WorldWideScience

Sample records for vivo hq exposure

  1. Hydroquinone PBPK model refinement and application to dermal exposure.

    Science.gov (United States)

    Poet, Torka S; Carlton, Betsy D; Deyo, James A; Hinderliter, Paul M

    2010-11-01

    A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was refined to include an expanded description of HQ-glucuronide metabolites and a description of dermal exposures to support route-to-route and cross-species extrapolation. Total urinary excretion of metabolites from in vivo rat dermal exposures was used to estimate a percutaneous permeability coefficient (K(p); 3.6×10(-5) cm/h). The human in vivo K(p) was estimated to be 1.62×10(-4) cm/h, based on in vitro skin permeability data in rats and humans and rat in vivo values. The projected total multi-substituted glutathione (which was used as an internal dose surrogate for the toxic glutathione metabolites) was modeled following an exposure scenario based on submersion of both hands in a 5% aqueous solution of HQ (similar to black and white photographic developing solution) for 2 h, a worst-case exposure scenario. Total multi-substituted glutathione following this human dermal exposure scenario was several orders of magnitude lower than the internal total glutathione conjugates in rats following an oral exposure to the rat NOEL of 20 mg/kg. Thus, under more realistic human dermal exposure conditions, it is unlikely that toxic glutathione conjugates (primarily the di- and, to a lesser degree, the tri-glutathione conjugate) will reach significant levels in target tissues. Copyright © 2010. Published by Elsevier Ltd.

  2. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    Energy Technology Data Exchange (ETDEWEB)

    Crabbe, Rory A. [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada); Hill, Kathleen A., E-mail: khill22@uwo.ca [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada)

    2010-09-10

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  3. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    International Nuclear Information System (INIS)

    Crabbe, Rory A.; Hill, Kathleen A.

    2010-01-01

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  4. Experimental searches for tHq

    CERN Document Server

    ,

    2014-01-01

    The Yukawa coupling of the Higgs boson to top quarks $\\text{Y}_\\text{t}$ is of particular interest as the top quark plays a special role in the electroweak symmetry breaking mechanism. Any deviation from its predicted value could hint at new physics. For this investigation the associated production of a Higgs boson and a single top quark (tHq) is a promising channel. Due to interference terms in the production amplitude the cross section $\\sigma_\\text{tHq}$ is not only sensitive to the magnitude of $\\text{Y}_\\text{t}$ but also to its sign making this channel special. In addition the branching ratio BR($\\text{H}\\to\\gamma\\gamma$) is sensitive to sign and magnitude of $\\text{Y}_\\text{t}$. The ATLAS and CMS collaborations exploit both effects to set upper limits on $\\sigma_\\text{tHq}$ and the deviation of $\\text{Y}_\\text{t}$ by applying inherently different approaches. The most recent results from both collaborations using the full data provided by the LHC are presented.

  5. Test Results of the LARP HQ02b Magnet at 1.9 K

    OpenAIRE

    Bajas, H; Bajko, M; Bottura, L; Chiuchiolo, A; Dunkel, O; Ferracin, P; Feuvrier, J; Giloux, Chr; Todesco, E; Ravaioli, E; Caspi, S; Dietderich, D; Felice, H; Hafalia, A R; Marchevsky, M

    2015-01-01

    The HQ magnet is a 120 mm aperture, 1-meter-long Nb3Sn quadrupole developed by the LARP collaboration in the framework of the High-Luminosity LHC project. A first series of coils was assembled and tested in 5 assemblies of the HQ01 series. The HQ01e model achieved a maximum gradient of 170 T/m at 4.5 K at LBNL in 2010-2011 and reached 184 T/m at 1.9 K at CERN in 2012. A new series of coils incorporating major design changes was fabricated for the HQ02 series. The first model, HQ02a, was teste...

  6. Test Results of the LARP Nb$_3$Sn Quadrupole HQ03a

    CERN Document Server

    DiMarco, J; Anerella, M; Bajas, H; Chlachidze, G; Borgnolutti, F; Bossert, R; Cheng, D W; Dietderich, D; Felice, H; Pan, H; Ferracin, P; Ghosh, A; Godeke, A; Hafalia, A R; Marchevsky, M; Orris, D; Ravaioli, E; Sabbi, G; Salmi, T; Schmalzle, J; Stoynev, S; Strauss, T; Sylvester, C; Tartaglia, M; Todesco, E; Wanderer, P; Wang, X R; Yu, M

    2016-01-01

    The US LHC Accelerator Research Program (LARP) has been developing $Nb_3Sn$ quadrupoles of progressively increasing performance for the high luminosity upgrade of the Large Hadron Collider. The 120 mm aperture High-field Quadrupole (HQ) models are the last step in the R&D; phase supporting the development of the new IR Quadrupoles (MQXF). Three series of HQ coils were fabricated and assembled in a shell-based support structure, progressively optimizing the design and fabrication process. The final set of coils consistently applied the optimized design solutions, and was assembled in the HQ03a model. This paper reports a summary of the HQ03a test results, including training, mechanical performance, field quality and quench studies.

  7. Test Results of the LARP HQ02b Magnet at 1.9 K

    CERN Document Server

    Bajas, H; Bottura, L; Chiuchiolo, A; Dunkel, O; Ferracin, P; Feuvrier, J; Giloux, Chr; Todesco, E; Ravaioli, E; Caspi, S; Dietderich, D; Felice, H; Hafalia, A R; Marchevsky, M; Sabbi, G L; Wang, X; Salmi, T; Ghosh, A; Schmalzle, J; Wanderer, P; Anerella, M; Ambrosio, G; Bossert, R; Chlachidze, G; Yu, M

    2015-01-01

    The HQ magnet is a 120 mm aperture, 1-meter-long Nb$_{3}$Sn quadrupole developed by the LARP collaboration in the framework of the High-Luminosity LHC project. A first series of coils was assembled and tested in 5 assemblies of the HQ01 series. The HQ01e model achieved a maximum gradient of 170 T/m at 4.5 K at LBNL in 2010-2011 and reached 184 T/m at 1.9 K at CERN in 2012. A new series of coils incorporating major design changes was fabricated for the HQ02 series. The first model, HQ02a, was tested at Fermilab where it reached 98% of the short sample limit at 4.5 K with a gradient of 182 T/m in 2013. However, the full training of the coils at 1.9 K could not be performed due to a current limit of 15 kA. Following this test, the azimuthal coil pre-load was increased by about 30 MPa and an additional current lead was installed at the electrical center of the magnet for quench protection studies. The test name of this magnet changed to HQ02b. In 2014, HQ02b was then shipped to CERN as the first opportunity for f...

  8. Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.

    Science.gov (United States)

    Renaud, Stéphanie; Corcé, Vincent; Cannie, Isabelle; Ropert, Martine; Lepage, Sylvie; Loréal, Olivier; Deniaud, David; Gaboriau, François

    2015-08-01

    Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Virtual Reality Treatment in Acrophobia : A Comparison with Exposure in Vivo

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.; Bruynzeel, M.; Drost, L.; Van der Mast, C.A.P.G.

    2001-01-01

    The aim of the present study was to evaluate the effectiveness of low-budget virtual reality exposure versus exposure in vivo in a within-group design in 10 individuals suffering from acrophobia. Virtual reality exposure was found to be at least as effective as exposure in vivo on anxiety and

  10. Prediction of the external work of the native heart from the dynamic H-Q curves of the rotary blood pumps during left heart bypass.

    Science.gov (United States)

    Yokoyama, Yoshimasa; Kawaguchi, Osamu; Kitao, Takashi; Kimura, Taro; Steinseifer, Ulrich; Takatani, Setsuo

    2010-09-01

    The ventricular performance is dependent on the drainage effect of rotary blood pumps (RBPs) and the performance of RBPs is affected by the ventricular pulsation. In this study, the interaction between the ventricle and RBPs was examined using the pressure-volume (P-V) diagram of the ventricle and dynamic head pressure-bypass flow (H-Q) curves (H, head pressure: arterial pressure minus ventricular pressure vs. Q, bypass flow) of the RBPs. We first investigated the relationships in a mock loop with a passive fill ventricle, followed by validation in ex vivo animal experiments. An apical drainage cannula with a micro-pressure sensor was especially fabricated to obtain ventricular pressure, while three pairs of ultrasonic crystals placed on the heart wall were used to derive ventricular volume. The mock loop-configured ventricular apical-descending aorta bypass revealed that the external work of the ventricle expressed by the area inside the P-V diagrams (EW(Heart) ) correlated strongly with the area inside dynamic H-Q curves (EW(VAD)), with the coefficients of correlation being R² = 0.869 ∼ 0.961. The results in the mock loop were verified in the ex vivo studies using three Shiba goats (10-25 kg in body weight), showing the correlation coefficients of R² = 0.802 ∼ 0.817. The linear regression analysis indicated that the increase in the bypass flow reduced pulsatility in the ventricle expressed in EW(Heart) as well as in EW(VAD) . Experimental results, both mock loop and animal studies, showed that the interaction between cardiac external work and H-Q performance of RBPs can be expressed by the relationships "EW(Heart) versus EW(VAD) ." The pulsatile nature of the native heart can be expressed in the area underneath the H-Q curves of RBPs EW(VAD) during left heart bypass indicating the status of the level of assistance by RBPs and the native heart function. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and

  11. Field Quality Measurements of LARP Nb$_{3}$Sn Magnet HQ02

    CERN Document Server

    DiMarco, J; Buehler, M; Chlachidze, G; Orris, D; Sylvester, C; Tartaglia, M; Velev, G; Yu, M; Zlobin, A; Ghosh, A; Schmalzle, J; Wanderer, P; Borgnolutti, F; Cheng, D; Dietderich, D; Felice, H; Godeke, A; Hafalia, R; Joseph, J; Lizarazo, J; Marchevsky, M; Prestemon, S O; Sabbi, G L; Salehi, A,; Wang, X; Ferracin, P; Todesco, E

    2014-01-01

    Large-aperture, high-field, Nb$_{3}$Sn quadrupoles are being developed by the US LHC accelerator research program (LARP) for the High luminosity upgrade of the Large Hadron Collider (HiLumi-LHC). The first 1 m long, 120 mm aperture prototype, HQ01, was assembled with various sets of coils and tested at LBNL and CERN. Based on these results, several design modifications have been introduced to improve the performance for HQ02, the latest model. From the field quality perspective, the most relevant improvements are a cored cable for reduction of eddy current effects, and more uniform coil components and fabrication processes. This paper reports on the magnetic measurements of HQ02 during recent testing at the Vertical Magnet Test Facility at Fermilab. Results of baseline measurements performed with a new multi-layer circuit board probe are compared with the earlier magnet. An analysis of probe and measurement system performance is also presented.

  12. Performance of HQ02, an optimized version of the 120 mm $Nb_3Sn$ LARP quadrupole

    CERN Document Server

    Chlachidze, G; Anerella, M; Borgnolutti, F; Bossert, R; Caspi, S; Cheng, D W; Dietderich, D; Felice, H; Ferracin, P; Ghosh, A; Godeke, A; Hafalia A R; Marchevsky, M; Orris, D; Roy, P K; Sabbi, G L; Salmi, T; Schmalzle, J; Sylvester, C; Tartaglia, M; Tompkins, J; Wanderer, P; Wang, X R; Zlobin, A V

    2014-01-01

    In preparation for the high luminosity upgrade of the Large Hadron Collider (LHC), the LHC Accelerator Research Program (LARP) is developing a new generation of large aperture high-field quadrupoles based on Nb$_{3}$Sn technology. One meter long and 120 mm diameter HQ quadrupoles are currently produced as a step toward the eventual aperture of 150 mm. Tests of the first series of HQ coils revealed the necessity for further optimization of the coil design and fabrication process. A new model (HQ02) has been fabricated with several design modifications, including a reduction of the cable size and an improved insulation scheme. Coils in this magnet are made of a cored cable using 0.778 mm diameter Nb$_{3}$Sn strands of RRP 108/127 sub-element design. The HQ02 magnet has been fabricated at LBNL and BNL, and then tested at Fermilab. This paper summarizes the performance of HQ02 at 4.5 K and 1.9 K temperatures.

  13. Evaluation of the highly sensitive chemiluminescent enzyme immunoassay "Lumipulse HBsAg-HQ" for hepatitis B virus screening.

    Science.gov (United States)

    Deguchi, Matsuo; Kagita, Masanori; Yoshioka, Nori; Tsukamoto, Hiroko; Takao, Miyuki; Tahara, Kazuko; Maeda, Ikuhiro; Hidaka, Yoh; Yamauchi, Satoshi; Kaneko, Atsushi; Miyakoshi, Hideo; Isomura, Mitsuo

    2017-10-06

    Ongoing efforts in the development of HBsAg detection kits are focused on improving sensitivity and specificity. The purpose of this study was to evaluate an improved, highly sensitive quantitative assay, "Lumipulse HBsAg-HQ", a chemiluminescent enzyme immunoassay designed for a fully automated instrument, the "Lumipulse G1200". Serum samples for reproducibility, dilution, correlation, sensitivity, and specificity studies were obtained from patients at the Osaka University Hospital. Seroconversion and sensitivity panels were purchased from a commercial vender. Subtype, sensitivity panels, and HBsAg recombinant proteins with one or two amino acid substitutions were prepared in-house. The coefficients of variation for the low, medium, and high concentration samples ranged from 1.93 to 2.55%. The HBsAg-HQ reagent for dilution testing showed good linearity in the 0.005-150 HBsAg IU/mL range and no prozone phenomenon. All 102 HBV carrier samples were positive by HBsAg-HQ, while other commercial reagents showed one or more to be negative. In the seroconversion panel, the 14-day blood sample was positive. The sensitivity against HBsAg-HQ "ad" and "ay" subtypes was 0.025 ng/mL. Comparisons among the HBsAg-HQ, HISCL, and Architect HBsAg reagents were performed using the Bland-Altman plot. Specificity for 1000 seronegative individuals was 99.7%. HBsAg-HQ detected 29 positive serum among 12 231 routinely obtained serum samples, which showed concentrations of 0.005-0.05 HBsAg IU/mL. According to these results, the Lumipulse HBsAg-HQ assay, with a highly sensitive limit of detection of 0.005 IU/mL, may facilitate the development of a better management strategy for a considerable proportion of infected patients. © 2017 Wiley Periodicals, Inc.

  14. 76 FR 365 - Exposure Modeling Public Meeting

    Science.gov (United States)

    2011-01-04

    ... classification for ecological risk assessments using aerial photography and GIS data. Dermal contact, movement... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2009-0879; FRL-8860-5] Exposure Modeling Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: An Exposure Modeling...

  15. Health risk characterization for exposure to benzene in service stations and petroleum refineries environments using human adverse response data.

    Science.gov (United States)

    Edokpolo, Benjamin; Yu, Qiming Jimmy; Connell, Des

    2015-01-01

    Health risk characterization of exposure to benzene in service stations and petroleum refineries has been carried out in previous studies using guideline values set by various agencies. In this work, health risk was characterized with the exposure data as cumulative probability distribution (CPD) plots but using human epidemiological data. This was achieved by using lowest observable adverse effects levels (LOAEL) data plotted as cumulative probability lowest effects distribution (CPLED). The health risk due to benzene was characterized by using probabilistic methods of hazard quotient (HQ 50/50 and HQ 95/5 ), Monte-Carlo simulation (MCS) and overall risk probability (ORP). CPD relationships of adverse health effects relationships and exposure data were in terms of average daily dose (ADD) and lifetime average daily dose (LADD) for benzene. For service station environments HQ 50/50 and HQ 95/5 were in a range of 0.000071-0.055 and 0.0049-21, respectively. On the other hand, the risk estimated for petroleum refinery environments suggests higher risk with HQ 50/50 and HQ 95/5 values ranging from 0.0012 to 77 and 0.17 to 560, respectively. The results of Monte-Carlo risk probability (MRP) and ORP indicated that workers in petroleum refineries (MRP of 2.9-56% and ORP of 4.6-52% of the affected population) were at a higher risk of adverse health effects from exposure to benzene as compared to exposure to benzene in service station environments (MRP of 0.051 -3.4% and ORP of 0.35-2.7% affected population). The adverse effect risk probabilities estimated by using the Monte-Carlo simulation technique and the ORP method were found to be generally consistent.

  16. Light Emission Requires Exposure to the Atmosphere in Ex Vivo Bioluminescence Imaging

    Directory of Open Access Journals (Sweden)

    Yusuke Inoue

    2006-04-01

    Full Text Available The identification of organs bearing luciferase activity by in vivo bioluminescence imaging (BLI is often difficult, and ex vivo imaging of excised organs plays a complementary role. This study investigated the importance of exposure to the atmosphere in ex vivo BLI. Mice were inoculated with murine pro-B cell line Ba/F3 transduced with firefly luciferase and p190 BCR-ABL. They were killed following in vivo BLI, and whole-body imaging was done after death and then after intraperitoneal air injection. In addition, the right knee was exposed and imaged before and after the adjacent bones were cut. Extensive light signals were seen on in vivo imaging. The luminescence disappeared after the animal was killed, and air injection restored the light emission from the abdomen only, suggesting a critical role of atmospheric oxygen in luminescence after death. Although no substantial light signal at the right knee was seen before bone cutting, light emission was evident after cutting. In conclusion, in ex vivo BLI, light emission requires exposure to the atmosphere. Bone destruction is required to demonstrate luciferase activity in the bone marrow after death.

  17. Fine structure in the inter-critical heat-affected zone of HQ130 super ...

    Indian Academy of Sciences (India)

    Unknown

    †Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, ... The microstructure in the inter-critical heat-affected zone (ICHAZ) of HQ130 steel, has been .... Ac3. The microhardness was measured by using the.

  18. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Cristina Botella

    Full Text Available Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31 versus an Augmented Reality system (N = 32 in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  19. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Science.gov (United States)

    Botella, Cristina; Pérez-Ara, M Ángeles; Bretón-López, Juana; Quero, Soledad; García-Palacios, Azucena; Baños, Rosa María

    2016-01-01

    Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  20. Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure.

    Science.gov (United States)

    Dang, Thanh D; Allen, Katrina J; J Martino, David; Koplin, Jennifer J; Licciardi, Paul V; Tang, Mimi L K

    2016-02-01

    Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. To examine changes in peripheral blood CD4(+) CD25(+) Foxp3(+) Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. Non-allergic infants showed stable total Treg frequencies over time; food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6); and food-allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Exposure-in-vivo containing interventions to improve work functioning of workers with anxiety disorder: a systematic review

    Directory of Open Access Journals (Sweden)

    Nieuwenhuijsen Karen

    2010-10-01

    Full Text Available Abstract Background Anxiety disorders are associated with functional disability, sickness absence, and decreased productivity. Effective treatments of anxiety disorders can result in remission of symptoms. However the effects on work related outcomes are largely unknown. Exposure in vivo is potentially well fit to improve work-related outcomes. This study systematically reviews the effectiveness of exposure-in-vivo containing interventions in reducing work-related adverse outcomes in workers with anxiety disorders. Methods A systematic study search was conducted in Medline, Cinahl, Embase and Psycinfo. Two reviewers independently extracted data and from each study assessed the quality of evidence by using the GRADE approach. We performed a meta-analysis if data showed sufficient clinical homogeneity. Results Seven studies containing 11 exposure-in-vivo interventions were included. Four studies were focused on Obsessive Compulsive Disorder (OCD, two on Post Traumatic Stress Disorder (PTSD, and one on a mixed group of OCD and severe phobias. The studies were grouped according to type of anxiety disorder and subsequently according to type of comparisons. For OCD, exposure-in-vivo containing interventions can yield better work-related outcomes compared to medication (SSRIs and relaxation but not better compared to response prevention. The results on anxiety outcomes were similar. The net contribution of exposure in vivo in two OCD intervention programs is also presented as a meta-analysis and shows significant positive results on work role limitations. The calculated pooled effect size with 95% confidence interval was 0.72 (0.28, 1.15. For PTSD, exposure-in-vivo containing interventions can yield better work-related and anxiety-related outcomes compared to a waiting-list but not better compared to imaginal exposure. Conclusions Exposure in vivo as part of an anxiety treatment can reduce work-related adverse outcomes in workers with OCD and PTSD

  2. Exposição a hidroquinona e ao fenol sobre a resposta inflamatória pulmonar induzida por bactéria Hydroquinone and phenol exposure on pulmonary inflammatory response induced by bacteria

    Directory of Open Access Journals (Sweden)

    Alexandre Ferreira

    2007-09-01

    compounds phenol (PHE and hydroquinone (HQ, are responsible for immunotoxicity. In this context, it has shown herein that male Wistar rats exposed to HQ (doses of 5 or 10 mg/kg/day; 13 days with 2-day intervals every 5 doses presented marked reduction in the number of mononuclear (MN and polymorphonuclear (PMN leukocytes in the bronchoalveolar fluid 24 hours after inhalation of Lipopolyssacaride of Salmonella abortus (LPS; 100 µg/mL. On the other hand, leukocyte migration into inflamed lungs was not altered in FE exposed rats, since values obtained were similar to those detected in control animals. Simultaneous exposure to HQ and PHE (5 mg/kg each compound maintained the decreased number of MN cells observed in HQ exposed rats and potentiated the reduction of PMN cells induced by HQ exposure. The impaired leukocyte migration into inflamed lung did not reflect alterations on number of circulating cells. Moreover, it is important to emphasize that schedule of intoxication did not alter the functional ability of liver and kidney, as detected by normal activity of transaminases and creatinine concentration in the serum. Therefore, it is shown herein that in vivo exposures to lower doses of HQ do not alter end points used as biological indicators of toxicity, nevertheless toxic effects are evident after a host defense.

  3. 210Pb in bone in vivo - a biodosimeter for assessing uranium miner radon progeny exposure

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Snipes, M.B.; Hoover, M.D.; Leggett, R.W.; Laurer, G.R.; Lambert, W.E.; Coons, T.A.; Gilliland, F.D.

    2002-01-01

    A joint analysis of the results of 11 epidemiological studies of lung cancer among uranium miners has shown a significant level of variability in the relative risk per unit of exposure - in the range of a factor of 30 (Lubin et al., 1994). A significant fraction of the uncertainty associated with these risk coefficients may be due to differences in the methods and quality of data used in calculating cumulative exposures, in WLM, for the various miner populations. We hypothesize that in vivo measurement of 210 Pb, a long-lived radon decay product that is retained in bone, will provide an improved measure of Rn progeny exposures received by individual miners during their mining careers. To accomplish such in vivo measurements, the lovelace in vivo bioassay facility (LIVBF) was modified to obtain an optimized counting geometry for measuring 210 Pb in the skull. Six 12.7 cm diameter phoswich detectors were positioned about the head of a reclining subject (one in the posterior, and one in the anterior position, and four about the mid-sagittal plane), and photon emission from the skull was measured using anticoincidence multichannel analysis electronics. We analyzed the in vivo data from about 90 former uranium miners from the grants mining district, and compared the recorded WLM exposures for each uranium miner (data from the UNM epidemiological data base) with a WLM exposure calculated using a model developed specifically for this study. This model couples a Pb biokinetic model with the ICRP publication 66 respiratory tract dosimetry model. The analyses show that the independent measurements of exposure are statistically correlated, but with a large degree of variability occurring among individual values, and that a major source of uncertainty in mining exposure estimation is the uncertainty involved in accounting for non-mining sources of 210 Pb. (orig.)

  4. Development and initial cohort validation of the Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ) for use across musculoskeletal care pathways.

    Science.gov (United States)

    Hill, Jonathan C; Kang, Sujin; Benedetto, Elena; Myers, Helen; Blackburn, Steven; Smith, Stephanie; Dunn, Kate M; Hay, Elaine; Rees, Jonathan; Beard, David; Glyn-Jones, Sion; Barker, Karen; Ellis, Benjamin; Fitzpatrick, Ray; Price, Andrew

    2016-08-05

    Current musculoskeletal outcome tools are fragmented across different healthcare settings and conditions. Our objectives were to develop and validate a single musculoskeletal outcome measure for use throughout the pathway and patients with different musculoskeletal conditions: the Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ). A consensus workshop with stakeholders from across the musculoskeletal community, workshops and individual interviews with a broad mix of musculoskeletal patients identified and prioritised outcomes for MSK-HQ inclusion. Initial psychometric validation was conducted in four cohorts from community physiotherapy, and secondary care orthopaedic hip, knee and shoulder clinics. Stakeholders (n=29) included primary care, physiotherapy, orthopaedic and rheumatology patients (n=8); general practitioners, physiotherapists, orthopaedists, rheumatologists and pain specialists (n=7), patient and professional national body representatives (n=10), and researchers (n=4). The four validation cohorts included 570 participants (n=210 physiotherapy, n=150 hip, n=150 knee, n=60 shoulder patients). Outcomes included the MSK-HQ's acceptability, feasibility, comprehension, readability and responder burden. The validation cohort outcomes were the MSK-HQ's completion rate, test-retest reliability and convergent validity with reference standards (EQ-5D-5L, Oxford Hip, Knee, Shoulder Scores, and the Keele MSK-PROM). Musculoskeletal domains prioritised were pain severity, physical function, work interference, social interference, sleep, fatigue, emotional health, physical activity, independence, understanding, confidence to self-manage and overall impact. Patients reported MSK-HQ items to be 'highly relevant' and 'easy to understand'. Completion rates were high (94.2%), with scores normally distributed, and no floor/ceiling effects. Test-retest reliability was excellent, and convergent validity was strong (correlations 0.81-0.88). A new

  5. Experimental studies on cytogenetic dosimetry for in vitro simulated and in vivo partial body exposure

    International Nuclear Information System (INIS)

    Han Baoguang; Chen Di; Jin Cuizhen; Liu Xiulin; Luo Yisheng

    1993-01-01

    The feasibility was examined of the contaminated Poisson distribution method as applied to dose estimation of in vitro simulated and in vivo partial body exposure of New Zealand rabbits. For this purpose, the preparatory experiments were conducted. Aberration yields were obtained for mixed cultures prepared from normal and irradiated peripheral lymphocytes with volume ratio 3 to 7 and for pure cultures of irradiated cells. Comparison of the dicentric yields from these two types of cultures indicated that the probability of cultured irradiated cells entering M 1 phase was exponentially decreased as the absorbed dose increased with a D 37 value of 2.41 Gy. Analysis of the dicentric yields obtained from pure cultures demonstrated that the dose-response relationship of dicentric yields was represented by a linear-quadratic model. Partial body exposures with irradiated fractions ranging from 90% to 30% were simulated by irradiating rabbit blood in vitro with 5 Gy 60 Co γ rays. The contaminated Poisson distribution method was utilized to derive the fraction of irradiated blood in the mixed culture and its absorbed dose. The results showed the estimations are in good agreement with true values. Moreover, the same results were arrived at for in vivo partial body irradiation in spite of many complicated factors inhered. Two groups of rabbits were irradiated in vivo on right halves along their backbones at 3.6 Gy and 5.0 Gy respectively. Heart blood was sampled 24 hours later. The result analysed by the same method approximated the true values. Before the in vivo irradiation, heart blood was sampled and irradiated in vitro to simulate half body and whole body exposure, which provided self-control for its in vivo data. These offered further proof for the previous results of in vitro simulated partial body exposure

  6. Virtual reality compared with in vivo exposure in the treatment of social anxiety disorder: a three-arm randomised controlled trial.

    Science.gov (United States)

    Bouchard, Stéphane; Dumoulin, Stéphanie; Robillard, Geneviève; Guitard, Tanya; Klinger, Évelyne; Forget, Hélène; Loranger, Claudie; Roucaut, François Xavier

    2017-04-01

    Background People with social anxiety disorder (SAD) fear social interactions and may be reluctant to seek treatments involving exposure to social situations. Social exposure conducted in virtual reality (VR), embedded in individual cognitive-behavioural therapy (CBT), could be an answer. Aims To show that conducting VR exposure in CBT for SAD is effective and is more practical for therapists than conducting exposure in vivo Method Participants were randomly assigned to either VR exposure ( n = 17), in vivo exposure ( n = 22) or waiting list ( n = 20). Participants in the active arms received individual CBT for 14 weekly sessions and outcome was assessed with questionnaires and a behaviour avoidance test. (Trial registration number ISRCTN99747069) Results Improvements were found on the primary (Liebowitz Social Anxiety Scale) and all five secondary outcome measures in both CBT groups compared with the waiting list. Conducting exposure in VR was more effective at post-treatment than in vivo on the primary outcome measure and on one secondary measure. Improvements were maintained at the 6-month follow-up. VR was significantly more practical for therapists than in vivo exposure. Conclusions Using VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure. © The Royal College of Psychiatrists 2017.

  7. 75 FR 33610 - Application To Export Electric Energy; H.Q. Energy Services (U.S.) Inc.

    Science.gov (United States)

    2010-06-14

    ... DEPARTMENT OF ENERGY [OE Docket No. EA-182-C] Application To Export Electric Energy; H.Q. Energy... electric energy from the United States to Canada pursuant to section 202(e) of the Federal Power Act (FPA... transmit electric energy from the United States to Canada as a power marketer using existing international...

  8. In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

    NARCIS (Netherlands)

    de Vos, Alex F.; Pater, Jennie M.; van den Pangaart, Petra S.; de Kruif, Martijn D.; van 't Veer, Cornelis; van der Poll, Tom

    2009-01-01

    In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative

  9. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    Science.gov (United States)

    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  10. PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-01-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses

  11. Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-07-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

  12. Quantitative determination of a synthetic amide derivative of gallic acid, SG-HQ2, using liquid chromatography tandem mass spectrometry, and its pharmacokinetics in rats.

    Science.gov (United States)

    Seo, Seung-Yong; Kang, Wonku

    2016-11-30

    An amide derivative of gallic acid (GA), 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2) was recently synthesized, and its inhibitory actions were previously shown on histamine release and pro-inflammatory cytokine expression. In this study, a simultaneous quantification method was developed for the determination of SG-HQ2 and its possible metabolite, GA, in rat plasma using liquid chromatography with a tandem mass spectrometry (LC-MS/MS). After simple protein precipitation with acetonitrile including diclofenac (internal standard, IS), the analytes were chromatographed on a reversed phased column with a mobile phase of acetonitrile and water (60:40, v/v, including 0.1% formic acid). The ion transitions of the precursor to the product ion were principally protonated ion [M+H] + at m/z 313.2→160.6 for SG-HQ2, and deprotonated ions [M-H] - at m/z 168.7→124.9 for GA and 296.0→251.6 for the IS. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was successfully applied to a pharmacokinetic study of SG-HQ2 after intravenous administration in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Assessing dietary exposure to cadmium in a metal recycling community in Vietnam: Age and gender aspects

    Energy Technology Data Exchange (ETDEWEB)

    Minh, Ngo Duc [Vietnamese Academy of Agriculture Sciences, Soils and Fertilizers Research Institute (SFRI), Tu Liem, Hanoi (Viet Nam); Hough, Rupert Lloyd, E-mail: rupert.hough@hutton.ac.uk [The James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH (United Kingdom); Thuy, Le Thi [Vietnamese Academy of Agriculture Science, Institute of Agricultural Environment (IAE), Tu Liem, Hanoi (Viet Nam); Nyberg, Ylva [Department of Crop Production Ecology, PO Box 7043, Swedish University of Agricultural Sciences (SLU), SE-750 07 Uppsala (Sweden); Mai, Le Bach [National Institute of Nutrition, 48b Tang Bat Ho, Hoan Kiem, Hanoi (Viet Nam); Vinh, Nguyen Cong [Vietnamese Academy of Agriculture Sciences, Soils and Fertilizers Research Institute (SFRI), Tu Liem, Hanoi (Viet Nam); Khai, Nguyen Manh [Faculty of Environmental Sciences, Ha Noi University of Science (HUS-VNU), 334 Nguyen Trai, Thanh Xuan, Ha Noi (Viet Nam); Oeborn, Ingrid [Department of Crop Production Ecology, PO Box 7043, Swedish University of Agricultural Sciences (SLU), SE-750 07 Uppsala (Sweden)

    2012-02-01

    This study estimates the dietary exposure to cadmium (Cd), and associated potential health risks, for individuals living and working in a metal recycling community (n = 132) in Vietnam in comparison to an agricultural (reference) community (n = 130). Individual-level exposure to Cd was estimated through analysis of staple foodstuffs combined with information from a food frequency questionnaire. Individual-level exposure estimates were compared with published 'safe' doses to derive a Hazard Quotient (HQ) for each member of the study population. Looking at the populations as a whole, there were no significant differences in the diets of the two villages. However, significantly more rice was consumed by working age adults (18-60 years) in the recycling village compared to the reference village (p < 0.001). Rice was the main staple food with individuals consuming 461 {+-} 162 g/d, followed by water spinach (103 {+-} 51 kg/d). Concentrations of Cd in the studied foodstuffs were elevated in the metal recycling village. Values of HQ exceeded unity for 87% of adult participants of the metal recycling community (39% had a HQ > 3), while 20% of adult participants from the reference village had an HQ > 1. We found an elevated health risk from dietary exposure to Cd in the metal recycling village compared to the reference community. WHO standard of 0.4 mg Cd/kg rice may not be protective where people consume large amounts of rice/have relatively low body weight. - Highlights: Black-Right-Pointing-Pointer First individual-level risk assessment of cadmium in recycling villages of Vietnam. Black-Right-Pointing-Pointer Dietary analysis undertaken for a recycling community and an agricultural community. Black-Right-Pointing-Pointer No significant differences were found between the diets of the two populations. Black-Right-Pointing-Pointer 87% of people in the recycling community had elevated health risk. Black-Right-Pointing-Pointer WHO standard (0.4 mg Cd/kg rice) may

  14. Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals.

    Science.gov (United States)

    Yamamura, Eiji; Aruga, Chinami; Muto, Shigeharu; Baba, Nobuyuki; Uno, Yoshifumi

    2018-01-01

    We examined the correlation between the results of in vitro and in vivo chromosomal damage tests by using in-house data of 18 pharmaceutical candidates that showed positive results in the in vitro chromosomal aberration or micronucleus test using CHL/IU cells, and quantitatively analyzed them especially in regard to exposure levels of the compounds. Eight compounds showed that the exposure levels [maximum plasma concentration (C max ) and AUC 0-24h ] were comparable with or higher than the in vitro exposure levels [the lowest effective (positive) concentration (LEC) and AUC vitro  = LEC (μg/mL) × treatment time (h)]. Among them, 3 compounds were positive in the in vivo rodent micronucleus assays using bone marrow cells. For 2 compounds, cytotoxicity might produce false-positive results in the in vitro tests. One compound showed in vitro positive results only in the condition with S9 mix which indicated sufficient concentration of unidentified active metabolite(s) might not reach the bone marrow to induce micronuclei. These facts suggested that the in vivo exposure levels being equal to or higher than the in vitro exposure levels might be an important factor to detect in vivo chromosomal damage induced by test chemicals.

  15. Monopole patch antenna for in vivo exposure to nanosecond pulsed electric fields.

    Science.gov (United States)

    Merla, C; Apollonio, F; Paffi, A; Marino, C; Vernier, P T; Liberti, M

    2017-07-01

    To explore the promising therapeutic applications of short nanosecond electric pulses, in vitro and in vivo experiments are highly required. In this paper, an exposure system based on monopole patch antenna is reported to perform in vivo experiments on newborn mice with both monopolar and bipolar nanosecond signals. Analytical design and numerical simulations of the antenna in air were carried out as well as experimental characterizations in term of scattering parameter (S 11 ) and spatial electric field distribution. Numerical dosimetry of the setup with four newborn mice properly placed in proximity of the antenna patch was carried out, exploiting a matching technique to decrease the reflections due to dielectric discontinuities (i.e., from air to mouse tissues). Such technique consists in the use of a matching dielectric box with dielectric permittivity similar to those of the mice. The average computed electric field inside single mice was homogeneous (better than 68 %) with an efficiency higher than 20 V m -1  V -1 for the four exposed mice. These results demonstrate the possibility of a multiple (four) exposure of small animals to short nanosecond pulses (both monopolar and bipolar) in a controlled and efficient way.

  16. 77 FR 72846 - H.Q. Energy Services (U.S.) Inc. v. ISO New England Inc.; Notice of Complaint

    Science.gov (United States)

    2012-12-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL13-25-000] H.Q. Energy Services (U.S.) Inc. v. ISO New England Inc.; Notice of Complaint Take notice that on November 28, 2012... ISO New England Inc. (Respondent), requesting the Commission to issue an order requiring the...

  17. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    International Nuclear Information System (INIS)

    Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

    2012-01-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p + CD8 − and peripheral CD4 + T cells was significantly reduced, whereas, CD8 + population was not affected. In contrast to conventional CD4 + T cells, Foxp3 + regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4 + T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4 + thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  18. Is virtual reality effective to motivate and raise interest in phobic children toward therapy? A clinical trial study of in vivo with in virtuo versus in vivo only treatment exposure.

    Science.gov (United States)

    St-Jacques, Julie; Bouchard, Stéphane; Bélanger, Claude

    2010-07-01

    The first objective of this study was to assess if a combined treatment with mostly virtual reality-based (in virtuo) exposure increases phobic children's motivation toward therapy compared to children who only receive in vivo exposure. Another objective was the assessment of motivation as a predictor of treatment outcome. Thirty-one DSM-IV-diagnosed arachnophobic participants aged from 8 to 15 years were randomly assigned to 1 of 2 treatment conditions: in vivo exposure alone or in virtuo plus in vivo exposure. Measures of motivation were taken at pretest and at the end of each part of the treatment; some other measures were taken at each session. The "Why Are You in Therapy?" questionnaire for children was the target measure of motivation and the main variable in the study. Outcome measures were taken at pretest, at the end of each part of the treatment, and at the 6-month follow-up. This study was conducted between September 2006 and March 2007. The results showed that children who received in virtuo exposure did not show a higher level of motivation toward their treatment than those who received in vivo exposure, but statistically significant interactions were found for both parts of the treatment. Multiple regression analysis confirmed that motivation was a significant predictor of outcome (P virtual reality did not increase motivation toward psychotherapy. At the end of the second part of therapy, all participants were comparably efficient in facing a live tarantula. These results bear important clinical implications concerning how to use virtual reality with children and concerning motivation of children toward therapy in general. They are discussed in the light of how to present in virtuo therapy to children. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

  19. Prediction of Relative In Vivo Metabolite Exposure from In Vitro Data Using Two Model Drugs: Dextromethorphan and Omeprazole

    Science.gov (United States)

    Lutz, Justin D.

    2012-01-01

    Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUCm/AUCp) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUCm/AUCp ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data. PMID:22010218

  20. Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Milton Levin

    2008-12-01

    Full Text Available The immunotoxic potential of domoic acid (DA, a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 µg/g b.w. and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 µM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr, a significant decrease in neutrophil phagocytosis (24-hr, a significant decrease in monocyte phagocytosis (48-hr, and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr. In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 µM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 µM, and significantly decreased at 100 µM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species.

  1. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Science.gov (United States)

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  2. Effect of Perinatal secondhand tobacco smoke exposure on in vivo and intrinsic airway structure/function in non-human primates

    International Nuclear Information System (INIS)

    Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.; Peake, Janice L.; Pinkerton, Kent E.

    2009-01-01

    Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in responsiveness. Pregnant rhesus monkeys were exposed to filtered air (FA) or SHS (1 mg/m 3 total suspended particulates) for 6 h/day, 5 days/week starting at 50 days gestational age. The mother/infant pairs continued the SHS exposures postnatally. At 3 months of age each infant: 1) had in vivo lung function measurements in response to inhaled methacholine, or 2) the right accessory lobe filled with agarose, precision-cut to 600 μm slices, and bathed in increasing concentrations of methacholine. The lumenal area of the central airway was determined using videomicrometry followed by fixation and histology with morphometry. In vivo tests showed that perinatal SHS increases baseline respiratory rate and decreases responsiveness to methacholine. Perinatal SHS did not alter intrinsic airway responsiveness in the bronchi. However in respiratory bronchioles, SHS exposure increased airway responsiveness at lower methacholine concentrations but decreased it at higher concentrations. Perinatal SHS did not change eosinophil profiles, epithelial volume, smooth muscle volume, or mucin volume. However it did increase the number of alveolar attachments in bronchi and respiratory bronchioles. In general, as mucin increased, airway responsiveness decreased. We conclude that perinatal SHS exposure alters in vivo and intrinsic airway responsiveness, and alveolar attachments

  3. Vasomotor function in rat arteries after ex vivo and intragastric exposure to food-grade titanium dioxide and vegetable carbon particles

    DEFF Research Database (Denmark)

    Jensen, Ditte Marie; Christophersen, Daniel Vest; Sheykhzade, Majid

    2018-01-01

    -grade particle exposure on vasomotor function and systemic oxidative stress in an ex vivo study and intragastrically exposed rats.Methods: In an ex vivo study, aorta rings from naive Sprague-Dawley rats were exposed for 30 min to food-grade TiO2 (E171), benchmark TiO2 (Aeroxide P25), food-grade vegetable carbon...... (E153) or benchmark carbon black (Printex 90). Subsequently, the vasomotor function was assessed in wire myographs. In an in vivo study, lean Zucker rats were exposed intragastrically once a week for 10 weeks to vehicle, E171 or E153. Doses were comparable to human daily intake. Vasomotor function...... no differences between groups.Conclusion: Gastrointestinal tract exposure to E171 and E153 was associated with modest albeit statistically significant alterations in the vasocontraction and vasorelaxation responses. Direct particle exposure to aorta rings elicited a similar type of response. The vasomotor...

  4. A new method for generating distributions of biomonitoring equivalents to support exposure assessment and prioritization.

    Science.gov (United States)

    Phillips, Martin B; Sobus, Jon R; George, Barbara J; Isaacs, Kristin; Conolly, Rory; Tan, Yu-Mei

    2014-08-01

    Biomonitoring data are now available for hundreds of chemicals through state and national health surveys. Exposure guidance values also exist for many of these chemicals. Several methods are frequently used to evaluate biomarker data with respect to a guidance value. The "biomonitoring equivalent" (BE) approach estimates a single biomarker concentration (called the BE) that corresponds to a guidance value (e.g., Maximum Contaminant Level, Reference Dose, etc.), which can then be compared with measured biomarker data. The resulting "hazard quotient" estimates (HQ=biomarker concentration/BE) can then be used to prioritize chemicals for follow-up examinations. This approach is used exclusively for population-level assessments, and works best when the central tendency of measurement data is considered. Complementary approaches are therefore needed for assessing individual biomarker levels, particularly those that fall within the upper percentiles of measurement distributions. In this case study, probabilistic models were first used to generate distributions of BEs for perchlorate based on the point-of-departure (POD) of 7μg/kg/day. These distributions reflect possible biomarker concentrations in a hypothetical population where all individuals are exposed at the POD. A statistical analysis was then performed to evaluate urinary perchlorate measurements from adults in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES). Each NHANES adult was assumed to have experienced repeated exposure at the POD, and their biomarker concentration was interpreted probabilistically with respect to a BE distribution. The HQ based on the geometric mean (GM) urinary perchlorate concentration was estimated to be much lower than unity (HQ≈0.07). This result suggests that the average NHANES adult was exposed to perchlorate at a level well below the POD. Regarding individuals, at least a 99.8% probability was calculated for all but two NHANES adults that a higher

  5. Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Marianne Pons

    2011-02-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly population. Debris (termed drusen below the retinal pigment epithelium (RPE have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV. The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1, pro-angiogenic vascular endothelial growth factor (VEGF and anti-angiogenic pigment epithelial derived factor (PEDF in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ, a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and

  6. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  7. Propensity of red blood cells to undergo P2X7 receptor-mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging.

    Science.gov (United States)

    Sophocleous, Reece A; Mullany, Phillip R F; Winter, Kelly M; Marks, Denese C; Sluyter, Ronald

    2015-08-01

    Phosphatidylserine (PS) exposure facilitates the removal of red blood cells (RBCs) from the circulation, potentially contributing to the loss of stored RBCs after transfusion, as well as senescent RBCs. Activation of the P2X7 receptor by extracellular adenosine 5'-triphosphate (ATP) can induce PS exposure on freshly isolated human RBCs, but whether this process occurs in stored RBCs or changes during RBC aging is unknown. RBCs were processed and stored according to Australian blood banking guidelines. PS exposure was determined by annexin V binding and flow cytometry. Efficacy of P2X antagonists was assessed by flow cytometric measurements of ATP-induced ethidium+ uptake in RPMI 8226 cells. Osmotic fragility was assessed by lysis in hypotonic saline. RBCs were fractionated by discontinuous density centrifugation. ATP (1 mmol/L) induced PS exposure on RBCs stored for less than 1 week. This process was near-completely inhibited by the P2X7 antagonists A438079 and AZ10606120 and the P2X1/P2X7 antagonist MRS2159 but not the P2X1 antagonist NF499. ATP-induced PS exposure on RBCs was not dependent on K+, Na+, or Cl- fluxes. ATP did not alter the osmotic fragility of stored RBCs. ATP-induced PS exposure was similar between RBCs of different densities. ATP-induced PS exposure was also similar between RBCs stored for less than 1 week or for 6 weeks. The propensity of RBCs to undergo P2X7-mediated PS exposure does not alter during in vivo and ex vivo aging. Thus, P2X7 activation is unlikely to be involved in the removal of senescent RBCs or stored RBCs after transfusion. © 2015 AABB.

  8. Fear of movement/(re)injury in chronic low back pain: education or exposure in vivo as mediator to fear reduction?

    Science.gov (United States)

    de Jong, Jeroen R; Vlaeyen, Johan W S; Onghena, Patrick; Goossens, Mariëlle E J B; Geilen, Mario; Mulder, Herman

    2005-01-01

    Clinical research of graded exposure in vivo with behavioral experiments in patients with chronic low back pain who reported fear of movement/(re)injury shows abrupt changes in self-reported pain-related fears and cognitions. The abrupt changes are more characteristics of insight learning rather than the usual gradual progression of trial and error learning. The educational session at the start of the exposure might have contributed to this insight. The current study examines the contribution of education and graded exposure versus graded activity in the reduction of pain-related fear and associated disability and physical activity. Six consecutive patients with chronic low back pain who reported substantial fear of movement/(re)injury were included in the study. After a no-treatment baseline measurement period, all the patients received a single educational session, followed again by a no-treatment period. Patients were then randomly assigned to either a graded exposure with behavioral experiments or an operant graded activity program. A diary was used to assess daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement. Standardized questionnaires of pain-related fear, pain vigilance, pain intensity, and pain disability were administered before and after each intervention and at the 6-month follow-up. An activity monitor was carried at baseline, during the interventions, and 1 week at 6-month follow-up. Randomization tests of the daily measures showed that improvements in pain-related fear and catastrophizing occurred after the education was introduced. The results also showed a further improvement when exposure in vivo followed the no-treatment period after the education and not during the operant graded activity program. Performance of relevant daily activities, however, were not affected by the educational session and improved significantly only in the exposure in vivo condition. All improvements remained at half

  9. IN VIVO EVIDENCE OF FREE RADICAL FORMATION IN THE RAT LUNG AFTER EXPOSURE TO AN EMISSION SOURCE AIR POLLUTION PARTICLE

    Science.gov (United States)

    Exposure to air pollution particles can be associated with increased human morbidity and mortality. The mechanism(s) of lung injury remains unknown. We tested the hypothesis that lung exposure to oil fly ash (an emission source air pollution particle) causes in vivo free radical ...

  10. Effect of diamond-like carbon coating on corrosion rate of machinery steel HQ 805

    Science.gov (United States)

    Slat, Winda Sanni; Malau, Viktor; Iswanto, Priyo Tri; Sujitno, Tjipto; Suprapto

    2018-04-01

    HQ 805 is known as a super strength alloys steel and widely applied in military equipment and, aircraft components, drilling device and so on. It is due to its excellent behavior in wear, fatigue, high temperature and high speed operating conditions. The weakness of this material is the vulnerablality to corrosion when employed in sour environments where hydrogen sulfide and chlorides are present. To overcome the problems, an effort should be made to improve or enhance the surface properties for a longer service life. There are varieties of coatings developed and used to improve surface material properties. There are several kinds of coating methods; chemical vapour deposition (CVD), physical vapour deposition (PVD), thermochemical treatment, oxidation, or plasma spraying. This paper presents the research result of the influence of Diamond-Like Carbon (DLC) coating deposited using DC plasma enhanced chemical vapor deposition (DC-PECVD) on corrosion rate (by potentiodynamic polarization method) of HQ 805 machinery steel. As a carbon sources, a mixture of argon (Ar) and methane (CH4) with ratio 76% : 24% was used in this experiment. The conditions of experiment were 400 °C of temperature, 1.2 mbar, 1.4 mbar, 1.6 mbar and 1.8 mbar of pressure of process. Investigated surface properties were hardness (microhardness tester), roughness (roughness test), chemical composition (Spectrometer), microstructure (SEM) and corrosion rate (potentiodynamic polarization). It has been found that the optimum condition with the lowest corrosion rate is at a pressure of 1.4 mbar with a deposition duration of 4 hours at a constant temperature of 400 °C. In this condition, the corrosion rate decreases from 12.326 mpy to 4.487 mpy.

  11. Exposure-in-vivo containing interventions to improve work functioning of workers with anxiety disorder : a systematic review

    NARCIS (Netherlands)

    Noordik, Erik; van der Klink, Jac J. L.; Klingen, Elmer F.; Nieuwenhuijsen, Karen; van Dijk, Frank J. H.

    2010-01-01

    Background: Anxiety disorders are associated with functional disability, sickness absence, and decreased productivity. Effective treatments of anxiety disorders can result in remission of symptoms. However the effects on work related outcomes are largely unknown. Exposure in vivo is potentially well

  12. Synthesis, crystal structure, growth, optical and third order nonlinear optical studies of 8HQ2C5N single crystal - An efficient third-order nonlinear optical material

    Energy Technology Data Exchange (ETDEWEB)

    Divya Bharathi, M.; Ahila, G.; Mohana, J. [Department of Physics, Presidency College, Chennai 600005 (India); Chakkaravarthi, G. [Department of Physics, CPCL Polytechnic College, Chennai 600068 (India); Anbalagan, G., E-mail: anbu24663@yahoo.co.in [Department of Nuclear Physics, University of Madras, Chennai 600025 (India)

    2017-05-01

    A neoteric organic third order nonlinear optical material 8-hydroxyquinolinium 2-chloro-5-nitrobenzoate dihydrate (8HQ2C5N) was grown by slow cooling technique using ethanol: water (1:1) mixed solvent. The calculated low value of average etch pit solidity (4.12 × 10{sup 3} cm{sup −2}) indicated that the title crystal contain less defects. From the single crystal X-ray diffraction data, it was endowed that 8HQ2C5N crystal belongs to the monoclinic system with centrosymmetric space group P2{sub 1}/c and the cell parameters values, a = 9.6546 (4) Ǻ, b = 7.1637(3) Ǻ, c = 24.3606 (12) Ǻ, α = γ = 90°, β = 92.458(2)° and volume = 1683.29(13) Ǻ{sup 3}. The FT-IR and FT-Raman spectrum were used to affirm the functional group of the title compound. The chemical structure of 8HQ2C5N was scrutinized by {sup 13}C and {sup 1}H NMR spectral analysis and thermal stability through the differential scanning calorimetry study. Using optical studies the lower cut-off wavelength and optical band gap of 8HQ2C5N were found to be 364 nm and 3.17 eV respectively. Using the single oscillator model suggested by Wemple – Didomenico, the oscillator energy (E{sub o}), the dispersion energy (E{sub d}) and static dielectric constant (ε{sub o}) were estimated. The third-order susceptibility were determined as Im χ{sup (3)} = 2.51 × 10{sup −5} esu and Re χ{sup (3)} = 4.46 × 10{sup −7} esu. The theoretical third-order nonlinear optical susceptibility χ{sup (3)} was calculated and the results were compared with experimental value. Photoluminescence spectrum of 8HQ2C5N crystal showed the yellow emission. The crystal had the single shot laser damage threshold of 5.562 GW/cm{sup 2}. Microhardness measurement showed that 8HQ2C5N belongs to a soft material category. - Highlights: • A new organic single crystals were grown and the crystal structure was reported. • Crystal possess, good transmittance, thermal and mechanical stability. • Single shot LDT value is found to be

  13. Health risk assessment of ambient air concentrations of benzene, toluene and xylene (BTX) in service station environments.

    Science.gov (United States)

    Edokpolo, Benjamin; Yu, Qiming Jimmy; Connell, Des

    2014-06-18

    A comprehensive evaluation of the adverse health effects of human exposures to BTX from service station emissions was carried out using BTX exposure data from the scientific literature. The data was grouped into different scenarios based on activity, location and occupation and plotted as Cumulative Probability Distributions (CPD) plots. Health risk was evaluated for each scenario using the Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. HQ50 and HQ95 > 1 were obtained with benzene in the scenario for service station attendants and mechanics repairing petrol dispensing pumps indicating a possible health risk. The risk was minimized for service stations using vapour recovery systems which greatly reduced the benzene exposure levels. HQ50 and HQ95 service station attendants than any other scenario.

  14. Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment

    International Nuclear Information System (INIS)

    Rovira, Joaquim; Nadal, Martí; Schuhmacher, Marta; Domingo, José L.

    2015-01-01

    Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10 −6 ) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. - Highlights: • We determined in skin-contact clothes the concentrations of a number of metals. • Dermal contact exposure and health risks for adults and for 1-year-old children were assessed. • Carcinogenic risks were considered as acceptable (<10 −6 ). • For non-carcinogenic risks, only Sb exceeded a 10% of the HQ for dermal contact with clothes

  15. 76 FR 23755 - Release of Draft Risk and Exposure Assessments and Final Integrated Review Plan for the National...

    Science.gov (United States)

    2011-04-28

    ... titled, ``Ozone National Ambient Air Quality Standards: Scope and Methods Plan for Health Risk and... Standards: Scope and Methods Plan for Welfare Risk and Exposure Assessment'' (REA Plan for the secondary... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 50 and 58 [EPA-HQ-OAR-2008-0699; FRL-9300-4] RIN 2060...

  16. MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Evan A. [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Birch, M. Eileen [National Institute for Occupational Safety and Health, Cincinnati, OH 45213 (United States); Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States)

    2015-11-01

    Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector

  17. The Evolution of Alq3 Films Exposure to Air

    OpenAIRE

    Wang, Min; Zhou, Yan; Hark, Sui Kong; Zhu, Xi

    2017-01-01

    Small molecular solar cell becomes more stable when a thin tris-(8-hydroxyquinoline) aluminum (Alq3) buffer layer instead of bathocuproine (BCP) is inserted between the active layer and electrode. In this work, we introduce a single layer device (ITO / Alq3 / Au) exposure to air to investigate the role of Alq3 in organic solar cells. The large PL intensity and undetectable Raman peaks of 8-hydroxyquinoline (8-Hq), a degradation product of Alq3 through chemical reaction, indicate that the degr...

  18. Measurement of charged-particle multiplicity distributions and their $H_q$ moments in hadronic Z decays at LEP

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Buijs, A.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; van Dalen, J.A.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; van Dierendonck, D.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Duinker, P.; Echenard, B.; Eline, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Ewers, A.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; van Gulik, R.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Hu, Y.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kafer, D.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Krenz, W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Lubelsmeyer, K.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mangeol, D.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Niessen, T.; Nisati, A.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Palomares, C.; Pandoulas, D.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Pothier, J.; Prokofev, D.O.; Prokofiev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, M.A.; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosier-Lees, S.; Roth, Stefan; Rosenbleck, C.; Roux, B.; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Sanders, M.P.; Schafer, C.; Schegelsky, V.; Schmidt-Kaerst, S.; Schmitz, D.; Schopper, H.; Schotanus, D.J.; Schwering, G.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Siedenburg, T.; Son, D.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobyov, A.A.; Wadhwa, M.; Wallraff, W.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wienemann, P.; Wilkens, H.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, A.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zilizi, G.; Zimmermann, B.; Zoller, M.

    2003-01-01

    The charged-particle multiplicity distribution and the inclusive momentum distribution, in terms of the variable $\\xi$, are measured for all hadronic events as well as for light-quark and b-quark events in $\\mathrm{e}^{+}\\mathrm{e}^{-}$ collisions at the Z pole. Moments of the charged-particle multiplicity distributions are calculated, and the peak positions of the $\\xi$ distributions determined. The multiplicity distributions are studied in terms of their $H_q$ moments. Their quasi-oscillations when plotted versus the rank of the moment are compared with different theoretical approaches.

  19. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    Science.gov (United States)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  20. Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rovira, Joaquim [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Nadal, Martí [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Schuhmacher, Marta [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Domingo, José L., E-mail: joseluis.domingo@urv.cat [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain)

    2015-07-15

    Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10{sup −6}) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. - Highlights: • We determined in skin-contact clothes the concentrations of a number of metals. • Dermal contact exposure and health risks for adults and for 1-year-old children were assessed. • Carcinogenic risks were considered as acceptable (<10{sup −6}). • For non-carcinogenic risks, only Sb exceeded a 10% of the HQ for dermal contact with clothes.

  1. In vivo exposure to northern diatoms arrests sea urchin embryonic development.

    Science.gov (United States)

    Gudimova, Elena; Eilertsen, Hans C; Jørgensen, Trond Ø; Hansen, Espen

    2016-01-01

    There are numerous reports indicating that marine diatoms may act harmful to early developmental stages of invertebrates. It is believed that the compounds responsible for these detrimental effects are oxylipins resulting from oxidized polyunsaturated fatty acids, and that they may function as grazing deterrents. Most studies reporting these effects have exposed test organisms to diatom extracts or purified toxins, but data from in vivo exposure to intact diatoms are scarce. We have conducted sea urchin egg incubation and plutei feeding experiments to test if intact diatom cells affected sea urchin embryo development and survival. This was done by exposing the common northern sea urchins Strongylocentrotus droebachiensis and Echinus acutus to northern strains of the diatoms Chaetoceros socialis, Skeletonema marinoi, Chaetoceros furcellatus, Attheya longicornis, Thalassiosira gravida and Porosira glacialis. The intact diatom cell suspensions were found to inhibit sea urchin egg hatching and embryogenesis. S. marinoi was the most potent one as it caused acute mortality in S. droebachiensis eggs after only four hours exposure to high (50 μg/L Chla) diatom concentrations, as well as 24 h exposure to normal (20 μg/L Chla) and high diatom concentrations. The second most potent species was T. gravida that caused acute mortality after 24 h exposure to both diatom concentrations. A. longicornis was the least harmful of the diatom species in terms of embryo development arrestment, and it was the species that was most actively ingested by S. droebachiensis plutei. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Exposure to low mercury concentration in vivo impairs myocardial contractile function

    International Nuclear Information System (INIS)

    Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2011-01-01

    Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl 2 (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and β-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na + -K + ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: → Unchanges blood pressure, heart rate, systolic pressure. → Increases end diastolic pressure. → Promotes cardiac contractility dysfunction. → Decreases NKA activity, NCX and SERCA, increases PLB protein expression. → Small concentrations constitutes

  3. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2018-01-01

    Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

  4. Hemocyte responses of Dreissena polymorpha following a short-term in vivo exposure to titanium dioxide nanoparticles: Preliminary investigations

    Energy Technology Data Exchange (ETDEWEB)

    Couleau, Nicolas; Techer, Didier [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Pagnout, Christophe [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); International Consortium for the Environmental Implications of Nanotechnology, iCEINT, http://www.i-ceint.org (France); Jomini, Stephane [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); Foucaud, Laurent; Laval-Gilly, Philippe; Falla, Jairo [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Bennasroune, Amar, E-mail: amar.bennasroune@univ-metz.fr [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France)

    2012-11-01

    The widespread use of titanium-based nanoparticles and their environmental release may pose a significant risk to aquatic organisms within freshwater ecosystems. Suspension-feeder invertebrates like bivalve molluscs represent a unique target group for nanoparticle toxicology. The aim of this work was to investigate the short-term responses of Dreissena polymorpha hemocytes after in vivo exposure to titanium dioxide nanoparticles (TiO{sub 2} NP). For this purpose, freshwater mussels were exposed to P25 TiO{sub 2} NP at the concentrations of 0.1, 1, 5 and 25 mg/L during 24 h. Viability, phagocytosis activity and mitogen activated protein kinase (MAPK) phosphorylation level of ERK 1/2 and p38 in hemocytes extracted from exposed mussels were compared to those from control specimens. Results demonstrated an inhibition of the phagocytosis activity after exposure to TiO{sub 2} NP at 0.1 and 1 mg/L. Similar trends, albeit less pronounced, were reported for higher concentrations of NP. Transmission electron microscopy showed for the first time the internalization of TiO{sub 2} NP into Dreissena polymorpha hemocytes. Besides, exposure to NP increased the ERK 1/2 phosphorylation levels in all treatments. Concerning the phosphorylation level of p38, only exposures to 5 and 25 mg/L of NP induced significant p38 activation in comparison to that of the control. Finally, these short-term effects observed at environmentally relevant concentrations highlighted the need for further studies concerning ecotoxicological evaluation of nanoparticle release into an aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Phagocytosis inhibition at TiO{sub 2} NP exposure concentrations of 0.1 and 1 mg/L. Black-Right-Pointing-Pointer Internalization of TiO{sub 2} NP in freshwater mussel hemocytes. Black-Right-Pointing-Pointer Increased phosphorylation level of p38 and ERK 1/2 after in vivo exposure to TiO{sub 2} NP.

  5. Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

    International Nuclear Information System (INIS)

    Burroughs, S.F.; Johnson, G.J.

    1990-01-01

    beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane

  6. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function

    Science.gov (United States)

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N.; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-07-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects.

  7. On the history of the quantum. Introduction to the HQ4 special issue

    Science.gov (United States)

    Navarro, Jaume; Blum, Alexander; Lehner, Christoph

    2017-11-01

    Eight years ago, a special issue in this journal published a dozen papers with new studies on the history of quantum physics. That issue was an output of a conference in Utrecht one year earlier, the second in a series organized by the then existing large-scale project coordinated by the Max Planck Institute for the History of Science and the Fritz Haber Institute. Since then, that project has produced a number of publications, workshops and other academic outcomes, but more importantly, it triggered the consolidation of an international community of historians and philosophers of science producing novel work on the history of quantum physics. Five years after the third meeting, which took place in Berlin in 2010, many of the scholars from that group and some new ones met for four days in Donostia/San Sebastian for the HQ4 meeting. The time was ripe for new results to be shared and discussed, and this issue collects some of the papers presented at that gathering.

  8. Persistent DNA damage after high dose in vivo gamma exposure of minipig skin.

    Directory of Open Access Journals (Sweden)

    Emad A Ahmed

    Full Text Available Exposure to high doses of ionizing radiation (IR can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin.IR-induced DNA damage, repair and cellular survival were studied in 15 cm(2 of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of 3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+ were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days.Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios.

  9. Assessing the Risk of Hg Exposure Associated with Rice Consumption in a Typical City (Suzhou) in Eastern China.

    Science.gov (United States)

    Wang, Gang; Gong, Yu; Zhu, Yi-Xin; Miao, Ai-Jun; Yang, Liu-Yan; Zhong, Huan

    2017-05-12

    Recent studies have revealed that not only fish but also rice consumption may significantly contribute to human exposure to mercury (Hg) in Asian countries. It is therefore essential to assess dietary exposure to Hg in rice and its associated health risk. However, risk assessments of Hg in rice in non-contaminated areas are generally lacking in Asian countries. In the present study, Hg concentrations were measured in rice samples collected from markets and supermarkets in Suzhou, a typical city in Eastern China. In addition, the rice ingestion rates (IR) were assessed via a questionnaire-based survey of Suzhou residents. The data were then used to assess the risk of Hg exposure associated with rice consumption, by calculating the hazard quotient (HQ). Hg contents in rice samples were well below the national standard (20 μg/kg), ranging from 1.46 to 8.48 ng/g. They were also significantly ( p > 0.05) independent of the area of production and place of purchase (markets vs. supermarkets in the different districts). Our results indicate a low risk of Hg exposure from rice in Suzhou (HQ: 0.005-0.05), despite the generally high personal IR (0.05-0.4 kg/day). The risk of Hg associated with rice consumption for Suzhou residents was not significantly affected by the age or sex of the consumer ( p > 0.05). Overall, our results provide a study of human exposure to Hg in rice in Chinese cities not known to be contaminated with Hg. Future studies should examine Hg exposure in different areas in China and in potentially vulnerable major food types.

  10. In vivo measurements of lead-210 for assessing cumulative radon exposure in uranium miners

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Laurer, G.R.; Lambert, W.E.; Gilliland, F.D.

    1995-01-01

    It has long been recognized that a major contributor to the uncertainty in risk analysis of lung cancer in uranium and other hard rock miners is the estimation of total radon progeny exposure of individual miners under study. These uncertainties arise from the fact that only a limited number of measurements of airborne 222 Rn progeny concentrations were made in the mines during the times that the miners were being exposed, and that dosimeters capable of integrating the Rn progeny exposures of the miners did not exist. Historically, the cumulative exposures for individual uranium and other hard rock miners have been calculated by combining the employee's work history, which may or may not have included time spent at different jobs within the mines and at different locations within the mines, with whatever periodic measurements of Rn and Rn progeny were available. The amount and quality of the measurement data varied enormously from mine to mine and from population to population. Because the quality of the exposure data collected during the period of active mining in the United STates cannot now be altered substantially, significant improvement in individual miner exposure estimates is only likely to be achieved if a new cumulative exposure metric is developed and implemented. The decay chain of Rn includes the production of 210 Pb, which can accumulate in the skeleton in amounts proportional to the intake of Rn progeny. We hypothesize that the in vivo measurement of 210 Pb in the skulls of miners will provide such a metric. In summary, the primary purpose of this pilot study to demonstrate the feasibility of measuring 210 Pb in the heads of former uranium miners has been accomplished

  11. Assessing dietary exposure to cadmium in a metal recycling community in Vietnam: Age and gender aspects

    International Nuclear Information System (INIS)

    Minh, Ngo Duc; Hough, Rupert Lloyd; Thuy, Le Thi; Nyberg, Ylva; Mai, Le Bach; Vinh, Nguyen Cong; Khai, Nguyen Manh; Öborn, Ingrid

    2012-01-01

    This study estimates the dietary exposure to cadmium (Cd), and associated potential health risks, for individuals living and working in a metal recycling community (n = 132) in Vietnam in comparison to an agricultural (reference) community (n = 130). Individual-level exposure to Cd was estimated through analysis of staple foodstuffs combined with information from a food frequency questionnaire. Individual-level exposure estimates were compared with published ‘safe’ doses to derive a Hazard Quotient (HQ) for each member of the study population. Looking at the populations as a whole, there were no significant differences in the diets of the two villages. However, significantly more rice was consumed by working age adults (18–60 years) in the recycling village compared to the reference village (p 3), while 20% of adult participants from the reference village had an HQ > 1. We found an elevated health risk from dietary exposure to Cd in the metal recycling village compared to the reference community. WHO standard of 0.4 mg Cd/kg rice may not be protective where people consume large amounts of rice/have relatively low body weight. - Highlights: ► First individual-level risk assessment of cadmium in recycling villages of Vietnam. ► Dietary analysis undertaken for a recycling community and an agricultural community. ► No significant differences were found between the diets of the two populations. ► 87% of people in the recycling community had elevated health risk. ► WHO standard (0.4 mg Cd/kg rice) may not be protective for rice-based cultures.

  12. In-vivo measurements of Pb-210 to determine cumulative exposure to radon daughters: A pilot study

    International Nuclear Information System (INIS)

    Laurer, G.R.; Cohen, N.; Stark, A.; Ju, C.

    1991-05-01

    The objective of this study is to demonstrate the feasibility of estimating cumulative exposure of individuals to low concentrations of radon by measuring the amount of Pb-A-10 in their skeletons. This report presents progress to date establishing the validity of an vivo technique to measure skeletal burdens of Pb-210, accumulated from exposure to radon and radon progeny. With the skeletal content of Pb--210 and a model for Pb metabolism, cumulative exposure to radon and its short-lived daughters (radon/daughters) may be calculated for use in deriving a dose-response relationship between lung cancer and exposure to radon/daughters. Data are presented for 29 subjects exposed to ''above-average'' radon concentrations in their homes, showing the correlation between measured Pb--210 burdens, and measured pCi/l and WLM exposure estimates. Their results are compared to measurements of a population of 24 subject's presumed exposed to average concentrations. Measurements of a Pennsylvania family exposed for a year in a home with an extremely high radon content are also presented. Update of results of an ongoing study of the biological half-time of Pb--210 in man involving measurements, of a retired radiation worker with a 40 year old skeletal burden of Pb-210

  13. Effects of depleted uranium chronic exposure on detoxification systems in vivo and in vitro

    International Nuclear Information System (INIS)

    Rouas, C.

    2010-01-01

    Uranium (U) is a heavy metal naturally presents in the environment. The aim of this work is to study effects of a U exposure on organs involved in the detoxification: the kidney and the liver (and notably the xenobiotics metabolizing enzymes (XME)). In order to mimic population chronic exposure, rats were contaminated during 9 months through the drinking water (40 mg/L). In vivo results show that U, in our experimental conditions, does not induce neither nephrotoxicity nor sensitivity to increase a renal toxicity induced by gentamicin. In the liver, U provokes impairments on the XME gene expression, particularly CYP3A. Nevertheless, paracetamole metabolism is modified only if it is administrated at a hepatotoxic dose. The in vitro results suggest an indirect effect of uranium on the XME, probably dependant of body adaptation mechanisms. Besides, in vitro studies were underline cytotoxic properties of U as well as the localisation of its soluble and/or participated forms in cytoplasmic and nuclear compartment. (author)

  14. Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

  15. Prevalidation of in vitro continuous flow exposure systems as alternatives to in vivo inhalation safety evaluation experimentations: outcome from MAAPHRI-PCRD5 research program.

    Science.gov (United States)

    Morin, Jean-Paul; Hasson, Virginie; Fall, Mamadou; Papaioanou, Eleni; Preterre, David; Gouriou, Frantz; Keravec, Veronika; Konstandopoulos, Athanasios; Dionnet, Frédéric

    2008-06-01

    Diesel engine emission aerosol-induced toxicity patterns were compared using both in vitro (organotypic cultures of lung tissue) and in vivo experimentations mimicking the inhalation situation with continuous aerosol flow exposure designs. Using liquid media resuspended diesel particles, we show that toxic response pattern is influenced by the presence of tensioactive agent in the medium which alter particle-borne pollutant bioavailability. Using continuous aerosol exposure in vitro, we show that with high sulfur fuel (300ppm) in the absence of oxidation catalysis, particulate matter was the main toxic component triggering DNA damage and systemic inflammation, while a very limited oxidant stress was evidenced. In contrast, with ultra-low sulfur fuel in the presence of strong diesel oxidation catalysis, the specific role of particulate matter is no longer evidenced and the gas phase then becomes the major component triggering strong oxidant stress, increased NO(2) being the most probable trigger. In vivo, plasma tumor necrosis factor alpha (TNFalpha), lung superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity levels varied in agreement with in vitro observations. Diesel emission treatment with oxycat provokes a marked systemic oxidant stress. Again NO(2) proved to account for a major part of these impacts. In conclusion, similar anti-oxidant responses were observed in in vitro and in vivo experiments after diesel emission aerosol continuous flow exposures. The lung slice organotypic culture model-exposed complex aerosol appears to be a very valuable alternative to in vivo inhalation toxicology experimentations in rodents.

  16. In vivo measurements of lead-210 for assessing cumulative radon exposure in uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R.A.; Laurer, G.R. [New York Univ. Inst. of Environmental Medicine, Tuxedo, NY (United States); Lambert, W.E.; Gilliland, F.D. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    It has long been recognized that a major contributor to the uncertainty in risk analysis of lung cancer in uranium and other hard rock miners is the estimation of total radon progeny exposure of individual miners under study. These uncertainties arise from the fact that only a limited number of measurements of airborne {sup 222}Rn progeny concentrations were made in the mines during the times that the miners were being exposed, and that dosimeters capable of integrating the Rn progeny exposures of the miners did not exist. Historically, the cumulative exposures for individual uranium and other hard rock miners have been calculated by combining the employee`s work history, which may or may not have included time spent at different jobs within the mines and at different locations within the mines, with whatever periodic measurements of Rn and Rn progeny were available. The amount and quality of the measurement data varied enormously from mine to mine and from population to population. Because the quality of the exposure data collected during the period of active mining in the United STates cannot now be altered substantially, significant improvement in individual miner exposure estimates is only likely to be achieved if a new cumulative exposure metric is developed and implemented. The decay chain of Rn includes the production of {sup 210}Pb, which can accumulate in the skeleton in amounts proportional to the intake of Rn progeny. We hypothesize that the in vivo measurement of {sup 210}Pb in the skulls of miners will provide such a metric. In summary, the primary purpose of this pilot study to demonstrate the feasibility of measuring {sup 210}Pb in the heads of former uranium miners has been accomplished.

  17. Occurrence, sources and human exposure assessment of SCCPs in indoor dust of northeast China.

    Science.gov (United States)

    Liu, Li-Hua; Ma, Wan-Li; Liu, Li-Yan; Huo, Chun-Yan; Li, Wen-Long; Gao, Chong-Jing; Li, Hai-Ling; Li, Yi-Fan; Chan, Hing Man

    2017-06-01

    Short-chain chlorinated paraffins (SCCPs) are widely used chemicals in household products and might cause adverse human health effects. However, limited information is available on the occurrence of SCCPs in indoor environments and their exposure risks on humans. In this study the concentrations, profiles and human exposure of SCCPs in indoor dust from five different indoor environments, including commercial stores, residential apartments, dormitories, offices and laboratories were characterized. The SCCPs levels ranged from 10.1 to 173.0 μg/g, with the median and mean concentration of 47.2 and 53.6 μg/g, respectively. No significant difference was found on concentrations among the five microenvironments. The most abundant compounds in indoor dust samples were homologues of C 13 group, Cl 7 group and N 20 (N is the total number of C and Cl) group. In the five microenvironments, commercial stores were more frequently exposed to shorter carbon chained and higher chlorinated homologues. Three potential sources for SCCPs were identified by the multiple linear regression of factor score model and correspondence analysis. The major sources of SCCPs in indoor dust were technical mixtures of CP-42 (42% chlorine, w/w) and CP-52 b (52% chlorine, w/w). The total daily exposure doses and hazard quotients (HQ) were calculated by the human exposure models, and they were all below the reference doses and threshold values, respectively. Monte Carlo simulation was applied to predict the human exposure risk of SCCPs. Infants and toddlers were at risk of SCCPs based on predicted HQ values, which were exceeded the threshold for neoplastic effects in the worst case. Our results on the occurrences, sources and human exposures of SCCPs will be useful to provide a better understanding of SCCPs behaviors in indoor environment in China, and to support environmental risk evaluation and regulation of SCCPs in the world. Copyright © 2017. Published by Elsevier Ltd.

  18. Evaluation of internal exposure of nuclear medicine staff through in vivo and in vitro bioassay techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lucena, E.A.; Araujo, F.; Sousa, W.O.; Dantas, A.L.A.; Dantas, B.M. [Instituto de Radioprotecao e Dosimetria, CNEN, Av. Salvador Allende s/n, CEP 22780-160 Rio de Janeiro (Brazil); Rebelo, A.M.O.; Corbo, R. [Hospital Universitario Clementino Fraga Filho, HU-UFRJ, Av. Brigadeiro Trompowsky, s/n, ILHA do Fundao, CEP 21945-560, Rio de Janeiro, RJ (Brazil)

    2007-07-01

    The manipulation of a wide variety of unsealed sources in Nuclear Medicine results in a significant risk of internal exposure of the workers. {sup 131}I should be highlighted among the most frequently used radionuclides because of its large application for diagnosis and therapy of thyroid diseases. The increasing use of radionuclides for medical purposes creates a demand for feasible methodologies to perform occupational control of internal contamination. Currently in Brazil, there are {approx}300 nuclear medicine centres in operation but individual monitoring is still restricted to the control of external exposure. This work presents the development of in vivo and in vitro bioassay techniques aimed to quantify incorporation of radionuclides used in Nuclear Medicine. It is also presented the results of a preliminary survey of internal exposure of a group of workers involved in the preparation of therapeutic doses of {sup 131}I. Workers were monitored with a gamma camera available in the Nuclear Medicine Service of the University Hospital of Rio de Janeiro and at the Institute of Radiation Protection and Dosimetry Whole-Body Counter (IRDWBC). The in vivo detection systems were calibrated with a neck-thyroid phantom developed in IRD. Urine samples from radiopharmacy workers were collected after preparation and administration of therapeutic doses (10-250 mCi) of {sup 131}I and measured with a HPGe detection system available in the Bioassay Laboratory of IRD. The results show that the bioassay methods developed in this work present enough sensitivity for routine monitoring of nuclear medicine workers. All workers monitored in this survey presented positive results for {sup 131}I in urine samples and two workers presented detectable activities in thyroid when measured at the IRD-WBC. The highest committed effective dose per preparation was estimated to be 17 {mu}Sv. (authors)

  19. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

    International Nuclear Information System (INIS)

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

    2009-01-01

    Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks α7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-β-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 μg/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

  20. Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takeshi [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Haradahira, Terushi [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)], E-mail: terushi@niu.ac.jp; Fujimoto, Noriko [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Okauchi, Takashi; Maeda, Jun; Suzuki, Kazutoshi; Suhara, Tetsuya [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Yamamoto, Fumihiko; Sasaki, Shigeki; Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Yamaguchi, Hiroshi [Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Maeda, Minoru [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-02-15

    High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[{sup 11}C]methoxyphenyl)-2(1H)-quinolone ([{sup 11}C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-D-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[{sup 11}C]4HQ (5Et-[{sup 11}C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[{sup 11}C]4HQ (5I-[{sup 11}C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[{sup 11}C]4HQ and 5I-[{sup 11}C]4HQ was quite similar to that previously observed between [{sup 11}C]L-703,717 and [{sup 11}C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these {sup 11}C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[{sup 11}C]4HQ at 1 min after intravenous injections were comparable to that of [{sup 11}C]4HQ, but they were 1.3-2.1 times higher than that of [{sup 11}C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [{sup 11}C]4HQ and 5Et-[{sup 11}C]4HQ in contrast to [{sup 11}C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[{sup 11}C]4HQ (16-36% inhibition) but not that of 5I-[{sup 11}C]4HQ. In this study, it was found that a small structural change in [{sup 11}C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [{sup 11}C]4-hydroxyquinolones on the NMDA ion channel

  1. Consequences of exposure to ionizing radiation for effector T cell function in vivo

    International Nuclear Information System (INIS)

    Rouse, B.T.; Hartley, D.; Doherty, P.C.

    1989-01-01

    The adoptive transfer of acutely primed and memory virus-immune CD8+ T cells causes enhanced meningitis in both cyclophosphamide (Cy) suppressed, and unsuppressed, recipients infected with lymphocytic choriomeningitis virus (LCMV). The severity of meningitis is assessed by counting cells in cerebrospinal fluid (CSF) obtained from the cisterna magna, which allows measurement of significant inflammatory process ranging from 3 to more than 300 times the background number of cells found in mice injected with virus alone. Exposure of the donor immune population to ionizing radiation prior to transfer has shown that activated T cells from mice primed 7 or 8 days previously with virus may still promote a low level of meningitis in unsuppressed recipients following as much as 800 rads, while this effect is lost totally in Cy-suppressed mice at 600 rads. Memory T cells are more susceptible and show no evidence of in vivo effector function in either recipient population subsequent to 400 rads, a dose level which also greatly reduces the efficacy of acutely-primed T cells. The results are interpreted as indicating that heavily irradiated cells that are already fully functional show evidence of primary localization to the CNS and a limited capacity to cause pathology. Secondary localization, and events that require further proliferation of the T cells in vivo, are greatly inhibited by irradiation

  2. Consequences of exposure to ionizing radiation for effector T cell function in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rouse, B.T.; Hartley, D.; Doherty, P.C. (Univ. of Tennessee, Knoxville (USA))

    1989-01-01

    The adoptive transfer of acutely primed and memory virus-immune CD8+ T cells causes enhanced meningitis in both cyclophosphamide (Cy) suppressed, and unsuppressed, recipients infected with lymphocytic choriomeningitis virus (LCMV). The severity of meningitis is assessed by counting cells in cerebrospinal fluid (CSF) obtained from the cisterna magna, which allows measurement of significant inflammatory process ranging from 3 to more than 300 times the background number of cells found in mice injected with virus alone. Exposure of the donor immune population to ionizing radiation prior to transfer has shown that activated T cells from mice primed 7 or 8 days previously with virus may still promote a low level of meningitis in unsuppressed recipients following as much as 800 rads, while this effect is lost totally in Cy-suppressed mice at 600 rads. Memory T cells are more susceptible and show no evidence of in vivo effector function in either recipient population subsequent to 400 rads, a dose level which also greatly reduces the efficacy of acutely-primed T cells. The results are interpreted as indicating that heavily irradiated cells that are already fully functional show evidence of primary localization to the CNS and a limited capacity to cause pathology. Secondary localization, and events that require further proliferation of the T cells in vivo, are greatly inhibited by irradiation.

  3. Mechanism and manipulation of DNA:RNA hybrid G-quadruplex formation in transcription of G-rich DNA.

    Science.gov (United States)

    Zhang, Jia-yu; Zheng, Ke-wei; Xiao, Shan; Hao, Yu-hua; Tan, Zheng

    2014-01-29

    We recently reported that a DNA:RNA hybrid G-quadruplex (HQ) forms during transcription of DNA that bears two or more tandem guanine tracts (G-tract) on the nontemplate strand. Putative HQ-forming sequences are enriched in the nearby 1000 nt region right downstream of transcription start sites in the nontemplate strand of warm-blooded animals, and HQ regulates transcription under both in vitro and in vivo conditions. Therefore, knowledge of the mechanism of HQ formation is important for understanding the biological function of HQ as well as for manipulating gene expression by targeting HQ. In this work, we studied the mechanism of HQ formation using an in vitro T7 transcription model. We show that RNA synthesis initially produces an R-loop, a DNA:RNA heteroduplex formed by a nascent RNA transcript and the template DNA strand. In the following round of transcription, the RNA in the R-loop is displaced, releasing the RNA in single-stranded form (ssRNA). Then the G-tracts in the RNA can jointly form HQ with those in the nontemplate DNA strand. We demonstrate that the structural cascade R-loop → ssRNA → HQ offers opportunities to intercept HQ formation, which may provide a potential method to manipulate gene expression.

  4. Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects

    International Nuclear Information System (INIS)

    Fracchiolla, Nicola Stefano; Todoerti, Katia; Bertazzi, Pier Alberto; Servida, Federica; Corradini, Paolo; Carniti, Cristiana; Colombi, Antonio; Cecilia Pesatori, Angela; Neri, Antonino; Deliliers, Giorgio Lambertenghi

    2011-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic diseases, diabetes, infertility, cancers and immunotoxicity. We analysed the in vitro TCDD effects on human CD34 + cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 257 differentially modulated probe sets, identifying 221 well characterized genes. A large part of these resulted associated to cell adhesion and/or angiogenesis and to transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34 + cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems. Our data support a role of dioxin in the neoplastic transformation of hemopoietic stem cells and in immune modulation processes after in vivo exposure, as indicated by the epidemiologic data in dioxin accidentally exposed populations, providing a molecular basis for it. In addition, TCDD alters genes associated to glucidic and lipidic metabolisms, to GABAergic transmission or involved in male and female fertility, thus providing a possible explanation of the diabetogenic, dyslipidemic, neurologic and fertility effects induced by TCDD in vivo exposure.

  5. Development, implementation and utilization of 210Pb in vivo measurement techniques as indicator of human being exposure to 222Rn - evaluation of associated parameters

    International Nuclear Information System (INIS)

    Dantas, Ana Leticia Almeida

    2005-01-01

    Radon and its decay products are present in the atmosphere and are the most important contributors for the internal exposure of humans to natural radiation. The execution of in vivo measurements of 210 Pb in the population and in individuals occupationally exposed in underground mines has been studied and recommended as one of the procedures for the estimation of the exposure to 222 Rn. The metabolism of 210 Pb and its distribution within the human body, mainly deposited in the bone tissue, suggests the regions of skull and knee as the most suitable for the in vivo monitoring of such radionuclide. A radiological survey in non uranium mines in Brazil indicated that an underground coal mine in the State of Parana, in the south of Brazil, had high radon concentration. The aim of this work were: (1) To investigate whether underground coal miners may also have elevated 210 Pb in the skeleton as a result of occupational exposure to radon in the coal mine; (2) To estimate the committed equivalent dose and the committed effective dose in different incorporation scenarios using a computer code. The calibration and the in vivo measurements of underground coal miners were performed in the IRD-CNEN Whole Body Counter shielded room using an array of four high resolution germanium detectors. The detection system was positioned at the head and knee geometries. The minimum detectable quantity of 210 Pb in the skeleton using this methodology was (50 Bq) and the positive results were verified using a mathematical method that applies a moving median smoothing function to the total spectrum for each measurement. In vivo measurements of 210 Pb in 6 out of the 32 underground coal miners ranged between 83 Bq and 164 Bq suggesting that these workers received significant occupational cumulative exposure to 222 Rn. The simulation of some exposure patterns of 222 Rn progeny and 210 Pb incorporation showed that the most important contribution for 210 Pb skeleton deposition was the intake of

  6. In Vivo acrylamide exposure may cause severe toxicity to mouse oocytes through its metabolite glycidamide.

    Directory of Open Access Journals (Sweden)

    Duru Aras

    Full Text Available High acrylamide (ACR content in heat-processed carbohydrate-rich foods, as well as roasted products such as coffee, almonds etc., has been found to be as a risk factor for carcinogenicity and genotoxicity by The World Health Organization. Glycidamide (GLY, the epoxide metabolite of ACR, is processed by the cytochrome P-450 enzyme system and has also been found to be a genotoxic agent. The aim of this study was to determine whether ACR and/or GLY have any detrimental effect on the meiotic cell division of oocytes. For this purpose, germinal vesicle-stage mouse oocytes were treated with 0, 100, 500, or 1000 μM ACR or 0, 25, or 250 μM GLY in vitro. In vivo experiments were performed after an intraperitoneal injection of 25 mg/kg/day ACR of female BALB/c mice for 7 days. The majority of in vitro ACR-treated oocytes reached the metaphase-II stage following 18 hours of incubation, which was not significantly different from the control group. Maturation of the oocytes derived from in vivo ACR-treated mice was impaired significantly. Oocytes, reaching the M-II stage in the in vivo ACR-treated group, were characterized by a decrease in meiotic spindle mass and an increase in chromosomal disruption. In vitro GLY treatment resulted in the degeneration of all oocytes, indicating that ACR toxicity on female germ cells may occur through its metabolite, GLY. Thus, ACR exposure must be considered, together with its metabolite GLY, when female fertility is concerned.

  7. Effective in vitro and in vivo gene delivery by the combination of liposomal bubbles (bubble liposomes) and ultrasound exposure.

    Science.gov (United States)

    Suzuki, Ryo; Maruyama, Kazuo

    2010-01-01

    Gene delivery with a physical mechanism using ultrasound (US) and nano/microbubbles is expected as an ideal system in terms of delivering plasmid DNA noninvasively into a specific target site. We developed novel liposomal bubbles (Bubble liposomes (BLs)) containing the lipid nanobubbles of perfluoropropane which were utilized for contrast enhancement in ultrasonography. BLs were smaller in diameter than conventional microbubbles and induced cavitation upon exposure ultrasound. In addition, when coupled with US exposure, BLs could deliver plasmid DNA into various types of cells in vitro and in vivo. The transfection efficiency with BLs and US was higher than that with conventional lipofection method. Therefore, the combination of BLs and US might be an efficient and novel nonviral gene delivery system.

  8. Influence of long-term in vivo exposure, debris accumulation and archwire material on friction force among different types of brackets and archwires couples.

    Science.gov (United States)

    Mezeg, Uroš; Primožic, Jasmina

    2017-11-30

    The aim was to assess the influence of long-term in vivo exposure, debris accumulation and archwire material on static and kinetic friction force among different types of brackets and archwires couples. Friction testing was performed among four lower incisors' brackets, conventional and self-ligating (SL), coupled with either nickel-titanium or stainless steel archwires, as-received and in vivo exposed in 18 subjects. The friction testing was performed for a sliding distance of 14 mm at a speed of 10 mm/min, with a starting force of 0.2 N. Wear and quantitative assessment of debris accumulation was performed on pictures of brackets obtained using a scanning electron microscope. Non parametric tests were used for statistical analysis. Only bracket type, but not exposure duration, amount of debris accumulation, archwire material or their manufacturer, was significantly correlated with both static (rho = 0.602, P bracket type no significant difference was observed between as-received and in vivo exposed brackets for any friction parameter except for the SL brackets in which significantly higher static and kinetic (P = 0.001, at least) friction forces were seen in in vivo exposed SL brackets (164.9 cN and 217.63 cN, respectively) in comparison with as-received SL brackets (19.69 cN and 55.72 cN, respectively). The frictional testing was performed in the dry condition which might have influenced the results. A significant correlation was seen between friction force and bracket type, while treatment duration, amount of debris accumulation, archwire material or their manufacturer was not significantly correlated to it. Nevertheless, higher friction forces were measured among in vivo aged SL brackets in comparison with as-received ones. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

  9. Health risk assessment for exposure to nitrate in drinking water from village wells in Semarang, Indonesia.

    Science.gov (United States)

    Sadler, Ross; Maetam, Brooke; Edokpolo, Benjamin; Connell, Des; Yu, Jimmy; Stewart, Donald; Park, M-J; Gray, Darren; Laksono, Budi

    2016-09-01

    The levels of nitrate in 52 drinking water wells in rural Central Java, Indonesia were evaluated in April 2014, and the results were used for a health risk assessment for the local populations by using probabilistic techniques. The concentrations of nitrate in drinking water had a range of 0.01-84 mg/L, a mean of 20 mg/L and a medium of 14 mg/L. Only two of the 52 samples exceeded the WHO guideline values of 50 mg/L for infant methaemoglobinaemia. The hazard quotient values as evaluated against the WHO guideline value at the 50 and 95 percentile points were HQ50 at 0.42 and HQ95 at 1.2, respectively. These indicated a low risk of infant methaemoglobinaemia for the whole population, but some risk for the sensitive portion of the population. The HQ50 and HQ95 values based on WHO acceptable daily intake dose for adult male and female were 0.35 and 1.0, respectively, indicating a generally a low level of risk. A risk characterisation linking birth defects to nitrate levels in water consumed during the first three months of pregnancy resulted in a HQ50/50 values of 1.5 and a HQ95/5 value of 65. These HQ values indicated an elevated risk for birth defects, in particular for the more sensitive population. A sanitation improvement program in the study area had a positive effect in reducing nitrate levels in wells and the corresponding risk for public health. For example, the birth defect HQ50/50 values for a subset of wells surveyed in both 2014 and 2015 was reduced from 1.1 to 0.71. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.

    Science.gov (United States)

    Zhu, Lin; Xue, Junyi; Xia, Qingsu; Fu, Peter P; Lin, Ge

    2017-02-01

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t 1/2α ) and 301 h (~12.5 days, t 1/2β ). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t 1/2α ) and 1736 h (~72.3 days, t 1/2β ). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure.

  11. El Software Hagáquê (HQ como una herramienta en la enseñanza y aprendizaje de la educación ambiental

    Directory of Open Access Journals (Sweden)

    Elizabeth Aparecida Assis Brandão Danhão

    2015-12-01

    Full Text Available Este estudio forma parte de la investigación para una tesis, la meta Cuyo fue analizar las Tecnologías de Información y Comunicación (TIC a través del uso de software Hagáquê (HQ en la educación y el aprendizaje de la educación ambiental. Esta encuesta se llevó a cabo de una manera multidisciplinar en una escuela del Programa Integral de Educación de la Secretaría de Educación del Estado de São Paulo (VER / SP, con sede en Sorocaba / SP, Brasil. Los sujetos del estudio fueron 30 alumnos (as de la Enseñanza Fundamental II (de 6º a 9º grado. Las herramientas metodológicas utilizadas fueron: análisis de documentos, observaciones de clases, el análisis de las historias producidas por los estudiantes y un cuestionario administrado al final de curso electivo. Las actividades se llevaron a cabo de una manera multidisciplinar y interdisciplinar, mediante la construcción de historias con temas ambientales, con diseños hechos a mano, manuscritos y digitalizada en el software Hagáquê (HQ. Esperamos que esta investigación colaboran para las reflexiones sobre el uso de las herramientas tecnológicas en el aula para ayudar en el proceso de enseñanza y aprendizaje y la educación ambiental.

  12. Modeling the in vivo case with in vitro nanotoxicity data.

    Science.gov (United States)

    Shelley, Michael L; Wagner, Andrew J; Hussain, Saber M; Bleckmann, Charles

    2008-01-01

    As more in vitro nanotoxicity data appear in the literature, these findings must be translated to in vivo effects to define nanoparticle exposure risk. Physiologically based pharmacokinetic (PBPK) modeling has played a significant role in guiding and validating in vivo studies for molecular chemical exposure and can develop as a significant tool in guiding similar nanotoxicity studies. This study models the population dynamics of a single cell type within a specific tissue. It is the first attempt to model the in vitro effects of a nanoparticle exposure, in this case aluminum (80 nm) and its impact on a population of rat alveolar macrophages (Wagner et al. 2007, J. Phys. Chem. B 111:7353-7359). The model demonstrates how in vitro data can be used within a simulation setting of in vivo cell dynamics and suggests that PBPK models should be developed quickly to interpret nanotoxicity data, guide in vivo study design, and accelerate nanoparticle risk assessment.

  13. Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone.

    Science.gov (United States)

    Liu, Linhua; Ling, Xiaoxuan; Liang, Hairong; Gao, Yuting; Yang, Hui; Shao, Junli; Tang, Huanwen

    2012-03-25

    Hydroquinone (HQ), one of the most important metabolites derived from benzene, is known to be associated with acute myelogenous leukemia (AML) risk, however, its carcinogenic mechanism remains unclear. In this study, the epigenetic mechanism of HQ exposure was investigated. We characterized the epigenomic response of TK6 cells to HQ exposure, and examined the mRNA expression of DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2 (MBD2) and six proto-oncogenes (MPL, RAF1, MYB, MYC, ERBB2 and BRAF). Compared to the control cells, HQ exposure (2.5, 5.0, 10.0 and 20.0 μM for 48 h) resulted in the decrease of DNMTs and MBD2 expression, the global hypomethylation and increase of MPL at mRNA level. Meanwhile, most of these changes were in dose-dependent manner. Moreover, inhibition of DNMTs induced by 5-aza-2'-deoxycytidine (5-AZA), an identified DNMT inhibitor, caused more induction of MPL expression at mRNA level compared to the HQ (10.0 μM) pre-treated group. Furthermore, treatment of HQ potentially led to MPL itself hypomethylation (10.0 and 20.0 μM reduced by 47% and 44%, respectively), further revealing that the activation of proto-oncogene MPL was related to hypomethylation in its DNA sequences. In conclusion, hypomethylation, including global and specific hypomethylation, might be involved in the activation of MPL, and the hypomethylation could be induced by decreased DNMTs in TK6 cells exposed to HQ. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Fractionated exposure of high energy iron ions has a sparing effect in vivo

    Science.gov (United States)

    Chang, P. Y.; Bakke, J.; Puey, A.

    The radiation environment in deep space is complex and includes a broad spectrum of charged and highly energetic particle radiations. Exposure to these types of radiations may pose potential health risks in manned space missions. The detection of particle radiation-induced genomic alterations in vivo, particularly in slow or non-dividing tissues, is therefore important to provide relevant information in estimating risks. We are using a plasmid-based lacZ transgenic mouse model system to rapidly measure, in a statistically reliable way, the mutagenic potential of charged particle radiations relevant in the space environment. The lacZ transgenic mouse has been constructed so that every cell of the animal contains multiple copies of an integrated target reporter gene, allowing us to measure tissue-specific radiation-induced changes as a function of dosing regime. The nature of these mutations can also be characterized by restriction fragment length polymorphisms (RFLP). To examine the impact of dose protraction, animals were exposed to a single dose or daily fractions of 1 GeV/n iron ions. Cytotoxicity in the peripheral blood was measured by enumerating the frequency of circulating micronucleated reticulocytes (fMN-RET) in a time course from 24 h up to 1 week after completion of the radiation protocol. Brain and spleen tissues were harvested at 8 weeks after exposure and mutant frequencies (MF) in the transgene in these tissues were measured. Results from the fractionated protocol were compared to the responses obtained after the animals were exposed to the single dose treatment. We noted significantly lower levels of micronucleated reticulocytes in peripheral blood at 48 h after fractionated doses of iron ions when compared to the same total dose delivered in a single exposure demonstrating that protracted exposures of particle radiation resulted in an overall sparing effect in cytogenetic toxicity in the hematopoietic system in animals. Transgene mutation analysis

  15. Human exposure and risk assessment associated with mercury contamination in artisanal gold mining areas in the Brazilian Amazon.

    Science.gov (United States)

    Castilhos, Zuleica; Rodrigues-Filho, Saulo; Cesar, Ricardo; Rodrigues, Ana Paula; Villas-Bôas, Roberto; de Jesus, Iracina; Lima, Marcelo; Faial, Kleber; Miranda, Antônio; Brabo, Edilson; Beinhoff, Christian; Santos, Elisabeth

    2015-08-01

    Mercury (Hg) contamination is an issue of concern in the Amazon region due to potential health effects associated with Hg exposure in artisanal gold mining areas. The study presents a human health risk assessment associated with Hg vapor inhalation and MeHg-contaminated fish ingestion, as well as Hg determination in urine, blood, and hair, of human populations (about 325 miners and 321 non-miners) from two gold mining areas in the Brazilian Amazon (São Chico and Creporizinho, Pará State). In São Chico and Creporizinho, 73 fish specimens of 13 freshwater species, and 161 specimens of 11 species, were collected for total Hg determination, respectively. The hazard quotient (HQ) is a risk indicator which defines the ratio of the exposure level and the toxicological reference dose and was applied to determine the threat of MeHg exposure. The mean Hg concentrations in fish from São Chico and Creporizinho were 0.83 ± 0.43 and 0.36 ± 0.33 μg/g, respectively. More than 60 and 22 % of fish collected in São Chico and Creporizinho, respectively, were above the Hg limit (0.5 μg/g) recommended by WHO for human consumption. For all sampling sites, HQ resulted from 1.5 to 28.5, except for the reference area. In Creporizinho, the values of HQ are close to 2 for most sites, whereas in São Chico, there is a hot spot of MeHg contamination in fish (A2-São Chico Reservoir) with the highest risk level (HQ = 28) associated with its human consumption. Mean Hg concentrations in urine, blood, and hair samples indicated that the miners group (in São Chico: urine = 17.37 μg/L; blood = 27.74 μg/L; hair = 4.50 μg/g and in Creporizinho: urine = 13.75 μg/L; blood = 25.23 μg/L; hair: 4.58 μg/g) was more exposed to mercury compared to non-miners (in São Chico: urine = 5.73 μg/L; blood = 16.50 μg/L; hair = 3.16 μg/g and in Creporizinho: urine = 3.91 μg/L; blood = 21.04 μg/L, hair = 1.88 μg/g). These high Hg levels (found

  16. Developing a method for the retrospective estimation of radon exposure from in vivo measurements of 210Pb activity in bone

    International Nuclear Information System (INIS)

    McKenzie, R.J.; Johnston, P.N.

    1999-01-01

    Radon is a naturally occurring radioactive gas which has been linked to lung cancer in occupationally exposed uranium mine workers. Where monitoring of an individual's exposure to radon and radon progeny has not occurred or is incomplete, it may be possible to determine this exposure retrospectively by the measurement of the long lived decay product 210 Pb which accumulates in the bones of exposed individuals. This paper describes a method being developed at the whole body monitor (WBM) facility of the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) to estimate the time integrated exposure to radon over a period of up to several decades from the in vivo measurements of 210 Pb activity in the knee of human subjects. Initial work has concentrated on characterising the WBM facility for this work using artificial bone phantoms. This project will serve as a test of the feasibility of the method before undertaking further studies on human subjects

  17. Virtual reality exposure therapy

    OpenAIRE

    Rothbaum, BO; Hodges, L; Kooper, R

    1997-01-01

    It has been proposed that virtual reality (VR) exposure may be an alternative to standard in vivo exposure. Virtual reality integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer- generated virtual environment. Virtual reality exposure is potentially an efficient and cost-effective treatment of anxiety disorders. VR exposure therapy reduced the fear of heights in the first control...

  18. Review-Research on the physical training model of human body based on HQ.

    Science.gov (United States)

    Junjie, Liu

    2016-11-01

    Health quotient (HQ) is the newest health culture and concept in the 21st century, and the analysis of the human body sports model is not enough mature at present, what's more, the purpose of this paper is to study the integration of the two subjects the health quotient and the sport model. This paper draws the conclusion that physical training and education in colleges and universities can improve the health quotient, and it will make students possess a more healthy body and mind. Then through a new rigid body model of sports to simulate the human physical exercise. After that this paper has an in-depth study on the dynamic model of the human body movement on the basis of establishing the matrix and equation. The simulation results of the human body bicycle riding and pole throwing show that the human body joint movement simulation can be realized and it has a certain operability as well. By means of such simulated calculation, we can come to a conclusion that the movement of the ankle joint, knee joint and hip joint's motion law and real motion are basically the same. So it further verify the accuracy of the motion model, which lay the foundation of other research movement model, also, the study of the movement model is an important method in the study of human health in the future.

  19. Induction and repair of DNA double-strand breaks in hippocampal neurons of mice of different age after exposure to 60Co γ-rays in vivo and in vitro

    Science.gov (United States)

    Kozhina, R. A.; Chausov, V. N.; Kuzmina, E. A.; Boreyko, A. V.

    2018-04-01

    One of the central problems of modern radiobiology is the study of DNA damage induction and repair mechanisms in central nervous system cells, in particular, in hippocampal cells. The study of the regularities of molecular damage formation and repair in the hippocampus cells is of special interest, because these cells, unlike most cells of the central nervous system (CNS), keep proliferative activity, i.e. ability to neurogenesis. Age-related changes in hippocampus play an important role, which could lead to radiosensitivity changes in neurons to the ionizing radiation exposure. Regularities in DNA double-strand breaks (DSB) induction and repair in different aged mice hippocampal cells in vivo and in vitro under the action of γ-rays 60Co were studied with DNA comet-assay. The obtained dose dependences of DNA DSB induction are linear both in vivo and in vitro. It is established that in young animals' cells, the degree of DNA damage is higher than in older animals. It is shown that repair kinetics is basically different for exposure in vivo and in vitro.

  20. Probabilistic meta-analysis of risk from the exposure to Hg in artisanal gold mining communities in Colombia.

    Science.gov (United States)

    De Miguel, Eduardo; Clavijo, Diana; Ortega, Marcelo F; Gómez, Amaia

    2014-08-01

    Colombia is one of the largest per capita mercury polluters in the world as a consequence of its artisanal gold mining activities. The severity of this problem in terms of potential health effects was evaluated by means of a probabilistic risk assessment carried out in the twelve departments (or provinces) in Colombia with the largest gold production. The two exposure pathways included in the risk assessment were inhalation of elemental Hg vapors and ingestion of fish contaminated with methyl mercury. Exposure parameters for the adult population (especially rates of fish consumption) were obtained from nation-wide surveys and concentrations of Hg in air and of methyl-mercury in fish were gathered from previous scientific studies. Fish consumption varied between departments and ranged from 0 to 0.3 kg d(-1). Average concentrations of total mercury in fish (70 data) ranged from 0.026 to 3.3 μg g(-1). A total of 550 individual measurements of Hg in workshop air (ranging from risk. All but two of the distributions of Hazard Quotients (HQ) associated with ingestion of Hg-contaminated fish for the twelve regions evaluated presented median values higher than the threshold value of 1 and the 95th percentiles ranged from 4 to 90. In the case of exposure to Hg vapors, minimum values of HQ for the general population exceeded 1 in all the towns included in this study, and the HQs for miner-smelters burning the amalgam is two orders of magnitude higher, reaching values of 200 for the 95th percentile. Even acknowledging the conservative assumptions included in the risk assessment and the uncertainties associated with it, its results clearly reveal the exorbitant levels of risk endured not only by miner-smelters but also by the general population of artisanal gold mining communities in Colombia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. H:q ratios and bilateral leg strength in college field and court sports players.

    Science.gov (United States)

    Cheung, Roy T H; Smith, Andrew W; Wong, Del P

    2012-06-01

    One of the key components in sports injury prevention is the identification of imbalances in leg muscle strength. However, different leg muscle characteristics may occur in large playing area (field) sports and small playing area (court) sports, which should be considered in regular injury prevention assessment. This study examined the isokinetic hamstrings-to-quadriceps (H:Q) ratio and bilateral leg strength balance in 40 male college (age: 23.4 ± 2.5 yrs) team sport players (field sport = 23, soccer players; court sport = 17, volleyball and basketball players). Five repetitions of maximal knee concentric flexion and concentric extension were performed on an isokinetic dynamometer at two speeds (slow: 60°·s(-1) and fast: 300°·s(-1)) with 3 minutes rest between tests. Both legs were measured in counterbalanced order with the dominant leg being determined as the leg used to kick a ball. The highest concentric peak torque values (Nm) of the hamstrings and quadriceps of each leg were analyzed after body mass normalization (Nm·kg(-1)). Court sport players showed significantly weaker dominant leg hamstrings muscles at both contraction speeds (P Sport-specific leg muscle strength was evident in college players from field and court sports. These results suggest the need for different muscle strength training and rehabilitation protocols for college players according to the musculature requirements in their respective sports.

  2. Induction of 6-thioguanine-resistant lymphocytes in Fischer 344 rats following in vivo exposure to N-ethyl-N-nitrosourea and cyclophosphamide

    International Nuclear Information System (INIS)

    Aidoo, A.; Lyn-Cook, L.E.; Mittelstaedt, R.A.; Heflich, R.H.; Casciano, D.A.

    1991-01-01

    The authors have developed a limiting dilution clonal assay for determining the frequency of 6-thioguanine-resistant (TG r ) lymphocytes produced in rats by in vivo exposure to genotoxic agents. Lymphocyte cloning efficiencies (CEs) were highest in plates containing both irradiated TK6 cells and irradiated autologous feeder cells. To measure the effects of chemical mutagens on the frequency of TG r lymphocytes, rats were given a single i.p. injection of N-ethyl-N-nitrosourea (ENU), a direct-acting alkylating agent, cyclophosphamide (CP), an indirect acting alkylating agent. Lymphocytes were isolated, primed, and cloned at 4 weeks after CP treatment and at 1,2,4 and 6 weeks after ENU treatment. CE in these cultures ranged from 12% to 27%. Cultures were also established for measuring CE in the presence of 6-thioguanine (TG). The dose-dependent responses obtained with both ENU and CP treatments suggest that rat lymphocytes are sensitive to direct- and indirect-acting alkylating agents administered in vivo and that the rat lymphocyte assay is a useful complement to the in vivo/in vitro mouse assay for determining the mutagenicity of environmental toxicants

  3. 77 FR 57546 - National Priorities List, Proposed Rule No. 57

    Science.gov (United States)

    2012-09-18

    ... Mulberry Streets PCE Plume Martinsville, IN EPA-HQ-SFUND-2012-0598. Former United Zinc & Associated Iola..., IL....... EPA-HQ-SFUND-1998-0010. Contamination. Submit your comments, identified by the appropriate..., surface water, soil exposure and air. As a matter of agency policy, those sites that score 28.50 or...

  4. New insight into the distribution pattern, levels, and risk diagnosis of FRs in indoor and outdoor air at low- and high-altitude zones of Pakistan: Implications for sources and exposure.

    Science.gov (United States)

    Khan, Muhammad Usman; Besis, Athanasios; Li, Jun; Zhang, Gan; Malik, Riffat Naseem

    2017-10-01

    Data regarding flame retardants (FRs) in indoor and outdoor air and their exposure to population are scarce and especially unknown in the case of Pakistan. The current study was designed to probe FR concentrations and distribution pattern in indoor and outdoor air at different altitudinal zones (DAZs) of Pakistan with special emphasis on their risk to the exposed population. In this study, passive air samplers for the purpose of FR deposition were deployed in indoor and outdoor air at the industrial, rural, and background/colder zones/sites. All the indoor and outdoor air samples collected from DAZs were analyzed for the target FRs (9.30-472.30 pg/m 3 ), showing a decreasing trend as follows: ∑NBFRs > ∑PBDEs > ∑DP. However, significant correlations among FRs in the indoor and outdoor air at DAZs signified a similar source of FR origin that is used in different consumer goods. Furthermore, air mass trajectories revealed that movement of air over industrial area sources influenced concentrations of FRs at rural sites. The FR concentrations, estimated daily intake (EDI) and the hazard quotient (HQ), were recorded to be higher in toddlers than those in adults. In addition, indoor air samples showed higher FR levels, EDI and HQ, than outdoor air samples. An elevated FR concentrations and their prevalent exposure risks were recorded in the industrial zones followed by rural and background zones. The HQ for BDE-47 and BDE-99 in the indoor and outdoor air samples at different industrial and rural sites were recorded to be >1 in toddlers and adults, this further warrants a health risk in the population. However, FR investigation in indoor and outdoor air samples will provide a baseline data in Pakistan to take further steps by the government and agencies for its implementations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Metabolites of 2,4,4'-tribrominated diphenyl ether (BDE-28) in pumpkin after in vivo and in vitro exposure.

    Science.gov (United States)

    Yu, Miao; Liu, Jiyan; Wang, Thanh; Sun, Jianteng; Liu, Runzeng; Jiang, Guibin

    2013-01-01

    There is currently limited knowledge on PBDE metabolism in plants although they could play an important role in the environmental transformation of these persistent organic pollutants. In this study, pumpkin (Cucurbita maxima × C. moschata) was chosen as the model to understand the fate of BDE-28 in plants. MeO-tri-BDEs, OH-tri-BDEs, and OH-tri-BDEs were found as metabolites in plant samples of both in vivo hydroponic and in vitro tissue culture exposure. Three MeO-tri-BDEs were further identified as para-substituted metabolites. MeO-BDEs and OH-BDEs, respectively, accounted for about 1.6% and 1.5% (recovery corrected) of initial amount of BDE-28 according to the semiquantitative results. Other PBDEs, especially less brominated PBDEs as impurities in the standard of BDE-28, were also detected. The impurities and evaporation of the standard must be considered when trace metabolites are studied in exposure experiments.

  6. Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

    International Nuclear Information System (INIS)

    Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

    1982-01-01

    Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

  7. Evaluation of biomonitoring data from the CDC National Exposure Report in a risk assessment context: perspectives across chemicals.

    Science.gov (United States)

    Aylward, Lesa L; Kirman, Christopher R; Schoeny, Rita; Portier, Christopher J; Hays, Sean M

    2013-03-01

    Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment-based values now allow interpretation of these biomonitoring data in a public health risk context. We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER. We identified available risk assessment-based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates. Most analytes in the NER show HQ values of chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10-4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.

  8. Regulation of ex vivo tyrosine hydroxylase (TH) activity is not altered by chronic lead (Pb) exposure

    International Nuclear Information System (INIS)

    Lasley, S.M.; Green, M.C.

    1991-01-01

    Previous studies have suggested that chronic Pb exposure results in impaired regulation of CNS dopamine (DA) synthesis in rats. The present study was designed to directly assess TH activity in exposed animals compared to controls, employing a pharmacological model that assesses the functional status of dopaminergic synthesis-modulating autoreceptors. At birth dams received 0.2% Pb acetate in drinking water. Offspring were weaned to and maintained on the same solution until termination at 60 or 120 days. Rats were given saline or a DA agonist (EMD 23448 or CGS 15855A) 45 min before sacrifice followed 15 min later by gamma-butyrolactone (GBL). Regional TH activity was measured by a modification of the tritium release method. DA content was determined by liquid chromatography. The ability of EMD 23448 to prevent the GBL-induced increase in DA content was significantly diminished in caudate-putamen (C-P) of exposed rats compared to controls, similar to previous observations. However, an analogous effect of Pb on TH activity in this drug model was not observed using CGS 15855A in rats either 60 or 120 days of age. These findings suggest that chronic Pb exposure has no effect on autoreceptor-mediated regulation of TH in DA neurons when TH activity is measured ex vivo

  9. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

    Directory of Open Access Journals (Sweden)

    Tornero-Velez Rogelio

    2008-11-01

    Full Text Available Abstract Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg or permethrin (1 – 100 mg/kg followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM and isotonic regression (PIR methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1 was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25% in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of

  10. 76 FR 4258 - Occupational Radiation Protection; Revision

    Science.gov (United States)

    2011-01-25

    ... instructions for submitting comments. E-mail: [email protected]hq.doe.gov . Include Docket Number HS- RM-09-835 and..., DC 20585. FOR FURTHER INFORMATION CONTACT: Judith Foulke, (301) 903-5865, e-mail: [email protected]hq.doe... Concentration (DAC) for Workers from External Exposure during Immersion in a Cloud of Airborne Radioactive...

  11. Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

  12. The in vivo relationship between cross-sectional area and CT dose index in abdominal multidetector CT with automatic exposure control

    Energy Technology Data Exchange (ETDEWEB)

    Meeson, S; Alvey, C M; Golding, S J, E-mail: stuart.meeson@nds.ox.ac.u [Radiology Group, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom)

    2010-06-15

    The relationship between patient cross-sectional area and both volume CT dose index (CTDI) and dose length product was explored for abdominal CT in vivo, using a 16 multidetector row CT (MDCT) scanner with automatic exposure control. During a year-long retrospective survey of patients with MDCT for symptoms of abdominal sepsis, cross-sectional areas were estimated using customised ellipses at the level of the middle of vertebra L3. The relationship between cross-sectional area and the exposure parameters was explored. Scans were performed using a LightSpeed 16 (GE Healthcare Medical Systems, Milwaukee, WI) operated with tube current modulation. From a survey of 94 patients it was found that the CTDI increased with the increase in patient cross-sectional area. The relationship was logarithmic rather than linear, with a least-squares fit to the data (R{sup 2} = 0.80). For abdominal CT the cross-sectional area gave a measure of patient size based on the region of the body to be exposed. Exposure parameters increased with increasing cross-sectional area and the greater radiation exposure of larger patients was partly a consequence of their size. Given increasing obesity levels we believe that cross-sectional area and scan length should be added to future dose surveys, allowing patient size to be considered as a factor of relevance when examining population doses.

  13. Methods of in-vivo mouse lung micro-CT

    Science.gov (United States)

    Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

    2005-04-01

    Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

  14. Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Codeca, Ilaria; Mangiaratti, Simona; Birindelli, Sarah; Minoia, Claudio; Turci, Roberta; Viviani, Barbara; Facchi, Alessandra; Vitelli, Nora; Lucchi, Laura; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2007-01-01

    Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG 1 and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-α production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity

  15. IN-VIVO EXPOSURE CHARACTERIZATION AND VISUALIZATION OF SWNH AGGREGATES

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, Rachel M [ORNL; Voy, Brynn H [ORNL; Zhao, Bin [ORNL; Mahurin, Shannon Mark [ORNL; Thundat, Thomas George [ORNL; Cheng, Mengdawn [ORNL; Passian, Ali [ORNL; Venmar, Katherine T [ORNL; Tetard, Laurene [ORNL

    2007-01-01

    As the manufacturing and use of nanomaterials and nanoparticle clusters/aggregates become prevalent in the future, it will be necessary to understand the biological interactions with this new class of materials introduced through various routes, intentionally or unintentionally. However, there currently exist a host of technical/methodological issues related to nanotoxicological study. For example, the ability to generate reproducible precision nanomaterial and nanoparticles is critically needed for both toxicological evaluation and pharmaceutical applications. Technology for tracing and visualization of nanomaterials in biological systems are also lacking. Single-walled carbon nanohorn (SWNH) is a unique carbon nanostructure belonging to the same family as the famous carbon nanotubes. SWNH aggregates can be produced through laser vaporization of carbon at room temperature; the aggregates are of particular interest to energy application such as hydrogen storage and new-generation of fuel cells. Unlike carbon nanotubes that are made using metal catalysts, SWNHs can be made without the use of a metal catalyst providing an opportunity for nanotoxicological study of purest carbon nanoparticles with no complication of trace metal toxicity that the nanotubes might have. We summarize results from our ongoing biological research on SWNHs. Our results were from in vivo animal aspiration experiments, in contrast to the results of a recent publication that were based on phenotypic observation of cell-line exposure experiments. The characterization results of ORNL-produced SWNHs are presented in Figure 1, which include low- (Figure 1a) and high-resolution (Figure 1b) structural images of SWNHs, the thermal gravimetric analysis (Figure 1c) and characteristic Raman (Figure 1d) results. We coated the SWNH powder with Pluronic F-127, which is a biocompatible polymer, to facilitate the dispersion of SWNHs in suspension during pressure-driven nebulization in mice aspiration and nose

  16. A porcine ex vivo lung perfusion model with maximal argon exposure to attenuate ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    An Martens

    2017-01-01

    Full Text Available Argon (Ar is a noble gas with known organoprotective effects in rodents and in vitro models. In a previous study we failed to find a postconditioning effect of Ar during ex vivo lung perfusion (EVLP on warm-ischemic injury in a porcine model. In this study, we further investigated a prolonged exposure to Ar to decrease cold ischemia-reperfusion injury after lung transplantation in a porcine model with EVLP assessment. Domestic pigs (n = 6/group were pre-conditioned for 6 hours with 21% O 2 and 79% N 2 (CONTR or 79% Ar (ARG. Subsequently, lungs were cold flushed and stored inflated on ice for 18 hours inflated with the same gas mixtures. Next, lungs were perfused for 4 hours on EVLP (acellular while ventilated with 12% O 2 and 88% N 2 (CONTR group or 88% Ar (ARG group. The perfusate was saturated with the same gas mixture but with the addition of CO 2 to an end-tidal CO 2 of 35-45 mmHg. The saturated perfusate was drained and lungs were perfused with whole blood for an additional 2 hours on EVLP. Evaluation at the end of EVLP did not show significant effects on physiologic parameters by prolonged exposure to Ar. Also wet-to-dry weight ratio did not improve in the ARG group. Although in other organ systems protective effects of Ar have been shown, we did not detect beneficial effects of a high concentration of Ar on cold pulmonary ischemia-reperfusion injury in a porcine lung model after prolonged exposure to Ar in this porcine model with EVLP assessment.

  17. Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

    Science.gov (United States)

    Kirsch-Volders, Micheline; Bonassi, Stefano; Knasmueller, Siegfried; Holland, Nina; Bolognesi, Claudia; Fenech, Michael F

    2014-01-01

    The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans. Copyright © 2014 The Authors. Published by Elsevier B.V. All

  18. Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control.

    Science.gov (United States)

    Zheng, Ke-wei; Xiao, Shan; Liu, Jia-quan; Zhang, Jia-yu; Hao, Yu-hua; Tan, Zheng

    2013-05-01

    G-quadruplex formation in genomic DNA is considered to regulate transcription. Previous investigations almost exclusively focused on intramolecular G-quadruplexes formed by DNA carrying four or more G-tracts, and structure formation has rarely been studied in physiologically relevant processes. Here, we report an almost entirely neglected, but actually much more prevalent form of G-quadruplexes, DNA:RNA hybrid G-quadruplexes (HQ) that forms in transcription. HQ formation requires as few as two G-tracts instead of four on a non-template DNA strand. Potential HQ sequences (PHQS) are present in >97% of human genes, with an average of 73 PHQSs per gene. HQ modulates transcription under both in vitro and in vivo conditions. Transcriptomal analysis of human tissues implies that maximal gene expression may be limited by the number of PHQS in genes. These features suggest that HQs may play fundamental roles in transcription regulation and other transcription-mediated processes.

  19. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin Uptake by Pancreatic Acinar Cells.

    Directory of Open Access Journals (Sweden)

    Padmanabhan Srinivasan

    Full Text Available Thiamin (vitamin B1, a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively. The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase, was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and THTR-2 proteins and mRNAs. This study demonstrates that chronic exposure of PAC to nicotine impairs the physiology and the molecular biology of the thiamin uptake process. Furthermore, the study suggests that the effect is, in part, mediated through transcriptional mechanism(s affecting the SLC19A2 and SLC19A3 genes.

  20. Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure

    Directory of Open Access Journals (Sweden)

    Paul Glogener

    2018-02-01

    Full Text Available A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

  1. Tratamento da fobia social circunscrita por exposição ao vivo e reestruturação cognitiva Treatment of the non-generalized social phobia by in vivo exposure and cognitive restructuring

    Directory of Open Access Journals (Sweden)

    Gustavo J. Fonseca D'el Rey

    2005-07-01

    Full Text Available A fobia social é um grave transtorno de ansiedade que traz incapacitação e sofrimento. Apresentamos um relato de caso de uma mulher de 26 anos com diagnóstico de fobia social circunscrita (medo severo de assinar seu nome em público com três anos de duração, que foi tratada em oito semanas, usando-se a exposição ao vivo e a reestruturação cognitiva. O progresso do tratamento foi mantido em diversas áreas de sua vida e no follow-up de seis meses.Social phobia is a severe anxiety disorder that brings disability and distress. We present a case report of a 26 year-old woman with a diagnosis of non-generalized social phobia (severe fear of signing her name in public with 3 years of duration. She was treated in 8 weeks with in vivo exposure and cognitive restructuring. The treatment progress was maintained in all measures at the 6-month follow-up.

  2. Flooding in imagination vs flooding in vivo: A comparison with agoraphobics

    NARCIS (Netherlands)

    Emmelkamp, Paul M.G.; Wessels, Hemmy

    In this investigation of agoraphobic patients, 3 different flooding procedures were compared: (1) prolonged exposure in vivo, (2) flooding in the imagination by a ‘live’ therapist and (3) a combination of flooding in the imagination and flooding in vivo. After an intermediate-test all clients were

  3. Phthalate ester plasticizers in freshwater systems of Venda, South Africa and potential health effects

    CSIR Research Space (South Africa)

    Fatoki, OS

    2010-01-01

    Full Text Available ://www.wrc.org.za ISSN 0378-4738 (Print) = Water SA Vol. 36 No. 1 January 2010 ISSN 1816-7950 (On-line) = Water SA Vol. 36 No. 1 January 2010 120 For toxic chemicals, a hazard quotient (HQ) is calculated, which compares the expected exposure to the agent... the chemicals. Figures 4 to 6 separate the toxicity posed by each chemical. The acceptable risk level or exposure threshold below which no adverse health effects are expected, is indicated with a solid line (HQ = 1). From Fig. 4, it is clear that DEP...

  4. The reduction of retinal autofluorescence caused by light exposure.

    Science.gov (United States)

    Morgan, Jessica I W; Hunter, Jennifer J; Merigan, William H; Williams, David R

    2009-12-01

    A prior study showed that long exposure to 568-nm light at levels below the maximum permissible exposure safety limit produces retinal damage preceded by a transient reduction in the autofluorescence of retinal pigment epithelial (RPE) cells in vivo. The present study shows how the effects of exposure power and duration combine to produce this autofluorescence reduction and find the minimum exposure causing a detectable autofluorescence reduction. Macaque retinas were imaged using a fluorescence adaptive optics scanning laser ophthalmoscope to resolve individual RPE cells in vivo. The retina was exposed to 568-nm light over a square subtending 0.5 degrees with energies ranging from 1 to 788 J/cm(2), where power and duration were independently varied. In vivo exposures of 5 J/cm(2) and higher caused an immediate decrease in autofluorescence followed by either full autofluorescence recovery (exposures or= 247 J/cm(2)). No significant autofluorescence reduction was observed for exposures of 2 J/cm(2) and lower. Reciprocity of exposure power and duration held for the exposures tested, implying that the total energy delivered to the retina, rather than its distribution in time, determines the amount of autofluorescence reduction. That reciprocity held is consistent with a photochemical origin, which may or may not cause retinal degeneration. The implementation of safe methods for delivering light to the retina requires a better understanding of the mechanism causing autofluorescence reduction. Finally, RPE imaging was demonstrated using light levels that do not cause a detectable reduction in autofluorescence.

  5. In vivo imaging of the retinal pigment epithelial cells

    Science.gov (United States)

    Morgan, Jessica Ijams Wolfing

    The retinal pigment epithelial (RPE) cells form an important layer of the retina because they are responsible for providing metabolic support to the photoreceptors. Techniques to image the RPE layer include autofluorescence imaging with a scanning laser ophthalmoscope (SLO). However, previous studies were unable to resolve single RPE cells in vivo. This thesis describes the technique of combining autofluorescence, SLO, adaptive optics (AO), and dual-wavelength simultaneous imaging and registration to visualize the individual cells in the RPE mosaic in human and primate retina for the first time in vivo. After imaging the RPE mosaic non-invasively, the cell layer's structure and regularity were characterized using quantitative metrics of cell density, spacing, and nearest neighbor distances. The RPE mosaic was compared to the cone mosaic, and RPE imaging methods were confirmed using histology. The ability to image the RPE mosaic led to the discovery of a novel retinal change following light exposure; 568 nm exposures caused an immediate reduction in autofluorescence followed by either full recovery or permanent damage in the RPE layer. A safety study was conducted to determine the range of exposure irradiances that caused permanent damage or transient autofluorescence reductions. Additionally, the threshold exposure causing autofluorescence reduction was determined and reciprocity of radiant exposure was confirmed. Light exposures delivered by the AOSLO were not significantly different than those delivered by a uniform source. As all exposures tested were near or below the permissible light levels of safety standards, this thesis provides evidence that the current light safety standards need to be revised. Finally, with the retinal damage and autofluorescence reduction thresholds identified, the methods of RPE imaging were modified to allow successful imaging of the individual cells in the RPE mosaic while still ensuring retinal safety. This thesis has provided a

  6. Disruption of thyroid hormone functions by low dose exposure of tributyltin: an in vitro and in vivo approach.

    Science.gov (United States)

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2014-09-15

    Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50μg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques: a case study with rice farmers in Vietnam.

    Science.gov (United States)

    Phung, Dung Tri; Connell, Des; Yu, Qiming; Chu, Cordia

    2013-09-01

    Various methods for risk characterization have been developed using probabilistic approaches. Data on Vietnamese farmers are available for the comparison of outcomes for risk characterization using different probabilistic methods. This article addresses the health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques obtained from a case study with rice farmers in Vietnam. Urine samples were collected from farmers and analyzed for trichloropyridinol (TCP), which was converted into absorbed daily dose of chlorpyrifos. Adverse health response doses due to chlorpyrifos exposure were collected from epidemiological studies to develop dose-adverse health response relationships. The health risk of chlorpyrifos was quantified using hazard quotient (HQ), Monte Carlo simulation (MCS), and overall risk probability (ORP) methods. With baseline (prior to pesticide spraying) and lifetime exposure levels (over a lifetime of pesticide spraying events), the HQ ranged from 0.06 to 7.1. The MCS method indicated less than 0.05% of the population would be affected while the ORP method indicated that less than 1.5% of the population would be adversely affected. With postapplication exposure levels, the HQ ranged from 1 to 32.5. The risk calculated by the MCS method was that 29% of the population would be affected, and the risk calculated by ORP method was 33%. The MCS and ORP methods have advantages in risk characterization due to use of the full distribution of data exposure as well as dose response, whereas HQ methods only used the exposure data distribution. These evaluations indicated that single-event spraying is likely to have adverse effects on Vietnamese rice farmers. © 2013 Society for Risk Analysis.

  8. Human exposure and risk assessment to airborne pesticides in a rural French community.

    Science.gov (United States)

    Coscollà, Clara; López, Antonio; Yahyaoui, Abderrazak; Colin, Patrice; Robin, Corine; Poinsignon, Quentin; Yusà, Vicent

    2017-04-15

    Outdoor air samples collected during the pesticide agricultural application period (spring and summer) from a rural community in the Centre Region (France) were analyzed to investigate temporal variation of atmospheric pesticide levels (2006-2013) and human inhalation exposure in adults, children and infants. The most frequently detected pesticides were herbicides (trifluralin, pendimethalin), fungicides (chlorothalonil) and insecticides (lindane and α-endosulfan). The three currently-used pesticides most frequently detected presented concentrations ranging from 0.18 to 1128.38ngm -3 ; 0.13 to 117.32ngm -3 and 0.16 to 25.80ngm -3 for chlorothalonil, pendimethalin and trifluralin, respectively. The estimated chronic inhalation risk, expressed as Hazard Quotient (HQ), for adults, children and infants, was exposure for detected organophosphorus and chloroacetamide pesticides, was estimated using the Relative Potency Factor (RPF) and Hazard Index (HI) as metrics, which was indicated that no risk was observed. The cancer risk classified as likely or possibly carcinogen was estimated to be <8.93 E-05 in infants, for the detected pesticides. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 'In-vivo' and bioassay results from two contrasting cases of plutonium-239 inhalation

    International Nuclear Information System (INIS)

    Ramsden, D.; Bains, M.E.D.; Fraser, D.C.

    1969-06-01

    'In-vivo' and bioassay measurements following two incidents involving plutonium-239 inhalation are described and contrasted. Incident 1, involving the inhalation of insoluble plutonium oxide, resulted in a lung content of about 20 nCi after the initial clearance. Urine excretion was negligible and the estimation of exposure was based on 'in-vivo' data and faecal excretion. Incident,2, involving the inhalation of soluble plutonium, proved negligible and the estimation of exposure, based on urinary excretion, was 0.6 nCi. (author)

  10. Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

    International Nuclear Information System (INIS)

    Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita; Pope, Carey

    2006-01-01

    This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted in any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some

  11. In Vivo Exposure of Kaempferol Is Driven by Phase II Metabolic Enzymes and Efflux Transporters.

    Science.gov (United States)

    Zheng, Liang; Zhu, Lijun; Zhao, Min; Shi, Jian; Li, Yuhuan; Yu, Jia; Jiang, Huangyu; Wu, Jinjun; Tong, Yunli; Liu, Yuting; Hu, Ming; Lu, Linlin; Liu, Zhongqiu

    2016-09-01

    Kaempferol is a well-known flavonoid; however, it lacks extensive pharmacokinetic studies. Phase II metabolic enzymes and efflux transporters play an important role in the disposition of flavonoids. This study aimed to investigate the mechanism by which phase II metabolic enzymes and efflux transporters determine the in vivo exposure of kaempferol. Pharmacokinetic analysis in Sprague-Dawley rats revealed that kaempferol was mostly biotransformed to conjugates, namely, kaempferol-3-glucuronide (K-3-G), kaempferol-7-glucuronide (K-7-G), and kaempferol-7-sulfate, in plasma. K-3-G represented the major metabolite. Compared with that in wild-type mice, pharmacokinetics in knockout FVB mice demonstrated that the absence of multidrug resistance protein 2 (MRP2) and breast cancer resistance protein (BCRP) significantly increased the area under the curve (AUC) of the conjugates. The lack of MRP1 resulted in a much lower AUC of the conjugates. Intestinal perfusion in rats revealed that the glucuronide conjugates were mainly excreted in the small intestine, but 7-sulfate was mainly excreted in the colon. In Caco-2 monolayers, K-7-G efflux toward the apical (AP) side was significantly higher than K-3-G efflux. In contrast, K-3-G efflux toward the basolateral (BL) side was significantly higher than K-7-G efflux. The BL-to-AP efflux was significantly reduced in the presence of the MRP2 inhibitor LTC4. The AP-to-BL efflux was significantly decreased in the presence of the BL-side MRPs inhibitor MK571. The BCRP inhibitor Ko143 decreased the glucuronide conjugate efflux. Therefore, kaempferol is mainly exposed as K-3-G in vivo, which is driven by phase II metabolic enzymes and efflux transporters (i.e., BCRP and MRPs).

  12. In vivo EPR dosimetry of accidental exposures to radiation: experimental results indicating the feasibility of practical use in human subjects

    International Nuclear Information System (INIS)

    Miyake, Minoru; Liu, K.J.; Walczak, T.M.; Swartz, H.M.

    2000-01-01

    Low frequency electron paramagnetic resonance (EPR) provides the potential advantage of making accurate and sensitive measurements of absorbed radiation dose in teeth in situ, i.e. without removing the teeth from the potential victim. The potential limiting factors for making such measurements are: (1) whether low frequency EPR is sufficiently sensitive to detect radiation-induced signal in human teeth; (2) whether sufficient sensitivity can be maintained under in vivo conditions. In this manuscript, we summarize results indicating that this approach is feasible. Using 1.2 GHz EPR spectroscopy, we found that the lower limit for these measurements in isolated human teeth is 0.2 Gy or lower. Measurements of radiation-induced EPR signals in the teeth of living rats were achieved with sufficient sensitivity to indicate that, when taking into consideration the larger mass of human teeth, similar measurements in human teeth in situ would provide sensitivity in the dose range for potential accidental exposures. We estimate that the current lower limit for detecting radiation doses in human teeth in situ (in vivo) is 0.5-1.0 Gy; this would be sufficient for determining if a person has been exposed to potentially life threatening doses of ionizing radiation. The limiting factor for sensitivity appears to be background signals rather than signal/noise, and there are feasible means to overcome this problem and further increase sensitivity. The additional instrumental developments required to make an effective in vivo EPR dosimetric spectrometer for the measurements in teeth in human subjects in situ, seem quite achievable

  13. Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

    Science.gov (United States)

    Borm, Paul J A; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; van Schooten, Frederik Jan; Oberdörster, Günter; Schins, Roel P F

    2005-06-01

    The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely.

  14. Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks

    International Nuclear Information System (INIS)

    Borm, Paul J.A.; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; Schooten, Frederik Jan van; Oberdoerster, Guenter; Schins, Roel P.F.

    2005-01-01

    Objective: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. Methods: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m 3 ). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 μM) and a mixture of 16 PAHs (0.1 μM) were used. Results: No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 μg/cm 2 ) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. Conclusion: The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely

  15. Thyroid endocrine system disruption by pentachlorophenol: an in vitro and in vivo assay.

    Science.gov (United States)

    Guo, Yongyong; Zhou, Bingsheng

    2013-10-15

    The present study aimed to evaluate the disruption caused to the thyroid endocrine system by pentachlorophenol (PCP) using in vitro and in vivo assays. In the in vitro assay, rat pituitary GH3 cells were exposed to 0, 0.1, 0.3, and 1.0 μM PCP. PCP exposure significantly downregulated basal and triiodothyronine (T3)-induced Dio 1 transcription, indicating the antagonistic activity of PCP in vitro. In the in vivo assay, zebrafish embryos were exposed to 0, 1, 3, and 10 μg/L of PCP until 14 days post-fertilization. PCP exposure resulted in decreased thyroxine (T4) levels, but elevated contents of whole-body T3. PCP exposure significantly upregulated the mRNA expression of genes along hypothalamic-pituitary-thyroid (HPT) axis, including those encoding thyroid-stimulating hormone, sodium/iodide symporter, thyroglobulin, Dio 1 and Dio 2, alpha and beta thyroid hormone receptor, and uridinediphosphate-glucuronosyl-transferase. PCP exposure did not influence the transcription of the transthyretin (TTR) gene. The results indicate that PCP potentially disrupts the thyroid endocrine system both in vitro and in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Ecotoxicity of bisphenol A to Caenorhabditis elegans by multigenerational exposure and variations of stress response in vivo across generations

    International Nuclear Information System (INIS)

    Zhou, Dong; Yang, Jie; Li, Hui; Lu, Qiang; Liu, Yong-di; Lin, Kuang-fei

    2016-01-01

    great relevance for environmental risk assessment. - Multigenerational exposure was conducted on Caenorhabditis elegans to better understand biological impacts of BPA across generations and changes of stress response in vivo.

  17. Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

    Directory of Open Access Journals (Sweden)

    Yakov Lomakin

    2017-07-01

    Full Text Available Multiple sclerosis (MS is an autoimmune chronic inflammatory disease of the central nervous system (CNS. Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV latent membrane protein 1 (LMP1. In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

  18. Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

    Science.gov (United States)

    Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading. PMID:28729867

  19. Exposure to the Epstein-Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo.

    Science.gov (United States)

    Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo . We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20-50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

  20. Effects of in vivo chronic exposure to pendimethalin on EROD activity and antioxidant defenses in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Danion, Morgane; Le Floch, Stéphane; Lamour, François; Quentel, Claire

    2014-01-01

    Pendimethalin, an herbicide active substance frequently used in terrestrial systems, has detected in European aquatic ecosystems. Reliable indicators still need to be found in order to properly assess the impact of pesticides in fish. After an in vivo chronic exposure to pendimethalin, the detoxification process and the antioxidant defense system were assessed in 120 adult rainbow trout, Oncorhynchus mykiss. Four nominal exposure conditions were tested: control (C), 500 ng L(-1) (P500), 800 ng L(-1) (P800) and the commercial formulation Prowl(®) at 500 ng L(-1) (Pw500). Fish samples were made after a 28 day exposure period (D28) and after a fifteen day recovery period in clean fresh water (D43). At D28, ethoxyresorufin-O-deethylase (EROD) activity was not activated in liver in spite of the pendimethalin uptake in fish. At D43, EROD activity in fish exposed to the commercial product was lower than in control fish, which may be explained by the high presence of herbicide in fish (613±163 ng g bile(-1)). Furthermore, antioxidant defense responses were set up by trout in gills and liver following chronic exposure to 800 ng L(-1) of pendimethalin concentration. While the glutathione content (GSH) decreased in gills, it increased in liver associated with higher activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). These disturbances could lead to reactive oxygen species production and oxidative stress in the vital organs in fish. After fifteen days in clean water, while the SOD activity was restored, the GSH content and GPx activity were still significantly disturbed in fish exposed to pendimethalin in comparison with control. These significant differences between treatments in antioxidant defenses parameters measured, attesting to the irreversibility of the effects. © 2013 Published by Elsevier Inc.

  1. Radiation exposure records management

    International Nuclear Information System (INIS)

    Boiter, H.P.

    1975-12-01

    Management of individual radiation exposure records begins at employment with the accumulation of data pertinent to the individual and any previous occupational radiation exposure. Appropriate radiation monitorinng badges or devices are issued and accountability established. A computer master file is initiated to include the individual's name, payroll number, social security number, birth date, assigned department, and location. From this base, a radiation exposure history is accumulated to include external ionizing radiation exposure to skin and whole body, contributing neutron exposure, contributing tritium exposure, and extremity exposure. It is used also to schedule bioassay sampling and in-vivo counts and to provide other pertinent information. The file is used as a basis for providing periodic reports to management and monthly exposure summaries to departmental line supervision to assist in planning work so that individual annual exposures are kept as low as practical. Radiation exposure records management also includes documentation of radiation surveys performed by the health physicist to establish working rates and the individual estimating and recording his estimated exposure on a day-to-day basis. Exposure information is also available to contribute to Energy Research and Development Administration statistics and to the National Transuranium Registry

  2. Health risk assessment of volatile organic compounds exposure near Daegu dyeing industrial complex in South Korea.

    Science.gov (United States)

    Shuai, Jianfei; Kim, Sunshin; Ryu, Hyeonsu; Park, Jinhyeon; Lee, Chae Kwan; Kim, Geun-Bae; Ultra, Venecio U; Yang, Wonho

    2018-04-20

    Studying human health in areas with industrial contamination is a serious and complex issue. In recent years, attention has increasingly focused on the health implications of large industrial complexes. A variety of potential toxic chemicals have been produced during manufacturing processes and activities in industrial complexes in South Korea. A large number of dyeing industries gathered together in Daegu dyeing industrial complex. The residents near the industrial complex could be often exposed to volatile organic compounds. This study aimed to evaluate VOCs levels in the ambient air of DDIC, to assess the impact on human health risks, and to find more convincing evidences to prove these VOCs emitted from DDIC. According to deterministic risk assessment, inhalation was the most important route. Residential indoor, outdoor and personal exposure air VOCs were measured by passive samplers in exposed area and controlled area in different seasons. Satisfaction with ambient environments and self-reported diseases were also obtained by questionnaire survey. The VOCs concentrations in exposed area and controlled area was compared by t-test. The relationships among every VOC were tested by correlation. The values of hazard quotient (HQ) and life cancer risk were estimated. The concentrations of measured VOCs were presented, moreover, the variety of concentrations according the distances from the residential settings to the industrial complex site in exposed area. The residential indoor, outdoor, and personal exposure concentrations of toluene, DMF and chloroform in exposed area were significantly higher than the corresponding concentrations in controlled area both in summer and autumn. Toluene, DMF, chloroform and MEK had significantly positive correlations with each other in indoor and outdoor, and even in personal exposure. The HQ for DMF exceeded 1, and the life cancer risk of chloroform was greater than 10 - 4 in exposed area. The prevalence of respiratory diseases

  3. Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy

    Directory of Open Access Journals (Sweden)

    Mitsunaga Makoto

    2012-08-01

    Full Text Available Abstract Background Near infrared (NIR photoimmunotherapy (PIT is a new type of cancer treatment based on a monoclonal antibody (mAb-NIR phthalocyanine dye, (IR700 conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult. Methods A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI was performed before and after PIT. Results Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2, however, in mice receiving lower intensity NIR (50 J/cm2, tumors recurred with gradually increasing BLI signal. Conclusion PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.

  4. Chromosome aberrations in monkey lymphocytes irradiated in vitro and in vivo

    International Nuclear Information System (INIS)

    Ziemba-Zak, B.

    1976-01-01

    The relationship between the X-ray dose and yield of dicentrics plus centric rings in monkey lymphocytes in vitro was studied. Frequency of these aberrations at different periods after in vivo exposure was also studied. No statistically significant differences were found between the yield of dicentrics plus centric rings obtained by in vitro and in vivo (up to 7 days) after irradiation. (author)

  5. Cellular responses to tritium exposure in rainbow trout: HTO- and OBT-spiked feed exposure experiments

    Energy Technology Data Exchange (ETDEWEB)

    Festarini, A.; Shultz, C.; Stuart, M.; Kim, S.B., E-mail: amy.festarini@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Ferreri, C. [National Research Council of Italy, Dept. of Chemical Sciences and Materials Technologies, Bologna (Italy)

    2016-06-15

    Biological effects were evaluated in rainbow trout (Oncorhynchus mykiss) exposed to tritiated water (HTO) or food spiked with organically bound tritium (OBT). An HTO exposure study was conducted using a tritium activity concentration of 7000 Bq/L, and an OBT exposure study was conducted using a tritium activity concentration of 30 000 Bq/L. Following 140 days of in vivo HTO exposure, liver, heart, spleen, kidney, and brain cells did not show statistically significant differences in viability; kidney, liver, and spleen cells did not show significant differences in DNA double-strand break repair activity compared with control cells. Membrane fatty acid composition analysis was conducted on liver cells and no effects of HTO exposure could be detected. Following 140 days of in vivo OBT exposure, viability and DNA double-strand break repair activity were not statistically different from controls in liver, heart, spleen, kidney, and brain cells. Changes, however, were noted in the fatty acid composition of liver and muscle tissues. For both studies, all measurements were performed on each tissue and on a fraction of the same tissue that was exposed to a gamma 4 Gy dose in vitro to test for adaptive responses, and no effects were observed except for fatty acid composition. The findings demonstrated that membrane fatty acid composition is a sensitive marker and that microscopic evaluation of gamma-H2AX foci is more sensitive than the flow cytometric approach. These studies are the first to correlate uptake and depuration with biological health indicators in edible fish for tritium exposures within worldwide drinking water guidelines. (author)

  6. Cellular responses to tritium exposure in rainbow trout: HTO- and OBT-spiked feed exposure experiments

    International Nuclear Information System (INIS)

    Festarini, A.; Shultz, C.; Stuart, M.; Kim, S.B.; Ferreri, C.

    2016-01-01

    Biological effects were evaluated in rainbow trout (Oncorhynchus mykiss) exposed to tritiated water (HTO) or food spiked with organically bound tritium (OBT). An HTO exposure study was conducted using a tritium activity concentration of 7000 Bq/L, and an OBT exposure study was conducted using a tritium activity concentration of 30 000 Bq/L. Following 140 days of in vivo HTO exposure, liver, heart, spleen, kidney, and brain cells did not show statistically significant differences in viability; kidney, liver, and spleen cells did not show significant differences in DNA double-strand break repair activity compared with control cells. Membrane fatty acid composition analysis was conducted on liver cells and no effects of HTO exposure could be detected. Following 140 days of in vivo OBT exposure, viability and DNA double-strand break repair activity were not statistically different from controls in liver, heart, spleen, kidney, and brain cells. Changes, however, were noted in the fatty acid composition of liver and muscle tissues. For both studies, all measurements were performed on each tissue and on a fraction of the same tissue that was exposed to a gamma 4 Gy dose in vitro to test for adaptive responses, and no effects were observed except for fatty acid composition. The findings demonstrated that membrane fatty acid composition is a sensitive marker and that microscopic evaluation of gamma-H2AX foci is more sensitive than the flow cytometric approach. These studies are the first to correlate uptake and depuration with biological health indicators in edible fish for tritium exposures within worldwide drinking water guidelines. (author)

  7. Tributyltin exposure at noncytotoxic doses dysregulates pancreatic β-cell function in vitro and in vivo.

    Science.gov (United States)

    Chen, Ya-Wen; Lan, Kuo-Cheng; Tsai, Jing-Ren; Weng, Te-I; Yang, Ching-Yao; Liu, Shing-Hwa

    2017-09-01

    Tributyltin (TBT) is an endocrine disruptor. TBT can be found in food and in human tissues and blood. Several animal studies revealed that organotins induced diabetes with decreased insulin secretion. The detailed effect and mechanism of TBT on pancreatic β-cell function still remain unclear. We investigated the effect and mechanism of TBT exposure at noncytotoxic doses relevant to human exposure on β-cell function in vitro and in vivo. The β-cell-derived RIN-m5F cells and pancreatic islets from mouse and human were treated with TBT (0.05-0.2 μM) for 0.5-4 h. Adult male mice were orally exposed to TBT (25 μg/kg/day) with or without antioxidant N-acetylcysteine (NAC) for 1-3 weeks. Assays for insulin secretion and glucose metabolism were carried out. Unlike previous studies, TBT at noncytotoxic concentrations significantly increased glucose-stimulated insulin secretion and intracellular Ca 2+ ([Ca 2+ ] i ) in β-cells. The reactive oxygen species (ROS) production and phosphorylation of protein kinase C (PKC-pan) and extracellular signal-regulated kinase (ERK)1/2 were also increased. These TBT-triggered effects could be reversed by antiestrogen ICI182780 and inhibitors of ROS, [Ca 2+ ] i , and PKC, but not ERK. Similarly, islets treated with TBT significantly increased glucose-stimulated insulin secretion, which could be reversed by ICI182780, NAC, and PKC inhibitor. Mice exposed to TBT for 3 weeks significantly increased blood glucose and plasma insulin and induced glucose intolerance and insulin resistance, which could be reversed by NAC. These findings suggest that low/noncytotoxic doses of TBT induce insulin dysregulation and disturb glucose homeostasis, which may be mediated through the estrogen receptor-regulated and/or oxidative stress-related signaling pathways.

  8. Examining the free radical bonding mechanism of benzoquinone– and hydroquinone–methanol passivation of silicon surfaces

    International Nuclear Information System (INIS)

    Kotulak, Nicole A.; Chen, Meixi; Schreiber, Nikolas; Jones, Kevin; Opila, Robert L.

    2015-01-01

    Highlights: • Photons are required for high levels of c-Si passivation by both BQ/ME and HQ/ME solutions. • Protons are required for high levels of c-Si passivation by both BQ/ME and HQ/ME solutions. • The free radical QH· is the likely passivating species for c-Si surfaces from BQ/ME and HQ/ME solutions. - Abstract: The surface passivation of p-benzoquinone (BQ) and hydroquinone (HQ) when dissolved in methanol (ME) has been examined through effective lifetime testing of crystalline silicon (c-Si) wafers treated with the aforementioned solutions. Changes in the availability of both photons and protons in the solutions were demonstrated to affect the level of passivation achieved. The requirement of both excess protons and ambient light exposure to maintain high effective lifetimes supports the presence of a free radical species that drives the surface passivation. Surface analysis suggests a 1:1 ratio of HQ-like bonds to methoxy bonds on the c-Si surface after treatment with a BQ/ME solution.

  9. Fetal microglial in vitro phenotype depends on prior in vivo inflammation

    Directory of Open Access Journals (Sweden)

    Mingju eCao

    2015-08-01

    Full Text Available Objective. Neuroinflammation in utero may result in life-long neurological disabilities. The molecular mechanisms whereby microglia contribute to this response remain incompletely understood. Methods. Lipopolysaccharide (LPS or saline were administered intravenously to non-anesthetized chronically instrumented near-term fetal sheep to model fetal inflammation in vivo. Microglia were then isolated from in vivo LPS and saline (naïve exposed animals. To mimic the second hit of neuroinflammation, these microglia were then re-exposed to LPS in vitro. Cytokine responses were measured in vivo and subsequently in vitro in the primary microglia cultures derived from these animals. We sequenced the whole transcriptome of naïve and second hit microglia and profiled their genetic expression to define molecular pathways disrupted during neuroinflammation.Results. In vivo LPS exposure resulted in IL-6 increase in fetal plasma 3 h post LPS exposure. Even though not histologically apparent, microglia acquired a pro-inflammatory phenotype in vivo that was sustained and amplified in vitro upon second hit LPS exposure as measured by IL-1β response in vitro and RNAseq analyses. While NFKB and Jak-Stat inflammatory pathways were up regulated in naïve microglia, heme oxygenase 1 (HMOX1 and Fructose-1,6-bisphosphatase (FBP genes were uniquely differentially expressed in the second hit microglia. Microglial calreticulin/LRP genes implicated in microglia-neuronal communication relevant for the neuronal development were up regulated in second hit microglia.Discussion. We identified a unique HMOX1down and FBPup phenotype of microglia exposed to the double-hit suggesting interplay of inflammatory and metabolic pathways as a memory of prior inflammatory insult. These findings suggest new therapeutic targets for early postnatal intervention to prevent brain injury.

  10. Relationship between polychlorinated biphenyl 126 treatment and cytochrome P4501A activity in chickens, as measured by in vivo caffeine and ex vivo ethoxyresorufin metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Feyk, L.A.; Giesy, J.P.; Lambert, G.H.

    1999-09-01

    Cytochrome P4501A (CYPIA) activity is often used as a biomarker of exposure of wildlife to polyhalogenated diaromatic hydrocarbons (PHDHs) and is usually measured ex vivo in liver tissue. A caffeine breath test with radiolabeled substrate ({sup 14}C-CBT) has been developed to measure in vivo avian CYPIA activity. Research goals were to develop stable isotope methods ({sup 13}C-CBT), determine dose-response relationships between caffeine N-demethylation (CNDM) and PHDH exposure, and assess the relative utility of the CBT and ex vivo ethoxyresorufin-O-deethylase (EROD) assay. The {sup 13}C-CBT methods were developed with 20 chickens (Gallus domesticus). Chickens received three intraperitoneal injections of 0, 1, 5, or 50 {micro}g 3,3{prime},4,4{prime},5-pentachlorobiphenyl (PCB 126)/kg body weight, and CNDM was quantified by measurement of {sup 13}CO{sub 2}/{sup 12}CO{sub 2} in expired breath. The {sup 13}C-CBT was not as sensitive or specific as the EROD assay as an indicator of PHDH exposure and effect in birds. Constitutive CNDM of great interindividual variability was observed, and the magnitude of induction was greater for EROD activity than for CNDM (approximately 1,000- and 2-fold, respectively). Variability associated with baseline {sup 13}CO{sub 2}/{sup 12}CO{sub 2} ratios in expired breath reduced the sensitivity of the {sup 13}C-CBT method.

  11. Active-imaginal exposure: examination of a new behavioral treatment for cynophobia (dog phobia)

    NARCIS (Netherlands)

    Rentz, T.O.; Powers, M.B.; Smits, J.A.J.; Cougle, J.R.; Telch, M.J.

    2003-01-01

    The aims of this study were to investigate exposure-based treatments for cynophobia (dog phobia) and to test a newly developed hybrid imaginal exposure treatment that we have named active imaginal exposure. The treatment introduces an in vivo coping component to imaginal exposure whereby the patient

  12. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    International Nuclear Information System (INIS)

    Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela; Venâncio, Mireli; Vieira Ronconi, João Vitor; Merlini, Aline; Streck, Emílio L.; Marques da Silva, Paula; Moraes de Andrade, Vanessa

    2012-01-01

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5–45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  13. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil); Venancio, Mireli; Vieira Ronconi, Joao Vitor; Merlini, Aline [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Streck, Emilio L. [Programa de Pos-Graduacao em Ciencias da Saude, Unidade Academica de Ciencias da Saude, Universidade do Extremo Sul Catarinense, Laboratorio de Fisiopatologia Experimental (Brazil); Marques da Silva, Paula [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Moraes de Andrade, Vanessa, E-mail: vmoraesdeandrade@yahoo.com.br [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil)

    2012-03-15

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5-45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  14. Virtual reality exposure therapy for anxiety disorders: A meta-analysis

    NARCIS (Netherlands)

    Powers, M.B.; Emmelkamp, P.M.G.

    2008-01-01

    There is now a substantial literature investigating virtual reality exposure therapy (VRET) as a viable treatment option for anxiety disorders. In this meta-analysis we provide effect size estimates for virtual reality treatment in comparison to in vivo exposure and control conditions (waitlist,

  15. In vivo transcriptome modulation after low dose of high energy neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Amendola, R; Fratini, E; Piscitelli, M; Sallustio, D E [ENEA, BAS BIOTEC MED, Roma (Italy); Angelone, M; Pillon, M [ENEA, FUS TEC, Frascati (Italy); Chiani, F; Licursi, V; Negri, R [Universita La Sapienza, Roma (Italy). Dip. Biologia Cellulare e dello Sviluppo

    2007-07-01

    Complete text of publication follows. Objective: This project aims to the identification of an hypothetical transcriptome modulation of mouse peripheral blood lymphocytes and skin after exposure to high energy neutron in vivo. Positive candidate genes isolated from mice in in vivo experiments will be selected and evaluated for both radioprotection issues dealing with cosmic ray exposure, and for biomedical issues mainly for low doses and non-cancer effects. Methods: High energy neutron irradiation is performed at the ENEA Frascati, neutron generator facilities (FNG), specifically dedicated to biological samples. FNG is a linear electrostatic accelerator that produces up to 1.0 x 10{sup 11} n/s 14 MeV neutrons via the D-T nuclear reaction. The dose-rate applied for this study is of 0.7 cGy/min. The functional genomic approach has been performed on six animals for each experimental points: un-irradiated; 20 cGy, 6 hours and 24 hours delayed time after exposure. Preliminarily, a pool of total RNA is evaluated on commercial micro-arrays containing large collections of mus musculus cDNAs. Statistical filtering and functional clustering of the data is carried out using dedicated software packages. Results: Candidate genes are selected on the basis of responsiveness to 20 cGy of exposure, with a defined temporal regulation. We plan to organize a systematic screen focused on genes responding to our selection criteria, in in vivo mouse experiments, and correlate their differential expression to the human counterparts. A specific cross species database will be created with all the functional information available in standardized format (MIAME: minimal information about micro-arrays experiments). Conclusions: A lack of information on in vivo experiments is still evident for low doses exposure, especially for neutron of cosmic interest. Individual susceptibility, extensive number of animals to be processed, lack of standardization methodologies are among problems to be solved

  16. Virtual reality exposure therapy for anxiety disorders: the state of the art

    NARCIS (Netherlands)

    Meyerbröker, K.; Emmelkamp, P.M.G.; Brahnam, S.; Jain, L.C.

    2011-01-01

    In the past 10 years virtual reality exposure therapy (VRET) has become a viable alternative for exposure in vivo, the gold standard for the treatment of anxiety disorders. VRET is often regarded as a natural extension of the systematic exposure component of (cognitive) behavior therapy. The

  17. Modification of the striatal dopaminergic neuron system by carbon monoxide exposure in free-moving rats, as determined by in vivo brain microdialysis

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Shuichi; Kurosaki, Kunihiko; Kuriiwa, Fumi; Endo, Takahiko [Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Mukai, Toshiji [Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-0015 (Japan)

    2002-10-01

    Acute carbon monoxide (CO) intoxication in humans results in motor deficits, which resemble those in Parkinson's disease, suggesting possible disturbance of the central dopaminergic (DAergic) neuronal system by CO exposure. In the present study, therefore, we explored the effects of CO exposure on the DAergic neuronal system in the striatum of freely moving rats by means of in vivo brain microdialysis. Exposure of rats to CO (up to 0.3%) for 40 min caused an increase in extracellular dopamine (DA) levels and a decrease in extracellular levels of its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum depending on the CO concentration. Reoxygenation following termination of the CO exposure resulted in a decline of DA to the control level and an overshoot in the recovery of DOPAC and HVA to levels higher than the control. A monoamine oxidase type A (MAO-A) inhibitor, clorgyline, significantly potentiated the CO-induced increase in DA and completely abolished the subsequent overshoot in the recovery of DOPAC and HVA. Tetrodotoxin, a Na{sup +} channel blocker, completely abolished both the CO-induced increase in DA and the overshoot of DOPAC and HVA. A DA uptake inhibitor, nomifensine, strongly potentiated the CO-induced increase in DA without affecting the subsequent overshoot of DOPAC and HVA. Clorgyline further potentiated the effect of nomifensine on the CO-induced increase in DA, although a slight overshoot of DOPAC and HVA appeared. These findings suggest that (1) CO exposure may stimulate Na{sup +}-dependent DA release in addition to suppressing DA metabolism, resulting in a marked increase in extracellular DA in rat striatum, and (2) CO withdrawal and subsequent reoxygenation may enhance the oxidative metabolism, preferentially mediated by MAO-A, of the increased extracellular DA. In the light of the neurotoxicity of DA per se and reactive substances, such as quinones and activated oxygen species

  18. Optimization of in-vivo monitoring program for radiation emergency response

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Wi Ho; Kim, Jong Kyung [Dept. of Nuclear Engineering, Hanyang University, Seoul (Korea, Republic of)

    2016-12-15

    In case of radiation emergencies, internal exposure monitoring for the members of public will be required to confirm internal contamination of each individual. In-vivo monitoring technique using portable gamma spectrometer can be easily applied for internal exposure monitoring in the vicinity of the on-site area. In this study, minimum detectable doses (MDDs) for '1'3'4Cs, {sup 137}Cs, and {sup 131}I were calculated adjusting minimum detectable activities (MDAs) from 50 to 1,000 Bq to find out the optimal in-vivo counting condition. DCAL software was used to derive retention fraction of Cs and I isotopes in the whole body and thyroid, respectively. A minimum detectable level was determined to set committed effective dose of 0.1 mSv for emergency response. We found that MDDs at each MDA increased along with the elapsed time. 1,000 Bq for {sup 134}Cs and {sup 137}Cs, and 100 Bq for {sup 131}I were suggested as optimal MDAs to provide in-vivo monitoring service in case of radiation emergencies. In-vivo monitoring program for emergency response should be designed to achieve the optimal MDA suggested from the present work. We expect that a reduction of counting time compared with routine monitoring program can achieve the high throughput system in case of radiation emergencies.

  19. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    International Nuclear Information System (INIS)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J.

    1987-01-01

    The effects of cold exposure and insulin injection on the rates of net 2-[ 3 H]deoxyglucose uptake (K i ) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K i values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K i increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K i that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake

  20. Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment

    International Nuclear Information System (INIS)

    Wetmore, Barbara A.

    2015-01-01

    High-throughput in vitro toxicity screening provides an efficient way to identify potential biological targets for environmental and industrial chemicals while conserving limited testing resources. However, reliance on the nominal chemical concentrations in these in vitro assays as an indicator of bioactivity may misrepresent potential in vivo effects of these chemicals due to differences in clearance, protein binding, bioavailability, and other pharmacokinetic factors. Development of high-throughput in vitro hepatic clearance and protein binding assays and refinement of quantitative in vitro-to-in vivo extrapolation (QIVIVE) methods have provided key tools to predict xenobiotic steady state pharmacokinetics. Using a process known as reverse dosimetry, knowledge of the chemical steady state behavior can be incorporated with HTS data to determine the external in vivo oral exposure needed to achieve internal blood concentrations equivalent to those eliciting bioactivity in the assays. These daily oral doses, known as oral equivalents, can be compared to chronic human exposure estimates to assess whether in vitro bioactivity would be expected at the dose-equivalent level of human exposure. This review will describe the use of QIVIVE methods in a high-throughput environment and the promise they hold in shaping chemical testing priorities and, potentially, high-throughput risk assessment strategies

  1. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  2. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Ren, Xuefeng; Gaile, Daniel P.; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R.; Kavanagh, Terrance J.; Wu, Hongmei

    2015-01-01

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  3. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  4. 75 FR 68306 - Modification of Significant New Uses of 2-Propen-1-one, 1-(4-morpholinyl)-

    Science.gov (United States)

    2010-11-05

    ... Constitution Ave., NW., Washington, DC. Attention: Docket ID Number EPA-HQ-OPPT-2009-0669. The DCO is open from...); required establishment of a hazard communication program; prohibited domestic manufacturing; prohibited... calculated Margins of Exposure (MOEs) for predicted workplace exposures. Based on these new data, concerns...

  5. Exposure and risk assessment for aluminium and heavy metals in Puerh tea

    International Nuclear Information System (INIS)

    Cao, Hongbin; Qiao, Li; Zhang, Hui; Chen, Jianjiang

    2010-01-01

    As the consumption of Puerh tea is booming because of its multiple health-promoting effects, the possible health risks resulting from long-term exposure to metals contained in this tea need to be evaluated. To assess the human risk associated with drinking Puerh tea, concentrations of aluminium, lead, cadmium, mercury, zinc, copper and arsenic were determined in samples of Puerh tea, tea leaves from the plants, and planted soil collected from the Yunnan province, China. Site-specific exposure parameters such as body weight and consumption rate of Puerh tea were investigated in Kunming and Puer cities using face-to-face surveys. Health risks were evaluated for the inhabitants of Kunming and Puer cities by gender and by age groups. Although the Puerh tea plant easily absorbs aluminium from soil, the concentrations of Al and six other elements in Puerh tea were all far below the safety concentration limits of China. Both the HQ (Hazard Quotient) values for single elements and the HI (Hazard Index) value for all seven elements were far below one, indicating no non-carcinogenic risks from these seven elements for inhabitants of Kunming and Puer under the current consumption rates of Puerh tea. However, probabilistic estimation of carcinogenic risk shows that the 95th percentile carcinogenic rate of arsenic in Puerh tea approaches the accepted risk level of 10 -4 for the highest exposure group. Therefore, the arsenic in Puerh tea is of concern.

  6. Deterministic hazard quotients (HQs): Heading down the wrong road

    International Nuclear Information System (INIS)

    Wilde, L.; Hunter, C.; Simpson, J.

    1995-01-01

    The use of deterministic hazard quotients (HQs) in ecological risk assessment is common as a screening method in remediation of brownfield sites dominated by total petroleum hydrocarbon (TPH) contamination. An HQ ≥ 1 indicates further risk evaluation is needed, but an HQ ≤ 1 generally excludes a site from further evaluation. Is the predicted hazard known with such certainty that differences of 10% (0.1) do not affect the ability to exclude or include a site from further evaluation? Current screening methods do not quantify uncertainty associated with HQs. To account for uncertainty in the HQ, exposure point concentrations (EPCs) or ecological benchmark values (EBVs) are conservatively biased. To increase understanding of the uncertainty associated with HQs, EPCs (measured and modeled) and toxicity EBVs were evaluated using a conservative deterministic HQ method. The evaluation was then repeated using a probabilistic (stochastic) method. The probabilistic method used data distributions for EPCs and EBVs to generate HQs with measurements of associated uncertainty. Sensitivity analyses were used to identify the most important factors significantly influencing risk determination. Understanding uncertainty associated with HQ methods gives risk managers a more powerful tool than deterministic approaches

  7. Results of adolescent health risk assesment on exposure to habitat water peroral factor in conditions of a large industrial city

    Science.gov (United States)

    Valeeva, E. R.; Stepanova, N. V.; Ismagilova, G. A.; Ziyatdinova, A. I.; Semanov, D. A.

    2018-01-01

    Results of the non-carcinogenic risk assessment on ingestion of chemical substances with drinking water showed that the risk value corresponded to the allowable level of the non-carcinogenic risk (HQ systems were identified: blood, CNS, kidneys, endocrine system, cardiovascular system, skeletal system and teeth. The total hazard indices in the 1st and the 4th zones deserve particular attention. The following elements: oil products (29.7% - 54.0%), nitrates (in NO3), chloroform and fluorides make a major contribution to the value of risk. In all other zones, irrespective of the value of exposure factors, total hazard quotients indicate alarming and unacceptable risk levels at HIMe = from 4 to 8.67; and at HI 95th Perc = from 8.7 to 16.8.

  8. Computer-aided detection of artificial pulmonary nodules using an ex vivo lung phantom: influence of exposure parameters and iterative reconstruction.

    Science.gov (United States)

    Wielpütz, Mark O; Wroblewski, Jacek; Lederlin, Mathieu; Dinkel, Julien; Eichinger, Monika; Koenigkam-Santos, M; Biederer, Jürgen; Kauczor, Hans-Ulrich; Puderbach, Michael U; Jobst, Bertram J

    2015-05-01

    To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT). Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n=162 artificial nodules of a clinically relevant volume and maximum diameter (46-1063 μl, and 6.2-21.5 mm). n=118 nodules were solid and n=44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction. The rate of true positive findings ranged between 88.9-91.4% for FBP and 88.3-90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, pvolumes 300 μl (p<0.05). Similarly, it was significantly lower for diameters <12 mm compared to ≥12 mm (p<0.05). The rate of true positives for solid and part-solid nodules was similar. Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to improve image quality in the setting of low-dose MDCT for lung cancer screening. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Damage Threshold of In Vivo Rabbit Cornea by 2 micron Laser Irradiation

    National Research Council Canada - National Science Library

    Chen, Bo; Oliver, Jeffery; Dutta, Soumak; Rylander, III, Grady H; Thomsen, Sharon L; Welch, Ashley J

    2007-01-01

    To support refinement of the Maximum Permissible Exposure (MPE) safety limits, a series of experiments were conducted in vivo on Dutch Belted rabbit corneas to determine corneal minimum visible lesion thresholds...

  10. DNA damage and repair process in earthworm after in-vivo and in vitro exposure to soils irrigated by wastewaters

    International Nuclear Information System (INIS)

    Qiao Min; Chen Ying; Wang Chunxia; Wang Zijian; Zhu Yongguan

    2007-01-01

    In this study, DNA damage to earthworms (Eisenia fetida) after in vivo exposure to contaminated soils was measured by detecting DNA strand breakages (DSBs) and causality was analyzed through fractionation based bioassays. A non-linear dose-response relationship existed between DNA damage and total soil PAHs levels. DNA damage, measured with the comet assay, and its repair process, were observed. To identify the chemical causality, an in vitro comet assay using coelomocytes was subsequently performed on the fractionated organic extracts from soils. The results showed that the PAHs in the soils were responsible for the exerting genotoxic effects on earthworms. When normalized to benzo(a)pyrene toxic equivalent (TEQ BaP ), the saturation dose in the dose-response curve was about 10 ng TEQ BaP g -1 soil (dw). - A non-linear dose-response relationship exists between earthworm DNA damage, measured with comet assay, and total PAHs levels in soils irrigated by wastewaters

  11. DNA damage and repair process in earthworm after in-vivo and in vitro exposure to soils irrigated by wastewaters

    Energy Technology Data Exchange (ETDEWEB)

    Qiao Min [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Chen Ying [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Wang Chunxia [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Wang Zijian [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)]. E-mail: wangzj@rcees.ac.cn; Zhu Yongguan [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

    2007-07-15

    In this study, DNA damage to earthworms (Eisenia fetida) after in vivo exposure to contaminated soils was measured by detecting DNA strand breakages (DSBs) and causality was analyzed through fractionation based bioassays. A non-linear dose-response relationship existed between DNA damage and total soil PAHs levels. DNA damage, measured with the comet assay, and its repair process, were observed. To identify the chemical causality, an in vitro comet assay using coelomocytes was subsequently performed on the fractionated organic extracts from soils. The results showed that the PAHs in the soils were responsible for the exerting genotoxic effects on earthworms. When normalized to benzo(a)pyrene toxic equivalent (TEQ{sub BaP}), the saturation dose in the dose-response curve was about 10 ng TEQ{sub BaP} g{sup -1} soil (dw). - A non-linear dose-response relationship exists between earthworm DNA damage, measured with comet assay, and total PAHs levels in soils irrigated by wastewaters.

  12. The distribution of 210Pb in human bone and its impact on methods for the retrospective estimation of 222Rn exposure from in vivo measurements.

    Science.gov (United States)

    Johnston, Peter N; Hult, Mikael; Gasparro, Joël; Martínez-Canet, María-José; Vasselli, Roberto; McKenzie, Raymond J; Solomon, Steven B; Lambrichts, Ivo

    2005-01-01

    It is possible to estimate radon exposure to man retrospectively by the in vivo measurement of the decay product (210)Pb, which accumulates in the bones. For in vivo methods, knowledge of the distribution of (210)Pb in the skeleton is needed to determine the optimal site for measurement, the skull or the knee. In this study the activity of (210)Pb in a variety of bone samples from 3 individuals have been measured in vitro using underground gamma-ray spectrometry. The individuals were unlikely to have had elevated intakes of Rn. These measurements give baseline data on the bone massic activity of (210)Pb. They show that the massic activity is similar for each of these people and there are similar massic activities of (210)Pb in the skull and the knee of the 2 individuals for which the skull was measured. Additionally for 2 of the individuals trabecular and cortical bone were separated and massic activities were found to be strongly correlated indicating that the (210)Pb is associated with the hydroxyapatite.

  13. The distribution of 210Pb in human bone and its impact on methods for the retrospective estimation of 222Rn exposure from in vivo measurements

    International Nuclear Information System (INIS)

    Johnston, Peter N.; Hult, Mikael; Gasparro, Jogl; Martinez-Canet, Maria-Jose; Vasselli, Roberto; McKenzie, Raymond J.; Solomon, Steven B.; Lambrichts, Ivo

    2005-01-01

    It is possible to estimate radon exposure to man retrospectively by the in vivo measurement of the decay product 210 Pb, which accumulates in the bones. For in vivo methods, knowledge of the distribution of 210 Pb in the skeleton is needed to determine the optimal site for measurement, the skull or the knee. In this study the activity of 210 Pb in a variety of bone samples from 3 individuals have been measured in vitro using underground γ-ray spectrometry. The individuals were unlikely to have had elevated intakes of Rn. These measurements give baseline data on the bone massic activity of 210 Pb. They show that the massic activity is similar for each of these people and there are similar massic activities of 210 Pb in the skull and the knee of the 2 individuals for which the skull was measured. Additionally for 2 of the individuals trabecular and cortical bone were separated and massic activities were found to be strongly correlated indicating that the 210 Pb is associated with the hydroxyapatite

  14. Correlative Ultratructural Investigations of Airway Epithelium Following Experimental Exposure to Defined Air Pollutants and Lifestyle Exposure to Tobacco Smoke

    Science.gov (United States)

    Context: Investigations of cell/molecular level effects of in vivo exposure of airway mucosa of experimental animals to common irritant gases have demonstrated structural and physiological changes reflective of breaches in epithelial barrier function, presence of inflammatory cel...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-15

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  17. Duration of in vivo endotoxin tolerance in horses.

    Science.gov (United States)

    Holcombe, Susan J; Jacobs, Carrie C; Cook, Vanessa L; Gandy, Jeffery C; Hauptman, Joseph G; Sordillo, Lorraine M

    2016-05-01

    Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin tolerance, in vivo, in horses based on physical, clinicopathologic, and proinflammatory gene expression responses to repeated endotoxin exposures. Six horses received 30 ng/kg LPS in saline infused over 30 min. Behavior pain scores, physical examination parameters, and blood for complete blood count and proinflammatory gene expression were obtained at predetermined intervals for 24h. Horses received a total of 3 endotoxin exposures. The first exposure was LPS 1, followed 7 days later by LPS 7 or 14-21 days later by LPS 14-21. Lipopolysaccharide exposures were allocated in a randomized, crossover design. Lipopolysaccharide produced clinical and clinicopathologic signs of endotoxemia and increased expression of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8, PHorses exhibited evidence of endotoxin tolerance following LPS 7 but not following LPS 14-21. Horses had significantly lower pain scores, heart rates, respiratory rates and duration of fever, after LPS 7 compared to LPS 1 and LPS 14-21, Phorses after LPS 7, P=0.05. Clinical parameters and TNFα gene expression were similar or slightly increased in horses following LPS 14-21 compared to measurements made in horses following LPS 1, suggesting that endotoxin tolerance had subsided. A minimum of 3 weeks between experiments is warranted if repeated measures designs are used to assess in vivo response to endotoxin in

  18. Analysis of renal cell transformation following exposure to trichloroethene in vivo and its metabolite S-(dichlorovinyl)-L-cysteine in vitro

    International Nuclear Information System (INIS)

    Mally, Angela; Walker, Cheryl L.; Everitt, Jeffrey I.; Dekant, Wolfgang; Vamvakas, Spiros

    2006-01-01

    Trichloroethene (TCE) is classified as a potential human carcinogen although there is a significant debate regarding the mechanism of TCE induced renal tumor formation. This controversy stems in part from the extremely high doses of TCE required to induce renal tumors and the potential contribution of the associated nephrotoxicity to tumorigenesis. We have used Eker rats, which are uniquely susceptible to renal carcinogens, to determine if exposures to TCE in vivo or exposure to its metabolite S-(dichlorovinyl)-L-cysteine (DCVC) in vitro can transform kidney epithelial cells in the absence of cytotoxicity. Treatment with TCE (0, 100, 250, 500, 1000 mg/kg bw by gavage, 5 days a week) for 13 weeks resulted in a significant increase in cell proliferation in kidney tubule cells, but did not enhance formation of preneoplastic lesions or tumor incidence in Eker rat kidneys as compared to controls. In vitro, concentrations of DCVC, which reduced cell survival to 50%, were able to transform rat kidney epithelial cells. However, no carcinogen-specific mutations were identified in the VHL or Tsc-2 tumor suppressor genes in the transformants. Taken together, the inability of TCE to enhance formation of preneoplastic changes or neoplasia and the absence of carcinogen-specific alteration of genes accepted to be critical for renal tumor development suggest that TCE mediated carcinogenicity may occur secondary to continuous toxic injury and sustained regenerative cell proliferation

  19. In vivo measurements of bone lead content in residents of southern Ontario

    International Nuclear Information System (INIS)

    Gamblin, C.; Gordon, C.L.; Webber, C.E.; Muir, D.C.F.; Chettle, D.R.

    1994-01-01

    In 111 subjects not occupationally exposed, bone lead content increased steadily with age in both men and women. Higher than expected bone lead levels were observed in two-thirds of 27 subjects working in occupations with potential for lead exposure. Five of 8 patients who displayed symptoms which might have been due to lead poisoning had increased bone lead levels. In vivo bone lead measurements reflect the cumulative extent of exposure to environmental and occupational sources of lead and allow the assessment of abnormal exposures. (Author)

  20. Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo.

    Science.gov (United States)

    Fröhlich, Eleonore

    2015-01-01

    Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.

  1. In vivo monitoring of toxic metals: assessment of neutron activation and x-ray fluorescence techniques

    International Nuclear Information System (INIS)

    Ellis, K.J.

    1986-01-01

    To date, cadmium, lead, aluminum, and mercury have been measured in vivo in humans. The possibilities of monitoring other toxic metals have also been demonstrated, but no human studies have been performed. Neutron activation analysis appears to be most suitable for Cd and Al measurements, while x-ray fluorescence is ideally suited for measurement of lead in superficial bone. Filtered neutron beams and polarized x-ray sources are being developed which will improve in vivo detection limits. Even so, several of the current facilities are already suitable for use in epidemiological studies of selected populations with suspected long-term low-level ''environmental'' exposures. Evaluation and diagnosis of patients presenting with general clinical symptoms attributable to possible toxic metal exposure may be assisted by in vivo examination. Continued in vivo monitoring of industrial workers, especially follow-up measurements, will provide the first direct assessment of changes in body burden and a direct measure of the biological life-times of these metals in humans. 50 refs., 4 figs., 2 tabs

  2. In vivo dermal absorption of pyrethroid pesticides in the rat.

    Science.gov (United States)

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and permethrin in the rat. Hair on the dorsal side of anesthetized adult m...

  3. Metal Exposure and Associated Health Risk to Human Beings by Street Dust in a Heavily Industrialized City of Hunan Province, Central China

    Directory of Open Access Journals (Sweden)

    Guangyi Sun

    2017-03-01

    Full Text Available Fifty-five urban street dust samples were collected from Zhuzhou, an industrial city in central China and analyzed for a range of toxic elements. Potential carcinogenic and non-carcinogenic health effects on children and adults due to exposure to street dust were assessed. Concerning the two subgroups, the child cohort is confronted with considerably greater health risks than adults. According to the Hazard Quotient (HQ method, ingestion of dust particles poses primary risk to children and adults, followed by dermal contact and inhalation for all of the metals investigated except Hg, for which inhalation of its elemental vapor constitute a slightly higher risk than ingestion. For children, Pb, As, Cd, Cr, Hg and Sb exposure were deemed as the highest contributors to non-cancer health risks, while As and Cr represent an enhanced cancer risk for children. For adults, risk indicator values for both cancer and non-cancer effects obtained were within the safety threshold. In a comparison with other locations within and outside mainland China, exposure to arsenic is prominent for the population of Zhuzhou, indicating more attention and preventive actions should been taken.

  4. Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology

    International Nuclear Information System (INIS)

    Weber, Michael H.; Sharp, Jonathan C.; Latta, Peter; Sramek, Milos; Hassard, H. Thomas; Orr, F. William

    2005-01-01

    Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 μm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological 'gold standard' The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure

  5. Radiation-induced bystander effects in vivo are sex specific

    International Nuclear Information System (INIS)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-01-01

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

  6. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  7. Radiation-induced bystander effects in vivo are sex specific.

    Science.gov (United States)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  8. Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother-newborn pairs

    DEFF Research Database (Denmark)

    Pedersen, Marie; Halldorsson, Thorhallur I; Mathiesen, Line

    2010-01-01

    In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential...... interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also...... determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased...

  9. Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

    Directory of Open Access Journals (Sweden)

    Fang Miao

    Full Text Available Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl oxy] phenol, D-Arb is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ. At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

  10. Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.

    Science.gov (United States)

    Miao, Fang; Shi, Ying; Fan, Zhi-Feng; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi

    2016-01-01

    Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.

  11. Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.

    Science.gov (United States)

    Lindsay, Angus; Othman, Mohd Izani; Prebble, Hannah; Davies, Sian; Gieseg, Steven P

    2016-07-01

    What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P cryotherapy attenuates in vitro T-cell and monocyte activation. This may explain the disparity in in vivo neopterin and total neopterin between cold water immersion and passive recovery following repetitive exposure during a high-intensity physical impact sport that remains independent of physical performance. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

  12. Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Yuta Inokuchi

    2006-01-01

    Full Text Available Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retina in vitro and/or in vivo. In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2 exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation, as also did trolox (water-soluble vitamin E. In mice in vivo, propolis (100 mg kg−1; intraperitoneally administered four times reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer induced by intravitreal in vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage both in vitro and in vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

  13. Dose-dependent in vivo cell-cycle changes following radon progeny exposure

    International Nuclear Information System (INIS)

    Johnson, N.F.; Carpenter, T.R.; Hickman, A.W.; Jaramillo, R.J.; Gurule, D.M.

    1994-01-01

    Exposures to low concentrations of alpha-emitting radon progeny are reported by the U.S. Environmental Protection Agency to be the second leading cause of lung cancer. Current risk estimates for lung cancer from the inhalation of radon progeny are based on data from underground uranium miners. To produce such risk estimates, calculations are based on several assumptions concerning exposure-response relationships rather than dose-response relationships. A better understanding of the mechanisms of interactions between alpha particles, the cells of the respiratory tract, and the progression toward cancer may validate the mathematical models used to derive risk estimates

  14. In vivo Microscale Measurements of Light and Photosynthesis during Coral Bleaching: Evidence for the Optical Feedback Loop?

    Science.gov (United States)

    Wangpraseurt, Daniel; Holm, Jacob B; Larkum, Anthony W D; Pernice, Mathieu; Ralph, Peter J; Suggett, David J; Kühl, Michael

    2017-01-01

    Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O 2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching.

  15. Low-dose radiation attenuates chemical mutagenesis in vivo. Cross adaptation

    International Nuclear Information System (INIS)

    Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

    2009-01-01

    The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea. (author)

  16. Psychological Distress and Physiological Reactivity During In Vivo Exposure in People With Aviophobia

    NARCIS (Netherlands)

    Busscher, B.; Spinhoven, P.; de Geus, E.J.C.

    2015-01-01

    Objectives Exposure is regarded to be a crucial component of therapies for phobias. According to emotional processing theory, the success of exposure therapy is predicted by activation of subjective and physiological fear responses and their within-session habituation and between-session adaptation.

  17. Acute in vitro and in vivo toxicity of a commercial grade boron nitride nanotube mixture.

    Science.gov (United States)

    Kodali, Vamsi K; Roberts, Jenny R; Shoeb, Mohammad; Wolfarth, Michael G; Bishop, Lindsey; Eye, Tracy; Barger, Mark; Roach, Katherine A; Friend, Sherri; Schwegler-Berry, Diane; Chen, Bean T; Stefaniak, Aleksandr; Jordan, Kevin C; Whitney, Roy R; Porter, Dale W; Erdely, Aaron D

    2017-10-01

    Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 µg/ml and C57BL/6 J male mice were treated with 40 µg of BNNT-M for in vitro and in vivo studies, respectively. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1β and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein production when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The observed results demonstrated acute

  18. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    International Nuclear Information System (INIS)

    Dasari, Sameera; Yuan, Yukun

    2009-01-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

  19. The distribution of {sup 210}Pb in human bone and its impact on methods for the retrospective estimation of {sup 222}Rn exposure from in vivo measurements

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Peter N. [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel (Belgium); Department of Applied Physics, Royal Melbourne Institute of Technology, GPO Box 2476V, Melbourne 3001 (Australia); Hult, Mikael [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel (Belgium)]. E-mail: mikael.hult@cec.eu.int; Gasparro, Jogl [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel (Belgium); Martinez-Canet, Maria-Jose [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel (Belgium); Vasselli, Roberto [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Retieseweg 111, B-2440 Geel (Belgium); McKenzie, Raymond J. [Department of Applied Physics, Royal Melbourne Institute of Technology, GPO Box 2476V, Melbourne 3001 (Australia); Solomon, Steven B. [Australian Radiation Protection and Nuclear Safety Agency, Lower Plenty Road, Yallambie 3085 (Australia); Lambrichts, Ivo [Department of Histology, Limburg University Centrum (LUC), Diepenbeek (Belgium)

    2005-07-01

    It is possible to estimate radon exposure to man retrospectively by the in vivo measurement of the decay product {sup 210}Pb, which accumulates in the bones. For in vivo methods, knowledge of the distribution of {sup 210}Pb in the skeleton is needed to determine the optimal site for measurement, the skull or the knee. In this study the activity of {sup 210}Pb in a variety of bone samples from 3 individuals have been measured in vitro using underground {gamma}-ray spectrometry. The individuals were unlikely to have had elevated intakes of Rn. These measurements give baseline data on the bone massic activity of {sup 210}Pb. They show that the massic activity is similar for each of these people and there are similar massic activities of {sup 210}Pb in the skull and the knee of the 2 individuals for which the skull was measured. Additionally for 2 of the individuals trabecular and cortical bone were separated and massic activities were found to be strongly correlated indicating that the {sup 210}Pb is associated with the hydroxyapatite.

  20. Quantification of inorganic arsenic exposure and cancer risk via consumption of vegetables in southern selected districts of Pakistan

    Science.gov (United States)

    Rehman, Zahir Ur; Khan, Sardar; Qin, Kun; Brusseau, Mark L; Shah, Mohammad Tahir; Din, Islamud

    2016-01-01

    Human exposures to arsenic (As) through different pathways (dietary and non-dietary) are considered to be one of the primary worldwide environmental health risks to humans. This study was conducted to investigate the presence of As in soil and vegetable samples collected from agricultural lands located in selected southern districts of Khyber Pakhtunkhwa (KPK) Province, Pakistan. We examined the concentrations of total arsenic (TAs), organic species of As such as monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA), and inorganic species including arsenite (AsIII) and arsenate (AsV) in both soil and vegetable. The data were used to determine several parameters to evaluate human health risk, including bioconcentration factor (BCF) from soil to plant, average daily intake (ADI), health risk index (HRI), incremental lifetime cancer risk (ILTCR), and hazard quotient (HQ). The total As concentration in soil samples of the five districts ranged from 3.0-3.9 mg kg−1, exhibiting minimal variations from site to site. The mean As concentration in edible portions of vegetable samples ranged from 0.03-1.38 mg kg−1. It was observed that As concentrations in 75% of the vegetable samples exceeded the safe maximum allowable limit (0.1 mg kg−1) set by WHO/FAO. The highest value of ADI for As was measured for M. charantia, while the lowest was for A. chinense. The results of this study revealed minimal health risk (HI vegetables for the local inhabitants. The ILTCR values for inorganic As indicated a minimal potential cancer risk through ingestion of vegetables. In addition, the HQ values for total As were <1, indicating minimal non-cancer risk. PMID:26820935

  1. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    Energy Technology Data Exchange (ETDEWEB)

    Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  2. Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.

    Directory of Open Access Journals (Sweden)

    Thomas Krusenstjerna-Hafstrøm

    2011-05-01

    Full Text Available GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1 after an intravenous GH bolus 2 after an intravenous GH bolus plus an oral glucose load (OGTT, and 3 after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA.GH increased AUC(glucose after an OGTT (p<0.05 without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473 and thr(308, and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1 A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2 Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3 The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997.

  3. Dietary exposure to the endocrine disruptor tolylfluanid promotes global metabolic dysfunction in male mice.

    Science.gov (United States)

    Regnier, Shane M; Kirkley, Andrew G; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A; Kamau, Wakanene; Thomas, Celeste C; Williams, Ayanna K; Hayes, Emily T; Massad, Nicole L; Johnson, Daniel N; Huang, Lei; Zhang, Chunling; Sargis, Robert M

    2015-03-01

    Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome.

  4. Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison

    International Nuclear Information System (INIS)

    Charles, Grantley D.; Gennings, Chris; Tornesi, Belen; Kan, H. Lynn; Zacharewski, Timothy R.; Bhaskar Gollapudi, B.; Carney, Edward W.

    2007-01-01

    In the evaluation of chemical mixture toxicity, it is desirable to develop an evaluation paradigm which incorporates some critical attributes of real world exposures, particularly low dose levels, larger numbers of chemicals, and chemicals from synthetic and natural sources. This study evaluated the impact of low level exposure to a mixture of six synthetic chemicals (SC) under conditions of co-exposure to various levels of plant-derived phytoestrogen (PE) compounds. Estrogenic activity was evaluated using an in vitro human estrogen receptor (ER) transcriptional activation assay and an in vivo immature rat uterotrophic assay. Initially, dose-response curves were characterized for each of the six SCs (methoxyclor, o,p-DDT, octylphenol, bisphenol A, β-hexachlorocyclohexane, 2,3-bis(4-hydroxyphenyl)-propionitrile) in each of the assays. The six SCs were then combined at equipotent ratios and tested at 5-6 dose levels spanning from very low, sub-threshold levels, to a dose in which every chemical in the mixture was at its individual estrogenic response threshold. The SC mixtures also were tested in the absence or presence of 5-6 different levels of PEs, for a total of 36 (in vitro) or 25 (in vivo) treatment groups. Both in vitro and in vivo, low concentrations of the SC mixture failed to increase estrogenic responses relative to those induced by PEs alone. However, significant increases in response occurred when each chemical in the SC mixture was near or above its individual response threshold. In vitro, interactions between high-doses of SCs and PEs were greater than additive, whereas mixtures of SCs in the absence of PEs interacted in a less than additive fashion. In vivo, the SC and PE mixture responses were consistent with additivity. These data illustrate a novel approach for incorporating key attributes of real world exposures in chemical mixture toxicity assessments, and suggest that chemical mixture toxicity is likely to be of concern only when the mixture

  5. Comparison of cytogenetic effects after occupational exposure to X-rays with those after foetal pelvimetric exposure

    International Nuclear Information System (INIS)

    Kirsch-Volders, M.; Poma, K.; Verschaeve, L.; Hens, L.; Susanne, C.; Elegem, P. van

    1978-01-01

    In utero acute low-level exposure to X-rays (300 to 350 mrads) induces a significant increase of band-loss in G-trypsin banded chromosomes of umbilical lymphocytes. Results, however, have to be confirmed by dose-effect relation studies and analysis with spectro-photometric scanning of deleted chromosomes. The same in utero exposure induces a significant dissociaton of chromosome pair 13 as revealed by centromere-centromere, angle and association tendency analysis of chromosome distribution in comparison with a control group. Occupational chronic low-level exposure to ionizing radiation does not modify significantly the amount of SCE in lymphocytes of peripheral blood. However, an analysis of centromere-centromere distances, angle values and associaton tendencies of the different chromosome combinations clearly shows an association of chromosome pair 12-16 after exposure to ionizing radiation. It is difficult to assess the exact biological importance of the observed chromosome modifications. However, referring to the already described dissociation of human acrocentric chromosomes after in vivo exposure to low levels of phenyl Hg acetate or inorganic Pb, the chromosome distribution seems not to be significantly disturbed by chronic or acute low-level exposure to ionizing radiation. (author)

  6. Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo.

    NARCIS (Netherlands)

    Draisma, A.; Goeij, M. de; Wouters, C.W.; Riksen, N.P.; Oyen, W.J.G.; Rongen, G.A.P.J.M.; Boerman, O.C.; Deuren, M. van; Hoeven, J.G. van der; Pickkers, P.

    2009-01-01

    Animal studies have shown that previous exposure to lipopolysaccharide (LPS) can limit ischemia-reperfusion injury. We tested whether pretreatment with LPS also protects against ischemia-reperfusion injury in humans in vivo. Fourteen volunteers received bolus injections of incremental dosages of LPS

  7. مدلول اسم HqA-s فى اللغة المصریة القدیمة

    Directory of Open Access Journals (Sweden)

    د.إسلام إبراهیم عامر محمد

    2015-01-01

    Full Text Available This paper deals with one of the mysterious and rare names, which appeared in the Pyramid text, a name HqA-s. The researchers and the ancient Egyptian language dictionaries presented many opinions about what this name means and what its demonstrative represents. Moreover it presents many different readings of this name. This paper aims at tackling those opinions and deriving the real meaning of this name from them. Whether this name refers to one of the ancient deities? Or it refers to a piece of royal clothes? Or represents one of the sacred, royal badges or decoration? Moreover this paper aims at identifying its demonstrative and correct transliterate of this name.

  8. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan's Pingtung Plain.

    Science.gov (United States)

    Liang, Ching-Ping; Chien, Yi-Chi; Jang, Cheng-Shin; Chen, Ching-Fang; Chen, Jui-Sheng

    2017-01-14

    Chronic arsenic (As) exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan's Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ) and target cancer risk (TR) established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process.

  9. Martensitic transformation of austenitic stainless steel orthodontic wires during intraoral exposure.

    Science.gov (United States)

    Izquierdo, Paula P; de Biasi, Ronaldo S; Elias, Carlos N; Nojima, Lincoln I

    2010-12-01

    Our purpose was to study the mechanical properties and phase transformations of orthodontic wires submitted to in-vivo exposure in the mouth for different periods of time. Stainless steel wires were tied to fixed orthodontic appliances of 30 patients from the orthodontics clinic of Universidade Federal do Rio de Janeiro School of Dentistry in Brazil. According to the duration of the clinical treatment, the patients were divided into 3 groups. After in-vivo exposure, the samples were studied by mechanical testing (torsion) and ferromagnetic resonance. Statistical analyses were carried out to evaluate the correlation between time of exposure, mechanical properties, and austenite-to-martensite transformation among the groups. The results were compared with as-received control samples. The torque values increased as time in the mouth increased. The increase in torque resistance showed high correlations with time of exposure (P = 0.005) and austenite-martensite phase transformation. The resistance of stainless steel orthodontic wires increases as the time in the mouth increases; this effect is attributed to the austenite-to-martensite transformation. Copyright © 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  10. Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

    Science.gov (United States)

    Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

    1991-11-01

    THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. In Vitro and In Vivo Effective Gene Delivery with Novel Liposomal Bubbles

    Science.gov (United States)

    Nishiie, Norihito; Suzuki, Ryo; Oda, Yusuke; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Negishi, Yoichi; Maruyama, Kazuo

    2010-03-01

    Microbubbles, which were ultrasound contrast agents, could improve the transfection efficiency by cavitation with ultrasound exposure. However, conventional microbubbles had some problems regarding size and targeting ability. To solve these problems, we paid attention to liposomes that had many advantages as drug, antigen and gene delivery carriers. Because they can easily be controlled their size and added a targeting function. And we succeeded to prepare novel liposomal bubbles (Bubble liposomes) entrapping perfluoropropane which was utilized for contrast enhancement in ultrasonography. In this study, we assessed the feasibility of Bubble liposomes as gene delivery tools utilized cavitation by ultrasound exposure. In vitro gene delivery, Bubble liposomes could deliver plasmid DNA to many cell types such as tumor cells, T cell line and endothelial cells without cytotoxicity. In vivo gene delivery, Bubble liposomes could effectively deliver plasmid DNA into mouse femoral artery. This method was more effectively than conventional lipofection. We conclude that Bubble liposomes are unique and efficient gene delivery tools in vitro and in vivo.

  12. Health risk assessment of groundwater arsenic pollution in southern Taiwan.

    Science.gov (United States)

    Liang, Ching-Ping; Wang, Sheng-Wei; Kao, Yu-Hsuan; Chen, Jui-Sheng

    2016-12-01

    Residents of the Pingtung Plain, Taiwan, use groundwater for drinking. However, monitoring results showed that a considerable portion of groundwater has an As concentration higher than the safe drinking water regulation of 10 μg/L. Considering residents of the Pingtung Plain continue to use groundwater for drinking, this study attempted to evaluate the exposure and health risk from drinking groundwater. The health risk from drinking groundwater was evaluated based on the hazard quotient (HQ) and target risk (TR) established by the US Environmental Protection Agency. The results showed that the 95th percentile of HQ exceeded 1 and TR was above the safe value of threshold value of 10 -6 . To illustrate significant variability of the drinking water consumption rate and body weight of each individual, health risk assessments were also performed using a spectrum of daily water intake rate and body weight to reasonably and conservatively assess the exposure and health risk for the specific subgroups of population of the Pingtung Plain. The assessment results showed that 0.01-7.50 % of the population's HQ levels are higher than 1 and as much as 77.7-93.3 % of the population being in high cancer risk category and having a TR value >10 -6 . The TR estimation results implied that groundwater use for drinking purpose places people at risk of As exposure. The government must make great efforts to provide safe drinking water for residents of the Pingtung Plain.

  13. Model-based ultrasound temperature visualization during and following HIFU exposure.

    Science.gov (United States)

    Ye, Guoliang; Smith, Penny Probert; Noble, J Alison

    2010-02-01

    This paper describes the application of signal processing techniques to improve the robustness of ultrasound feedback for displaying changes in temperature distribution in treatment using high-intensity focused ultrasound (HIFU), especially at the low signal-to-noise ratios that might be expected in in vivo abdominal treatment. Temperature estimation is based on the local displacements in ultrasound images taken during HIFU treatment, and a method to improve robustness to outliers is introduced. The main contribution of the paper is in the application of a Kalman filter, a statistical signal processing technique, which uses a simple analytical temperature model of heat dispersion to improve the temperature estimation from the ultrasound measurements during and after HIFU exposure. To reduce the sensitivity of the method to previous assumptions on the material homogeneity and signal-to-noise ratio, an adaptive form is introduced. The method is illustrated using data from HIFU exposure of ex vivo bovine liver. A particular advantage of the stability it introduces is that the temperature can be visualized not only in the intervals between HIFU exposure but also, for some configurations, during the exposure itself. 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

    Directory of Open Access Journals (Sweden)

    Yoichi Negishi

    2011-01-01

    Full Text Available Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL entrapping an ultrasound (US imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

  15. Search for flavour-changing neutral current top quark decays $t\\to Hq$ in $pp$ collisions at $\\sqrt{s}=8$ TeV with the ATLAS detector

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdinov, Ovsat; Aben, Rosemarie; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Agricola, Johannes; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baak, Max; Baas, Alessandra; Baca, Matthew John; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bain, Travis; Baines, John; Baker, Oliver Keith; Baldin, Evgenii; Balek, Petr; Balestri, Thomas; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James Baker; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Kathrin; Becker, Maurice; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Janna Katharina; Belanger-Champagne, Camille; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bender, Michael; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Beringer, Jürg; Bernard, Clare; Bernard, Nathan Rogers; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertsche, Carolyn; Bertsche, David; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Biedermann, Dustin; Biesuz, Nicolo Vladi; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bjergaard, David Martin; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blanco, Jacobo Ezequiel; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Bogaerts, Joannes Andreas; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bruscino, Nello; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burckhart, Helfried; Burdin, Sergey; Burgard, Carsten Daniel; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Casper, David William; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerda Alberich, Leonor; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Colasurdo, Luca; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cúth, Jakub; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Du, Yanyan; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Gareth Thomas; Fletcher, Gregory; Fletcher, Rob Roy MacGregor; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; French, Sky; Fressard-Batraneanu, Silvia; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fusayasu, Takahiro; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geich-Gimbel, Christoph; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Geng, Cong; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghasemi, Sara; Ghazlane, Hamid; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gignac, Matthew; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Grafström, Per; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Yicheng; Gupta, Shaun; Gustavino, Giuliano; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Haney, Bijan; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henkelmann, Steffen; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohlfeld, Marc; Hohn, David; Holmes, Tova Ray; Homann, Michael; Hong, Tae Min; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Ince, Tayfun; Introzzi, Gianluca; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Johnson, William Joseph; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kaplan, Laser Seymour; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karentzos, Efstathios; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kasahara, Kota; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Kato, Chikuma; Katre, Akshay; Katzy, Judith; Kawade, Kentaro; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kido, Shogo; Kim, Hee Yeun; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Knapik, Joanna; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Kolb, Mathis; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kukla, Romain; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Xingguo; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Hao; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loew, Kevin Michael; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Haonan; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luedtke, Christian; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Maček, Boštjan; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Monden, Ryutaro; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morton, Alexander; Morvaj, Ljiljana; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onogi, Kouta; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Pan, Yibin; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pin, Arnaud Willy J; Pina, João Antonio; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pires, Sylvestre; Pirumov, Hayk; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Prell, Soeren; Price, Darren; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reisin, Hernan; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Roe, Shaun; Røhne, Ole; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Salazar Loyola, Javier Esteban; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sannino, Mario; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sasaki, Yuichi; Sato, Koji; Sauvage, Gilles; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitt, Stefan; Schmitz, Simon; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyedruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sidebo, Per Edvin; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosa, David; Sosebee, Mark; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Spanò, Francesco; Spearman, William Robert; Sperlich, Dennis; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; St Denis, Richard Dante; Stabile, Alberto; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Ray; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsui, Ka Ming; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valderanis, Chrysostomos; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloce, Laurelle Maria; Veloso, Filipe; Velz, Thomas; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Tingting; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; Wharton, Andrew Mark; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winter, Benedict Tobias; Wittgen, Matthias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wu, Mengqing; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamada, Miho; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yuen, Stephanie P; Yurkewicz, Adam; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zeng, Qi; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Chen; Zhou, Lei; Zhou, Li; Zhou, Mingliang; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zwalinski, Lukasz

    2015-12-10

    A search for flavour-changing neutral current decays of a top quark to an up-type quark ($q=u, c$) and the Standard Model Higgs boson, where the Higgs boson decays to $b\\bar{b}$, is presented. The analysis searches for top quark pair events in which one top quark decays to $Wb$, with the $W$ boson decaying leptonically, and the other top quark decays to $Hq$. The search is based on $pp$ collisions at $\\sqrt{s}=8$ TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider and uses an integrated luminosity of 20.3 fb$^{-1}$. Data are analysed in the lepton-plus-jets final state, characterised by an isolated electron or muon and at least four jets. The search exploits the high multiplicity of $b$-quark jets characteristic of signal events, and employs a likelihood discriminant that uses the kinematic differences between the signal and the background, which is dominated by $t\\bar{t} \\to WbWb$ decays. No significant excess of events above the background expectation is found, and observed (expec...

  16. Cannabidiol Does Not Convert to Δ9-Tetrahydrocannabinol in an In Vivo Animal Model

    OpenAIRE

    Wray, Louise; Stott, Colin; Jones, Nicholas; Wright, Stephen

    2017-01-01

    Abstract Introduction: Cannabidiol (CBD) can convert to Δ9-tetrahydrocannabinol (THC) in vitro with prolonged exposure to simulated gastric fluid; however, in vitro conditions may not be representative of the in vivo gut environment. Using the minipig, we investigated whether enteral CBD converts to THC in vivo. Materials and Methods: Synthetic CBD (100 mg/mL) was administered orally in a sesame oil formulation twice daily to minipigs (N=3) in 15 mg/kg doses for 5 consecutive days. Blood samp...

  17. In vivo XRF measurements of heavy elements: Summary of a workshop

    International Nuclear Information System (INIS)

    Wielopolski, L.; Ryon, R.W.

    1995-01-01

    This is a brief summary of the first workshop of open-quotes In Vivo XRF Measurements of Heavy Elements,close quotes at the Denver Conference on Applications of X-Ray Analysis. In vivo x-ray fluorescence has been applied to medical applications since the 1960's, with much of the pioneering work being done in Sweden (1). First measurements were of iodine in the thyroid. Elements from iron ID uranium have now been measured, at natural and elevated levels. Elevated levels occur either unintentionally through occupational or environmental exposure, or intentionally through medical administration. Examples of measurements are cadmium in kidney and liver, platinum in kidneys and tumors, mercury in the wrists and skulls of dentists, lead in various near-surface bones, copper in the eye and iron in skin. Nearly all measurements make use of either silicon or germanium detectors; radioisotopes and less frequently x-ray tubes are used for excitation. One question that those who work in an analytical chemistry laboratory often ask concerns radiation doses. Concern for x-ray safety ordinarily precludes putting living subjects into the x-ray beam. It turns out that radiation exposure due to in vivo x-ray fluorescence is quite low. The effective dose values for measurement of tibia lead concentration using a 109 Cd source (30 minute exposure) ranges from 0.036 uSv for adults to 1.1 uSv for infants (less than one tenth of a single dental x-ray) (2). Lower effective doses were reported when an x-ray machine was Used to measure L x-rays (3). These values are far below proposed limits of negligibility (10 USv) and average annual U.S. natural background radiation (3000 uSv). 17 refs

  18. Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo

    Directory of Open Access Journals (Sweden)

    Fröhlich E

    2015-05-01

    Full Text Available Eleonore Fröhlich Center for Medical Research, Medical University of Graz, Graz, Austria Abstract: Nanoparticles (NPs present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs. Keywords: immunotoxicity, phagocytes, cytokines, respiratory burst, nitric oxide generation, phagocytosis

  19. Evaluation of a flat-panel detector system

    International Nuclear Information System (INIS)

    Sato, Masami; Eguchi, Yoichi; Yamada, Kinichi; Kaga, Yuji; Endo, Yutaka; Yamazaki, Tatsuya

    2001-01-01

    We evaluated the imaging performance of a flat-panel detector digital radiography system (CXDI-11 X-ray Digital Camera, Canon Inc.) and a computed radiography system (FCR9000C-HQ, Fuji Film). The characteristics of the two detectors and of the overall systems were compared. This included evaluation and comparison of the fundamental physical characteristics, including x-ray response curve, modulation transfer function (MTF), Wiener spectra, noise-equivalent quanta, and x-ray tube voltage-dependent detector response. Overall system performance was evaluated using receiver operating characteristic (ROC) analysis. The results of the study showed that the dynamic range of the CXDI-11 measured relative to the input x-ray flux was 10 3 , similar to that of the FCR9000C-HQ. Both systems showed similar final MTFs, although the pre-sampling MTF of the CXDI-11 was better than that of the FCR9000C-HQ. Noise analysis, based on noise-equivalent quanta and Wiener spectra, showed that for normal exposure conditions the CXDI-11 had superior performance. With both systems, x-ray response (system output/incident x-ray exposure) increased with increasing x-ray tube voltage. ROC analysis indicated that the CXDI-11 was superior in overall performance. (author)

  20. Risk Assessment and Implication of Human Exposure to Road Dust Heavy Metals in Jeddah, Saudi Arabia.

    Science.gov (United States)

    Shabbaj, Ibrahim I; Alghamdi, Mansour A; Shamy, Magdy; Hassan, Salwa K; Alsharif, Musaab M; Khoder, Mamdouh I

    2017-12-26

    Data dealing with the assessment of heavy metal pollution in road dusts in Jeddah, Saudi Arabia and its implication to human health risk of human exposure to heavy metals, are scarce. Road dusts were collected from five different functional areas (traffic areas (TA), parking areas (PA), residential areas (RA), mixed residential commercial areas (MCRA) and suburban areas (SA)) in Jeddah and one in a rural area (RUA) in Hada Al Sham. We aimed to measure the pollution levels of heavy metals and estimate their health risk of human exposure applying risk assessment models described by United States Environmental Protection Agency (USEPA). Using geo-accumulation index (I geo ), the pollution level of heavy metals in urban road dusts was in the following order Cd > As > Pb > Zn > Cu > Ni > Cr > V > Mn > Co > Fe. Urban road dust was found to be moderately to heavily contaminated with As, Pb and Zn, and heavily to extremely contaminated with Cd. Calculation of enrichment factor (EF) revealed that heavy metals in TA had the highest values compared to that of the other functional areas. Cd, As, Pb, Zn and Cu were severely enriched, while Mn, V, Co, Ni and Cr were moderately enriched. Fe was considered as a natural element and consequently excluded. The concentrations of heavy metals in road dusts of functional areas were in the following order: TA > PA > MCRA > SA > RA > RUA. The study revealed that both children and adults in all studied areas having health quotient (HQ) exposure route was ingestion. The cancer risk for children and adults from exposure to Pb, Cd, Co, Ni, and Cr was found to be negligible (≤1 × 10 -6 ).

  1. Evaluating In Vitro-In Vivo Extrapolation of Toxicokinetics.

    Science.gov (United States)

    Wambaugh, John F; Hughes, Michael F; Ring, Caroline L; MacMillan, Denise K; Ford, Jermaine; Fennell, Timothy R; Black, Sherry R; Snyder, Rodney W; Sipes, Nisha S; Wetmore, Barbara A; Westerhout, Joost; Setzer, R Woodrow; Pearce, Robert G; Simmons, Jane Ellen; Thomas, Russell S

    2018-05-01

    Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more under-estimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks.

  2. In vivo and In vitro neurochemical-based assessments of wastewater effluents from the Maumee River area of concern

    International Nuclear Information System (INIS)

    Arini, Adeline; Cavallin, Jenna E.; Berninger, Jason P.; Marfil-Vega, Ruth; Mills, Marc; Villeneuve, Daniel L.; Basu, Niladri

    2016-01-01

    Wastewater treatment plant (WWTP) effluents contain potentially neuroactive chemicals though few methods are available to screen for the presence of such agents. Here, two parallel approaches (in vivo and in vitro) were used to assess WWTP exposure-related changes to neurochemistry. First, fathead minnows (FHM, Pimephales promelas) were caged for four days along a WWTP discharge zone into the Maumee River (Ohio, USA). Grab water samples were collected and extracts obtained for the detection of alkylphenols, bisphenol A (BPA) and steroid hormones. Second, the extracts were then used as a source of in vitro exposure to brain tissues from FHM and four additional species relevant to the Great Lakes ecosystem (rainbow trout (RT), river otter (RO), bald eagle (BE) and human (HU)). The ability of the wastewater (in vivo) or extracts (in vitro) to interact with enzymes (monoamine oxidase (MAO) and glutamine synthetase (GS)) and receptors (dopamine (D2) and N-methyl-D-aspartate receptor (NMDA)) involved in dopamine and glutamate-dependent neurotransmission were examined on brain homogenates. In vivo exposure of FHM led to significant decreases of NMDA receptor binding in females (24–42%), and increases of MAO activity in males (2.8- to 3.2-fold). In vitro, alkylphenol-targeted extracts significantly inhibited D2 (66% in FHM) and NMDA (24–54% in HU and RT) receptor binding, and induced MAO activity in RT, RO, and BE brains. Steroid hormone-targeted extracts inhibited GS activity in all species except FHM. BPA-targeted extracts caused a MAO inhibition in FHM, RT and BE brains. Using both in vivo and in vitro approaches, this study shows that WWTP effluents contain agents that can interact with neurochemicals important in reproduction and other neurological functions. Additional work is needed to better resolve in vitro to in vivo extrapolations (IVIVE) as well as cross-species differences. - Highlights: • We conducted in vivo and in vitro neurochemical

  3. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan’s Pingtung Plain

    Science.gov (United States)

    Liang, Ching-Ping; Chien, Yi-Chi; Jang, Cheng-Shin; Chen, Ching-Fang; Chen, Jui-Sheng

    2017-01-01

    Chronic arsenic (As) exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan’s Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ) and target cancer risk (TR) established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process. PMID:28098817

  4. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan’s Pingtung Plain

    Directory of Open Access Journals (Sweden)

    Ching-Ping Liang

    2017-01-01

    Full Text Available Chronic arsenic (As exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan’s Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ and target cancer risk (TR established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process.

  5. Gamma-ray mutagenesis of cultured mammalian cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Suzuki, Norio; Okada, Shigefumi

    1977-01-01

    The in vitro assay system used to study the reversion of L5178Y-Ala32 cells from an alanine requiring state to a non-requiring state, has been modified in order to be of use in selected in vivo systems. Gamma-ray induced mutations were compared between cells cultured in vitro and those grown in vivo in the intraperitoneal cavity of mice. The expression time was chosen to be 2 days for cells grown in vitro and 5 days for those grown in vivo. The dose-response curve can be described as cumulative for cells grown in vitro and linear for those grown in vivo. A doserate effect was observed in both systems. The cells grown in vivo were less sensitive to γ-rays with respect to both mutation rate per rad and cell killing as compared to cells grown in vitro. The delayed expression and reduced sensitivity of cells in vivo with respect to induced mutation may be due to factors such as hypoxia and/or reduced availability of essential nutrients. Sensitization in vitro by BUdR was detectable at a concentration as low as 10 -6 M, using an exposure time of 15 h. Under these conditions, BUdR alone did not induce any observable mutations

  6. Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations.

    Science.gov (United States)

    Häcker, Axel; Peters, Kristina; Knoll, Thomas; Marlinghaus, Ernst; Alken, Peter; Jenne, Jürgen W; Michel, Maurice Stephan

    2006-11-01

    To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

  7. In vivo toxicity assessment of non-cadmium quantum dots in BALB/c mice.

    Science.gov (United States)

    Lin, Guimiao; Ouyang, Qingling; Hu, Rui; Ding, Zhangchi; Tian, Jinglin; Yin, Feng; Xu, Gaixia; Chen, Qiang; Wang, Xiaomei; Yong, Ken-Tye

    2015-02-01

    Along with widespread usage of QDs in electronic and biomedical industries, the likelihood of QDs exposure to the environment and humans is deemed to occur when the QD products are degraded or handled as waste for processing. To date, there are very few toxicological reports available in the literature for non-cadmium QDs in animal models. In this work, we studied the long term in vivo toxicity of InP/ZnS QDs in BALB/c mice. The biodistribution, body weight, hematology, blood biochemistry, and organ histology were determined at a very high dosage (25 mg/kg) of InP/ZnS QDs over 84 days period. Our results manifested that the QDs formulation did not result in observable toxicity in vivo within the evaluation period, thereby suggesting that the InP/ZnS QDs can be utilized as optical probes or nanocarrier for selected in vivo biological applications when an optimized dosage is employed. This study investigated the toxicity of quantum dots in BALB/c mice, and concluded that no organotoxicity was detectable despite of using high concentration of InP/ZnS quantum dots with prolonged exposure of 3 months. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Development of an ex vivo BrdU labeling procedure for the murine LLNA

    Science.gov (United States)

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  9. Alcohol-cue exposure effects on craving and attentional bias in underage college-student drinkers.

    Science.gov (United States)

    Ramirez, Jason J; Monti, Peter M; Colwill, Ruth M

    2015-06-01

    The effect of alcohol-cue exposure on eliciting craving has been well documented, and numerous theoretical models assert that craving is a clinically significant construct central to the motivation and maintenance of alcohol-seeking behavior. Furthermore, some theories propose a relationship between craving and attention, such that cue-induced increases in craving bias attention toward alcohol cues, which, in turn, perpetuates craving. This study examined the extent to which alcohol cues induce craving and bias attention toward alcohol cues among underage college-student drinkers. We designed within-subject cue-reactivity and visual-probe tasks to assess in vivo alcohol-cue exposure effects on craving and attentional bias on 39 undergraduate college drinkers (ages 18-20). Participants expressed greater subjective craving to drink alcohol following in vivo cue exposure to a commonly consumed beer compared with water exposure. Furthermore, following alcohol-cue exposure, participants exhibited greater attentional biases toward alcohol cues as measured by a visual-probe task. In addition to the cue-exposure effects on craving and attentional bias, within-subject differences in craving across sessions marginally predicted within-subject differences in attentional bias. Implications for both theory and practice are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  10. RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Maria Simona Aguzzi

    Full Text Available Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-10-01

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

  12. MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh

    International Nuclear Information System (INIS)

    Sokka, S D; King, R; Hynynen, K

    2003-01-01

    In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand white rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MR T2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI

  13. Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence

    Science.gov (United States)

    Flynn, Padrig B.; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P.; Elliott, Christopher T.; Laverty, Garry; Gorman, Sean P.; Graham, William G.; Gilmore, Brendan F.

    2016-01-01

    The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa. PMID:27242335

  14. New Radiofrequency Exposure System with Real Telecommunication Signals

    Directory of Open Access Journals (Sweden)

    Jakub Misek

    2018-01-01

    Full Text Available In recent years, there has been an increase in the number of studies on biological effects of Electromagnetic (EM fields emitted from Base Transceiver Stations (BTSs. The biological effects of generated and real telecommunication signals produced by different types of exposure systems are discussed. However, the proper exposure methods for such experiments are very limited. We successfully developed a simple and cost-effective exposure unit with real GSM/DCS/UMTS signal from BTS containing proper modulations or intermittence (continuous, interrupted. Signal processing and conditioning unit is based on a Radiofrequency (RF repeater. The downlink signal is filtered by integrated high selectivity passband filters and amplified to a required level. The main part of exposure unit is a Faraday cage with the specimen (exposure area measuring 150 x 250 mm with E-field percent deviation less than 18%. This exposure system can be helpful in experiments with living organisms in in vivo studies and in vitro studies with normal or pathological cells and other micro scale structures being exposed to RF EM fields from BTS.

  15. [Potential health risks from consumption of water with arsenic in Colima, Mexico].

    Science.gov (United States)

    Mendoza-Cano, Oliver; Sánchez-Piña, Ramón Alberto; Barrón-Quintana, Julián; Cuevas-Arellano, Herguin Benjamin; Escalante-Minakata, Pilar; Solano-Barajas, Ramón

    2017-01-01

    To estimate potential health risks due to chronic ingestion of arsenic from groundwater in Colima, Mexico. Samples were randomly taken in 36 wells from 10 local aquifers. Analysis was performed by ICP-OES following international standards. Geostatistical interpolation was performed with ArcGIS, implementing a model weighting inverse distance to estimate arsenic routes of exposure and consumption on each locality. The Hazard Quotient Ratio (HQ) and carcinogenic risk (R) for As were estimated. The weighted average HQ for arsenic in Colima is 2.41. There are HQ> 1 values indicating adverse non-cancer health effects by continuous and prolonged intake of water with arsenic, which could affect 183 832 individuals in the state. The risk of developing any type of cancer among the population in this study due to high arsenic concentrations in groundwater (R) is 1.089E-3, which could statistically cause 446 cases of cancer. Current levels of arsenic in groundwater increase carcinogenic and non-carcinogenic human health risks in Colima.

  16. Analysis of Cigarette Smoke Deposition Within an In Vitro Exposure System for Simulating Exposure in the Human Respiratory Tract

    Directory of Open Access Journals (Sweden)

    Ishikawa Shinkichi

    2016-01-01

    Full Text Available For the risk assessment of airborne chemicals, a variety of in vitro direct exposure systems have been developed to replicate airborne chemical exposure in vivo. Since cells at the air-liquid interface are exposed to cigarette smoke as an aerosol in direct exposure systems, it is possible to reproduce the situation of cigarette smoke exposure in the human respiratory system using this device. However it is difficult to know whether the exposed cigarette smoke in this system is consistent with the smoke retained in the human respiratory tract. The purpose of this study is to clarify this point using the CULTEX® RFS module which is a recently developed direct exposure system. For this purpose, solanesol and acetaldehyde were respectively chosen as the particulate and gas/vapor phase representatives of smoke constituents, and their deposition and balance per unit area of cell culture surface of the RFS module were measured (dosimetry. We also conducted human retention studies to compare with the dosimetry data. By comparing inhaled smoke and exhaled smoke under three inhalation conditions, we estimated the regional retention and balance of each representative per unit surface area of the respiratory tract (mouth, bronchi, and alveoli separately. The deposition of solanesol and acetaldehyde per unit area of cell culture surface in the RFS module decreased dependent on the dilution flow rate and ranged from 0.26-0.0076%/cm2 in our experimental conditions. The ratio of deposited acetaldehyde to deposited solanesol ranged from 0.96-1.96 in the RFS module. The retention of solanesol and acetaldehyde per unit surface area in the mouth and the bronchi ranged from 0.095-0.0083%/cm2 in this study. The retention per unit surface area of alveoli was far lower than in the other two regions (0.0000063%/cm2. The ratio of retained acetaldehyde to retained solanesol ranged from 0.54-1.97. From these results, we concluded that the CULTEX® RFS module can simulate

  17. In vivo x-ray fluorescence estimation of bone lead concentrations in Queensland adults

    International Nuclear Information System (INIS)

    Price, J.; Baddeley, H.; Kenardy, J.A.; Thomas, B.J.; Thomas, B.W.

    1984-01-01

    A group of 200 Queensland adults without known health problems had in-vivo estimation of finger bone lead concentrations using X-ray fluorescence analysis (XRF). Forty of these subjects had elevated levels of bone lead of 25 ppm or more, consistent with exposure to the metal. Although the correlation between Queensland residence during childhood and raised bone lead levels was not significant, there were significant correlations between childhood residence in a painted wooden house and raised levels, and between occupational exposure and raised levels. Of the 40 subjects with elevated lead levels only two had neither a history of occupational exposure or childhood residence in a wooden house, whereas 11 of the 25 who had a history of both occupational and residential exposure were positive. The data are consistent with lead in housepaint, or absorbed during occupational exposure, being the two major sources of raised bone lead concentrations. (author)

  18. Zebrafish as an In Vivo Model to Assess Epigenetic Effects of Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Eva Yi Kong

    2016-12-01

    Full Text Available Exposure to ionizing radiations (IRs is ubiquitous in our environment and can be categorized into “targeted” effects and “non-targeted” effects. In addition to inducing deoxyribonucleic acid (DNA damage, IR exposure leads to epigenetic alterations that do not alter DNA sequence. Using an appropriate model to study the biological effects of radiation is crucial to better understand IR responses as well as to develop new strategies to alleviate exposure to IR. Zebrafish, Danio rerio, is a scientific model organism that has yielded scientific advances in several fields and recent studies show the usefulness of this vertebrate model in radiation biology. This review briefly describes both “targeted” and “non-targeted” effects, describes the findings in radiation biology using zebrafish as a model and highlights the potential of zebrafish to assess the epigenetic effects of IR, including DNA methylation, histone modifications and miRNA expression. Other in vivo models are included to compare observations made with zebrafish, or to illustrate the feasibility of in vivo models when the use of zebrafish was unavailable. Finally, tools to study epigenetic modifications in zebrafish, including changes in genome-wide DNA methylation, histone modifications and miRNA expression, are also described in this review.

  19. Monitoring UV-induced signalling pathways in an ex vivo skin organ culture model using phospho-antibody array.

    Science.gov (United States)

    Lenain, Christelle; Gamboa, Bastien; Perrin, Agnes; Séraïdaris, Alexia; Bertino, Béatrice; Rival, Yves; Bernardi, Mathieu; Piwnica, David; Méhul, Bruno

    2018-05-01

    We investigated UV-induced signalling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analysed in time-course experiments following exposure to solar-simulated UV and validated by Western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT, which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signalling events following perturbations. As the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure

    NARCIS (Netherlands)

    Broeders, Jessica J W; Hermens, Joop L M; Blaauboer, Bas J; Zurich, Marie-Gabrielle

    2015-01-01

    Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo

  1. Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

    Directory of Open Access Journals (Sweden)

    Norbert Stich

    2014-05-01

    Full Text Available Toxic shock syndrome (TSS results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs. There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1 neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation, determination of IL-2 release in the cell supernatant (ELISA, and IL-2 gene activation (real-time PCR (RT-PCR. Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure.

  2. Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

    Energy Technology Data Exchange (ETDEWEB)

    Stapleton, P.A.; McBride, C.R.; Yi, J.; Nurkiewicz, T.R., E-mail: tnurkiewicz@hsc.wvu.edu

    2015-11-01

    With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO{sub 2} aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m{sup 3}, 5 h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10{sup −4} M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated. - Highlights: • Female reproductive health associated with nanomaterial exposure is understudied. • We examined uterine microvascular alterations 24-hours after nano

  3. Munitions Operations AFSC 465X0

    Science.gov (United States)

    1991-03-01

    DPAL 3 3HQ AFSC/TTA 1 1HQ ATC/DPAE 3 3HQ ATC/TTOA -2 1HQ MAC/DPAT 3 3HQ MAC/TTA 1 1HQ PACAF/DPAT 3 3HQ PACAF/TTA 1 1HQ SAC/DPAT 3 3HQ SAC/TTA 1 IHQ TAC...DPATJ 3 3HQ TAC/TTA 1 1HQ USAF/LGMW 3 3 HQ USAF/DPPE IHQ USAFE/DPAT 3 3HQ USAFE/TTA 1 1NODAC I11 AF/TTA 1 13400 TCHTW/TTGX (LOWRY AFB CO) 5 3 5 53400...32 Training Emphasis (TE) and Task Difficulty ( TD ) Data ...... 32 Specialty Training Standard (STS) .... ............... .... 37

  4. Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study

    Science.gov (United States)

    Reid, Caroline H.; Finnerty, Niall J.

    2017-01-01

    We detail an extensive characterisation study on a previously described dual amperometric H2O2 biosensor consisting of H2O2 detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H2O2 sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes. Furthermore, there was no compromise in pre- and post-implanted catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations performed in anaesthetised mice confirmed the ability of the H2O2 biosensor to detect increases in amperometric current following locally perfused/infused H2O2 and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent recordings in freely moving mice identified negligible effects of control saline and sodium ascorbate interference injections on amperometric H2O2 current. Furthermore, the stability of the amperometric current was confirmed over a five-day period and analysis of 24-h signal recordings identified the absence of diurnal variations in amperometric current. Collectively, these findings confirm the biosensor current responds in vivo to increasing exogenous and endogenous H2O2 and tentatively supports measurement of H2O2 dynamics in freely moving NOD SCID mice. PMID:28698470

  5. Fruit-flies in low-dose exposure experiments

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Sheptyakova, A.I.

    2002-01-01

    In vivo exposure of fruit-flies of Drosophila melanogaster line to low doses provided new data indicating that mechanisms of induced genetic instability are involved in radiation-induced alteration of genotype. It is true for increase of genetic variance due to change in transposition number, for change in adaptation capabilities due to modification of gene expression, and for mutability-associated reparation and apoptosis. (author)

  6. In vitro and in vivo experimental data for pyrethroid pharmacokinetic models: the case of bifenthrin

    Science.gov (United States)

    Pyrethroids are a class of neurotoxic synthetic pesticides. Exposure to pyrethroids has increased due to declining use of other classes of pesticides. Our studies are focused on generating in vitro and in vivo data for the development of pharmacokinetic models for pyrethroids. Us...

  7. 75 FR 39252 - Release of Final Documents Related to the Review of the National Ambient Air Quality Standards...

    Science.gov (United States)

    2010-07-08

    ... Quality Standards: Scope and Methods Plan for Health Risk and Exposure Assessment and Particulate Matter... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2007-0492; FRL-9171-8] Release of Final Documents...: Environmental Protection Agency (EPA). ACTION: Notice of Availability. SUMMARY: The Office of Air Quality...

  8. Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice

    International Nuclear Information System (INIS)

    Zhang Lianzhen; Deng Zhicheng

    1993-01-01

    The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)

  9. Exposure from diagnostic nuclear medicine procedures

    International Nuclear Information System (INIS)

    Iacob, O.; Diaconescu, C.; Isac, R.

    2002-01-01

    According to our last national study on population exposures from natural and artificial sources of ionizing radiation, 16% of overall annual collective effective dose represent the contribution of diagnostic medical exposures. Of this value, 92% is due to diagnostic X-ray examinations and only 8% arise from diagnostic nuclear medicine procedures. This small contribution to collective dose is mainly the result of their lower frequency compared to that of the X-ray examinations, doses delivered to patients being, on average, ten times higher. The purpose of this review was to reassess the population exposure from in vivo diagnostic nuclear medicine procedures and to evaluate the temporal trends of diagnostic usage of radiopharmaceuticals in Romania. The current survey is the third one conducted in the last decade. As in the previous ones (1990 and 1995), the contribution of the Radiation Hygiene Laboratories Network of the Ministry of Health and Family in collecting data from nuclear medicine departments in hospitals was very important

  10. In vivo Host-Pathogen Interaction as Revealed by Global Proteomic Profiling of Zebrafish Larvae

    Directory of Open Access Journals (Sweden)

    Francisco Díaz-Pascual

    2017-07-01

    Full Text Available The outcome of a host-pathogen interaction is determined by the conditions of the host, the pathogen, and the environment. Although numerous proteomic studies of in vitro-grown microbial pathogens have been performed, in vivo proteomic approaches are still rare. In addition, increasing evidence supports that in vitro studies inadequately reflect in vivo conditions. Choosing the proper host is essential to detect the expression of proteins from the pathogen in vivo. Numerous studies have demonstrated the suitability of zebrafish (Danio rerio embryos as a model to in vivo studies of Pseudomonas aeruginosa infection. In most zebrafish-pathogen studies, infection is achieved by microinjection of bacteria into the larvae. However, few reports using static immersion of bacterial pathogens have been published. In this study we infected 3 days post-fertilization (DPF zebrafish larvae with P. aeruginosa PAO1 by immersion and injection and tracked the in vivo immune response by the zebrafish. Additionally, by using non-isotopic (Q-exactive metaproteomics we simultaneously evaluated the proteomic response of the pathogen (P. aeruginosa PAO1 and the host (zebrafish. We found some zebrafish metabolic pathways, such as hypoxia response via HIF activation pathway, were exclusively enriched in the larvae exposed by static immersion. In contrast, we found that inflammation mediated by chemokine and cytokine signaling pathways was exclusively enriched in the larvae exposed by injection, while the integrin signaling pathway and angiogenesis were solely enriched in the larvae exposed by immersion. We also found important virulence factors from P. aeruginosa that were enriched only after exposure by injection, such as the Type-III secretion system and flagella-associated proteins. On the other hand, P. aeruginosa proteins involved in processes like biofilm formation, and cellular responses to antibiotic and starvation were enriched exclusively after exposure by

  11. Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

    Directory of Open Access Journals (Sweden)

    Chantelle Venter

    2017-10-01

    Full Text Available Background/Aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd and chromium (Cr on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. Methods: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM in conjunction with thromboelastography®. Results: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. Conclusion: This study identified the blood as an important target system of Cd and Cr toxicity.

  12. Method for continuous exposure of blood in vitro and in vivo to light, radiation or gas

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kook-Hyun (Seoul National Univ. (Republic of Korea). Coll. of Medicine); Takeshita, Jiro; Kushiyama, Sanzo; Morioka, Tohru

    1989-07-01

    Various medical treatments with extracorporeal circulation have increased the opportunities of exposing blood to light, radiation, or gas. In this paper, several simple methods of exposing blood to these bioactive exogenic agents are introduced. In in vitro method, blood is divided into two cylindrical glass bottles which have openings on both ends. After the bottles are connected with a vinyl tube to make a circuit, they are mounted parallel on the axis of a rotating rod. The air (or laboratory gas) is circulated by a vibration pump incorporated into this gas circuit to equalize the temperature in the two bottles. When the rod is rotated, a thin film of blood is formed over the internal surface of the bottles. This method permits blood to be in contact with the gas inside and to be exposed to light from the outside of the bottle. In in vitro method, blood is divided into two thin-walled, transparent, rectangular bags placed parallel on a tilting board. When the board is tilted intermittently, a thin blood layer is formed in each bag. If the bags are installed with inlet and outlet tubes and connected with blood accesses to either animals or humans, this device will become a circuit for an in vivo study. When one of the two bottles or bags is covered with metal foil to shield it from light or radiation, it can be used as a control. These devices will offer a laboratory method to study the effects of the exposure of blood to some exogenous bioactive agents as well as a new therapeutic method with such agents. (author).

  13. Exogenous ochronosis superimposed on chronic kidney disease: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Ishrat Hussain Dar

    2018-01-01

    Full Text Available Ochronosis is a rare disease characterized by speckled and diffuse pigmentation symmetrically over the face, neck, and photo-exposed areas. It can present in exogenous or endogenous form. Endogenous ochronosis or alkaptonuria is an autosomal recessive disease caused by a deficiency of homogentisic acid (HGA oxidase, which results in the accumulation of HGA, a hydroquinone (HQ metabolite of tyrosine. Some evidence suggests that it is not HGA itself but a by-product of its oxidation, a benzoquinone acetic acid, that can polymerize to a melanin-like pigment by unknown mechanisms and accumulates both inter and intracellularly in connective tissue, most commonly the joints, cardiovascular system, kidney, skin, and glands, a pathological condition known as ochronosis (Development of an in vitro model to investigate joint ochronosis in alkaptonuria. Tinti L, Taylor AM et al. Rheumatology 2010; Oct 15: 1-7. doi: 10.1093/rheumatology/keq246. Exogenous ochronosis (EO is a rare, cosmetically disfiguring condition, resulting from the long-term use of topical HQ in the treatment of melasma. It manifests as grey-brown or blue-black macules in HQ-exposed regions, characterized histologically by banana-shaped ocher-colored deposits in the dermis. HQ the topical bleaching agent of choice is widely prescribed by physicians and often used by patients without a prescription. The principal adverse effects of its chronic use are confetti-like depigmentation and rarely EO. EO is an avoidable dermatosis that needs to be recognized early with immediate discontinuation of HQ as treatment is difficult. Sun exposure facilitates the formation of EO and must be strictly avoided. We report case of a 65-year-old man who had chronic kidney disease but developed EO while using topical HQ.

  14. Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

    Science.gov (United States)

    Inami, Koichi; Abe, Masaaki; Takeda, Kazuyoshi; Hagiwara, Yoshiaki; Maeda, Masahiro; Segawa, Tatsuya; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

    2010-04-01

    Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

  15. Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

    Science.gov (United States)

    Dalterio, S; Steger, R; Mayfield, D; Bartke, A

    1984-01-01

    Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

  16. Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    Energy Technology Data Exchange (ETDEWEB)

    Waal, E.J. de (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)); Rademakers, L.H.P.M. (Dept. of Pathology, University Hospital, Utrecht (Netherlands)); Schuurman, H.J. (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands) Dept. of Pathology, University Hospital, Utrecht (Netherlands) Dept. of Internal Medicine, University Hospital, Utrecht (Netherlands)); Loveren, H. van (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)); Vos, J.G. (National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands))

    1993-09-01

    The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 [mu]g/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from 'pale' to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 [mu]g/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 [mu]g/kg dose level focal epithelial cell aggregated were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. (orig./MG)

  17. Comparison of the bioavailability of elemental waste laden soils using ''in vivo'' and ''in vitro'' analytical methodology and refinement of exposure/dose models. 1998 annual progress report

    International Nuclear Information System (INIS)

    Buckley, B.; Gallo, M.; Georgopoulos, P.; Lioy, P.J.; Tate, R.

    1998-01-01

    'The authors hypotheses are: (1) the more closely the synthetic, in vitro, extractant mimics the extraction properties of the human digestive bio-fluids, the more accurate will be the estimate of an internal dose; (2) performance can be evaluated by in vivo studies with a rat model and quantitative examination of a mass balance, calculation and dose estimates from model simulations for the in vitro and in vivo system; and (3) the concentration of the elements Pb, Cd, Cr and selected Radionuclides present in the bioavailable fraction obtained with a synthetic extraction system will be a better indicator of contaminant ingestion from a contaminated soil because it represents the portion of the mass which can yield exposure, uptake and then the internal dose to an individual. As of April 15, 1998, they have made significant progress in the development of a unified approach to the examination of bioavailability and bioaccessibility of elemental contamination of soils for the ingestion route of exposure. This includes the initial characterization of the soil, in vitro measurements of bioaccessibility, and in vivo measurements of bioavailability. They have identified the basic chemical and microbiological characteristics of waste laden soils. These have been used to prioritize the soils for potential mobility of the trace elements present in the soil. Subsequently they have employed a mass balance technique, which for the first time tracked the movement and distribution of elements through an in vitro or in vivo experimental protocol to define the bioaccessible and the bioavailable fractions of digested soil. The basic mass balance equation for the in vitro system is: MT = MSGJ + MIJ + MR. where MT is the total mass extractable by a specific method, MSGJ, is the mass extracted by the saliva and the gastric juices, MIJ is the mass extracted by the intestinal fluid, and MR is the unextractable portion of the initial mass. The above is based upon the use of a synthetic

  18. Active Approach Does not Add to the Effects of in Vivo Exposure

    NARCIS (Netherlands)

    van Uijen, Sophie; van den Hout, Marcel; Engelhard, Iris

    2015-01-01

    In exposure therapy, anxiety patients actively approach feared stimuli to violate their expectations of danger and reduce fear. Prior research has shown that stimulus evaluation and behavior are reciprocally related. This suggests that approach behavior itself may decrease fear. This study tested

  19. Secondary aerosols from power plant effluents: delivery and in vivo detection systems

    International Nuclear Information System (INIS)

    Parks, N.J.; Raabe, O.G.; Bradley, E.; Raub, J.

    1976-01-01

    An experimental system is described for the generation of radiolabeled monodisperse aerosols, which are physico-chemically analogous to aerosols produced as secondary products of gaseous fossil fuel power plant emissions of SO 2 and NO 2 . The experimental system for inhalation exposure of non-human primates to these particles and the in vivo determination of systemic distribution and target organs is discussed

  20. An Analysis of Cumulative Risks Indicated by Biomonitoring Data of Six Phthalates Using the Maximum Cumulative Ratio

    Science.gov (United States)

    The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single component of a chemical mixture drives the cumulative risk of a receptor.1 This study used the MCR, the Hazard Index (HI) and Hazard Quotient (HQ) to evaluate co-exposures to six phthalates using biomonito...

  1. Radiation exposure during in-vivo analysis of human dental enamel by proton irradiation

    International Nuclear Information System (INIS)

    Baijot-Stroobants, J.; Bodart, F.; Deconninck, G.; Vreven, J.

    Fluorine can be analysed by proton activation, with detection of prompt γ-rays. Using external beams, it is possible to make in-vivo determinations and to follow the concentration in fluoridated enamel. Radiation damage and radiation hazards are investigated. It is found that the dose rate is very small and that the technique can be used without radiation problems. Local destruction on the enamel surface is investigated using a scanning microscope, no modification is observed in the cristallite structure after irradiation. (author)

  2. Virtual reality exposure therapy in the treatment of driving phobia

    Directory of Open Access Journals (Sweden)

    Rafael Thomaz da Costa

    Full Text Available A growing number of researches has appeared on virtual reality exposure therapy (VRET to treat anxiety disorders. The purpose of this article was to review some evidences that support the VRET efficacy to treat driving phobia. The studies were identified through computerized search (PubMed/Medline, Web of Science, and Scielo databases from 1984 to 2007. Some findings are promising. Anxiety/avoidance ratings declined from pre to post-treatment. VRET may be used as a first step in the treatment of driving phobia, as long as it may facilitate the in vivo exposure, thus reducing risks and high costs of such exposure. Notwithstanding, more randomized/controlled clinical trials are required to prove its efficacy.

  3. Biological effects from electromagnetic fields: Research progress and exposure measurements

    International Nuclear Information System (INIS)

    Mauro, F.; Lovisolo, G.A.; Raganella, L.

    1992-01-01

    Although it is commonly accepted that exposure to high levels of electromagnetic, micro- and radiofrequency waves produces harmful effects to the health of man, the formulation of exposure limits is still an open process and dependent upon the evolving level of knowledge in this field. This paper surveys the current level of knowledge gained through 'in vitro' and 'in vivo' radiological and epidemiological studies on different types of electromagnetic radiation derived effects - chromosomal, mutagenic, carcinogenic. It then reviews efforts by international organizations, e. g., the International Radiation Protection Association, to establish exposure limits for radiofrequency electromagnetic fields. Brief notes are given on the electromagnetic radiation monitoring campaign being performed by public health authorities in the Lazio Region of Italy

  4. Heavy metals in soils along unpaved roads in south west Cameroon: Contamination levels and health risks.

    Science.gov (United States)

    Ngole-Jeme, Veronica M

    2016-04-01

    Soils enriched with heavy metals from vehicular emission present a significant exposure route of heavy metals to individuals using unpaved roads. This study assessed the extent of Cd, Cr, Co, Cu, Ni, Pb and Zn contamination of soils along unpaved roads in Cameroon, and the health risks presented by incidental ingestion and dermal contact with the soils using metal contamination factor (CF) pollution load index, hazard quotients (HQ) and chronic hazard index (CHI). CF values obtained (0.9-12.2) indicate moderate to high contamination levels. HQ values for Cr, Cd and Pb exceeded the reference doses. Moderate health hazard exists for road users in the areas with intense anthropogenic activities and high average daily traffic (ADT) volume according to CHI values (1-4) obtained. The economy and quality of life in cities with unpaved roads could be threatened by health challenges resulting from long-term exposure to heavy metal derived from high ADT volumes.

  5. Micronuclei induced by municipal landfill leachate in mouse bone marrow cells in vivo

    International Nuclear Information System (INIS)

    Li Guangke; Sang Nan; Zhao Youcai

    2004-01-01

    The induction of micronuclei (MN) in polychromatic erythrocytes (PCE) of mouse bone marrow by municipal landfill leachate was studied in vivo. Results showed that mouse exposure via drinking water containing various concentrations of leachate caused a significant increase of MN frequencies in a concentration (Chemical oxygen demand measured with potassium dichromate oxidation, COD Cr )-dependent manner. MN induction in female and male mice was different at higher concentrations. This implies that leachate is a genotoxic agent in mammalian cells and that exposure to leachate in an aquatic environment may pose a potential genotoxic risk to human beings

  6. Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients from Malda district, West Bengal- A case study.

    Science.gov (United States)

    Golui, Debasis; Guha Mazumder, D N; Sanyal, S K; Datta, S P; Ray, P; Patra, P K; Sarkar, S; Bhattacharya, K

    2017-10-01

    Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients was established in Malda district of West Bengal. Out of 182 participants examined, 80 (43.9%) participants showed clinical features of arsenicosis, characterized by arsenical skin lesion (pigmentation and keratosis), while 102 participants did not have any such lesion (control). Experimental results of the twenty eight soils (own field) of the participants showed the mean Olsen extractable and total arsenic concentration of 0.206 and 6.70mgkg -1 , respectively. Arsenic concentration in rice grain ranged from 2.00 to 1260μgkg -1 with the mean value of 146μgkg -1 . The hazard quotient (HQ) for intake of As by human through consumption of rice varied from 0.03 to 3.52. HQ exceeds 1.0 for drinking water and rice grain grown in the study area in many cases. As high as 77.6% variation in As content in rice grain could be explained by the solubility-free ion activity model. Toxic limit of extractable As in soil for rice in relation to soil properties and human health hazard, associated with consumption of rice grain by human, was established. For example, the permissible limit of Olsen extractable As in soil would be 0.43mgkg -1 for rice cultivation, if soil pH and organic carbon content were 7.5% and 0.50%, respectively. However, the critical limit of Olsen extractable As in soil would be 0.54mgkg -1 , if soil pH and organic carbon were 8.5% and 0.75%, respectively. The conceptual framework of fixing the toxic limit of arsenic in soils with respect to soil properties and human health under modeling-framework was established. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. DNA damage and transcriptional changes induced by tributyltin (TBT) after short in vivo exposures of Chironomus riparius (Diptera) larvae.

    Science.gov (United States)

    Morales, Mónica; Martínez-Paz, Pedro; Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-08-01

    Tributyltin (TBT) is a widespread environmental contaminant in aquatic systems whose adverse effects in development and reproduction are related to its well-known endocrine-disrupting activity. In this work, the early molecular effects of TBT in Chironomus riparius (Diptera) were evaluated by analyzing its DNA damaging potential and the transcriptional response of different endocrine-related genes. Twenty-four-hour in vivo exposures of the aquatic larvae, at environmentally relevant doses of TBT, revealed genotoxic activity as shown by significant increases in DNA strand breaks quantified with the comet assay. TBT was also able to induce significant increases in transcripts from the ecdysone receptor gene (EcR), the ultraspiracle gene (usp) (insect ortholog of the retinoid X receptor), the estrogen-related receptor (ERR) gene and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. In contrast, the expression of the vitellogenin (vg) gene remained unaltered, while the hsp70 gene appeared to be down-regulated. The ability of TBT to up-regulate hormonal target genes provides the first evidence, at genomic level, of its endocrine disruptive effects and also suggests a mechanism of action that mimics ecdysteroid hormones in insects. These data reveal for the first time the early genomic effects of TBT on an insect genome. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. An in vivo model fish system to test chemical effects on sexual differentiation and development: exposure to ethinyl estradiol

    Science.gov (United States)

    Papoulias, Diana M.; Noltie, Douglas B.; Tillitt, Donald E.

    2000-01-01

    A model system was characterized which may be used as an in vivo screen for effects of chemicals or environmental mixtures on sexual differentiation and development of reproductive organs and gametes. We evaluated the effects of a model environmental estrogen, ethinyl estradiol (EE2), on the d-rR strain of medaka, Oryzias latipes, using a nano-injection exposure. Gonad histopathology indicated that a single injection of 0.5–2.5 ng EE2/egg can cause phenotypic sex-reversal of genetic males to females. Sex-reversals could be detected as early as 7 days post-hatch. Sex-reversed males had female-typical duct development and the secondary sex characteristics we measured were generally consistent with phenotype, with the exception of a few EE2-exposed XX and XY females which possessed ambiguous anal fins. Using discriminant analysis, we determined that the presence or absence of the secondary sex characteristic, a dorsal fin notch, was a very reliable indicator of gonadal sex. No instances of gonadal intersexes were observed. Ethinyl estradiol also appeared to reduce growth but not condition (weight-at-length) and exposed XX females appeared to have a higher incidence of atretic follicles relative to controls. Our results suggest that estrogenic chemicals may influence sexual differentiation and development and that the medaka model is well suited to assessing these effects.

  9. Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

    Science.gov (United States)

    Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

    2014-01-01

    Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

  10. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials

    Science.gov (United States)

    Lee, Ted T.; García, José R.; Paez, Julieta I.; Singh, Ankur; Phelps, Edward A.; Weis, Simone; Shafiq, Zahid; Shekaran, Asha; Del Campo, Aránzazu; García, Andrés J.

    2015-03-01

    Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have recently been realized for cells in culture, the impact of in vivo temporal ligand presentation on cell-material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell-adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active. We demonstrate that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted biomaterials.

  11. 75 FR 28488 - Silver Nitrate; Exemption from the Requirement of a Tolerance

    Science.gov (United States)

    2010-05-21

    ... ( regulations.gov ) under the docket number EPA-HQ-OPP- 2009-0663. Silver nitrate is a water soluble inorganic... polymers and fatty acids; carriers such as clay and diatomaceous earth; thickeners such as carrageenan and... for which there is reliable information.'' This includes exposure through drinking water and in...

  12. In vivo plasma concentration for lindane after 6 hour exposure in human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset is a time course description of lindane disappearance in blood plasma after dermal exposure in human volunteers. This dataset is associated with the...

  13. Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy: study protocol for a randomized controlled non-inferiority trial.

    Science.gov (United States)

    Miloff, Alexander; Lindner, Philip; Hamilton, William; Reuterskiöld, Lena; Andersson, Gerhard; Carlbring, Per

    2016-02-02

    Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facilitating access, decreasing cost, and increasing acceptability and effectiveness. The aim of this study is to compare traditional OST with in vivo spiders and a human therapist with a newly developed single-session gamified VR exposure therapy application with modern VR hardware, virtual spiders, and a virtual therapist. Participants with specific phobia to spiders (N = 100) will be recruited from the general public, screened, and randomized to either VR exposure therapy (n = 50) or traditional OST (n = 50). A behavioral approach test using in vivo spiders will serve as the primary outcome measure. Secondary outcome measures will include spider phobia questionnaires and self-reported anxiety, depression, and quality of life. Outcomes will be assessed using a non-inferiority design at baseline and at 1, 12, and 52 weeks after treatment. VR exposure therapy has previously been evaluated as a treatment for specific phobias, but there has been a lack of high-quality randomized controlled trials. A new generation of modern, consumer-ready VR devices is being released that are advancing existing technology and have the potential to improve clinical availability and treatment effectiveness. The VR medium is also particularly suitable for taking advantage of recent phobia treatment research emphasizing engagement and new learning, as opposed to physiological habituation. This study compares a market-ready, gamified VR spider phobia exposure application, delivered using consumer VR hardware, with

  14. The current status of exposure-driven approaches for chemical safety assessment: A cross-sector perspective.

    Science.gov (United States)

    Sewell, Fiona; Aggarwal, Manoj; Bachler, Gerald; Broadmeadow, Alan; Gellatly, Nichola; Moore, Emma; Robinson, Sally; Rooseboom, Martijn; Stevens, Alexander; Terry, Claire; Burden, Natalie

    2017-08-15

    For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  15. Predicting patient exposure to nickel released from cardiovascular devices using multi-scale modeling.

    Science.gov (United States)

    Saylor, David M; Craven, Brent A; Chandrasekar, Vaishnavi; Simon, David D; Brown, Ronald P; Sussman, Eric M

    2018-04-01

    Many cardiovascular device alloys contain nickel, which if released in sufficient quantities, can lead to adverse health effects. However, in-vivo nickel release from implanted devices and subsequent biodistribution of nickel ions to local tissues and systemic circulation are not well understood. To address this uncertainty, we have developed a multi-scale (material, tissue, and system) biokinetic model. The model links nickel release from an implanted cardiovascular device to concentrations in peri-implant tissue, as well as in serum and urine, which can be readily monitored. The model was parameterized for a specific cardiovascular implant, nitinol septal occluders, using in-vitro nickel release test results, studies of ex-vivo uptake into heart tissue, and in-vivo and clinical measurements from the literature. Our results show that the model accurately predicts nickel concentrations in peri-implant tissue in an animal model and in serum and urine of septal occluder patients. The congruity of the model with these data suggests it may provide useful insight to establish nickel exposure limits and interpret biomonitoring data. Finally, we use the model to predict local and systemic nickel exposure due to passive release from nitinol devices produced using a wide range of manufacturing processes, as well as general relationships between release rate and exposure. These relationships suggest that peri-implant tissue and serum levels of nickel will remain below 5 μg/g and 10 μg/l, respectively, in patients who have received implanted nitinol cardiovascular devices provided the rate of nickel release per device surface area does not exceed 0.074 μg/(cm 2  d) and is less than 32 μg/d in total. The uncertainty in whether in-vitro tests used to evaluate metal ion release from medical products are representative of clinical environments is one of the largest roadblocks to establishing the associated patient risk. We have developed and validated a multi

  16. Profiling of Cytokines Secreted by Conventional Aqueous Outflow Pathway Endothelial Cells Activated In Vitro and Ex Vivo With Laser Irradiation.

    Science.gov (United States)

    Alvarado, Jorge A; Chau, Phuonglan; Wu, Jianfeng; Juster, Richard; Shifera, Amde Selassie; Geske, Michael

    2015-11-01

    To profile which cytokine genes are differentially expressed (DE) as up- or downregulated by cultured human trabecular meshwork (TMEs) and Schlemm's canal endothelial cells (SCEs) after three experimental treatments consisting of selective laser trabeculoplasty (SLT) irradiation, exposure to media conditioned either by SLT-irradiated TMEs (TME-cm) or by SCEs (SCE-cm). Also, to profile which cytokines are upregulated ex vivo in SLT-irradiated human conventional aqueous outflow pathway (CAOP) tissues. After each treatment, Affymetrix microarray assays were used to detect upregulated and downregulated genes for cytokines and their receptors in TMEs and SCEs. ELISA and protein antibody arrays were used to detect upregulated cytokines secreted in SLT-irradiated CAOP tissues ex vivo. The SLT irradiation upregulated numerous cytokine genes in TMEs, but only a few in SCEs. Exposure to TME- and SCE-cm induced SCEs to upregulate many more cytokine genes than TMEs. Selective laser trabeculoplasty irradiation and exposure to TME-cm downregulated several cytokine genes in TMEs but none in SCEs. Selective laser trabeculoplasty irradiation induced one upregulated and three downregulated cytokine-receptor genes in TMEs but none in SCEs. Exposure to TME-cm induced upregulation of one and downregulation of another receptor gene in TMEs, whereas two unique cytokine-receptor genes were upregulated in SCEs. Cytokine protein expression analysis showed that at least eight cytokines were upregulated in SLT-irradiated human CAOP tissues in situ/ex vivo. This study has helped us identify a cytokine signaling pathway and to consider newly identified mechanisms regulating aqueous outflow that may lay the foundation for the future development of cytokine-based glaucoma therapies.

  17. The change in heat shock protein expression in avermectin induced neurotoxicity of the pigeon (Columba livia) both in vivo and in vitro.

    Science.gov (United States)

    Li, Ming; Wang, Xian-Song; Xu, Feng-Ping; Liu, Shuang; Xu, Shi-Wen; Li, Shu

    2014-12-01

    The expression of heat shock proteins (Hsps) commonly increases to provide neuroprotection when brain tissues are under stress conditions. Residues of avermectins (AVMs) have neurotoxic effects on a number of non-target organisms. The aim of this study was to investigate the effects of AVM exposure on the expression levels of Hsp 60, Hsp 70 and Hsp 90 for pigeon (Columba livia) neurons both in vivo and in vitro. The results showed that in general, the mRNA and protein levels of Hsps were increased in treated groups relative to control groups after AVM exposure for 30d, 60d and 90d in the cerebrum, cerebellum and optic lobe in vivo. However, AVM exposure had no significant effects on the transcription expression of Hsps for 90d in the optic lobe and decreased the translation expression of Hsps significantly for 90d in the optic lobe. In vitro, the LC50 of avermectin for King pigeon neurons is between 15μgL(-1) and 20μgL(-1). Following AVM (2.5-20μgL(-1)) exposure, the mRNA expression of the 3 Hsps was up-regulated to different degrees. Compared with the control groups, a significant decrease, a remarkable increase and a non-significant change was found in the protein expression of Hsp 60, Hsp 70 and Hsp 90 separately following AVM (2.5-20μgL(-1)) exposure. Based on these results, we conclude that AVM exposure can induce a protective stress response in pigeons by means of promoting the mRNA and protein expression of Hsps under in vivo and in vitro conditions, thus easing the neurotoxic effects of AVM to some extent. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Association between Exposure to p,p'-DDT and Its Metabolite p,p'-DDE with Obesity: Integrated Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Cano-Sancho, German; Salmon, Andrew G; La Merrill, Michele A

    2017-09-18

    The prevalence of obesity is increasing in all countries, becoming a substantial public health concern worldwide. Increasing evidence has associated obesity with persistent pollutants such as the pesticide DDT and its metabolite p,p '-DDE. Our objective was to systematically review the literature on the association between exposure to the pesticide DDT and its metabolites and obesity to develop hazard identification conclusions. We applied a systematic review-based strategy to identify and integrate evidence from epidemiological, in vivo , and in vitro studies. The evidence from prospective epidemiological studies was quantitatively synthesized by meta-analysis. We rated the body of evidence and integrated the streams of evidence to systematically develop hazard identification conclusions. We identified seven epidemiological studies reporting prospective associations between exposure to p,p' -DDE and adiposity assessed by body mass index (BMI) z -score. The results from the meta-analysis revealed positive associations between exposure to p,p' -DDE and BMI z -score (β=0.13 BMI z -score (95% CI: 0.01, 0.25) per log increase of p,p' -DDE). Two studies constituted the primary in vivo evidence. Both studies reported positive associations between exposure to p,p' -DDT and increased adiposity in rodents. We identified 19 in vivo studies and 7 in vitro studies that supported the biological plausibility of the obesogenic effects of p,p' -DDT and p,p' -DDE. We classified p,p' -DDT and p,p' -DDE as "presumed" to be obesogenic for humans, based on a moderate level of primary human evidence, a moderate level of primary in vivo evidence, and a moderate level of supporting evidence from in vivo and in vitro studies. https://doi.org/10.1289/EHP527.

  19. A method for continuous exposure of blood in vitro and in vivo to light, radiation or gas

    International Nuclear Information System (INIS)

    Lee, Kook-Hyun; Takeshita, Jiro; Kushiyama, Sanzo; Morioka, Tohru.

    1989-01-01

    Various medical treatments with extracorporeal circulation have increased the opportunities of exposing blood to light, radiation, or gas. In this paper, several simple methods of exposing blood to these bioactive exogenic agents are introduced. In in vitro method, blood is divided into two cylindrical glass bottles which have openings on both ends. After the bottles are connected with a vinyl tube to make a circuit, they are mounted parallel on the axis of a rotating rod. The air (or laboratory gas) is circulated by a vibration pump incorporated into this gas circuit to equalize the temperature in the two bottles. When the rod is rotated, a thin film of blood is formed over the internal surface of the bottles. This method permits blood to be in contact with the gas inside and to be exposed to light from the outside of the bottle. In in vitro method, blood is divided into two thin-walled, transparent, rectangular bags placed parallel on a tilting board. When the board is tilted intermittently, a thin blood layer is formed in each bag. If the bags are installed with inlet and outlet tubes and connected with blood accesses to either animals or humans, this device will become a circuit for an in vivo study. When one of the two bottles or bags is covered with metal foil to shield it from light or radiation, it can be used as a control. These devices will offer a laboratory method to study the effects of the exposure of blood to some exogenous bioactive agents as well as a new therapeutic method with such agents. (author)

  20. Novel approach to integrated DNA adductomics for the assessment of in vitro and in vivo environmental exposures.

    Science.gov (United States)

    Chang, Yuan-Jhe; Cooke, Marcus S; Hu, Chiung-Wen; Chao, Mu-Rong

    2018-06-25

    Adductomics is expected to be useful in the characterization of the exposome, which is a new paradigm for studying the sum of environmental causes of diseases. DNA adductomics is emerging as a powerful method for detecting DNA adducts, but reliable assays for its widespread, routine use are currently lacking. We propose a novel integrated strategy for the establishment of a DNA adductomic approach, using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS), operating in constant neutral loss scan mode, screening for both known and unknown DNA adducts in a single injection. The LC-QqQ-MS/MS was optimized using a representative sample of 23 modified 2'-deoxyribonucleosides reflecting a range of biologically relevant DNA lesions. Six internal standards (ISTDs) were evaluated for their ability to normalize, and hence correct, possible variation in peak intensities arising from matrix effects, and the quantities of DNA injected. The results revealed that, with appropriate ISTDs adjustment, any bias can be dramatically reduced from 370 to 8.4%. Identification of the informative DNA adducts was achieved by triggering fragmentation spectra of target ions. The LC-QqQ-MS/MS method was successfully applied to in vitro and in vivo studies to screen for DNA adducts formed following representative environmental exposures: methyl methanesulfonate (MMS) and five N-nitrosamines. Interestingly, five new DNA adducts, induced by MMS, were discovered using our adductomic approach-an added strength. The proposed integrated strategy provides a path forward for DNA adductomics to become a standard method to discover differences in DNA adduct fingerprints between populations exposed to genotoxins, and facilitate the field of exposomics.

  1. Comparison of surface contamination monitors for in vivo measurement of 131I in thyroid

    International Nuclear Information System (INIS)

    Oliveira, S.M.; Dantas, A.L.A.; Dantas, B.M.

    2015-01-01

    The routine handling of radiopharmaceuticals in nuclear medicine represents a significant risk of internal exposure to the staff. The IAEA recommends the implementation of monitoring plans for all workers subject to a risk of exposures above 1 mSv per year. However, in Brazil, such recommendation is practically unfeasible due to the lack of a sufficient number of qualified internal dosimetry services over the country. This work presents an alternative based on a simple and inexpensive methodology aimed to perform in-vivo monitoring of 131 I in thyroid using portable surface contamination probes. All models evaluated showed suitable sensitivity for such application. (author)

  2. 76 FR 20489 - Occupational Radiation Protection

    Science.gov (United States)

    2011-04-13

    ...-5865, e-mail: [email protected]hq.doe.gov . SUPPLEMENTARY INFORMATION: I. Background The requirements in... Exposure during Immersion in a Cloud of Airborne Radioactive Material. The calculations done for the 2007... absorbed by the body; they affect the worker only while immersed in a cloud of airborne radioactivity. A...

  3. Helmholtz international Summer school quantum field theory at the limits. From strong fields to heavy quarks (HQ 2016). Proceedings

    International Nuclear Information System (INIS)

    Ali, Ahmed; Blaschke, David; Issadykov, Aidos; Ivanov, Mikhail

    2017-04-01

    The Helmholtz International Summer School (HISS) entitled ''Quantum Field Theory at the Limits: from Strong Fields to Heavy Quarks (SF→HQ)'', was held in the period July 18-30, 2016 at the Bogolyubov Laboratory of Theoretical Physics (BLTP) of the Joint Institute for Nuclear Research (JINR) in Dubna, Russia, as part of the activities of the Dubna International Advanced School of Theoretical Physics (DIAS-TH). It was co-organized by Ahmed Ali (DESY Hamburg), David Blaschke (JINR Dubna, MEPhI and Univ. Wroclaw), Holger Gies (HI Jena), and Mikhail Ivanov (JINR Dubna), and was attended by 82 participants (faculty+students), not counting the JINR physicists who attended some lectures as non-registered participants. The school (SF→HQ) continued the workshops and schools of the HISS series held earlier in Dubna (1993, 1996, 2000, 2005, 2008, 2013), Bad Honnef (1994) and Rostock (1997). The scientific program of the school consisted of five regular (one-hour long) lectures in the morning and afternoon sessions, with typically two contributed talks given by younger participants (students and postdocs), each half-hour long, in the late afternoons. Altogether, we had sixty lectures by the faculty and participants. In addition, black-board exercises were held in the post-lunch periods on selected aspects of strong fields and field theory. The HISS series of schools has played an important role in bringing together an international faculty and young physicists (Ph.D. and postdocs), mostly from Russia and Germany, but increasingly also from other countries, including those affiliated to JINR Dubna. They participate in two-week long intense scientific discourse, mainly dedicated lectures on selected topics covering the foundation and the frontiers of high energy physics and cosmology. The novelty of this year's school was its bifocal interest, which brought together two different physical science communities - particle and laser physicists. There were

  4. Helmholtz international Summer school quantum field theory at the limits. From strong fields to heavy quarks (HQ 2016). Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ahmed; Blaschke, David; Issadykov, Aidos; Ivanov, Mikhail (eds.)

    2017-04-15

    The Helmholtz International Summer School (HISS) entitled ''Quantum Field Theory at the Limits: from Strong Fields to Heavy Quarks (SF→HQ)'', was held in the period July 18-30, 2016 at the Bogolyubov Laboratory of Theoretical Physics (BLTP) of the Joint Institute for Nuclear Research (JINR) in Dubna, Russia, as part of the activities of the Dubna International Advanced School of Theoretical Physics (DIAS-TH). It was co-organized by Ahmed Ali (DESY Hamburg), David Blaschke (JINR Dubna, MEPhI and Univ. Wroclaw), Holger Gies (HI Jena), and Mikhail Ivanov (JINR Dubna), and was attended by 82 participants (faculty+students), not counting the JINR physicists who attended some lectures as non-registered participants. The school (SF→HQ) continued the workshops and schools of the HISS series held earlier in Dubna (1993, 1996, 2000, 2005, 2008, 2013), Bad Honnef (1994) and Rostock (1997). The scientific program of the school consisted of five regular (one-hour long) lectures in the morning and afternoon sessions, with typically two contributed talks given by younger participants (students and postdocs), each half-hour long, in the late afternoons. Altogether, we had sixty lectures by the faculty and participants. In addition, black-board exercises were held in the post-lunch periods on selected aspects of strong fields and field theory. The HISS series of schools has played an important role in bringing together an international faculty and young physicists (Ph.D. and postdocs), mostly from Russia and Germany, but increasingly also from other countries, including those affiliated to JINR Dubna. They participate in two-week long intense scientific discourse, mainly dedicated lectures on selected topics covering the foundation and the frontiers of high energy physics and cosmology. The novelty of this year's school was its bifocal interest, which brought together two different physical science communities - particle and laser physicists. There were

  5. Radiation exposure in medicare-occupational and medical exposure

    International Nuclear Information System (INIS)

    Morozumi, Kunihiko

    2012-01-01

    Recent cases of the occupational and medical exposures are discussed in relation to the justification of practice, optimization of protection and effort to reduce the dose. Instances of the occupational exposure in doctors and nurses like 26.5 mSv/15 mo and 53.9 mSv/y, and of skin cancer were reported in newspapers of 1999-2004, which might have had been prevented by their self evaluation of daily and monthly exposed dose. For reasonably lowering the occupational dose and number of exposed stuff in the present law, the prior radiation protection measures are to be taken in consideration of social/economical factors to conduct beneficial radiation medicare without restriction of practice under safest conditions, protecting personal determinative hazard and preventing stochastic effect. Medical stuff must be equipped with personal dosimeter. Further, recent media also commented such cases as unwished abortions after careless X-CT of pregnant women, and risk of increased cancer prevalence (3.2% in Japan) due to medical exposure, etc (200-2010). The prevalence is calculated on the linear non-threshold (LNT) hypothesis and is probably overestimated, possibly causing patient's fear. There has been a history of proposal by IAEA (1996) of the guidance levels of the ordinary roentgenography and in vivo nuclear medical test, and introduction of the concept of dose constraint by ICRP (Pub. 60). The incident dose rate to the patient under fluoroscopy defined by Japan Medical Service Law (2001) is, as an air-kerma rate, 15,600 residents for their contamination as well as remains, and measured the ambient dose rate of cities nearby. (T.T.)

  6. Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration.

    Science.gov (United States)

    Laliberté, Alex M; MacPherson, Thomas C; Micks, Taft; Yan, Alex; Hill, Kathleen A

    2011-12-01

    Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p retina (p retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    International Nuclear Information System (INIS)

    Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

    2012-01-01

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

  8. Proposal of a methodology to evaluate occupational internal exposure to Fluorine-18

    International Nuclear Information System (INIS)

    Oliveira, C.M.; Dantas, A.L.A.; Dantas, B.M.

    2008-01-01

    The increasing use of 18 F for diagnostic procedures in nuclear medicine through PET technology leads to the growth in the number of occupationally exposed workers to this radionuclide. The external and internal exposures may occur both in the production of the radiopharmaceutical fluorodeoxyglucose ( 18 FDG) and during its clinical use in nuclear medicine departments. Workers involved in such activities are usually monitored routinely for the control of external exposure. However it is important provide methods for internal monitoring promptly after a suspicion of incorporation. Therefore, the objective of this work is to develop procedures for internal monitoring of 18 F to be applied in cases of possible incorporation of fluoride and 18 FDG, using in vivo and in vitro methods of measurements. The NaI(Tl) 8x4 scintillation detector of the IRD-Whole Body Counter was calibrated for in vivo measurements with a whole body anthropomorphic phantom, simulating homogeneous distribution of 18 F in the body. The NaI(Tl) 3x3 scintillation detector of the IRD-Whole Body Counter was calibrated for in vivo measurements with a brain phantom inserted in an artificial skull, simulating 18 FDG incorporation. The HPGe detection system of the IRD-Bioassay Laboratory was calibrated for in vitro measurements of urine samples with 1 liter plastic bottles containing standard liquid source. A methodology for bioassay data interpretation, based on standard ICRP models edited with the software AIDE-version 6, was established. It is concluded that in vivo measurements have sufficient sensitivity for the monitoring of 18 F in the forms of fluoride and 18 FDG. The use of both in vitro and in vivo bioassay data can provide useful information for the interpretation of bioassay data in cases of accidental incorporation in order to identify the most likely route of intake, chemical form of 18 F incorporated and time of intake. (author)

  9. A translatable predictor of human radiation exposure.

    Science.gov (United States)

    Lucas, Joseph; Dressman, Holly K; Suchindran, Sunil; Nakamura, Mai; Chao, Nelson J; Himburg, Heather; Minor, Kerry; Phillips, Gary; Ross, Joel; Abedi, Majid; Terbrueggen, Robert; Chute, John P

    2014-01-01

    Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

  10. A translatable predictor of human radiation exposure.

    Directory of Open Access Journals (Sweden)

    Joseph Lucas

    Full Text Available Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB and humans treated with total body irradiation (TBI. Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

  11. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇİGİL

    2012-07-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  12. Modified expression of several sperm proteins after chronic exposure to the antiandrogenic compound vinclozolin.

    Science.gov (United States)

    Auger, Jacques; Eustache, Florence; Maceiras, Paula; Broussard, Cédric; Chafey, Philippe; Lesaffre, Corinne; Vaiman, Daniel; Camoin, Luc; Auer, Jana

    2010-10-01

    Little is known about the molecular impact of in vivo exposure to endocrine disruptors (EDs) on sperm structures and functions. We recently reported that the lifelong exposure of rats to the antiandrogenic compound vinclozolin results in low epididymal weight, changes in sperm kinematic parameters, and immature sperm chromatin condensation, together with the impairment of several fertility end points. These results led us to focus specifically on possible molecular abnormalities in sperm. Sperm samples were recovered from the frozen epididymides of rats exposed during the previous study. The proteins present in the samples from six exposed and six control rats were analyzed in pairs, by two-dimensional fluorescence difference gel electrophoresis, to investigate possible exposure-induced changes to sperm protein profiles. Twelve proteins, from the 380 matched spots observed in at least five gels, were present in larger or smaller amounts after vinclozolin exposure. These proteins were identified by mass spectrometry, and several are known to play a crucial role in the sperm fertilizing ability, among which, two mitochondrial enzymes, malate dehydrogenase 2 and aldehyde dehydrogenase (both of which were present in smaller amounts after treatment) and A-kinase anchor protein 4 (larger amounts of precursor after treatment). Finally, Ingenuity Pathway Analysis revealed highly significant interactions between proteins over- and underexpressed after treatment. This is the first study to show an association between in vivo exposure to an ED and changes to the sperm protein profile. These modifications may be at least partly responsible for the reproductive abnormalities and impaired fertility recently reported in this rat model of vinclozolin exposure.

  13. Imidazopyridine CB2 agonists: optimization of CB2/CB1 selectivity and implications for in vivo analgesic efficacy.

    Science.gov (United States)

    Trotter, B Wesley; Nanda, Kausik K; Burgey, Christopher S; Potteiger, Craig M; Deng, James Z; Green, Ahren I; Hartnett, John C; Kett, Nathan R; Wu, Zhicai; Henze, Darrell A; Della Penna, Kimberly; Desai, Reshma; Leitl, Michael D; Lemaire, Wei; White, Rebecca B; Yeh, Suzie; Urban, Mark O; Kane, Stefanie A; Hartman, George D; Bilodeau, Mark T

    2011-04-15

    A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was ineffective despite substantial CNS exposure, while administration of a moderately selective CB2/CB1 agonist exhibited significant analgesic effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Infrared skin damage thresholds from 1319-nm continuous-wave laser exposures

    Science.gov (United States)

    Oliver, Jeffrey W.; Vincelette, Rebecca; Noojin, Gary D.; Clark, Clifton D.; Harbert, Corey A.; Schuster, Kurt J.; Shingledecker, Aurora D.; Kumru, Semih S.; Maughan, Justin; Kitzis, Naomi; Buffington, Gavin D.; Stolarski, David J.; Thomas, Robert J.

    2013-12-01

    A series of experiments were conducted in vivo using Yucatan miniature pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1319-nm continuous-wave Nd:YAG laser irradiation. Experiments employed exposure durations of 0.25, 1.0, 2.5, and 10 s and beam diameters of ˜0.6 and 1 cm. Thermal imagery data provided a time-dependent surface temperature response from the laser. A damage endpoint of fifty percent probability of a minimally visible effect was used to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Resultant trends with respect to exposure duration and beam diameter are compared with current standardized exposure limits for laser safety. Mathematical modeling agreed well with experimental data, predicting that though laser safety standards are sufficient for exposures <10 s, they may become less safe for very long exposures.

  15. Through the smoke: Use of in vivo and in vitro cigarette smoking models to elucidate its effect on female fertility

    International Nuclear Information System (INIS)

    Camlin, Nicole J.; McLaughlin, Eileen A.; Holt, Janet E.

    2014-01-01

    A finite number of oocytes are established within the mammalian ovary prior to birth to form a precious ovarian reserve. Damage to this limited pool of gametes by environmental factors such as cigarette smoke and its constituents therefore represents a significant risk to a woman's reproductive capacity. Although evidence from human studies to date implicates a detrimental effect of cigarette smoking on female fertility, these retrospective studies are limited and present conflicting results. In an effort to more clearly understand the effect of cigarette smoke, and its chemical constituents, on female fertility, a variety of in vivo and in vitro animal models have been developed. This article represents a systematic review of the literature regarding four of experimental model types: 1) direct exposure of ovarian cells and follicles to smoking constituents’ in vitro, 2) direct exposure of whole ovarian tissue with smoking constituents in vitro, 3) whole body exposure of animals to smoking constituents and 4) whole body exposure of animals to cigarette smoke. We summarise key findings and highlight the strengths and weaknesses of each model system, and link these to the molecular mechanisms identified in smoke-induced fertility changes. - Highlights: • In vivo exposure to individual cigarette smoke chemicals alters female fertility. • The use of in vitro models in determining molecular mechanisms • Whole cigarette smoke inhalation animal models negatively affect ovarian function

  16. Through the smoke: Use of in vivo and in vitro cigarette smoking models to elucidate its effect on female fertility

    Energy Technology Data Exchange (ETDEWEB)

    Camlin, Nicole J. [School of Environment and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); McLaughlin, Eileen A., E-mail: eileen.mclaughlin@newcastle.edu.au [School of Environment and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Holt, Janet E. [School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308 (Australia)

    2014-12-15

    A finite number of oocytes are established within the mammalian ovary prior to birth to form a precious ovarian reserve. Damage to this limited pool of gametes by environmental factors such as cigarette smoke and its constituents therefore represents a significant risk to a woman's reproductive capacity. Although evidence from human studies to date implicates a detrimental effect of cigarette smoking on female fertility, these retrospective studies are limited and present conflicting results. In an effort to more clearly understand the effect of cigarette smoke, and its chemical constituents, on female fertility, a variety of in vivo and in vitro animal models have been developed. This article represents a systematic review of the literature regarding four of experimental model types: 1) direct exposure of ovarian cells and follicles to smoking constituents’ in vitro, 2) direct exposure of whole ovarian tissue with smoking constituents in vitro, 3) whole body exposure of animals to smoking constituents and 4) whole body exposure of animals to cigarette smoke. We summarise key findings and highlight the strengths and weaknesses of each model system, and link these to the molecular mechanisms identified in smoke-induced fertility changes. - Highlights: • In vivo exposure to individual cigarette smoke chemicals alters female fertility. • The use of in vitro models in determining molecular mechanisms • Whole cigarette smoke inhalation animal models negatively affect ovarian function.

  17. Effects of in vivo exposure to UV filters (4-MBC, OMC, BP-3, 4-HB, OC, OD-PABA) on endocrine signaling genes in the insect Chironomus riparius.

    Science.gov (United States)

    Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-07-01

    There is increasing evidence indicating that several UV filters might have endocrine disruptive effects. Numerous studies have evaluated hormonal effects in vertebrates, mainly reporting estrogenic and androgenic activities in mammals and fishes. There is only limited knowledge about potential endocrine activity in invertebrate hormonal systems. In this work, the effects on endocrine signaling genes of six frequently used UV filters were investigated in Chironomus riparius, a reference organism in aquatic toxicology. The UV filters studied were: octyl-p-methoxycinnamate (OMC) also called 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4-MBC); benzophenone-3 (BP-3); 4-hidroxybenzophenone (4-HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). After in vivo exposure at different dosages, expression levels of the genes coding for the ecdysone receptor (EcR), the ultraspiracle (usp, ortholog of the RXR) and the estrogen-related receptor (ERR) were quantified by Real Time PCR. The EcR gene was significantly upregulated by 4-MBC, OMC/EHMC and OD-PABA, with a dose-related response following 24h exposure. In contrast, the benzophenones, BP-3 and 4-HB, as well as OC did not alter this gene at the same exposure conditions. The transcription profiles of the usp and ERR genes were not significantly affected, except for BP-3 that inhibited the usp gene at the highest concentration. To our knowledge, this is the first experimental evidence in invertebrates of a direct effect of UV filters on endocrine-related genes, and is consistent with the known effects on vertebrate hormonal receptor genes. The capability of 4-MBC, OMC/EHMC and OD-PABA to stimulate the expression of the ecdysone receptor, a key transcription factor for the ecdysone-genomic response in arthropods, suggests the possibility of a broad and long-term effect on this hormonal pathway. These findings strengthen the need for further research about the ecotoxicological implications

  18. Engineering Assistant Career Ladder AFS 553XO.

    Science.gov (United States)

    1983-12-01

    2 2 2 HQ AFESC/DEP 1 1 1HQ AFISC/DAP I I HQ AFLC/MPCA 3 3 3HQ AFSC/MPAT 3 3 3HQ ATC/DPAE I I IHQ ATC/TTQC 1 1 1HQ MAC/DPAT 3 3 3HQ PACAF/DPAL 1 1...senior 553X0 personnel also completed a second booklet for either training emphasis (TE) or task difficulty ( TD ). The TE and TD booklets were processed

  19. In vivo elemental analysis in occupational medicine using X-ray fluorescence

    International Nuclear Information System (INIS)

    Christoffersson, J.O.

    1986-01-01

    A technique for the in vivo determination of cadmium in the kidney cortex using X-ray fluorescence analysis (XRF) has been developed for clinical use. The method uses the Cd K-alfa X-rays. The radiation from the tube was polarized by scattering at 90 degrees in a plastic disc. Using a Si(Li) detector the minimum detectable concentration (MDC) of cadmium in the renal cortex was about 6 ppm for an effective dose equivalent of 3 micro-Sievert. The precision of the method was estimated to be about 23 percent. The clinical usefulness was confirmed by studying 20 occupationally exposed cadmium workers and three controls. The cadmium workers showed levels of cadmium in the kidney in the range 47-317 ppm, and controls showed levels below 30 ppm. Using XRF in vivo large-scale measurements of lead in the fingerbone of more than 100 lead workers were performed. The technique used included two 57-Co sources for excitation and a higher-purity Ge detector for the analysis of the Pb K-alfa X-rays. The MDC was about 20 ppm for an effective dose equivalent of 0.1 micro-Sievert. The precision of the method was estimated to be about 15 per cent. The in vivo measurements showed levels of fingerbone-Pb up to 148 ppm. The existence of a significant endogenous exposure from lead in the skeleton was confirmed. The fingerbone-Pb was correlated to time-integrated blood-Pb indicating that it could be used as a rough estimated of time-integrated exposure. The results from the measurements were used to develop a three-compartment (cortical bone, trabecular bone, blood/soft tissues) model. Using this model, lead levels in fingerbone, vertebrae and blood could be predicted in good agreement with observations. (author)

  20. DNA damage in grasshopper Chorthippus brunneus (Orthoptera) hatchlings following paraquat exposure.

    Science.gov (United States)

    Augustyniak, M; Nocoń, Ł; Kędziorski, A; Łaszczyca, P; Sawczyn, T; Tarnawska, M; Zawisza-Raszka, A

    2015-04-01

    Comet assay was applied to study genotoxic damage induced by paraquat (PQ) in brain cells of Chorthippus brunneus (Insecta: Orthoptera) hatchlings. Percentage of the comet fluorescence in the tail (TDNA), length of the comet tail (TL) and Olive tail moment (OTM) were used for quantitative assessment of the DNA damage. Multiple regression analysis supplemented standard statistical elaboration of the results. Increasing PQ concentrations applied either directly to the brain cells suspension (10, 50, and 250 μM PQ final concentration--in vitro protocol) or indirectly (50, 250, and 1250 μM PQ final concentration--in vivo protocol) provoked significant increase of oxidative damage to DNA (higher median TDNA and OTM values). The damage increased with time of exposure (0, 5, 15, and 30 min) following in vitro application, but decreased in longer interval (3 vs 24 h) after in vivo administration of paraquat. On contrary, median TL values did not correlate with paraquat concentration irrespectively of the exposure protocol. Possible reason of this discrepancy in light of paraquat toxicity is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

    International Nuclear Information System (INIS)

    Bensoussan, H.

    2009-01-01

    Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

  2. An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction

    International Nuclear Information System (INIS)

    Astuti, Suryani Dyah; Prasaja, Brahma Indra; Prijo, Tri Anggono

    2017-01-01

    This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice ( Musmuculus ) suffering from kidney organ damage in mice ( Musmuculus ) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice. (paper)

  3. An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction

    Science.gov (United States)

    Dyah Astuti, Suryani; Indra Prasaja, Brahma; Anggono Prijo, Tri

    2017-05-01

    This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice (Musmuculus) suffering from kidney organ damage in mice (Musmuculus) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice.

  4. Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation

    Science.gov (United States)

    Williams, Benjamin B.; Dong, Ruhong; Nicolalde, Roberto J.; Matthews, Thomas P.; Gladstone, David J.; Demidenko, Eugene; Zaki, Bassem I.; Salikhov, Ildar K.; Lesniewski, Piotr N.; Swartz, Harold M.

    2014-01-01

    Purpose The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need. Materials and methods A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy. Results A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 + 0.3 Gy. Conclusions These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population. PMID:21696339

  5. Currently used organophosphate flame retardants determined in the settled dust of masjids and hotels of Saudi Arabia, a new insight into human health implications of dust exposure.

    Science.gov (United States)

    Ali, Nadeem; Ibrahim Ismail, Iqbal Mohammad; Kadi, Mohammad W; Salem Ali Albar, Hussain Mohammed

    2018-05-23

    Indoor settled dust particles are considered as an important source of human exposure to chemicals such as organophosphate flame retardants (PFRs). In recent decades the Kingdom of Saudi Arabia (KSA) has experienced tremendous growth in population, as a result the number of masjids has also increased significantly to provide sufficient space for the public to offer prayers. The hospitality industry in KSA is also expanding to cater for the ever-increasing number of pilgrims visiting the two holy cities of the kingdom. However, limited data are available on the indoor pollution of masjids and hotels. In this study, PFRs were analyzed in the settled dust collected from various hotels and masjids of Jeddah, KSA. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tris(1-chloro-2-propyl) phosphate (TCPP) were the major PFRs in masjid (median = 2490 and 2055 ngg-1) and hotel (median = 2360 and 3315 ngg-1) dust, respectively. A public health risk assessment was carried out by determining the incremental lifetime cancer risk (ILCR), and daily exposure via dust ingestion, inhalation, and dermal contact of PFRs. The calculated daily exposure via dust ingestion was well below the reference dose (RfD) values, and also the calculated hazardous quotient (HQ) and carcinogenic risk were well below the risk mark. However, the ILCR for PFRs was below the reference values of USEPA, which suggested that long-term exposure to these chemicals has a limited cause for concern. The study showed that the general public is exposed to PFRs in the studied microenvironments and the major exposure routes are dermal contact and ingestion.

  6. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice.

    Science.gov (United States)

    Buckley, Jill; Willingham, Emily; Agras, Koray; Baskin, Laurence S

    2006-02-21

    Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors alpha and beta, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen alpha and beta, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor alpha mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor alpha and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. The results suggest that

  7. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

    Directory of Open Access Journals (Sweden)

    Baskin Laurence S

    2006-02-01

    Full Text Available Abstract Background Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. Methods We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors α and β, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females, we measured the lengths of the casts and performed ANOVA analysis on these data. Results Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias and masculinizing females (longer urethras. Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen α and β, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor α mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor α and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl

  8. Diaphragmatic Breathing during Virtual Reality Exposure Therapy for Aviophobia: Functional Coping Strategy or Avoidance Behavior?

    OpenAIRE

    Mühlbauer, Andreas; Shiban, Youssef; Diemer, Julia Elisabeth; Müller, Jana; Brütting-Schick, Johanna; Pauli, Paul

    2017-01-01

    Background Although there is solid evidence for the efficacy of in vivo and virtual reality (VR) exposure therapy for a specific phobia, there is a significant debate over whether techniques promoting distraction or relaxation have impairing or enhancing effects on treatment outcome. In the present pilot study, we investigated the effect of diaphragmatic breathing (DB) as a relaxation technique during VR exposure treatment. Method Twenty-nine patients with aviophobia were randomly a...

  9. Groundwater contamination by polycyclic aromatic hydrocarbon due to diesel spill from a telecom base station in a Nigerian City: assessment of human health risk exposure.

    Science.gov (United States)

    Ugochukwu, Uzochukwu Cornelius; Ochonogor, Alfred

    2018-03-26

    Diesel pollution of groundwater poses great threat to public health, mainly as a result of the constituent polycyclic aromatic hydrocarbons (PAHs). In this study, the human health risk exposure to polycyclic aromatic hydrocarbons (PAHs) in diesel contaminated groundwater used by several families at Ring Road, Jos, Nigeria (as caused by diesel spill from a telecom base station) was assessed. Prior to the groundwater being treated, the residents were using the water after scooping off the visible diesel sheen for purposes of cooking, washing, and bathing. Until this study, it is not clear whether the groundwater contamination had resulted in sub-chronic exposure of the residents using the water to polycyclic aromatic hydrocarbons (PAHs) to the extent of the PAHs posing a health risk. The diesel contaminated groundwater and uncontaminated nearby groundwater (control) were collected and analyzed for PAHs using gas chromatography-mass spectrometry (GC-MS). The dosage of the dermal and oral ingestion entry routes of PAHs was determined. The estimation of the non-carcinogenic health risk was via hazard quotients (HQ) and the associated hazard index (HI), while the estimation of the carcinogenic health risk was via lifetime cancer risks (LCR) and the associated risk index (RI). Obtained results indicate that the exposure of the residents to the PAHs may have made them susceptible to the risk of non-carcinogenic health effects of benzo(a)pyrene and the carcinogenic health effects of benzo(a)anthracene and benzo(a)pyrene.

  10. CT volumetry of artificial pulmonary nodules using an ex vivo lung phantom: Influence of exposure parameters and iterative reconstruction on reproducibility

    Energy Technology Data Exchange (ETDEWEB)

    Wielpütz, Mark O., E-mail: Mark.wielpuetz@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Lederlin, Mathieu, E-mail: mathieu.lederlin@chu-bordeaux.fr [Department of Thoracic and Cardiovascular Imaging, University Hospital of Bordeaux, Av de Magellan, 33600 Pessac (France); Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Wroblewski, Jacek, E-mail: JacekWr@gmx.net [Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Dinkel, Julien, E-mail: jdinkel@partners.org [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States); Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Eichinger, Monika, E-mail: Monika.eichinger@thoraxklinik-heidelberg.de [Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Amalienstr. 5, 69126 Heidelberg (Germany); Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); and others

    2013-09-15

    Objectives: To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the measurement variability of computer-aided nodule volumetry on chest multidetector computed tomography (MDCT). Materials and methods: N = 7 porcine lung explants were inflated in a dedicated ex vivo phantom and prepared with n = 162 artificial nodules. MDCT was performed eight consecutive times (combinations of 120 and 80 kV with 120, 60, 30 and 12 mA s), and reconstructed with filtered back projection (FBP) and IR. Nodule volume and diameter were measured semi-automatically with dedicated software. The absolute percentage measurement error (APE) was computed in relation to the 120 kV 120 mA s acquisition. Noise was recorded for each nodule in every dataset. Results: Mean nodule volume and diameter were 0.32 ± 0.15 ml and 12.0 ± 2.6 mm, respectively. Although IR reduced noise by 24.9% on average compared to FBP (p < 0.007), APE with IR was equal to or slightly higher than with FBP. Mean APE for volume increased significantly below a volume computed tomography dose index (CTDI) of 1.0 mGy: for 120 kV 12 mA s APE was 3.8 ± 6.2% (FBP) vs. 4.0 ± 5.2% (IR) (p < 0.007); for 80 kV 12 mA s APE was 8.0 ± 13.0% vs. 9.3 ± 15.8% (n.s.), respectively. Correlating APE with image noise revealed that at identical noise APE was higher with IR than with FBP (p < 0.05). Conclusions: Computer-aided volumetry is robust in a wide range of exposure settings, and reproducibility is reduced at a CTDI below 1.0 mGy only, but the error rate remains clinically irrelevant. Noise reduction by IR is not detrimental for measurement error in the setting of semi-automatic nodule volumetry on chest MDCT.

  11. CT volumetry of artificial pulmonary nodules using an ex vivo lung phantom: Influence of exposure parameters and iterative reconstruction on reproducibility

    International Nuclear Information System (INIS)

    Wielpütz, Mark O.; Lederlin, Mathieu; Wroblewski, Jacek; Dinkel, Julien; Eichinger, Monika

    2013-01-01

    Objectives: To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the measurement variability of computer-aided nodule volumetry on chest multidetector computed tomography (MDCT). Materials and methods: N = 7 porcine lung explants were inflated in a dedicated ex vivo phantom and prepared with n = 162 artificial nodules. MDCT was performed eight consecutive times (combinations of 120 and 80 kV with 120, 60, 30 and 12 mA s), and reconstructed with filtered back projection (FBP) and IR. Nodule volume and diameter were measured semi-automatically with dedicated software. The absolute percentage measurement error (APE) was computed in relation to the 120 kV 120 mA s acquisition. Noise was recorded for each nodule in every dataset. Results: Mean nodule volume and diameter were 0.32 ± 0.15 ml and 12.0 ± 2.6 mm, respectively. Although IR reduced noise by 24.9% on average compared to FBP (p < 0.007), APE with IR was equal to or slightly higher than with FBP. Mean APE for volume increased significantly below a volume computed tomography dose index (CTDI) of 1.0 mGy: for 120 kV 12 mA s APE was 3.8 ± 6.2% (FBP) vs. 4.0 ± 5.2% (IR) (p < 0.007); for 80 kV 12 mA s APE was 8.0 ± 13.0% vs. 9.3 ± 15.8% (n.s.), respectively. Correlating APE with image noise revealed that at identical noise APE was higher with IR than with FBP (p < 0.05). Conclusions: Computer-aided volumetry is robust in a wide range of exposure settings, and reproducibility is reduced at a CTDI below 1.0 mGy only, but the error rate remains clinically irrelevant. Noise reduction by IR is not detrimental for measurement error in the setting of semi-automatic nodule volumetry on chest MDCT

  12. In vivo SPECT reporter gene imaging of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Ehsan Sharif-Paghaleh

    Full Text Available Regulatory T cells (Tregs were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4(+CD25(+FoxP3(+ cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ((99mTcO(4(- and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6 mice by SPECT/CT using (99mTcO(4(-. After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models.

  13. Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening

    Science.gov (United States)

    Mazurenka, M.; Behrendt, L.; Meinhardt-Wollweber, M.; Morgner, U.; Roth, B.

    2017-10-01

    A combined optical coherence tomography (OCT)-Raman probe was designed and built into a spectral domain OCT head, and its performance was evaluated and compared to the most common Raman probe setups, based on a fiber bundle and confocal free space optics. Due to the use of the full field of view of an OCT scanning lens, the combined probe has a superior performance within maximum permissible exposure limits, compared to the other two probes. Skin Raman spectra, recorded in vivo, further prove the feasibility of the OCT-Raman probe for the future in vivo clinical applications in skin cancer screening.

  14. In Vivo Radiofrequency Heating in Swine in a 3T (123.2 MHz) Birdcage Whole-Body Coil

    Science.gov (United States)

    Shrivastava, Devashish; Utecht, Lynn; Tian, Jinfeng; Hughes, John; Vaughan, J. Thomas

    2014-01-01

    Purpose To study in vivo radiofrequency (RF) heating produced due to power deposition from a 3T (Larmour frequency = 123.2 MHz), birdcage, whole-body coil. Methods The RF heating was simulated in a digital swine by solving the mechanistic generic bioheat transfer model (GBHTM) and the conventional, empirical Pennes bioheat transfer equation for the following two cases: (1) when the porcine head was in the isocenter, and (2) when the porcine trunk was in the isocenter. The simulation results were validated by making direct fluoroptic temperature measurements in the skin, brain, simulated hot regions, and rectum of ten swine (Case 1, N= 5, mean animal weight = 84.03 ± 6.85 kg, Whole-body average SAR = 2.65 ± 0.22 W/kg; Case 2, N= 5, mean animal weight = 81.59 ± 6.23 kg, Whole-body average SAR = 2.77 ± 0.26 W/kg) during one hour of exposure to a turbo spin echo sequence. Results The GBHTM simulated the RF heating more accurately compared to the Pennes equation. In vivo temperatures exceeded safe temperature thresholds with allowable SAR exposures. Hot regions may be produced deep inside the body, away from the skin. Conclusion SAR exposures to produce safe temperature thresholds may need re-investigation. PMID:24259413

  15. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇÝGÝL

    2012-08-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

  16. Comparison of in vivo and ex vivo imaging of the microvasculature with 2-photon fluorescence microscopy

    Science.gov (United States)

    Steinman, Joe; Koletar, Margaret; Stefanovic, Bojana; Sled, John G.

    2016-03-01

    This study evaluates 2-Photon fluorescence microscopy of in vivo and ex vivo cleared samples for visualizing cortical vasculature. Four mice brains were imaged with in vivo 2PFM. Mice were then perfused with a FITC gel and cleared in fructose. The same regions imaged in vivo were imaged ex vivo. Vessels were segmented automatically in both images using an in-house developed algorithm that accounts for the anisotropic and spatially varying PSF ex vivo. Through non-linear warping, the ex vivo image and tracing were aligned to the in vivo image. The corresponding vessels were identified through a local search algorithm. This enabled comparison of identical vessels in vivo/ex vivo. A similar process was conducted on the in vivo tracing to determine the percentage of vessels perfused. Of all the vessels identified over the four brains in vivo, 98% were present ex vivo. There was a trend towards reduced vessel diameter ex vivo by 12.7%, and the shrinkage varied between specimens (0% to 26%). Large diameter surface vessels, through a process termed 'shadowing', attenuated in vivo signal from deeper cortical vessels by 40% at 300 μm below the cortical surface, which does not occur ex vivo. In summary, though there is a mean diameter shrinkage ex vivo, ex vivo imaging has a reduced shadowing artifact. Additionally, since imaging depths are only limited by the working distance of the microscope objective, ex vivo imaging is more suitable for imaging large portions of the brain.

  17. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

    International Nuclear Information System (INIS)

    Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia; Chuai, Manli; Lee, Kenneth Ka Ho; Wan, Chao; Yang, Xuesong

    2014-01-01

    Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10 −8 –10 −6 μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased

  18. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Chuai, Manli [Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH (United Kingdom); Lee, Kenneth Ka Ho; Wan, Chao [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Yang, Xuesong, E-mail: yang_xuesong@126.com [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Institute of Fetal-Preterm Labor Medicine, Jinan University, Guangzhou 510632 (China)

    2014-11-15

    Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10{sup −8}–10{sup −6} μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly

  19. Operating Procedures to Improve Efficiencies of In vitro Exposure Systems at the Air-Liquid Interface

    Science.gov (United States)

    The expanding use of in vitro exposure systems for toxicity assessments has created regulatory concerns. Many of these same concerns surround the proper conduct of in vivo inhalation toxicology studies that are addressed in guidelines and Good Laboratory Practice (GLPs) regulatio...

  20. In vivo measurements of nitrogen, hydrogen, and carbon in genetically obese and lean pigs

    International Nuclear Information System (INIS)

    Ellis, K.J.; Shypailo, R.J.; Sheng, H.-P.; Pond, W.G.

    1992-01-01

    Characteristic gamma-rays are emitted promptly by elements during exposure to neutrons. These emissions enable a radioanalytical analysis of the body's composition of protein (nitrogen), water (hydrogen), and fat (carbon). We have used this method in vivo to determine the body composition of obese and lean pigs (10 to 20 kg body wt) fed an altered cholesterol diet. (author) 10 refs.; 5 figs.; 1 tab

  1. Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.

    Science.gov (United States)

    Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A; Chlopik, Agata; Hoang, Mai P; Pinkhasov, Omar R; Caravan, Peter; Rox Anderson, R; Haedersdal, Merete

    2018-04-10

    The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry techniques, we demonstrated that fractional CO 2 laser pretreatment (196 microchannels/cm 2 , 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

    Directory of Open Access Journals (Sweden)

    Silvina G. Castro

    2013-01-01

    Full Text Available The main objectives of this study were (a to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form.

  3. DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining Virtual Reality and Augmented Reality.

    Science.gov (United States)

    Ben-Moussa, Maher; Rubo, Marius; Debracque, Coralie; Lange, Wolf-Gero

    2017-01-01

    The present paper explores the benefits and the capabilities of various emerging state-of-the-art interactive 3D and Internet of Things technologies and investigates how these technologies can be exploited to develop a more effective technology supported exposure therapy solution for social anxiety disorder. "DJINNI" is a conceptual design of an in vivo augmented reality (AR) exposure therapy mobile support system that exploits several capturing technologies and integrates the patient's state and situation by vision-based, audio-based, and physiology-based analysis as well as by indoor/outdoor localization techniques. DJINNI also comprises an innovative virtual reality exposure therapy system that is adaptive and customizable to the demands of the in vivo experience and therapeutic progress. DJINNI follows a gamification approach where rewards and achievements are utilized to motivate the patient to progress in her/his treatment. The current paper reviews the state of the art of technologies needed for such a solution and recommends how these technologies could be integrated in the development of an individually tailored and yet feasible and effective AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI could be part of classical cognitive behavioral treatment and how to validate such a setup.

  4. DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining Virtual Reality and Augmented Reality

    Science.gov (United States)

    Ben-Moussa, Maher; Rubo, Marius; Debracque, Coralie; Lange, Wolf-Gero

    2017-01-01

    The present paper explores the benefits and the capabilities of various emerging state-of-the-art interactive 3D and Internet of Things technologies and investigates how these technologies can be exploited to develop a more effective technology supported exposure therapy solution for social anxiety disorder. “DJINNI” is a conceptual design of an in vivo augmented reality (AR) exposure therapy mobile support system that exploits several capturing technologies and integrates the patient’s state and situation by vision-based, audio-based, and physiology-based analysis as well as by indoor/outdoor localization techniques. DJINNI also comprises an innovative virtual reality exposure therapy system that is adaptive and customizable to the demands of the in vivo experience and therapeutic progress. DJINNI follows a gamification approach where rewards and achievements are utilized to motivate the patient to progress in her/his treatment. The current paper reviews the state of the art of technologies needed for such a solution and recommends how these technologies could be integrated in the development of an individually tailored and yet feasible and effective AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI could be part of classical cognitive behavioral treatment and how to validate such a setup. PMID:28503155

  5. DJINNI: A Novel Technology Supported Exposure Therapy Paradigm for SAD Combining Virtual Reality and Augmented Reality

    Directory of Open Access Journals (Sweden)

    Maher Ben-Moussa

    2017-04-01

    Full Text Available The present paper explores the benefits and the capabilities of various emerging state-of-the-art interactive 3D and Internet of Things technologies and investigates how these technologies can be exploited to develop a more effective technology supported exposure therapy solution for social anxiety disorder. “DJINNI” is a conceptual design of an in vivo augmented reality (AR exposure therapy mobile support system that exploits several capturing technologies and integrates the patient’s state and situation by vision-based, audio-based, and physiology-based analysis as well as by indoor/outdoor localization techniques. DJINNI also comprises an innovative virtual reality exposure therapy system that is adaptive and customizable to the demands of the in vivo experience and therapeutic progress. DJINNI follows a gamification approach where rewards and achievements are utilized to motivate the patient to progress in her/his treatment. The current paper reviews the state of the art of technologies needed for such a solution and recommends how these technologies could be integrated in the development of an individually tailored and yet feasible and effective AR/virtual reality-based exposure therapy. Finally, the paper outlines how DJINNI could be part of classical cognitive behavioral treatment and how to validate such a setup.

  6. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  7. Cigarette smoke induced genotoxicity and respiratory tract pathology: evidence to support reduced exposure time and animal numbers in tobacco product testing.

    Science.gov (United States)

    Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Walker, David; Camacho, Oscar M; Büttner, Ansgar; Dillon, Debbie; Meredith, Clive

    2016-06-01

    Many laboratories are working to develop in vitro models that will replace in vivo tests, but occasionally there remains a regulatory expectation of some in vivo testing. Historically, cigarettes have been tested in vivo for 90 days. Recently, methods to reduce and refine animal use have been explored. This study investigated the potential of reducing animal cigarette smoke (CS) exposure to 3 or 6 weeks, and the feasibility of separate lung lobes for histopathology or the Comet assay. Rats were exposed to sham air or CS (1 or 2 h) for 3 or 6 weeks. Respiratory tissues were processed for histopathological evaluation, and Alveolar type II cells (AEC II) isolated for the Comet assay. Blood was collected for Pig-a and micronucleus quantification. Histopathological analyses demonstrated exposure effects, which were generally dependent on CS dose (1 or 2 h, 5 days/week). Comet analysis identified that DNA damage increased in AEC II following 3 or 6 weeks CS exposure, and the level at 6 weeks was higher than 3 weeks. Pig-a mutation or micronucleus levels were not increased. In conclusion, this study showed that 3 weeks of CS exposure was sufficient to observe respiratory tract pathology and DNA damage in isolated AEC II. Differences between the 3 and 6 week data imply that DNA damage in the lung is cumulative. Reducing exposure time, plus analyzing separate lung lobes for DNA damage or histopathology, supports a strategy to reduce and refine animal use in tobacco product testing and is aligned to the 3Rs (replacement, reduction and refinement).

  8. Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response, Biodistribution and In Vitro/In Vivo Toxicity Evaluation

    Directory of Open Access Journals (Sweden)

    Valeria De Matteis

    2017-10-01

    Full Text Available The development of different kinds of nanoparticles, showing different physico-chemical properties, has fostered their large use in many fields, including medicine. As a consequence, inorganic nanoparticles (e.g., metals or semiconductors, have raised issues about their potential toxicity. The scientific community is investigating the toxicity mechanisms of these materials, in vitro and in vivo, in order to provide accurate references concerning their use. This review will give the readers a thorough exploration on the entry mechanisms of inorganic nanoparticles in the human body, such as titanium dioxide nanoparticles (TiO2NPs, silicon dioxide nanoparticles (SiO2NPs, zinc oxide nanoparticles (ZnONPs, silver nanoparticles (AgNPs, gold nanoparticles (AuNPs and quantum dots (QDsNPs. In addition, biodistribution, the current trends and novelties of in vitro and in vivo toxicology studies will be discussed, with a particular focus on immune response.

  9. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, C-H; Lim, S-I [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ({sup 1}H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo {sup 1}H MRS. Methods: We used high-field {sup 1}H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  10. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

    International Nuclear Information System (INIS)

    Yoo, C-H; Lim, S-I; Song, K-H; Choe, B-Y; Woo, D-C

    2016-01-01

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ("1H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo "1H MRS. Methods: We used high-field "1H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  11. Tobacco use and second-hand smoke exposure in young adolescents aged 12–15 years: data from 68 low-income and middle-income countries

    Directory of Open Access Journals (Sweden)

    Prof. Bo Xi, PhD

    2016-11-01

    Funding: This work was partly supported by the Young Scholars Program of Shandong University (2015WLJH51, the Shandong Provincial Natural Science Foundation (ZR2012HQ033, and the National Natural Science Foundation (81302496.

  12. Development and evaluation of a technique for in vivo monitoring of 60Co in human liver

    Science.gov (United States)

    Gomes, GH; Silva, MC; Mello, JQ; Dantas, ALA; Dantas, BM

    2018-03-01

    60Co is an artificial radioactive metal produced by activation of iron with neutrons. It decays by beta particles and gamma radiation and represents a risk of internal exposure of workers involved in the maintenance of nuclear power reactors. Intakes can be quantified through in vivo monitoring. This work describes the development of a technique for the quantification of 60Co in human liver. The sensitivity of the method is evaluated based on the minimum detectable effective doses. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes.

  13. Effect of cadmium on lipid metabolism of brain. In vivo incorporation of labelled acetate into lipids

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, S; Gill, K D; Nath, R

    1987-01-01

    The effect of early postnatal cadmium exposure on the in vivo incorporation of (1-/sup 14/C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd-exposed animals compared to controls.

  14. Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

    Science.gov (United States)

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares; Lepera, José Salvador

    2015-10-01

    Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. In vivo behavior of Co and evaluation of exposure to Co

    International Nuclear Information System (INIS)

    Inaba, Jiro

    1983-01-01

    Metabolism of Co was studied in vivo in mammalian animals. Approximately 3% of inorganic Co, 60 CoCl 2 , was absorbed in the digestive tract in rats. In humans, the absorption rate of 60 CoCl 2 approximated to that in rats, seemingly being influenced by the presence of carriers. Residue curves revealed that 60 CoCl 2 in the body was present in several forms. The distribution of 60 CoCl 2 was highest in the kidneys in rats and in the liver in humans. On the other hand, the absorption rate of organic Co, 58 Co-cyanocobalamin, into the digestive tract was 50% or more in rats, as well as in humans, greatly depending upon the presence of carriers. 58 Co-cyanocobalamin was present in a single form, and the distribution pattern of 58 Co-cyanocobalamin in organs was similar to that of 60 CoCl 2 . The residue value of Co 9 days after incorporation from foods into the body of rats was 20-30 times higher than that in the control group. This was marked especially in the kidneys. (Namekawa, K.)

  16. Laser injury and in vivo multimodal imaging using a mouse model

    Science.gov (United States)

    Pocock, Ginger M.; Boretsky, Adam; Gupta, Praveena; Oliver, Jeff W.; Motamedi, Massoud

    2011-03-01

    Balb/c wild type mice were used to perform in vivo experiments of laser-induced thermal damage to the retina. A Heidelberg Spectralis HRA confocal scanning laser ophthalmoscope with a spectral domain optical coherence tomographer was used to obtain fundus and cross-sectional images of laser induced injury in the retina. Sub-threshold, threshold, and supra-threshold lesions were observed using optical coherence tomography (OCT), infrared reflectance, red-free reflectance, fluorescence angiography, and autofluorescence imaging modalities at different time points post-exposure. Lesions observed using all imaging modalities, except autofluorescence, were not visible immediately after exposure but did resolve within an hour and grew in size over a 24 hour period. There was a decrease in fundus autofluorescence at exposure sites immediately following exposure that developed into hyper-fluorescence 24-48 hours later. OCT images revealed threshold damage that was localized to the RPE but extended into the neural retina over a 24 hour period. Volumetric representations of the mouse retina were created to visualize the extent of damage within the retina over a 24 hour period. Multimodal imaging provides complementary information regarding damage mechanisms that may be used to quantify the extent of the damage as well as the effectiveness of treatments without need for histology.

  17. Toxic actions of dinoseb in medaka (Oryzias latipes) embryos as determined by in vivo 31P NMR, HPLC-UV and 1H NMR metabolomics.

    Science.gov (United States)

    Viant, Mark R; Pincetich, Christopher A; Hinton, David E; Tjeerdema, Ronald S

    2006-03-10

    Changes in metabolism of Japanese medaka (Oryzias latipes) embryos exposed to dinoseb (2-sec-butyl-4,6-dinitrophenol), a substituted dinitrophenol herbicide, were determined by in vivo (31)P NMR, high-pressure liquid chromatography (HPLC)-UV, and (1)H NMR metabolomics. ATP and phosphocreatine (PCr) metabolism were characterized within intact embryos by in vivo (31)P NMR; concentrations of ATP, GTP, ADP, GDP, AMP and PCr were determined by HPLC-UV; and changes in numerous polar metabolites were characterized by (1)H NMR-based metabolomics. Rangefinding exposures determined two sublethal doses of dinoseb, 50 and 75 ppb, in which embryos survived from 1-day post fertilization (DPF) through the duration of embryogenesis. In vivo (31)P NMR data were acquired from 900 embryos in 0, 50, and 75 ppb dinoseb at 14, 62, and 110 h (n = 6 groups) after initiation of exposure. After 110 h, embryos were observed for normal development and hatching success, then either preserved in 10% formalin for growth analysis or flash frozen and extracted for HPLC-UV and (1)H NMR analysis. Dinoseb exposure at both concentrations resulted in significant declines in [ATP] and [PCr] at 110 h as measured by in vivo (31)P NMR (p fashion. Metabolic effects measured by in vivo (31)P NMR showed a significant increase in orthophosphate levels (P(i); p < 0.05), and significant decreases in [ATP], [PCr] and the PCr/P(i) ratio (p < 0.05). Metabolomics revealed a dose-response relationship between dinoseb and endogenous metabolite changes, with both dinoseb concentrations producing significantly different metabolic profiles from controls (p < 0.05). Metabolic changes included decreased concentrations of ATP, PCr, alanine and tyrosine, and increased concentrations of lactate with medaka embryotoxicity. This study demonstrated that medaka embryos respond to dinoseb with significant changes in metabolism, reduced growth and heart rates, and increased abnormal development and post-exposure mortality. All

  18. In vivo radioprotection by alpha-TMG: preliminary studies.

    Science.gov (United States)

    Satyamitra, M; Devi, P U; Murase, H; Kagiya, V T

    2001-08-08

    alpha-TMG is a novel water-soluble derivative of Vitamin E that has shown excellent antioxidant activity. The parent compound has demonstrated protection against radiation induced chromosomal damage in vivo. Hence, the preliminary experiments to determine the radioprotective activity of alpha-TMG were carried out in adult Swiss albino mice. Acute toxicity of the drug was studied taking 24h, 72 h and 30 day mortality after a single intraperitoneal injection of 500-2000 mg/kg body weight of the drug. The drug LD(50) for 24h and 72 h/30 day survival were found to be 1120 and 1000 mg/kg body weight, respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 600 mg/kg of the drug 15 min before or within 5, 15 or 30min after 3Gy whole body gamma radiation resulted in a significant decrease in the aberrant metaphases percent at 24h post-irradiation; the maximum effect was seen when the drug was given immediately after irradiation. Injection of 200-800 mg/kg TMG within 5 min of irradiation with 3 Gy produced a significant dose-dependent reduction in the radiation induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 600 mg/kg body weight. At this dose, TMG produced 70 and >60% reduction in the radiation induced percent aberrant metaphases and micronucleated erythrocytes, respectively. The high water solubility and effectiveness when administered post-irradiation favor TMG as a likely candidate for protection in case of accidental exposures.

  19. Comparison of surface contamination monitors for in vivo measurement of {sup 131}I in thyroid

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, S.M.; Dantas, A.L.A.; Dantas, B.M., E-mail: salomao.marques@ymail.com [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    The routine handling of radiopharmaceuticals in nuclear medicine represents a significant risk of internal exposure to the staff. The IAEA recommends the implementation of monitoring plans for all workers subject to a risk of exposures above 1 mSv per year. However, in Brazil, such recommendation is practically unfeasible due to the lack of a sufficient number of qualified internal dosimetry services over the country. This work presents an alternative based on a simple and inexpensive methodology aimed to perform in-vivo monitoring of {sup 131}I in thyroid using portable surface contamination probes. All models evaluated showed suitable sensitivity for such application. (author)

  20. Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways.

    Science.gov (United States)

    Xu, Yuan; Cardell, Lars-Olaf

    2017-09-01

    Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine's effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg -1 ·day -1 ) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections. Copyright © 2017 the American Physiological Society.

  1. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    Science.gov (United States)

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  2. Ecological and human health risks associated with abandoned gold mine tailings contaminated soil.

    Directory of Open Access Journals (Sweden)

    Veronica Mpode Ngole-Jeme

    Full Text Available Gold mining is a major source of metal and metalloid emissions into the environment. Studies were carried out in Krugersdorp, South Africa, to evaluate the ecological and human health risks associated with exposure to metals and metalloids in mine tailings contaminated soils. Concentrations of arsenic (As, cadmium (Cd, chromium (Cr, cobalt (Co, copper (Cu, lead (Pb, manganese (Mn, nickel (Ni, and zinc (Zn in soil samples from the area varied with the highest contamination factors (expressed as ratio of metal or metalloid concentration in the tailings contaminated soil to that of the control site observed for As (3.5x102, Co (2.8x102 and Ni (1.1x102. Potential ecological risk index values for metals and metalloids determined from soil metal and metalloid concentrations and their respective risk factors were correspondingly highest for As (3.5x103 and Co (1.4x103, whereas Mn (0.6 presented the lowest ecological risk. Human health risk was assessed using Hazard Quotient (HQ, Chronic Hazard Index (CHI and carcinogenic risk levels, where values of HQ > 1, CHI > 1 and carcinogenic risk values > 1×10-4 represent elevated risks. Values for HQ indicated high exposure-related risk for As (53.7, Cr (14.8, Ni (2.2, Zn (2.64 and Mn (1.67. Children were more at risk from heavy metal and metalloid exposure than adults. Cancer-related risks associated with metal and metalloid exposure among children were also higher than in adults with cancer risk values of 3×10-2 and 4×10-2 for As and Ni respectively among children, and 5×10-3 and 4×10-3 for As and Ni respectively among adults. There is significant potential ecological and human health risk associated with metal and metalloid exposure from contaminated soils around gold mine tailings dumps. This could be a potential contributing factor to a setback in the health of residents in informal settlements dominating this mining area as the immune systems of some of these residents are already compromised by high

  3. Stimulus-dependent changes of extracellular glucose in the rat hippocampus determined by in vivo microdialysis.

    Science.gov (United States)

    Rex, A; Bert, B; Fink, H; Voigt, J-P

    2009-10-19

    Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

  4. Development and Utilization of an Ex Vivo Bromodeoxyuridine Local Lymph Node Assay (LLNA) Protocol for Assessing Potential Chemical Sensitizers

    Science.gov (United States)

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  5. Virtual reality exposure in anxiety disorders: impact on psychophysiological reactivity.

    Science.gov (United States)

    Diemer, Julia; Mühlberger, Andreas; Pauli, Paul; Zwanzger, Peter

    2014-08-01

    Anxiety disorders are among the most frequently encountered psychiatric disorders. Recommended treatments include cognitive behavioural therapy (CBT) and/or medication. In recent years, beneficial effects of virtual reality (VR) exposure therapy have been shown, making this technique a promising addition to CBT. However, the ability of VR to mimic threatening stimuli in a way comparable to in vivo cues has been discussed. In particular, it has been questioned whether VR is capable of provoking psychophysiological symptoms of anxiety. Since psychophysiological arousal is considered a prerequisite for effective exposure treatment, this systematic review aims to evaluate the evidence for the potential of VR exposure to evoke and modulate psychophysiological fear reactions. PubMed and PsycINFO/Academic Search Premier databases were searched. Thirty-eight studies investigating challenge or habituation effects were included. VR exposure does provoke psychophysiological arousal, especially in terms of electrodermal activity. Results on psychophysiological habituation in VR are inconclusive. Study design and methodological rigour vary widely. Despite several limitations, this review provides evidence that VR exposure elicits psychophysiological fear reactions in patients and healthy subjects, rendering VR a promising treatment for anxiety disorders, and a potent research tool for future investigations of psychophysiological processes and their significance during exposure treatment.

  6. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06vivo dataset, and 100% accuracy for discriminating patients who received total body radiation. Three genes of this panel (CDKN1A, FDXR and BBC3 were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  7. Aluminium sulfate exposure: A set of effects on hydrolases from brain, muscle and digestive tract of juvenile Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Oliveira, Vagne Melo; Assis, Caio Rodrigo Dias; Costa, Helane Maria Silva; Silva, Raquel Pereira Freitas; Santos, Juliana Ferreira; Carvalho, Luiz Bezerra; Bezerra, Ranilson Souza

    2017-01-01

    Aluminium is a major pollutant due to its constant disposal in aquatic environments through anthropogenic activities. The physiological effects of this metal in fish are still scarce in the literature. This study investigated the in vivo and in vitro effects of aluminium sulfate on the activity of enzymes from Nile tilapia (Oreochromis niloticus): brain acetylcholinesterase (AChE), muscle cholinesterases (AChE-like and BChE-like activities), pepsin, trypsin, chymotrypsin and amylase. Fish were in vivo exposed during 14days when the following experimental groups were assayed: control group (CG), exposure to Al 2 (SO 4 ) 3 at 1μg·mL -1 (G1) and 3μg·mL -1 (G3) (concentrations compatible with the use of aluminium sulfate as coagulant in water treatment). In vitro exposure was performed using animals of CG treatment. Both in vivo and in vitro exposure increased cholinesterase activity in relation to controls. The highest cholinesterase activity was observed for muscle BChE-like enzyme in G3. In contrast, the digestive enzymes showed decreased activity in both in vivo and in vitro exposures. The highest inhibitory effect was observed for pepsin activity. The inhibition of serine proteases was also quantitatively analyzed in zymograms using pixel optical densitometry as area under the peaks (AUP) and integrated density (ID). These results suggest that the inhibition of digestive enzymes in combination with activation of cholinesterases in O. niloticus is a set of biochemical effects that evidence the presence of aluminium in the aquatic environment. Moreover, these enzymatic alterations may support further studies on physiological changes in this species with implications for its neurological and digestive metabolisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.

    Directory of Open Access Journals (Sweden)

    Peter A Anton

    Full Text Available Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.HIV-1 seronegative, sexually-abstinent men and women (N = 36 were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25% with placebo gel (1∶1∶1. Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.All 36 subjects enrolled completed the 7-14 week trial (100% retention including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm. There were 81 Grade 1 adverse events (AEs and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV

  9. In vivo measurements of nitrogen, hydrogen, carbon and potassium in genetically obese and lean pigs

    International Nuclear Information System (INIS)

    Ellis, K.J.; Shypailo, R.J.; Sheng, H.P.; Mersmann, H.J.; Pond, W.G.

    1991-01-01

    Characteristic gamma rays are emitted promptly by elements during exposure to neutrons. Gamma ray emissions enable a radioanalytical analysis of the body's composition of protein (nitrogen), water (hydrogen), fat (carbon), and muscle (natural 40 K). The authors have used this method in vivo to detect changes in the body composition of obese and lean pigs (10-20 kg body wt) in response to an altered cholesterol diet

  10. Evaluation of the in vivo and ex vivo optical properties in a mouse ear model

    Energy Technology Data Exchange (ETDEWEB)

    Salomatina, E; Yaroslavsky, A N [Wellman Center for Photomedicine, 40 Blossom Street, Boston, MA 02114 (United States)], E-mail: Yaroslav@helix.mgh.harvard.edu

    2008-06-07

    Determination of in vivo optical properties is a challenging problem. Absorption and scattering measured ex vivo are often used for in vivo applications. To investigate the validity of this approach, we have obtained and compared the optical properties of mouse ears in vivo and ex vivo in the spectral range from 370 to 1650 nm. Integrating sphere spectrophotometry in combination with the inverse Monte Carlo technique was employed to determine absorption coefficients, {mu}{sub a}, scattering coefficients, {mu}{sub s}, and anisotropy factors, g. Two groups of mice were used for the study. The first group was measured in vivo and ex vivo within 5-10 min post mortem. The second group was measured in vivo and ex vivo every 24 h for up to 72 h after sacrifice. Between the measurements the tissues were kept at 4 deg. C wrapped in a gauze moistened with saline solution. Then the specimens were frozen at -25 deg. C for 40 min, thawed and measured again. The results indicate that the absorption coefficients determined in vivo and ex vivo within 5-10 min post mortem differed considerably only in the spectral range dominated by hemoglobin. These changes can be attributed to rapid deoxygenation of tissue and blood post mortem. Absorption coefficients determined ex vivo up to 72 h post mortem decreased gradually with time in the spectral regions dominated by hemoglobin and water, which can be explained by the continuing loss of blood. Absorption properties of the frozen-thawed ex vivo tissues showed increase in oxygenation, which is likely caused by the release of hemoglobin from hemolyzed erythrocytes. Scattering of the ex vivo tissues decreased gradually with time in the entire spectral range due to the continuing loss of blood and partial cell damage. Anisotropy factors did not change considerably.

  11. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  12. In vivo radiofrequency heating in swine in a 3T (123.2-MHz) birdcage whole body coil.

    Science.gov (United States)

    Shrivastava, Devashish; Utecht, Lynn; Tian, Jinfeng; Hughes, John; Vaughan, J Thomas

    2014-10-01

    To study in vivo radiofrequency (RF) heating produced due to power deposition from a 3T (Larmour frequency = 123.2 MHz), birdcage, whole body coil. The RF heating was simulated in a digital swine by solving the mechanistic generic bioheat transfer model (GBHTM) and the conventional, empirical Pennes bioheat transfer equation for two cases: 1) when the swine head was in the isocenter and 2) when the swine trunk was in the isocenter. The simulation results were validated by making direct fluoroptic temperature measurements in the skin, brain, simulated hot regions, and rectum of 10 swine (case 1: n = 5, mean animal weight = 84.03 ± 6.85 kg, whole body average SAR = 2.65 ± 0.22 W/kg; case 2: n = 5, mean animal weight = 81.59 ± 6.23 kg, whole body average SAR = 2.77 ± 0.26 W/kg) during 1 h of exposure to a turbo spin echo sequence. The GBHTM simulated the RF heating more accurately compared with the Pennes equation. In vivo temperatures exceeded safe temperature thresholds with allowable SAR exposures. Hot regions may be produced deep inside the body, away from the skin. SAR exposures that produce safe temperature thresholds need reinvestigation. Copyright © 2013 Wiley Periodicals, Inc.

  13. In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

    Science.gov (United States)

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

    2012-01-01

    One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

  14. Studies of cadmium, mercury and lead in man. The value of X-ray fluorescence measurements in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Boerjesson, J

    1996-10-01

    Two XRF methods have been used for in vivo studies of mercury, cadmium and lead. Persons with a history of long-term occupational mercury exposure had elevated mercury concentrations in their kidneys (up to 65 {mu}g/g). The minimum detectable concentration varied between 12 and 45 {mu}g/g. Battery plant workers had elevated cadmium concentrations in their kidneys (up to 350 {mu}g/g) and liver (up to 80 {mu}g/g), with mean values about 3-5 times higher than the general population. The mean ratio between concentrations of cadmium in kidney and liver was 7. Levels in kidney and liver indicated that a simple integration of cadmium in work-place air is not sufficient to describe the body burden. Fingerbone lead in smelters was 6-8 times higher than in members of the general population. The half-time of bone lead in active workers was estimated to about 5 years during the accumulation phase. A model for description of a person`s lead exposure in terms of lead in fingerbone, lead in blood and time of exposure has been developed and can be used, e.g. for retrospective blood lead estimates if the period of exposure and the current fingerbone lead is known. This will be of value for the evaluation of toxic effects of long-term lead exposure when data on previous lead levels are lacking. In total, in vivo measurements of mercury, cadmium and lead give unique information, which has shown to be an important tool for understanding of metal kinetics and toxicity. If the precision and accuracy of the method can be further improved, the technique will also have a given place in the clinical practice. 168 refs, 9 figs, 3 tabs

  15. Development and evaluation of a technique for in vivo monitoring of {sup 60}Co in human liver

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, B.M.; Dantas, A.L.A.; Gomes, G.H.; Silva, M.C.; Mello, J.Q., E-mail: bmdantas@ird.gov.br [Instituto de Radioproteção e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2017-07-01

    {sup 60}Co is an artificial radioactive metal produced by activation of iron with neutrons. It decays by beta particles and gamma radiation and represents a risk of internal exposure of workers involved in the maintenance of nuclear power reactors. Intakes can be quantified through in vivo monitoring. This work describes the development of a technique for the quantification of {sup 60}Co in human liver. The sensitivity of the method is evaluated based on the minimum detectable effective doses. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes. (author)

  16. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    Science.gov (United States)

    Tassinari, Roberta; La Rocca, Cinzia; Stecca, Laura; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca

    2015-06-01

    In European Union, titanium dioxide (TiO2) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm2 levels of TiO2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO2 NP toxicity by direct exposure both in vivo and in vitro models.

  17. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    International Nuclear Information System (INIS)

    Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca; Stecca, Laura

    2014-01-01

    In European Union, titanium dioxide (TiO 2 ) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO 2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO 2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO 2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm 2 levels of TiO 2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO 2 NP toxicity by direct exposure both in vivo and in vitro models

  18. Non-occupational radiation exposures from 222Rn and daughters to residents of Grand Junction, Colorado

    International Nuclear Information System (INIS)

    Spitz, H.B.; Cohen, N.; Wrenn, M.E.

    1975-01-01

    Six individuals from GRAND Junction, Colorado were examined for 210 Pb body burdens as a result of living in homes where concentrations of 222 Rn were elevated due to the presence of uranium mill tailings beneath the building foundation. In vivo detection for 210 Pb using three NaI--CsI (Tl) thin crystals in the standard NYU head geometry identified two persons with estimaed body burdens above 1.1 nCi. Bioassay for 210 Pb was also performed to compare with the in vivo analysis and to further substantiate the relationship between 210 Pb in bone, blood, and urine. estimates of exposure in cumulative working level months (CWLM), range 85 to 566 CWLM, were used to calculate expected body burdens of 210 Pb. The NYU continuous readout radon monitor provided diurnal measurements of 222 Rn in the homes of the volunteer subjects so that, considering assumptions about ventilation and residence times, actual exposures could be determined. (U.S.)

  19. Phthalate exposure and childhood obesity

    Directory of Open Access Journals (Sweden)

    Shin Hye Kim

    2014-06-01

    Full Text Available Phthalates are commonly used as plasticizers and vehicles for cosmetic ingredients. Phthalate metabolites have documented biochemical activity including activating peroxisome proliferator-activated receptor and antiandrogenic effects, which may contribute to the development of obesity. In vitro and in vivo studies suggest that phthalates have significant effects on the development of obesity, especially after prenatal exposure at low doses. Although few studies have examined the effects of phthalate on obesity development in humans, some work has shown that phthalates affect humans and animals similarly. In this paper, we review the possible mechanisms of phthalate-induced obesity, and discuss evidence supporting the role of phthalates in the development of obesity in humans.

  20. Assessment and characterisation of yeast-based products intended to mitigate ochratoxin exposure using in vitro and in vivo models.

    Science.gov (United States)

    Pfohl-Leszkowicz, A; Hadjeba-Medjdoub, K; Ballet, N; Schrickx, J; Fink-Gremmels, J

    2015-01-01

    The aim of this paper was to evaluate the capacity of several yeast-based products, derived from baker's and brewer's yeasts, to sequester the mycotoxin ochratoxin A (OTA) and to decrease its rate of absorption and DNA adduct formation in vivo. The experimental protocol included in vitro binding studies using isotherm models, in vivo chicken experiments, in which the serum and tissue concentrations of OTA were analysed in the absence and presence of the test compounds, and the profile of OTA-derived metabolites and their associated DNA adducts were determined. Additionally in vitro cell culture studies (HK2 cells) were applied to assess further the effects for yeast cell product enriched with glutathione (GSH) or selenium. Results of the in vitro binding assay in a buffer system indicated the ability of the yeast-based products, as sequester of OTA, albeit at a different level. In the in vitro experiments in chickens, decreased serum and tissue concentrations of treated animals confirmed that yeast-based products are able to prevent the absorption of OTA. A comparison of the binding affinity in a standard in vitro binding assay with the results obtained in an in vivo chicken experiment, however, showed a poor correlation and resulted in a different ranking of the products. More importantly, we could show that yeast-based products actively modulate the biotransformation of OTA in vivo as well as in vitro in a cell culture model. This effect seems to be attributable to residual enzymatic activities in the yeast-based products. An enrichment of yeast cell wall products with GSH or selenium further modulated the profile of the generated OTA metabolites and the associated pattern of OTA-induced DNA adducts by increasing the conversion of OTA into less toxic metabolites such as OTA, OTB and 4-OH-OTA. A reduced absorption and DNA adduct formation was particularly observed with GSH-enriched yeast, whereas selenium-enriched yeasts could counteract the OTA-induced decrease

  1. Development and evaluation of a technique for in vivo monitoring of 60Co in the lungs

    International Nuclear Information System (INIS)

    Mello, J.Q. de; Lucena, E.A.; Dantas, A.L.A.; Dantas, B.M.

    2015-01-01

    60 Co is a fission product of 235 U and represents a risk of internal exposure of workers in nuclear power plants, especially those involved in the maintenance of potentially contaminated parts and equipment. The control of 60 Co intake by inhalation can be performed through in vivo monitoring. This work describes the evaluation of a technique through the minimum detectable activity and the corresponding minimum detectable effective doses, based on biokinetic and dosimetric models of 60 Co in the human body. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes. (author)

  2. Effect of timing of joint application of hydroquinone and dicyandiamide on nitrous oxide emission from irrigated lowland rice paddy field.

    Science.gov (United States)

    Li, Xianglan; Zhang, Guangbin; Xu, Hua; Cai, Zucong; Yagi, Kazuyuki

    2009-06-01

    A field experiment was conducted to study the effect of timing of joint application of urease inhibitor hydroquinone (HQ) and nitrification inhibitor dicyandiamide (DCD) on N(2)O emission from irrigated lowland rice paddy field. Four treatments including Treatment CK (the control with urea alone), HQ/DCD-1 (application of HQ and DCD together with fertilizer before transplanting), HQ/DCD-2 (HQ and DCD with fertilizer at tillering stage) and HQ/DCD-3 (HQ and DCD with fertilizer at panicle initiation stage) were designed and implemented separately during rice growth period. Seasonal peaks of N(2)O flux occurred during midseason drainage and significant negative correlation between N(2)O flux and water layer depth was observed (r=-0.69 to -0.75, P<0.01). Mean N(2)O flux was the highest in the control with urea alone, while joint addition of HQ and DCD with urea lowered mean N(2)O flux considerably (P<0.05). Total N(2)O emission during rice growth season in Treatment CK, HQ/DCD-1, HQ/DCD-2 and HQ/DCD-3 was 3.90, 2.98, 1.73 and 3.23kgN(2)O-N ha(-1), respectively. Application of HQ and DCD together with basal fertilizer, tillering fertilizer and panicle initiation fertilizer decreased the total N(2)O emission by 24%, 56% and 17%, respectively, while increased grain yield by 10%, 18% and 6%, respectively. Effect of application of inhibitors on N(2)O emission during the continuous period from incorporation of HQ and DCD to rice harvest was also studied, where results indicating that the highest inhibiting efficiency of inhibitors on N(2)O emission was recorded when HQ and DCD applied with fertilizer at tillering stage.

  3. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  4. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    International Nuclear Information System (INIS)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-01-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  5. Influence of 8-hydroxyquinoline on properties of anodic coatings obtained by micro arc oxidation on AZ91 magnesium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R.F. [Jiangxi Key Laboratory of Surface Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); School of Material Science and Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Zhang, S.F., E-mail: zhangshufang790314@sina.com [Jiangxi Key Laboratory of Surface Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); School of Material Science and Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Yang, N.; Yao, L.J.; He, F.X.; Zhou, Y.P.; Xu, X.; Chang, L.; Bai, S.J. [School of Material Science and Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China)

    2012-10-25

    Highlights: Black-Right-Pointing-Pointer 8-HQ can promote the coating formation and change the coating color. Black-Right-Pointing-Pointer 8-HQ can increase the coating thickness and decrease the pore size. Black-Right-Pointing-Pointer Insoluble Mg(HQ){sub 2} is formed in anodic coatings in an alkaline solution with 8-HQ. Black-Right-Pointing-Pointer 8-HQ improves the corrosion resistance of the anodized magnesium alloys. - Abstract: The influence of 8-hydroxyquinoline (8-HQ) on formation and properties of anodic coatings obtained by micro arc oxidation (MAO) on AZ91 magnesium alloys was studied by scanning electron microscope (SEM), energy dispersive spectrometry (EDS), Fourier transform infrared (FT-IR) spectroscopy and potentiodynamic polarization tests. The results demonstrate that 8-HQ can decrease the solution conductivity, take part in the coating formation and change the coating color. By developing anodic coatings with increasing thickness, insoluble Mg(HQ){sub 2} and small pore size, 8-HQ improves the corrosion resistance of the anodized magnesium alloys. The coating shows the best corrosion resistance in the solution of 10 g/L NaOH and 18 g/L Na{sub 2}SiO{sub 3} with 2 g/L 8-HQ.

  6. In vivo potency revisited - Keep the target in sight.

    Science.gov (United States)

    Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

    2018-04-01

    Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50

  7. Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

    Science.gov (United States)

    Smina, T P; Joseph, Jini; Janardhanan, K K

    2016-11-01

    The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

  8. Calculating radiation exposures during use of (14)C-labeled nutrients, food components, and biopharmaceuticals to quantify metabolic behavior in humans.

    Science.gov (United States)

    Kim, Seung-Hyun; Kelly, Peter B; Clifford, Andrew J

    2010-04-28

    (14)C has long been used as a tracer for quantifying the in vivo human metabolism of food components, biopharmaceuticals, and nutrients. Minute amounts (food components, biopharmaceuticals, or nutrients to be organized into models suitable for quantitative hypothesis testing and determination of metabolic parameters. In vivo models are important for specification of intake levels for food components, biopharmaceuticals, and nutrients. Accurate estimation of the radiation exposure from ingested (14)C is an essential component of the experimental design. Therefore, this paper illustrates the calculation involved in determining the radiation exposure from a minute dose of orally administered (14)C-beta-carotene, (14)C-alpha-tocopherol, (14)C-lutein, and (14)C-folic acid from four prior experiments. The administered doses ranged from 36 to 100 nCi, and radiation exposure ranged from 0.12 to 5.2 microSv to whole body and from 0.2 to 3.4 microSv to liver with consideration of tissue weighting factor and fractional nutrient. In comparison, radiation exposure experienced during a 4 h airline flight across the United States at 37000 ft was 20 microSv.

  9. Photoreactivity of nifedipine in vitro and in vivo.

    Science.gov (United States)

    de Vries, H; Beijersbergen van Henegouwen, G M

    1998-06-01

    Side effects of nitroaromatics used as drugs are often assumed to be caused by incomplete enzymatic reduction of the nitro group. However, photoactivation, although usually not considered as a cause of the toxic effects of nitroaromatics, can play a considerable role. Nifedipine, a nitroaromatic as well, is an important drug used in the treatment of myocardial ischaemia and hypertension. It is extremely sensitive to ultraviolet and visible light up to 450 nm and forms a nitroso derivative in vitro. In the present study it is shown that the nitroso compound is a short-lived intermediate in blood and plasma. It reacts with other constituents to form a stable lactam. In vivo, this lactam proves to be rapidly clear from the blood of rats and is excreted almost quantitatively via the bile. The first photoproduct of nifedipine, nitroso nifedipine, is shown to be converted into the lactam mentioned. Beside the lactam, two other products, which are considered to be derivatives of the lactam, are found. One of these two products is also found in the bile of a rat that was exposed to UVA light after intravenous nifedipine administration. This shows that in an in vivo situation, photoproducts can reach organs other than those exposed to the light. In vitro about 45 to 50% of the original amount of nifedipine is not recovered after exposure of nifedipine to UVA in the presence of bovine serum albumin or after incubation of nitroso nifedipine with bovine serum albumin in the dark. As complex binding of nifedipine of plasma proteins is high, the latter finding may have important implications for the situation in vivo.

  10. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  11. Virtual reality exposure therapy in anxiety disorders: a quantitative meta-analysis.

    Science.gov (United States)

    Opriş, David; Pintea, Sebastian; García-Palacios, Azucena; Botella, Cristina; Szamosközi, Ştefan; David, Daniel

    2012-02-01

    Virtual reality exposure therapy (VRET) is a promising intervention for the treatment of the anxiety disorders. The main objective of this meta-analysis is to compare the efficacy of VRET, used in a behavioral or cognitive-behavioral framework, with that of the classical evidence-based treatments, in anxiety disorders. A comprehensive search of the literature identified 23 studies (n = 608) that were included in the final analysis. The results show that in the case of anxiety disorders, (1) VRET does far better than the waitlist control; (2) the post-treatment results show similar efficacy between the behavioral and the cognitive behavioral interventions incorporating a virtual reality exposure component and the classical evidence-based interventions, with no virtual reality exposure component; (3) VRET has a powerful real-life impact, similar to that of the classical evidence-based treatments; (4) VRET has a good stability of results over time, similar to that of the classical evidence-based treatments; (5) there is a dose-response relationship for VRET; and (6) there is no difference in the dropout rate between the virtual reality exposure and the in vivo exposure. Implications are discussed. © 2011 Wiley Periodicals, Inc.

  12. [Exposure to addictogenic substances, conditioned response and treatment of the exposure with response prevention].

    Science.gov (United States)

    Khazaal, Y; Frésard, E; Zullino, D

    2007-01-01

    his/her natural environment. The difficulties encountered in the development of EPR treatments, despite the appealing reasoning behind them, could be explained by the tendency of conditional stimuli to re-occur spontaneously. However, it is clear from the studies reviewed that by selecting EPR conditions more rigorously, more efficient procedures might be developed at least for some patients. It seems that the place and the conditions of exposure are factors essential to the success of these therapeutic procedures. Exposure in vivo is better than exposure in imagination. Prolonged exposure over an hour is more effective than exposure lasting 10 minutes. Exposures in close succession are also associated with a better extinction of conditioned responses. The moment that the stimulus occurs, how appropriate it is and its proximity with potential reinforcement are also essential elements for the conditioning procedures. Improving the conditions in which EPR is applied could then enhance the therapeutic potential of this approach.

  13. In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Hadrup, Niels; Boberg, Julie

    2013-01-01

    , indicating increased aromatase activity. The pesticide-mixtures were also investigated in vivo in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. All 5 pesticides could be detected in the amniotic fluid, demonstrating exposure of the fetuses. Decreased estradiol...... with steroidogenesis, and it is suggested that one underlying mechanism for these pesticides is disturbance of steroidogenic enzymes....

  14. Radon and its daughters in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rundo, J

    1984-05-01

    Prolonged exposure to radon should build up a reservoir of radon in body fat and fluids. Movement of the subject to an environment with a lower radon concentration from an environment with a higher level of radon would result in an exhalation of radon, and the initial exhalation rate of radon should depend on the radon concentration inhaled. This paper describes the behavior of radon and its daughters in vivo and a relationship between the radon exhalation rate and the time after a meal. A major but short-lived postprandial increase in the exhalation rate of radon was observed. We report a similar effect in the exhalation rate of radon by persons containing no radium. It should be noted that the possibility exists that a large amount of radon daughters in the chest may interfere in the investigation of possible internal contamination with plutonium or other actinides by external counting. (author).

  15. Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

    Science.gov (United States)

    Leite-Silva, Vânia R; Liu, David C; Sanchez, Washington Y; Studier, Hauke; Mohammed, Yousuf H; Holmes, Amy; Becker, Wolfgang; Grice, Jeffrey E; Benson, Heather Ae; Roberts, Michael S

    2016-05-01

    We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo. Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis. All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected. Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.

  16. Andrographia paniculata a Miracle Herbs for cancer treatment: In vivo and in vitro studies against Aflatoxin B1 Toxicity

    Directory of Open Access Journals (Sweden)

    Md. Sultan Ahmad

    2014-04-01

    Conclusion: In conclusion A. paniculata extracts significantly reduced the number of aberrant cells and frequencies of aberration per cell at each concentration and duration of exposure in vivo; similarly it reduced chromosomal aberrations and sister chromatid exchanges and replication index was enhanced in vitro that was statistically significant at <0.05 level.

  17. In vivo demonstration of ultrasound power delivery to charge implanted medical devices via acute and survival porcine studies.

    Science.gov (United States)

    Radziemski, Leon; Makin, Inder Raj S

    2016-01-01

    Animal studies are an important step in proving the utility and safety of an ultrasound based implanted battery recharging system. To this end an Ultrasound Electrical Recharging System (USER™) was developed and tested. Experiments in vitro demonstrated power deliveries at the battery of up to 600 mW through 10-15 mm of tissue, 50 mW of power available at tissue depths of up to 50 mm, and the feasibility of using transducers bonded to titanium as used in medical implants. Acute in vivo studies in a porcine model were used to test reliability of power delivery, temperature excursions, and cooling techniques. The culminating five-week survival study involved repeated battery charging, a total of 10.5h of ultrasound exposure of the intervening living tissue, with an average RF input to electrical charging efficiency of 20%. This study was potentially the first long term cumulative living-tissue exposure using transcutaneous ultrasound power transmission to an implanted receiver in situ. Histology of the exposed tissue showed changes attributable primarily due to surgical implantation of the prototype device, and no damage due to the ultrasound exposure. The in vivo results are indicative of the potential safe delivery of ultrasound energy for a defined set of source conditions for charging batteries within implants. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. The ichthyotoxic alga Chattonella marina induces Na+, K+-ATPase, and CFTR proteins expression in fish gill chloride cells in vivo

    International Nuclear Information System (INIS)

    Tang, Janet Y.M.; Wong, Chris K.C.; Au, Doris W.T.

    2007-01-01

    Our previous studies demonstrated that the ichthyotoxic Chattonella marina stimulated proliferation of branchial chloride cell (CC) and induced osmotic distress akin to hyperactive elimination of ions in fish (Rhabdosargus sarba). To ascertain the in vivo effects of C. marina on key CC ion transporters, the localization and expression of Na + , K + -ATPase (NKA) and cystic fibrosis transmembrane conductance regulator (CFTR) proteins in response to C. marina exposure were investigated, using a quantitative immunocytochemical approach. The polarized distributions of NKA (α subunit) and CFTR proteins in branchial CCs of R. sarba remained unchanged under C. marina exposure. However, significant inductions of these two ion-transporters were detected in CCs of fish after 6 h exposure. By real-time PCR, no significant changes in gill NKA and CFTR mRNA expressions were detected, suggesting a post-transcriptional pathway is likely involved in regulating the ion transporters abundance. This study is the first to demonstrate the in vivo effects of harmful algal toxin on NKA and CFTR protein expressions in gill transepithelial cells. Taken together, an augmentation of branchial CCs together with hyper-stimulation of NKA and CFTR in CCs attribute to the rapid development of osmotic distress in C. marina susceptible fish

  19. Estimated daily intake and hazard quotients and indices of phthtalate diesters for young danish men

    DEFF Research Database (Denmark)

    Kranich, Selma K; Frederiksen, Hanne; Andersson, Anna-Maria

    2014-01-01

    Because of wide exposure to phthalates, we investigated whether simultaneous exposure to several phthalates reached levels that might cause adverse antiandrogenic effects. Thirty three healthy young Danish men each delivered three 24-h urine samples during a three months period. The daily intakes...... of the sum of di-n-butyl and di-iso-butyl phthalate, di(2-ethylhexyl) phthalate, di-iso-nonyl phthalate, and butylbenzyl phthalate were estimated based on urinary excretion of the metabolites. Based on a hazard quotient (HQ) of the individual phthalate (i.e., the ratio between the daily intake...

  20. Study on advancement of in vivo counting using mathematical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kinase, Sakae [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2003-05-01

    To obtain an assessment of the committed effective dose, individual monitoring for the estimation of intakes of radionuclides is required. For individual monitoring of exposure to intakes of radionuclides, direct measurement of radionuclides in the body - in vivo counting- is very useful. To advance in a precision in vivo counting which fulfills the requirements of ICRP 1990 recommendations, some problems, such as the investigation of uncertainties in estimates of body burdens by in vivo counting, and the selection of the way to improve the precision, have been studied. In the present study, a calibration technique for in vivo counting application using Monte Carlo simulation was developed. The advantage of the technique is that counting efficiency can be obtained for various shapes and sizes that are very difficult to change for phantoms. To validate the calibration technique, the response functions and counting efficiencies of a whole-body counter installed in JAERI were evaluated using the simulation and measurements. Consequently, the calculations are in good agreement with the measurements. The method for the determination of counting efficiency curves as a function of energy was developed using the present technique and a physiques correction equation was derived from the relationship between parameters of correction factor and counting efficiencies of the JAERI whole-body counter. The uncertainties in body burdens of {sup 137}Cs estimated with the JAERI whole-body counter were also investigated using the Monte Carlo simulation and measurements. It was found that the uncertainties of body burdens estimated with the whole-body counter are strongly dependent on various sources of uncertainty such as radioactivity distribution within the body and counting statistics. Furthermore, the evaluation method of the peak efficiencies of a Ge semi-conductor detector was developed by Monte Carlo simulation for optimum arrangement of Ge semi-conductor detectors for

  1. In vivo measurement of Pb-210 in the skull for retrospective assessment of exposure to radon; Die in-vivo Messung von Pb-210 im Schaedel zur retrospektiven Bestimmung von Radon-Expositionen

    Energy Technology Data Exchange (ETDEWEB)

    Doerfel, H. [Forschungszentrum Karlsruhe GmbH (Germany). Hauptabteilung Sicherheit/Dosimetrie

    1997-12-01

    The study shows that the new HPGe detectors with a larger surface are significantly better in terms of results and performance than the Phoswich detectors hitherto used for in vivo measurement of Pb-210 in the human skull. The experimental evaluations indicate that smaller HPGe detectors likewise are better than the Phoswich detectors, but some additional studies are required for final evaluation of these instruments. (orig./CB) [Deutsch] Die Untersuchungen haben gezeigt, dass die neuen grossflaechigen HPGe-Detektoren wesentlich besser zur in-vivo Messung von Pb-210 im Skelett geeignet sind als die bisher eingesetzten Phoswich-Detektoren. Auch kleinere HPGe-Detektoren sind offenbar besser geeignet als Phoswich-Detektoren, allerdings sind hier noch einige ergaenzende Untersuchungen erforderlich. (orig./SR)

  2. Adult mortality and blood feeding behavioral effects of α-amyrin acetate, a novel bioactive compound on in vivo exposed females of Anopheles stephensi Liston (Diptera: Culicidae).

    Science.gov (United States)

    Chenniappan, Kuppusamy; Kadarkari, Murugan

    2012-06-01

    The effect of α-amyrin acetate on mortality and blood feeding behavior in females of Anopheles stephensi was assessed by in vivo exposure on treated guinea pig skin. In vivo exposure to α-amyrin acetate caused mosquito knock down in the form of rapidly and normally reversible paralysis and the subsequent record at the end of a 24 h, revealed mortality rates of females increased from 0.0% (Control) to 76.9% at 1.6% α-amyrin acetate, the highest concentration which implies the contact toxicity of the α-amyrin acetate received through the sensitive parts of test species. The mean probing time responses significantly increased (P blood feeding rates and the mean engorgement times were significantly shorter when compared to the control. The mean blood feeding rates of exposed females decreased from 91.7% (control) to 41.5% at 0.8% α-amyrin acetate concentrations, the mean engorgement time also decreased from 278.6 s (Control) to 158.7 s at 0.8% α-amyrin acetate concentrations. Mean blood feeding rates and mean engorgement time were statistically significant (P blood meal size have played a more important role in decline of fecundity. In vivo exposure to α-amyrin acetate caused increased mean probing time, decreased blood engorgement time and feeding rate and declined fecundity which reduce the overall survival and reproductive capacity of the malaria vector A. stephensi.

  3. 10′(Z),13′(E)-Heptadecadienylhydroquinone Inhibits Swarming and Virulence Factors and Increases Polymyxin B Susceptibility in Proteus mirabilis

    Science.gov (United States)

    Wang, Won-Bo; Yuan, Yu-Han; Hsueh, Po-Ren; Liaw, Shwu-Jen

    2012-01-01

    In this study, we demonstrated that 10′(Z), 13′(E)-heptadecadienylhydroquinone (HQ17-2), isolated from the lacquer tree, could decrease swarming motility and hemolysin activity but increase polymyxin B (PB) susceptibilityof Proteus mirabilis which is intrinsically highly-resistant to PB. The increased PB susceptibility induced by HQ17-2 was also observed in clinical isolates and biofilm-grown cells. HQ17-2 could inhibit swarming in the wild-type and rppA mutant but not in the rcsB mutant, indicating that HQ17-2 inhibits swarming through the RcsB-dependent pathway, a two-component signaling pathway negatively regulating swarming and virulence factor expression. The inhibition of hemolysin activity by HQ17-2 is also mediated through the RcsB-dependent pathway, because HQ17-2 could not inhibit hemolysin activity in the rcsB mutant. Moreover, the finding that HQ17-2 inhibits the expression of flhDC gene in the wild-type and rcsB-complemented strain but not in the rcsB mutant supports the notion. By contrast, HQ17-2 could increase PB susceptibility in the wild-type and rcsB mutant but not in the rppA mutant, indicating that HQ17-2 increases PB susceptibility through the RppA-dependent pathway, a signaling pathway positively regulating PB resistance. In addition, HQ17-2 could inhibit the promoter activities of rppA and pmrI, a gene positively regulated by RppA and involved in PB resistance, in the wild-type but not in the rppA mutant. The inhibition of rppA and pmrI expression caused lipopolysaccharide purified from HQ17-2-treated cells to have higher affinity for PB. Altogether, this study uncovers new biological effects of HQ17-2 and provides evidence for the potential of HQ17-2 in clinical applications. PMID:23029100

  4. A probabilistic risk assessment approach used to prioritize chemical constituents in mainstream smoke of cigarettes sold in China.

    Science.gov (United States)

    Xie, Jianping; Marano, Kristin M; Wilson, Cody L; Liu, Huimin; Gan, Huamin; Xie, Fuwei; Naufal, Ziad S

    2012-03-01

    The chemical and physical complexity of cigarette mainstream smoke (MSS) presents a challenge in the understanding of risk for smoking-related diseases. Quantitative risk assessment is a useful tool for assessing the toxicological risks that may be presented by smoking currently available commercial cigarettes. In this study, yields of a selected group of chemical constituents were quantified in machine-generated MSS from 30 brands of cigarettes sold in China. Using constituent yields, exposure estimates specific to and representative of the Chinese population, and available dose-response data, a Monte Carlo method was applied to simulate probability distributions for incremental lifetime cancer risk (ILCR), hazard quotient (HQ), and margin of exposure (MOE) values for each constituent as appropriate. Measures of central tendency were extracted from the outcome distributions and constituents were ranked according to these three risk assessment indices. The constituents for which ILCR >10(-4), HQ >1, and MOE risk contributed by each MSS constituent, this approach provides a plausible and objective framework for the prioritization of toxicants in cigarette smoke and is valuable in guiding tobacco risk management. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Assay of new systems in vivo mutagenesis for determining the effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Bauluz, C.; Sierra, I.; Martin, L.; Real, A.; Vidania, R. de

    1997-01-01

    Ionizing radiation reacts directly and indirectly with the genetic material in living cells and produces DNA damage. Processing of this damage by correcting enzymes may result in appearing of mutations which, in turn, may lead to carcinogenesis. We have focused on the determination of in vivo mutagenesis induced after exposure to X-rays, aiming at establishing methods to evaluate the effect of low doses of radiation. In vivo mutagenesis has been addressed in the Muta Mouse model that carries a lacZ marker gene and provides a relatively simple assay of appearance of mutations. Mutation frequencies were determined in the lacZ gene copies recovered from mice irradiated with 1Gy or 4Gy of X-rays, acute or fractionated. Liver, spleen and bone marrow DNA samples were isolated at different times after irradiation, ranging from 1 day to 2 months, and evolution of mutations was studied. Results showed different responses depending on the organ and especially on the time of analysis, suggesting that the mutagenic process in vivo is much more complex than previously deduced from in vitro experiments. Therefore, determination of the relationship between dose and mutagenic effect in vivo will require additional studies. (author)

  6. In vitro and in vivo models for testing arrhythmogenesis in drugs.

    Science.gov (United States)

    Carlsson, L

    2006-01-01

    The steadily increasing list of drugs associated with prolongation of the QT interval and torsades de pointes (TdP) constitute a medical problem of major concern. Hence, there is a need at an early stage to identify drug candidates with an inherent capacity to induce repolarization-related proarrhythmias, avoiding exposure of large populations to potentially harmful drugs. Furthermore, the availability of clinically relevant and predictive animal models should reduce the risk that effective and potentially life-saving drugs never reach the market. This review will discuss the pros and cons of some in vivo and in vitro animal models for assessing proarrhythmia liability.

  7. Comet assay in gill cells of Prochilodus lineatus exposed in vivo to cypermethrin.

    Science.gov (United States)

    Poletta, G L; Gigena, F; Loteste, A; Parma, M J; Kleinsorge, E C; Simoniello, M F

    2013-11-01

    Agricultural chemicals can induce genetic alterations on aquatic organisms that have been associated with effects on growth, reproduction and population dynamics. The evaluation of DNA damage in fish using the comet assay (CA) frequently involves the utilization of erythrocytes. However, epithelial gill cells (EGC) can be more sensitive, as they are constantly dividing and in direct contact with potentially stressing compounds from the aquatic environment. The aim of the present study was to evaluate (1) the sensitivity and suitability of epithelial gill cells of Prochilodus lineatus in response to different genotoxic agents through the application of the CA, (2) the induction of DNA damage in this cell population after in vivo exposure to cypermethrin. Baseline value of the CA damage index (DI) for EGC of juvenile P. lineatus was 144.68±5.69. Damage increased in a dose-dependent manner after in vitro exposure of EGC to methyl methanesulfonate (MMS) and H2O2, two known genotoxic agents. In vivo exposure of fish to cypermethrin induced a significant increase in DNA DI of EGC at 0.150μg/l (DI: 239.62±6.21) and 0.300μg/l (270.63±2.09) compared to control (150.25±4.38) but no effect was observed at 0.075μg/l (168.50±10.77). This study shows that EGC of this species are sensitive for the application of the CA, demonstrating DNA damage in response to alkylation (MMS), oxidative damage (H2O2), and to the insecticide cypermethryn. These data, together with our previous study on DNA damage induction on erythrocytes of this species, provides useful information for future work involving biomonitoring in regions where P. lineatus is naturally exposed to pesticides and other genotoxic agents. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Intestinal microflora as potential modifiers of sensitizer activity in vivo

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.

    1984-01-01

    Treatment of mice (some bearing Lewis lung tumors), with penicillin (PEN) at 500 mg/l drinking water for one week prior to treatment with misonidazole (MIS), resulted in: the elimination of their anaerobic cecal flora; a decrease in MIS-induced neurotoxicity; an increase in pharmacological exposure to MIS; a decrease in MIS chemopotentiation; a probable increase in MIS radiosensitization; an increase in MIS induced hypothermia. Assuming no chemical interaction between PEN and MIS, these observations indicate that the intestinal microflora can influence the activity of MIS in vivo. The observed reduction in the neurotoxic but not the radiosensitizing potential of MIS following PEN treatment indicates a therapeutic benefit

  9. Development and evaluation of a technique for in vivo monitoring of {sup 60}Co in the lungs

    Energy Technology Data Exchange (ETDEWEB)

    Mello, J.Q. de; Lucena, E.A.; Dantas, A.L.A.; Dantas, B.M., E-mail: bmdantas@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    {sup 60}Co is a fission product of {sup 235}U and represents a risk of internal exposure of workers in nuclear power plants, especially those involved in the maintenance of potentially contaminated parts and equipment. The control of {sup 60}Co intake by inhalation can be performed through in vivo monitoring. This work describes the evaluation of a technique through the minimum detectable activity and the corresponding minimum detectable effective doses, based on biokinetic and dosimetric models of {sup 60}Co in the human body. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes. (author)

  10. Electrosensitization Increases Antitumor Effectiveness of Nanosecond Pulsed Electric Fields In Vivo.

    Science.gov (United States)

    Muratori, Claudia; Pakhomov, Andrei G; Heller, Loree; Casciola, Maura; Gianulis, Elena; Grigoryev, Sergey; Xiao, Shu; Pakhomova, O N

    2017-01-01

    Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors in mice. Nanosecond pulsed electric field ablations were produced using a 2-needle probe with a 6.5-mm interelectrode distance. In agarose gel, splitting a pulsed electric field dose of 300, 300-ns pulses (20 Hz, 4.4-6.4 kV) in 2 equal fractions increased cell death up to 3-fold compared to single-train treatments. We then compared the antitumor effectiveness of these treatments in vivo. At 24 hours after treatment, sensitizing tumors by a split-dose pulsed electric field exposure (150 + 150, 300-ns pulses, 20 Hz, 6.4 kV) caused a 4- and 2-fold tumor volume reduction as compared to sham and single-train treatments, respectively. Tumor volume reduction that exceeds 75% was 43% for split-dose-treated animals compared to only 12% for single-dose treatments. The difference between the 2 experimental groups remained statistically significant for at least 1 week after the treatment. The results show that electrosensitization occurs in vivo and can be exploited to assist in vivo cancer ablation.

  11. Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

    Science.gov (United States)

    Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

    2018-03-01

    The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. 3D morphological analysis of the mouse cerebral vasculature: Comparison of in vivo and ex vivo methods.

    Directory of Open Access Journals (Sweden)

    Joe Steinman

    Full Text Available Ex vivo 2-photon fluorescence microscopy (2PFM with optical clearing enables vascular imaging deep into tissue. However, optical clearing may also produce spherical aberrations if the objective lens is not index-matched to the clearing material, while the perfusion, clearing, and fixation procedure may alter vascular morphology. We compared in vivo and ex vivo 2PFM in mice, focusing on apparent differences in microvascular signal and morphology. Following in vivo imaging, the mice (four total were perfused with a fluorescent gel and their brains fructose-cleared. The brain regions imaged in vivo were imaged ex vivo. Vessels were segmented in both images using an automated tracing algorithm that accounts for the spatially varying PSF in the ex vivo images. This spatial variance is induced by spherical aberrations caused by imaging fructose-cleared tissue with a water-immersion objective. Alignment of the ex vivo image to the in vivo image through a non-linear warping algorithm enabled comparison of apparent vessel diameter, as well as differences in signal. Shrinkage varied as a function of diameter, with capillaries rendered smaller ex vivo by 13%, while penetrating vessels shrunk by 34%. The pial vasculature attenuated in vivo microvascular signal by 40% 300 μm below the tissue surface, but this effect was absent ex vivo. On the whole, ex vivo imaging was found to be valuable for studying deep cortical vasculature.

  13. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca, E-mail: francesca.maranghi@iss.it [Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Stecca, Laura [European Commission-Joint Research Centre, Institute for Health and Consumer Protection Chemical assessment and Testing Unit, Via E. Fermi, 2749I-21027 Ispra (Italy)

    2015-06-23

    In European Union, titanium dioxide (TiO{sub 2}) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO{sub 2} NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO{sub 2} NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO{sub 2} NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm{sup 2} levels of TiO{sub 2} NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO{sub 2} NP toxicity by direct exposure both in vivo and in vitro models.

  14. Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit.

    Science.gov (United States)

    North, Ashley; Swant, Jarod; Salvatore, Michael F; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K; Heltsley, Rebecca; Clark, John T; Khoshbouei, Habibeh

    2013-05-01

    Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure. Copyright © 2012 Wiley Periodicals, Inc.

  15. Prenatal Exposure to Tributyltin Decreases GluR2 Expression in the Mouse Brain.

    Science.gov (United States)

    Ishida, Keishi; Saiki, Takashi; Umeda, Kanae; Miyara, Masatsugu; Sanoh, Seigo; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), a common environmental contaminant, is widely used as an antifouling agent in paint. We previously reported that exposure of primary cortical neurons to TBT in vitro decreased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) expression and subsequently increased neuronal vulnerability to glutamate. Therefore, to identify whether GluR2 expression also decreases after TBT exposure in vivo, we evaluated the changes in GluR2 expression in the mouse brain after prenatal or postnatal exposure to 10 and 25 ppm TBT through pellet diets. Although the mean feed intake and body weight did not decrease in TBT-exposed mice compared with that in control mice, GluR2 expression in the cerebral cortex and hippocampus decreased after TBT exposure during the prenatal period. These results indicate that a decrease in neuronal GluR2 may be involved in TBT-induced neurotoxicity, especially during the fetal period.

  16. 76 FR 13089 - National Priorities List, Final Rule No. 51

    Science.gov (United States)

    2011-03-10

    ...) at issue. That is, the NPL site would include all releases evaluated as part of that HRS analysis... County, MT.... EPA-HQ-SFUND-2010-0072. Wright Chemical Corporation......... Riegelwood, NC........ EPA-HQ... Landfill Nassau, NY EPA-HQ-SFUND-2010-0075. Milford Contaminated Aquifer........ Milford, OH EPA-HQ-SFUND...

  17. Biological effects of cell-phone radiofrequency waves exposure on fertilization in mice; an in vivo and in vitro study

    Directory of Open Access Journals (Sweden)

    Daryoush Fatehi

    2018-06-01

    Full Text Available Increasing use of cell-phone is one of the most important risk factors for population health. We designed an experimental study aimed at evaluating the effects of cell-phone radiofrequency (RF waves exposure on fertilization in mice. Two hundred male and female NMRI-mice were used. One hundred males divided in five groups (n = 20 as control and exposed groups. Those irradiated with cell-phone RF in “Standby-mode” 1, 5 and 10 h daily named groups II, III and IV; respectively. Group V irradiated with cell-phone on “Active-mode” one hour daily. After 30 days irradiation, 50 males and 50 females were kept 24 h to assess their embryos. Fifty males were scarified to evaluate both in vitro and in vivo parameters, and 50 females received PMSG & HCG for both quantitative and qualitative evaluation. Comparing groups III, IV and V with control-group showed significantly decreased in the number of two-cell embryos (p = .000; however, a significant increase was found in the number of dead embryos (p = .000. Furthermore, 5 h daily irradiation significantly decreased grade-A embryos (p = .015; while, it significantly increased grade-B, C and D embryos (p-values = 0.026, 0.007, 0.006; respectively. Moreover, comparing groups IV and V to control-group, significant increase was found in pregnancy duration (p = .005, p = .009; respectively. However, in the mentioned groups a significant decrease was seen in number of newborn mice (p = .001, p = .004; respectively. In conclusion our findings showed that the cell-phone radiation can affect development of embryos as well as the number of newborn and pregnancy duration in NMRI-mouse, which might be a significant cause of reproductive failure. Keywords: Fertility, IVF, RF, Cell-phone, Embryo

  18. In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, Roger M.; Stanwell, Peter; Stretch, Jonathan R.; Scolyer, Richard A.; Thompson, John F.; Mountford, Carolyn E.; Lean, Cynthia L

    2005-03-01

    In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

  19. Virtual reality exposure therapy for social anxiety disorder: a randomized controlled trial.

    Science.gov (United States)

    Anderson, Page L; Price, Matthew; Edwards, Shannan M; Obasaju, Mayowa A; Schmertz, Stefan K; Zimand, Elana; Calamaras, Martha R

    2013-10-01

    This is the first randomized trial comparing virtual reality exposure therapy to in vivo exposure for social anxiety disorder. Participants with a principal diagnosis of social anxiety disorder who identified public speaking as their primary fear (N = 97) were recruited from the community, resulting in an ethnically diverse sample (M age = 39 years) of mostly women (62%). Participants were randomly assigned to and completed 8 sessions of manualized virtual reality exposure therapy, exposure group therapy, or wait list. Standardized self-report measures were collected at pretreatment, posttreatment, and 12-month follow-up, and process measures were collected during treatment. A standardized speech task was delivered at pre- and posttreatment, and diagnostic status was reassessed at 3-month follow-up. Analysis of covariance showed that, relative to wait list, people completing either active treatment significantly improved on all but one measure (length of speech for exposure group therapy and self-reported fear of negative evaluation for virtual reality exposure therapy). At 12-month follow-up, people showed significant improvement from pretreatment on all measures. There were no differences between the active treatments on any process or outcome measure at any time, nor differences on achieving partial or full remission. Virtual reality exposure therapy is effective for treating social fears, and improvement is maintained for 1 year. Virtual reality exposure therapy is equally effective as exposure group therapy; further research with a larger sample is needed, however, to better control and statistically test differences between the treatments.

  20. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

    2012-12-15

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

  1. Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production

    Science.gov (United States)

    In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis. The DPB metabolite mono‐butyl phthalate (MBP) is hypothesized to produce these changes by ...

  2. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  3. Evaluation of the morphological effects of TDT 067 (terbinafine in Transfersome) and conventional terbinafine on dermatophyte hyphae in vitro and in vivo.

    Science.gov (United States)

    Ghannoum, M; Isham, N; Henry, W; Kroon, H-A; Yurdakul, S

    2012-05-01

    TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.

  4. Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Keping Xu

    2011-02-01

    Full Text Available Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK was removed and carboxymethylcellulose (CMC was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%, bromfenac 0.09%, and nepafenac 0.1%.Methods: Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM, corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control, or MEM (negative control, followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels. Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results: The mean (±SD original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments, 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM. In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%, 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P < 0.01 vs MEM and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs

  5. Exposure assessment of organophosphorus and organobromine flame retardants via indoor dust from elementary schools and domestic houses.

    Science.gov (United States)

    Mizouchi, Shigekazu; Ichiba, Masayoshi; Takigami, Hidetaka; Kajiwara, Natsuko; Takamuku, Toshiyuki; Miyajima, Toru; Kodama, Hiroki; Someya, Takashi; Ueno, Daisuke

    2015-03-01

    To assess the exposure of flame retardants (FRs) for school-children, organophosphorus flame retardants and plasticizers (PFRs) and organobromine flame retardants (BFRs) were determined in the indoor dust samples collected from elementary schools and domestic houses in Japan in 2009 and 2010. PFRs were detected in all the dust samples analyzed and the highest concentration of total PFRs was thousand-fold higher than that of BFRs. Among the PFRs, tris(butoxyethyl)phosphate (TBOEP) showed the highest concentration with a median (med.) of 270,000 ng g(-1) dry weight (3700-5,500,000 ng g(-1) dry weight), followed by tris(methylphenyl)phosphate (TMPPs)>triphenyl phosphate (TPHP)=tris(1,3-dichloro-2-propyl)phosphate (TDCIPP)=tris(2-chloroisopropyl)phosphate (TCIPP)=tris(2chloroethyl)phosphate (TCEP)>ethylhexyl diphenyl phosphate (EHDPP). Significantly higher concentrations of TBOEP, tri-n-butyl phosphate (TNBP), TPHP, TMPPs, and total-PFRs were found in dust samples from elementary schools than from domestic houses. It might be due to that higher concentrations of TBOEP (as leveling agent) were detected from the floor polisher/wax products collected in those elementary schools. On the other hand, significantly higher concentrations of TCEP, TCIPPs, and total chloroalkyl-PFRs were found in domestic houses than in elementary schools. Exposure assessments of PFRs via indoor dust from elementary schools and domestic houses were conducted by calculating the hazard quotient (HQ). Among PFRs, HQs for TBOEP exceeded 1 (higher than reference dose: RfD) and its highest value was 1.9. To reduce the intake of TBOEP by school-children, it is recommended that the use of floor polisher/wax containing TBOEP be reduced in schools. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Virtual reality exposure therapy for fear of driving: analysis of clinical characteristics, physiological response, and sense of presence.

    Science.gov (United States)

    Costa, Rafael T da; Carvalho, Marcele R de; Ribeiro, Pedro; Nardi, Antonio E

    2018-01-01

    To investigate the reactions of women with driving phobia to a therapeutic program of scheduled virtual reality exposure treatment (VRET) sessions. The study intervention consisted of a computer game with car-driving scenarios that included several traffic situations. We investigated the participants' sense of presence, subjective distress, and physiological responses during eight virtual-reality exposures. We also evaluated clinical characteristics, driving cognitions, and quality of life in the participants. Thirteen women were selected. Eight were able to complete the protocol. After VRET, there was a decrease in the frequency of distorted thoughts and state anxiety scores, as well as a slight improvement in quality of life. Subjective discomfort scores, heart rate variation, and sense of presence scores confirmed that there was sense of presence in the virtual reality environment. All patients showed some degree of improvement and demonstrated different levels of anxiety in subsequent in vivo driving experiences. Our findings suggest that VRET could be used to facilitate in vivo exposure, because it can induce presence/immersion and reduce anxiety in patients with specific phobia. Furthermore, VRET is not associated with any type of risk.

  7. Virtual reality exposure therapy for fear of driving: analysis of clinical characteristics, physiological response, and sense of presence

    Directory of Open Access Journals (Sweden)

    Rafael T. da Costa

    2018-02-01

    Full Text Available Objective: To investigate the reactions of women with driving phobia to a therapeutic program of scheduled virtual reality exposure treatment (VRET sessions. Methods: The study intervention consisted of a computer game with car-driving scenarios that included several traffic situations. We investigated the participants’ sense of presence, subjective distress, and physiological responses during eight virtual-reality exposures. We also evaluated clinical characteristics, driving cognitions, and quality of life in the participants. Results: Thirteen women were selected. Eight were able to complete the protocol. After VRET, there was a decrease in the frequency of distorted thoughts and state anxiety scores, as well as a slight improvement in quality of life. Subjective discomfort scores, heart rate variation, and sense of presence scores confirmed that there was sense of presence in the virtual reality environment. Conclusion: All patients showed some degree of improvement and demonstrated different levels of anxiety in subsequent in vivo driving experiences. Our findings suggest that VRET could be used to facilitate in vivo exposure, because it can induce presence/immersion and reduce anxiety in patients with specific phobia. Furthermore, VRET is not associated with any type of risk.

  8. Radon and its daughters in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rundo, J

    1984-05-01

    Prolonged exposure to radon should build up a reservoir of radon in body fat and fluids. If the subject moved to an environment with a lower radon concentration from an environment with a higher level of radon, the result would be an exhalation of radon, and the initial exhalation rate of radon should depend of the radon concentration inhaled. This paper describes the behavior of radon and its daughters in vivo and a relationship between the radon exhalation rate and the time after a meal. A major but short-lived postprandial increase in the exhalation rate of radon was observed. The author reports a similar effect in the exhalation rate of radon by persons containing no radium. It should be noted that the possibility exists that a large amount of radon daughters in the chest may interfere in the investigation of possible internal contamination with plutonium or other actinides by external counting. 8 figures.

  9. Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

    DEFF Research Database (Denmark)

    Li, Ying; Han, Meihua; Liu, Tingting

    2017-01-01

    The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...

  10. A comparative in vivo and in vitro L-band EPR study of irradiated rat incisors

    International Nuclear Information System (INIS)

    Zdravkova, M.; Gallez, B.; Debuyst, R.

    2005-01-01

    L-band (∼1GHz) EPR has the potential to measure the absorbed radiation dose in human teeth inside the mouth (in vivo analyses). One crucial point in the development of the method is to know if dosimetry evaluation carried out in vivo after accidental exposures can be reliably based on calibration curves built in vitro. The aim of the present work is to specifically address this point. First, we compared L-band in vitro and in vivo analyses in irradiated rat teeth and estimated the possible loss in in vivo experiments due to rat movements and mouth proximity. Second, the lower pair of rat incisors were analysed by L-band EPR before and after irradiation (50Gy), first on the living rat, then on the same dead rat, finally after extraction of the teeth. X-band powder spectra were also taken after crushing of the two teeth. Irradiations of dead rats and extracted teeth were also carried out. Comparing L-band spectra obtained with living rats and removed heads does not show any significant difference due to possible small rat movements or breathing. Relative standard deviations of the amplitudes of the dosimetric signal are quite high (27-54%). Nevertheless, it seems to be a tendency to have higher signals in irradiated extracted teeth than in irradiated animals

  11. Use of human metabolic studies and urinary arsenic speciation is assessing arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.R.; Farmer, J.G. (Memphis State Univ., TN (United States) Univ. of Edinburgh (United Kingdom))

    1991-01-01

    The use of hair and nail analyses to assess human exposure to the trace metalloid arsenic (As) is hindered by the possibility of external contamination. Even though urine represents the major excretory route, its use as an indicator of exposure is limited when no distinction is made between the nontoxic organoarsenical (arsenobetaine) excreted following the consumption of seafood and the toxic inorganic forms of As and related metabolites. The development of analytical techniques capable of separating the different chemical species of As in urine have shown that the ingestion of inorganic As (AsV or AsIII) by animals and man triggers an in vivo reduction/methylation process resulting in excretion of the less toxic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA). This paper establishes the uptake, bio-transformation and elimination patterns reflected in urinary As following carefully controlled experimental exposure.

  12. In Vivo Nanotoxicity Testing using the Zebrafish Embryo Assay.

    Science.gov (United States)

    Rizzo, Larissa Y; Golombek, Susanne K; Mertens, Marianne E; Pan, Yu; Laaf, Dominic; Broda, Janine; Jayapaul, Jabadurai; Möckel, Diana; Subr, Vladimir; Hennink, Wim E; Storm, Gert; Simon, Ulrich; Jahnen-Dechent, Willi; Kiessling, Fabian; Lammers, Twan

    2013-06-10

    Nanoparticles are increasingly used for biomedical purposes. Many different diagnostic and therapeutic applications are envisioned for nanoparticles, but there are often also serious concerns regarding their safety. Given the fact that numerous new nanomaterials are being developed every day, and that not much is known about the long-term toxicological impact of exposure to nanoparticles, there is an urgent need to establish efficient methods for nanotoxicity testing. The zebrafish (Danio rerio) embryo assay has recently emerged as an interesting 'intermediate' method for in vivo nanotoxicity screening, enabling (semi-) high-throughput analyses in a system significantly more complex than cultured cells, but at the same time also less 'invasive' and less expensive than large-scale biocompatibility studies in mice or rats. The zebrafish embryo assay is relatively well-established in the environmental sciences, but it has not yet gained wide notice in the nanomedicine field. Using prototypic polymeric drug carriers, gold-based nanodiagnostics and nanotherapeutics, and iron oxide-based nanodiagnostics, we here show that toxicity testing using zebrafish embryos is easy, efficient and informative, and faithfully reflects, yet significantly extends, cell-based toxicity testing. We therefore expect that the zebrafish embryo assay will become a popular future tool for in vivo nanotoxicity screening.

  13. Workers’ cytokines profiling upon exposure to MWCNT aerosol in occupational settings

    Science.gov (United States)

    Fatkhutdinova, L. M.; Khaliullin, T. O.; Zalyalov, R. R.; Vasilyeva, O. L.; Valeeva, I. Kh; Mustafin, I. G.

    2015-11-01

    Recent studies have found that upon pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) animals develop primarily fibrosis and granulomas in lungs. In vitro and in vivo studies also give reason to assume that local exposure could be related to remote effects, including immune system and the endothelium. To investigate the remote effect hypothesis, we have analyzed blood, nasal lavage and induced sputum samples taken from workers in the frame of the Russian epidemiological study on Carbon Nanotubes Exposure and Risk Assessment (CNT-ERA). In serum and nasal lavage no significant differences between exposure and control groups were observed with a high variability to the cytokines content. In the samples of induced sputum from exposed workers the content of IL-1b, IL-6, IL-8, TNF-a, IL-4, IL-5, IFN-g exceeded the control group values, but after the regression models construction and bootstrap analysis, significant differences were found only for IL-1b. This study could not provide evidences of blood cytokines changes following local cytokine production in airways in workers exposed to MWCNTs. Cytokines variability in serum and nasal lavage may indicate the absence of severe systemic inflammatory response upon the existing occupational exposure to MWCNTs. Other systemic responses (including allergy-like or autoimmune reactions) should be regarded as w