; De Bari, A.; Bayes, R.; Bertoni, R.; Bonesini, M.; Blackmore, V.J.; Blot, S.; Bogomilov, M.; Booth, C.N.; Bowring, D.; Boyd, S.; Bravar, U.

    2016-01-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ∼1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is f π  < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling

  16. Pion contamination in the MICE muon beam

    CERN Document Server

    Bogomilov, M.; Vankova-Kirilova, G.; Bertoni, R.; Bonesini, M.; Chignoli, F.; Mazza, R.; Palladino, V.; de Bari, A.; Cecchet, G.; Capponi, M.; Iaciofano, A.; Orestano, D.; Pastore, F.; Tortora, L.; Kuno, Y.; Sakamoto, H.; Ishimoto, S.; Japan, Ibaraki; Filthaut, F.; Hansen, O.M.; Ramberger, S.; Vretenar, M.; Asfandiyarov, R.; Blondel, A.; Drielsma, F.; Karadzhov, Y.; Charnley, G.; Collomb, N.; Gallagher, A.; Grant, A.; Griffiths, S.; Hartnett, T.; Martlew, B.; Moss, A.; Muir, A.; Mullacrane, I.; Oates, A.; Owens, P.; Stokes, G.; Warburton, P.; White, C.; Adams, D.; Barclay, P.; Bayliss, V.; Bradshaw, T.W.; Courthold, M.; Francis, V.; Fry, L.; Hayler, T.; Hills, M.; Lintern, A.; Macwaters, C.; Nichols, A.; Preece, R.; Ricciardi, S.; Rogers, C.; Stanley, T.; Tarrant, J.; Watson, S.; Wilson, A.; Bayes, R.; Nugent, J.C.; Soler, F.J.P.; Cooke, P.; Gamet, R.; Alekou, A.; Apollonio, M.; Barber, G.; Colling, D.; Dobbs, A.; Dornan, P.; Hunt, C.; Lagrange, J-B.; Long, K.; Martyniak, J.; Middleton, S.; Pasternak, J.; Santos, E.; Savidge, T.; Uchida, M.A.; Blackmore, V.J.; Carlisle, T.; Cobb, J.H.; Lau, W.; Rayner, M.A.; Tunnell, C.D.; Booth, C.N.; Hodgson, P.; Langlands, J.; Nicholson, R.; Overton, E.; Robinson, M.; Smith, P.J.; Dick, A.; Ronald, K.; Speirs, D.; Whyte, C.G.; Young, A.; Boyd, S.; Franchini, P.; Greis, J.R.; Pidcott, C.; Taylor, I.; Gardener, R.; Kyberd, P.; Littlefield, M.; Nebrensky, J.J.; Bross, A.D.; Fitzpatrick, T.; Leonova, M.; Moretti, A.; Neuffer, D.; Popovic, M.; Rubinov, P.; Rucinski, R.; Roberts, T.J.; Bowring, D.; DeMello, A.; Gourlay, S.; Li, D.; Prestemon, S.; Virostek, S.; Zisman, M.; Drews, M.; Hanlet, P.; Kafka, G.; Kaplan, D.M.; Rajaram, D.; Snopok, P.; Torun, Y.; Winter, M.; Blot, S.; Kim, Y.K.; Bravar, U.; Onel, Y.; Cremaldi, L.M.; Hart, T.L.; Luo, T.; Sanders, D.A.; Summers, D.J.; Cline, D.; Yang, X.; Coney, L.; Hanson, G.G.; Heidt, C.

    2016-01-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\\sim$1\\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\\pi < 1.4\\%$ at 90\\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.

  17. Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Dell` Omo, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Fiore, M [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Petruzzi, S [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Alleva, E [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Bignami, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy)

    1995-09-01

    Outbred CD-1 mice were exposed continuously to ozone (O{sub 3}, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O{sub 3} and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multitrial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O{sub 3} offspring showed a long-lasting reduction in body weight without modification of sec differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training. (orig.)

  18. Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

    Directory of Open Access Journals (Sweden)

    Anne K. McGavigan

    2017-03-01

    Full Text Available Bariatric surgery, such as vertical sleeve gastrectomy (VSG, causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed ad libitum or were food restricted to match their body mass to VSG-operated mice to determine the role of body mass in the ability of VSG to lower blood pressure. Blood pressure was then measured in freely moving unstressed mice by radiotelemetry. VSG decreased energy intake, body mass and fat mass. Mean arterial blood pressure (MAP was reduced in VSG-operated mice compared with both sham-operated groups. VSG-induced reductions in MAP were accompanied by a body mass-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic nervous system tone. Assessment of gut microbial populations revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and Enterococcus, and decreases in Adlercreutzia. These results suggest that VSG reduces blood pressure, but this is only partly due to the reduction in body weight. VSG-induced reductions in blood pressure may be driven by a decrease in hypothalamic ER stress and inflammatory signaling, and shifts in gut microbial populations.

  19. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

    Science.gov (United States)

    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  20. Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans.

    Directory of Open Access Journals (Sweden)

    Yvonne Ritze

    Full Text Available OBJECTIVE: Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. METHODS: Five iso-caloric diets, enriched with liquid (in water 30% vol/vol or solid (in diet 65% g/g fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5 and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. RESULTS: In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001. Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. CONCLUSIONS: We show that the form of sugar intake (liquid versus solid is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals.

  1. Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone.

    Science.gov (United States)

    Dell'Omo, G; Fiore, M; Petruzzi, S; Alleva, E; Bignami, G

    1995-01-01

    Outbred CD-1 mice were exposed continuously to ozone (O3, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O3 and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multi-trial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O3 offspring showed a long-lasting reduction in body weight without modification of sex differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training.

  2. The homeostatic and circadian sleep recovery responses after total sleep deprivation in mice.

    Science.gov (United States)

    Dispersyn, Garance; Sauvet, Fabien; Gomez-Merino, Danielle; Ciret, Sylvain; Drogou, Catherine; Leger, Damien; Gallopin, Thierry; Chennaoui, Mounir

    2017-10-01

    Many studies on sleep deprivation effects lack data regarding the recovery period. We investigated the 2-day homeostatic and circadian sleep recovery response to 24 h of total sleep deprivation (TSD) induced by brief rotation of an activity wheel. Eight mice were implanted with telemetry transmitters (DSI F40-EET) that recorded simultaneously their electroencephalography (EEG), locomotor activity and temperature during 24 h of baseline (BSL), TSD and 2 days of recovery (D1 and D2). In a second experiment, two groups of five non-implanted mice underwent TSD or ad libitum sleep, after which they were killed, adrenal glands were weighed and blood was collected for analysis of corticosterone concentration. During TSD mice were awake at least 97% of the time, with a consecutive sleep rebound during D1 that persisted during D2. This was characterized by increases of non-rapid eye movement (NREM) sleep (44.2 ± 6.9% for D1 and 43.0 ± 7.7% for D2 versus 33.8 ± 9.2% for BSL) and the relative delta band power (179.2 ± 34.4% for D1 and 81.9 ± 11.2% for D2). Greater NREM and REM sleep amounts were observed during the 'light' periods. Temperature and locomotor activity characteristics were unchanged during D1 and D2 versus BSL. In non-implanted mice, corticosterone levels as well as adrenal gland and overall body weights did not differ between TSD and ad libitum sleep groups. In conclusion, 24 h of TSD in an activity wheel without stress responses influence homeostatic sleep regulation with no effect on the circadian regulation over at least 2 days of recovery in mice. © 2017 European Sleep Research Society.

  3. Mobile optogenetic modules for mice

    Science.gov (United States)

    Rusakov, Konstantin; Radzewicz, Czesław; Czajkowski, Rafał; Konopka, Witold; Chilczuk, Joanna

    2017-08-01

    We present a set of novel optogenetic devices for mice freely moving in cages. The purpose of the devices is to stimulate specific brain regions using light. The devices we have constructed consist of an electrical connector, cannula and micro- LED chip operating at 470 nm as light source for delivering light into the stimulated region of the mouse brain. We have also demonstrated light conversion from 470 nm to 590 nm by applying a silicate orange phosphor directly to the LED chip. The measured conversion efficiency is approximately 80% for ZIP595I phosphor. We discuss the properties of various forms of implant needles with respect to the ease of LED attachment and experimental validation of the constructed optogenetic implants.

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

    Directory of Open Access Journals (Sweden)

    Yan Zhou

    2016-11-01

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

  5. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial.

    Science.gov (United States)

    Patz, Edward F; Greco, Erin; Gatsonis, Constantine; Pinsky, Paul; Kramer, Barnett S; Aberle, Denise R

    2016-05-01

    -211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial. Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

    OpenAIRE

    Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

    2003-01-01

    In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

  7. Bodyweight Assessment of Enamelin Null Mice

    Directory of Open Access Journals (Sweden)

    Albert H.-L. Chan

    2013-01-01

    Full Text Available The Enam null mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG. We compared the BWG of Enam−/− and wild-type mice from birth (D0 to Day 42 (D42. Wild-type (WT and Enam−/− (N mice were given either hard chow (HC or soft chow (SC. Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW and the average litter bodyweight (ALBW were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW of Enam−/− mice maintained on hard chow (NHC was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW of Enam−/− mice maintained on soft chow (NSC trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.

  8. Aerobic exercise training performed by parents reduces mice offspring adiposity.

    Science.gov (United States)

    Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

    2018-07-01

    The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

  9. Vacuolating encephalitis in mice infected by human coronavirus OC43

    International Nuclear Information System (INIS)

    Jacomy, Helene; Talbot, Pierre J.

    2003-01-01

    Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals

  10. Scleral fibroblast response to experimental glaucoma in mice

    Science.gov (United States)

    Tezel, Gülgün; Cone-Kimball, Elizabeth; Steinhart, Matthew R.; Jefferys, Joan; Pease, Mary E.; Quigley, Harry A.

    2016-01-01

    Purpose To study the detailed cellular and molecular changes in the mouse sclera subjected to experimental glaucoma. Methods Three strains of mice underwent experimental bead-injection glaucoma and were euthanized at 3 days and 1, 3, and 6 weeks. Scleral protein expression was analyzed with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using 16O/18O labeling for quantification in 1- and 6-week tissues. Sclera protein samples were also analyzed with immunoblotting with specific antibodies to selected proteins. The proportion of proliferating scleral fibroblasts was quantified with Ki67 and 4’,6-diamidino-2-phenylindole (DAPI) labeling, and selected proteins were studied with immunohistochemistry. Results Proteomic analysis showed increases in molecules involved in integrin-linked kinase signaling and actin cytoskeleton signaling pathways at 1 and 6 weeks after experimental glaucoma. The peripapillary scleral region had more fibroblasts than equatorial sclera (p=0.001, n=217, multivariable regression models). There was a sixfold increase in proliferating fibroblasts in the experimental glaucoma sclera at 1 week and a threefold rise at 3 and 6 weeks (p=0.0005, univariate regression). Immunoblots confirmed increases for myosin, spectrin, and actinin at 1 week after glaucoma. Thrombospondin-1 (TSP-1), HINT1, vimentin, actinin, and α-smooth muscle actin were increased according to immunohistochemistry. Conclusions Scleral fibroblasts in experimental mouse glaucoma show increases in actin cytoskeleton and integrin-related signaling, increases in cell division, and features compatible with myofibroblast transition. PMID:26900327

  11. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  12. Protective effects of escin against indomethacin-induced gastric ulcer in mice.

    Science.gov (United States)

    Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

    2014-12-01

    Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.

  13. Chronotoxicity of glufosinate ammonium in mice.

    Science.gov (United States)

    Yoshiyama, Y; Kobayashi, T; Kondo, R; Tomonaga, F; Ohwada, T

    1995-02-01

    The effect of a circadian-stage dependent dosing schedule on the toxicity of glufosinate was studied in mice. Male ICR mice were housed in a standardized 12:12 light:dark cycle for 3 w. Each animal was given 1500 or 3000 mg glufosinate/kg po. A highly significant circadian rhythm occurred in the resulting mortality, with the highest mortality from doses given during the light phase and the lowest from doses administered during the dark phase. The circadian-stage dependent dosing schedule had a marked influence on the pattern of acute glufosinate toxicity in mice.

  14. Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment

    International Nuclear Information System (INIS)

    Kataoka, Masateru; Kawamuro, Yuki; Shiraki, Nobuaki; Miki, Rika; Sakano, Daisuke; Yoshida, Tetsu; Yasukawa, Takanori; Kume, Kazuhiko; Kume, Shoen

    2013-01-01

    Highlights: ► We monitored long-term beta cell regeneration in neonatal mice treated with low dose STZ. ► Low-dose STZ neonatal female mice recovered blood glucose in 150 days. ► Glucose intolerance of the STZ treated mice significantly improved in 150 days. -- Abstract: Administration of streptozotocin (STZ) induces destruction of β-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of β-cells, β-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, β-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in β-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of β-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of β-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35–50. This was followed by a spontaneous regeneration of β-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the β-cell mass revealed that the β-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the β-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, β-cell duplication is one of the cell sources for β-cell regeneration

  15. Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kataoka, Masateru; Kawamuro, Yuki; Shiraki, Nobuaki [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Miki, Rika; Sakano, Daisuke [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Yoshida, Tetsu; Yasukawa, Takanori; Kume, Kazuhiko [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Kume, Shoen, E-mail: skume@kumamoto-u.ac.jp [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan)

    2013-01-18

    Highlights: ► We monitored long-term beta cell regeneration in neonatal mice treated with low dose STZ. ► Low-dose STZ neonatal female mice recovered blood glucose in 150 days. ► Glucose intolerance of the STZ treated mice significantly improved in 150 days. -- Abstract: Administration of streptozotocin (STZ) induces destruction of β-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of β-cells, β-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, β-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in β-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of β-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of β-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35–50. This was followed by a spontaneous regeneration of β-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the β-cell mass revealed that the β-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the β-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, β-cell duplication is one of the cell sources for β-cell regeneration.

  16. Terminal ileum of patients who underwent colonoscopy: endoscopic, histologic and clinical aspects Íleo terminal de pacientes submetidos a colonoscopia: aspectos endoscópicos, histológicos e clínicos

    Directory of Open Access Journals (Sweden)

    Marcelo Maia Caixeta de Melo

    2009-06-01

    Full Text Available CONTEXT: For the diagnosis of the diseases which affect the terminal ileum, the colonoscopy allows macroscopic evaluation and the performing of biopsies. Studies with criteria for the endoscopic and histological characterization of this segment are scarce and there are still some doubts about the need of biopsies in patients with normal ileoscopy. OBJECTIVE: Study the terminal ileum of patients who underwent colonoscopy considering: endoscopic and histological correlation; agreement between results of the initial histological evaluation and slides review, and the chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea to show histological alterations. METHODS: In a prospective study, 111 patients who presented smooth mucosa without enanthema in the endoscopic exam of the terminal ileum were selected. Biopsies of the ileal mucosa of such patients were performed, being the slides routinely examined and reviewed afterwards. RESULTS: The correlation between patients with normal ileoscopy and ileum with preserved histological architecture was of 99.1%. The agreement between initial histological evaluation and slides review calculated by the Kappa test was 0.21. In patients with abdominal pain and/or chronic diarrhea, the chance of showing histological alterations was 2.5 times higher than the others. CONCLUSIONS: The correlation between endoscopic and histological findings was high. The agreement between the initial histologic evaluation and slides review was not satisfactory. The chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea, showing histological alterations was higher in relation to the asymptomatic ones or with other symptoms, although the clinical importance of this datum was not evaluated.CONTEXTO: Para o diagnóstico de doenças que afetam o íleo terminal, a colonoscopia permite avaliação macroscópica e realização de biopsias. Estudos com critérios para caracteriza

  17. Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.

    Science.gov (United States)

    Singamsetty, Srikanth; Shah, Faraaz Ali; Guo, Lanping; Watanabe, Yoshio; McDonald, Sherie; Sharma, Rohit; Zhang, Yingze; Alonso, Laura C; O'Donnell, Christopher P; McVerry, Bryan J

    2016-01-01

    Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose dextrose (∼ 20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.

  18. Principles of Economic Rationality in Mice.

    Science.gov (United States)

    Rivalan, Marion; Winter, York; Nachev, Vladislav

    2017-12-12

    Humans and non-human animals frequently violate principles of economic rationality, such as transitivity, independence of irrelevant alternatives, and regularity. The conditions that lead to these violations are not completely understood. Here we report a study on mice tested in automated home-cage setups using rewards of drinking water. Rewards differed in one of two dimensions, volume or probability. Our results suggest that mouse choice conforms to the principles of economic rationality for options that differ along a single reward dimension. A psychometric analysis of mouse choices further revealed that mice responded more strongly to differences in probability than to differences in volume, despite equivalence in return rates. This study also demonstrates the synergistic effect between the principles of economic rationality and psychophysics in making quantitative predictions about choices of healthy laboratory mice. This opens up new possibilities for the analyses of multi-dimensional choice and the use of mice with cognitive impairments that may violate economic rationality.

  19. Immunity to Trichinella spiralis in irradiated mice

    International Nuclear Information System (INIS)

    Wakelin, D.; Wilson, M.M.

    1980-01-01

    Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

  20. Aged mice have increased inflammatory monocyte concentration ...

    Indian Academy of Sciences (India)

    monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

  1. Bortezomib alters sour taste sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Akihiro Ohishi

    Full Text Available Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the control level on cessation of its administration. These results suggest that an increase in protein expression of PKD2L1 enhances the sour taste sensitivity in bortezomib-administered mice, and this alteration is reversed on cessation of its administration. Keywords: Taste disorder, Bortezomib, Sour taste, Chemotherapy, Adverse effect

  2. Cytochrome P450 humanised mice

    Directory of Open Access Journals (Sweden)

    Gonzalez Frank J

    2004-05-01

    Full Text Available Abstract Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s. These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach.

  3. Cytochrome P450 humanised mice

    Science.gov (United States)

    2004-01-01

    Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s). These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach. PMID:15588489

  4. Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

    Science.gov (United States)

    Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

    2015-11-01

    During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

  5. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

    Science.gov (United States)

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  6. Wound Healing in Mac-1 Deficient Mice

    Science.gov (United States)

    2017-05-01

    Dentistry, University of Illinois at Chicago, Chicago, IL, USA. 2 Department of Defense Biotechnology High Performance Computing Software...study, we used a commercially available Mac-1 deficient strain to examine whether this deficit 5 extends to slightly smaller wounds and incisional...levels of Collagen I and Collagen III in wounds from the two strains of mice at any time point. Unwounded skin from both WT and Mac-1 -/- mice contained

  7. Normal Conducting RF Cavity for MICE

    International Nuclear Information System (INIS)

    Li, D.; DeMello, A.; Virostek, S.; Zisman, M.; Summers, D.

    2010-01-01

    Normal conducting RF cavities must be used for the cooling section of the international Muon Ionization Cooling Experiment (MICE), currently under construction at Rutherford Appleton Laboratory (RAL) in the UK. Eight 201-MHz cavities are needed for the MICE cooling section; fabrication of the first five cavities is complete. We report the cavity fabrication status including cavity design, fabrication techniques and preliminary low power RF measurements.

  8. Metabolic characteristics of long-lived mice

    Directory of Open Access Journals (Sweden)

    Andrzej eBartke

    2012-12-01

    Full Text Available Genetic suppression of insulin/insulin-like growth factor signaling (IIS can extend longevity in worms, insects, and mammals. In laboratory mice, mutations with the greatest, most consistent, and best documented positive impact on lifespan are those that disrupt growth hormone (GH release or actions. These mutations lead to major alterations in IIS but also have a variety of effects that are not directly related to the actions of insulin or insulin-like growth factor (IGF-1. Long-lived GH-resistant GHRKO mice with targeted disruption of the GH receptor gene, as well as Ames dwarf (Prop1df and Snell dwarf (Pit1dw mice lacking GH (along with prolactin and TSH, are diminutive in size and have major alterations in body composition and metabolic parameters including increased subcutaneous adiposity, increased relative brain weight, small liver, hypoinsulinemia, mild hypoglycemia, increased adiponectin levels and insulin sensitivity, and reduced serum lipids. Body temperature is reduced in Ames, Snell, and female GHRKO mice. Indirect calorimetry revealed that both Ames dwarf and GHRKO mice utilize more oxygen per gram (g of body weight than sex- and age-matched normal animals from the same strain. They also have reduced respiratory quotient (RQ, implying greater reliance on fats, as opposed to carbohydrates, as an energy source. Differences in oxygen consumption (VO2 were seen in animals fed or fasted during the measurements as well as in animals that had been exposed to 30% calorie restriction or every-other-day feeding. However, at the thermoneutral temperature of 30°C, VO2 did not differ between GHRKO and normal mice. Thus, the increased metabolic rate of the GHRKO mice, at a standard animal room temperature of 23°C, is apparently related to increased energy demands for thermoregulation in these diminutive animals. We suspect that increased oxidative metabolism combined with enhanced fatty acid oxidation contribute to the extended longevity of

  9. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  10. Men and mice: Relating their ages.

    Science.gov (United States)

    Dutta, Sulagna; Sengupta, Pallav

    2016-05-01

    Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice.

    Science.gov (United States)

    Hwa, Lara S; Nathanson, Anna J; Shimamoto, Akiko; Tayeh, Jillian K; Wilens, Allison R; Holly, Elizabeth N; Newman, Emily L; DeBold, Joseph F; Miczek, Klaus A

    2015-08-01

    Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20 % EtOH. Aggressive and nonaggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5-mg/kg dose in mice with a history of 8 weeks of EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks of EtOH compared to 1 week of EtOH or 8 weeks of water. Five milligrams per kilogram of memantine increased glutamate in 8-week EtOH mice, but also in 1-week EtOH and water drinkers. These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior.

  12. Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment.

    Science.gov (United States)

    Karlsson, Louise; Carlsson, Björn; Hiemke, Christoph; Ahlner, Johan; Bengtsson, Finn; Schmitt, Ulrich; Kugelberg, Fredrik C

    2013-11-01

    According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10mg/kg) or escitalopram (5mg/kg) Serum and brain samples were collected 1-6h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S- and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  13. Experimental study of hypoxia-imaging agent 99mTc-HL91 in mice bearing glioblastoma G422

    International Nuclear Information System (INIS)

    Zhou Ying; Qu Wanying; Yao Zhiming; Chen Fang; Zhu Ming; Zhu Lin

    1999-01-01

    Objective: To evaluate the ability of detecting cerebral tumor by 99m Tc-HL91 in mice bearing glioblastoma G422. Methods: Six model mice underwent static whole body planar imagings at once and at 1,2,3,4,6,7,8 h postinjection of 99m Tc-HL91. Three mice each were killed at 4 h and 8 h, respectively. the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around tumor, head, contralateral axilla and chest in whole body planar images, and the radioactivity ratios of tumor to head (T/H), contralateral axilla (T/A) and chest (T/C) were calculated. Results: Increased tumor activity was identified in static whole body planar images since 1 h postinjection. At 2h postinjection, T/H, T/A and T/C were 2.93 +- 0.51, 4.86 +- 0.79 and 2.00 +- 0.35 respectively, which were significantly higher than those at once and at 1h postinjection (P 99m Tc-HL91 in tumor tissue of mice bearing glioblastoma G422 is increased and clearance rate is decreased. 99m Tc-HL91 imaging is suitable for glioblastoma at 2 h postinjection. It is appropriate to image tumors in head, neck, thorax, bone and soft tissues, but not in abdominal area

  14. Metabolism and disposition of ABT-894, a novel α4β2 neuronal acetylcholine receptor agonist, in mice and monkeys.

    Science.gov (United States)

    Liu, Hong; Fu, Wentao; Wetter, Jill; Xu, Hongyu; Guan, Zhiwen; Stuart, Patricia

    2014-06-01

    1.  Metabolism and disposition of ABT-894 was investigated in hepatocytes, in mice and monkeys receiving [(14)C]ABT-894. 2.  In hepatocytes, turnover rate of ABT-894 was slow in all species with more than 90% of parent remaining. M3 (carbamoyl glucuronide) and M6 (mono-oxidation) were detected across species. 3.  ABT-894 showed species-specific disposition profiles. ABT-894 was primarily eliminated by renal secretion in mice. Whereas, monkey mainly cleared ABT-894 metabolically. 4.  ABT-894 underwent two primary routes of metabolism in monkeys: N-carbamoyl glucuronidation to form M3 and oxidation product M1. M3 was the major metabolite in monkey excreta. M3 was observed in mice urine. Circulating levels of M3 in terms of M3/ABT-894 ratios were essentially absent in mice, but were high in monkeys. 5.  Understanding the species difference in the clearance mechanism is the key to the accurate projection of the human clearance and preclinical safety assessment. Lack of species difference in the metabolism of ABT-894 in hepatocytes certainly creates a challenge in predicting its metabolism and pharmacokinetics in human. Based on available metabolism and pharmacokinetic data of ABT-894 in human, monkey is the preferred species in predicting human clearance since it presents a similar clearance mechanism from that observed in human.

  15. The effects of social defeat on behavior and dopaminergic markers in mice.

    Science.gov (United States)

    Jin, H-M; Shrestha Muna, S; Bagalkot, T R; Cui, Y; Yadav, B K; Chung, Y-C

    2015-03-12

    The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. The behavioral tests comprised tests of locomotion, light/dark preference, social interaction, as well as the novel object recognition test (NORT), Morris water maze, and forced swimming test (FST). We measured the expression of D1Rs, D2Rs, total DARPP-32, phospho-Thr34 or Thr75-DARPP-32 using Western blotting. The defeated mice showed increased anxiety- and depression-like behaviors, and impaired cognition. No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Effect of limb demand ischemia on autophagy and morphology in mice.

    Science.gov (United States)

    Albadawi, Hassan; Oklu, Rahmi; Milner, John D; Uong, Thuy P; Yoo, Hyung-Jin; Austen, William G; Watkins, Michael T

    2015-10-01

    Obesity is a major risk factor for diabetes and peripheral arterial disease, which frequently leads to lower limb demand ischemia. Skeletal muscle autophagy and mitochondrial biogenesis are important processes for proper oxidative capacity and energy metabolism, which are compromised in diabetes. This study compares autophagy, mitochondrial biogenesis, energy metabolism, and morphology in the hind limbs of obese diabetic mice subjected to demand or sedentary ischemia. Unilateral hind limb demand ischemia was created in a group of diet-induced obese mice after femoral artery ligation and 4 wk of daily exercise. A parallel group of mice underwent femoral artery ligation but remained sedentary for 4 wk. Hind limb muscles were analyzed for markers of autophagy, mitochondrial biogenesis, adenosine triphosphate, and muscle tissue morphology. At the end of the 4-wk exercise period, demand ischemia increased the autophagy mediator Beclin-1, but it did not alter the autophagy indicator, LC3B-II/I ratio, or markers of mitochondrial biogenesis, optic atrophy/dynamin-related protein. In contrast, exercise significantly increased the level of mitochondrial protein-succinate dehydrogenase subunit-A and reduced adipocyte accumulation and the percentage of centrally nucleated myofibers in the demand ischemia limb. In addition, demand ischemia resulted in decreased uncoupling protein-3 levels without altering muscle adenosine triphosphate or pS473-Akt levels. Limb demand ischemia markedly decreased adipocyte accumulation and enhanced muscle regeneration in obese mice, but it did not appear to enhance autophagy, mitochondrial biogenesis, energy metabolism, or insulin sensitivity. Future studies aimed at evaluating novel therapies that enhance autophagy and mitochondrial biogenesis in diabetes with peripheral arterial disease are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Exploring Bhavana samskara using Tinospora cordifolia and Phyllanthus emblica combination for learning and memory in mice

    Directory of Open Access Journals (Sweden)

    Harshad Onkarrao Malve

    2015-01-01

    Full Text Available Background: Current medications for dementia and enhancement of learning and memory are limited hence we need to explore traditional medicinal systems like Ayurveda to investigate agents that can improve learning and enhance memory. Objective: The present study was carried out to evaluate effects and mechanisms of Ayurveda drug formulations, Tinospora cordifolia (Tc and Phyllanthus emblica (Pe with and without Bhavana samskara on learning and memory of mice. Materials and Methods: After approval of Animal Ethics Committee, Swiss albino mice were divided into seven groups, administered orally: Distilled water, Rivastigmine (2.4 mg/kg, Tc (100 mg/kg, Pe (300 mg/kg, formulation 1 (Tc + Pe: 400 mg/kg and formulation 2 (Tc + Pe + Ocimum sanctum: 400 mg/kg daily for 15 days. Piracetam (200 mg/kg was injected daily intraperitoneally for 8 days. The mice underwent a learning session using elevated plus maze. Memory was tested 24 hours later. Results: Mice pretreated with all the drugs showed a trend toward reducing transfer latencies but values were comparable to vehicle control. In all drug-treated groups, a significant reduction in transfer latency was observed after 24 h. Improvement in learning and memory by both formulations were comparable to individual plant drugs, Tc and Pe. Conclusion: The plant drugs showed improvements in learning and memory. The fixed-dose formulations with Bhavana samskara, showed encouraging results as compared to individual agents but the difference was not statistically significant. Hence, the concept of Bhavana samskara could not be explored in the present study. However, these drugs showed comparable or better effects than the modern medicinal agents thus, their therapeutic potential as nootropics needs to be explored further.

  18. Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

    International Nuclear Information System (INIS)

    Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

    2003-01-01

    Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G 4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

  19. Safety, tolerability, and biomarkers of the treatment of mice with aerosolized toll-like receptor ligands

    Directory of Open Access Journals (Sweden)

    Victoria eAlfaro

    2014-02-01

    Full Text Available We have previously discovered a synergistically therapeutic combination of two Toll-like receptor (TLR ligands, an oligodeoxynucleotide (ODN and Pam2CSK4. Aerosolization of these ligands stimulates innate immunity within the lungs to prevent pneumonia from bacterial and viral pathogens. Here we examined the safety and tolerability of this treatment in mice, and characterized the expression of biomarkers of innate immune activation. We found that neutrophils appeared in lung lavage fluid 4 hours after treatment, reached a peak at 48 hours, and resolved by 7 days. The peak of neutrophil influx was accompanied by a small increase in lung permeability. Despite the abundance of neutrophils in lung lavage fluid, only rare neutrophils were visible histopathologically in the interstitium surrounding bronchi and veins and none were visible in alveolar airspaces. The cytokines IL-6, TNF and CXCL2 rose several hundred-fold in lung lavage fluid 4 hours after treatment in a dose-dependent and synergistic manner, providing useful biomarkers of lung activation. IL-6 rose five-fold in serum with delayed kinetics compared to its rise in lavage fluid, and might serve as a systemic biomarker of immune activation of the lungs. The dose-response relationship of lavage fluid cytokines was preserved in mice that underwent myeloablative treatment with cytosine arabinoside to model the treatment of hematologic malignancy. There were no overt signs of distress in mice treated with ODN/Pam2CSK4 in doses up to 8-fold the therapeutic dose, and no changes in temperature, respiratory rate, or behavioral signs of sickness including sugar water preference, food disappearance, cage exploration or social interaction, though there was a small degree of transient weight loss. We conclude that treatment with aerosolized ODN/Pam2CSK4 is well tolerated in mice, and that innate immune activation of the lungs can be monitored by the measurement of inflammatory cytokines in lung lavage

  20. Effects of neonatal oxytocin manipulation on development of social behaviors in mice.

    Science.gov (United States)

    Mogi, Kazutaka; Ooyama, Rumi; Nagasawa, Miho; Kikusui, Takefumi

    2014-06-22

    The oxytocin (OT) neural system is thought to be involved in the underlying mechanisms that guide the development of social behaviors. In the present study, we examined the effects of neonatal oxytocin manipulation in mice. Within 24 hours after birth, pups in the treatment group randomly received an intraperitoneal injection of OT or OT antagonist (OTA), and those in the control group received a saline injection or handling only. Some of these mic